journal of medical college c h a n d i g a r h · cholangitis and cholecystitis: tokyo guidelines....

Vol. 6 No. 2, Sept. 2016

JOURNAL OF MEDICAL COLLEGE

C H A N D I G A R H

ISSN 2321 – 3973

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JOURNAL OF MEDICAL COLLEGE CHANDIGARH

VOLUME 6, NUMBER 2, SEPTEMBER 2016 (SILVER JUBILEE ISSUE)

CONTENTS

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EDITORIAL i-ii

Acute cholangitis: The “scope” of treatment iAtul Sachdev

REVIEW ARTICLES

Acute cholangitis- An overview of diagnosis and medical management 1-8Monica Gupta, Atul Sachdev

Role of Biomarkers in Diagnosis of Sepsis 9-16Varsha Gupta, Vibha Mehta

ORIGINAL ARTICLE

Balance and functional assessment in ambulatory elderly patients using Timed Get Up and Go test 17-22Aakanksha Sharma, Monica Gupta, Sarabmeet Singh Lehl

CASE REPORTS

Splenic Preservation in Blunt Pancreatic Trauma – Report of a Case 23-25Gaurav Shanker Pandey, Simrandeep Singh, Robin Kaushik

Hypotensive transfusion reaction – a case report 26-27Kshitija Mittal, Rakesh Kumar, Gagandeep Kaur, Paramjit Kaur, Tanvi Sood, Ravneet Kaur

Lichen scrofulosorum associated with active pulmonary tuberculosis in an adult 28-29Manjit Kaur, Mala Bhalla, Gurvinder P. Thami

Intracapsular dissection in cervical sympathetic chain schwannoma: a case report 30-32Naiya Rao, Manish Gupta

Dermatomyositis overlapping with Rheumatoid arthritis: a rare clinical entity 33-35Mandip Singh Bhatia, Ritu Attri, Monica Gupta

Medial Calcaneal Nerve block for plantar fasciitis pain: A case series 36-38Deepak Thapa, Vanita Ahuja, Ankita Mittal, Manjot Singh

INSTRUCTIONS TO AUTHOR

Guidelines to Contributors 39-40

i Journal of Medical College Chandigarh, 2016, Vol. 6, No.2

Editorial

Acute cholangitis: The “scope” of treatment

In this issue of the journal, a comprehensive review on acute cholangitis has been published, where the authors have discussed the new insights in its pathophysiology and current management guidelines. Until recently, acute cholangitis has been a difficult disease to diagnose and treat due to variable clinical presentations, and no standard definitions or set criteria to diagnose the disease. The ambiguity in the judgment of severity made further management discretionary and suboptimal leading to poor outcomes.

Acute biliary infections can present as mild disease in the form of cholecystitis or as severe life threatening cholangitis. In the past, acute cholangitis occurred more in the context of choledocholithiasis, but recently a larger number of cases are arising due to malignancy and non-surgical instrumentation of the biliary tract. The incidence of health-care-associated acute cholangitis has also been on the rise. Any delay in diagnosis and imprecision in severity assessment can lead to fatal complications. Clear and reliable criteria are essential, so that the biliary drainage or other procedures are carried out without undue delay.

Several attempts have been made to evolve a consensus on developing objective and reliable diagnostic criteria in the past but most of them had several limitations and did not exhibit enough sensitivity and specificity to be applicable in the clinical settings. Besides most of the patients especially the elderly do not present to the clinicians with the typical textbook description or historically characteristic picture of Charcot's triad. The Tokyo guidelines 2007 for the first time laid down essential framework delineating the diagnostic criteria and severity assessment for cases of acute

1cholangitis. These were extensively used worldwide as the primary standard until 2013 when revised guidelines were updated to further improve the reliability and diagnostic accuracy of severity assessment. The TG13 updated version

2is much more objective and implementation friendly. Based on evidence, five predictive factors for poor prognosis have been identified; these include hyperbilirubinemia, high fever, leucocytosis, elderly patient and hypoalbuminemia.

Patients with acute cholangitis are prone to develop severe and potentially fatal infections such as sepsis unless appropriate medical care is instituted promptly. Although advanced antimicrobial therapy is the cornerstone to management of acute cholangitis, biliary tract decompression is obligatory as a therapeutic measure particularly for moderate to severe cases. With the rapid advances in the endoscopic techniques (endoscopic retrograde cholangiopancreatography, endoscopic ultrasound) and widespread availability of endoscopy, the management of acute cholangitis has become the primary realm of the skilled endoscopists. The Tokyo TG13 guidelines also recommend endoscopic biliary drainage as the first choice therapy for biliary decompression in acute cholangitis with non-

3surgically altered anatomy because it is less invasive and associated with lower mortality and shorter hospital stay.

single or double-balloon enteroscopy-assisted biliary drainage and endoscopic ultrasonography-guided biliary drainage have been added to the armamentarium of endoscopic management to further improve the “scope” of acute cholangitis treatment.

1. Kimura Y, Takada T, Kawarada Y, Nimura Y, Hirata K, Sekimoto M, et al. Definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg 2007;14:15-26.

2. Takada T, Strasberg SM, Solomkin JS, Pitt HA, Gomi H, Yoshida M, et al. TG13: Updated Tokyo Guidelines for the management of acute cholangitis and cholecystitis. J Hepatobiliary Pancreat Sci 2013;20:1-7

3. Kiriyama S, Takada T, Strasberg SM, Solomkin JS, Mayumi T, Pitt HA, et al. TG13 guidelines for diagnosis and severity grading of acute cholangitis (with videos). J Hepatobiliary Pancreat Sci 2013;20:24-34.

Prof. Atul SachdevChief Editor

Department of Medicine, GMCH, Chandigarhemail: [email protected]

Percutaneous transhepatic biliary drainage may be considered as alternative methods when endoscopic biliary drainage is difficult. Various newer techniques like

REFERENCES

1 Journal of Medical College Chandigarh, 2016, Vol. 6, No.2

Introduction

Acute cholangitis is a systemic disease resulting from bacterial infection superimposed on partially or completely obstructed biliary system. Acute cholangitis is defined as a morbid condition with acute inflammation

1and infection in the bile duct. Infectious cholangitis encompass a wide spectrum of infectious processes affecting biliary tree. It may present as a local biliary infection or progressive systemic inflammatory response syndrome (SIRS), or more rapidly advancing sepsis with or without multi-organ dysfunction. Others are indolent infections that may predispose a patient to liver failure or cholangiocarcinoma. Viral cholangitides primarily affect immune-compromised patients. Parasitic cholangitis is generally seen in tropical countries. Rapid diagnosis and severity estimation are essential for proper management, including intensive medical support and urgent biliary drainage.

Pathophysiology

Although bile is normally sterile, microorganisms gain access to biliary tree by retrograde ascent from duodenum or from portal venous system. Progressive biliary obstruction causes an elevated intraluminal pressure, that spreads the infection into the biliary

2canaliculi, hepatic veins, and perihepatic lymphatics. In absence of obstruction and raised intra-ductal pressures, bile is unlikely to get infected and cause clinical cholangitis. Increased bacterial colonization of small bowel and diminished host immune defenses set the stage for translocation of local bacteria into the systemic circulation, resulting in potentially life-threatening septicemia. The lack of endothelial lining between bile

canaliculi and liver capillaries also predisposes to early septicemia.

History

Acute cholangitis was initially described in literature by Dr. Jean-Martin Charcot as “hepatic fever” in 1877. Charcot's triad is characterized by classical features of acute cholangitis; intermittent fever with chills, right

3upper quadrant pain, and jaundice. The Reynold's pentad was coined in 1959 by Reynolds and Dragan, who described a severe form of cholangitis with septic shock and mental confusion, in addition to triad of

4Charcot. However, the actual occurrence of Charcot's triad is observed in 15.4% to 72% of patients with acute cholangitis, and Reynolds' pentad is exceedingly

5,6uncommon, reported in only 3.5%–7.7% of patients.

Epidemiology

Etiology

The circumstances leading to biliary stasis or obstruction result in bacterial infection and cholangitis. Partial blockage has a higher incidence of infection than complete obstruction. Choledocholithiasis is the commonest reason of acute cholangitis. The propensity of bactibilia increases with presence of gallbladder or common bile duct (CBD) stones. Bile cultures are

7affirmative in 50% of patients with choledocholithiasis. Earlier choledocholithiasis accounted for about 80% cases of acute cholangitis. However, recently health care associated acute cholangitis related to growing endoscopic and radiological interventions and bilio-pancreatic malignancy is becoming more frequent. The incidence of acute cholangitis after endoscopic retrograde cholangiopancreatography (ERCP) is

8,90.5–1.7%. Malignancies currently account for 10–30% of all cases. South-east Asians are more prone to have primary stones attributable to chronic biliary infections, parasites, bile stasis, and biliary strictures.

In tropical countries like India or Latin America, parasitic infestations of biliary tract are responsible for

Review Article

Acute cholangitis- An overview of diagnosis and medical management

Monica Gupta, Atul Sachdev

Professor

Department of General Medicine, Government Medical College and Hospital, Chandigarh

Corresponding Author :

Dr. Monica GuptaM. D., D.N.B. Medicine, ProfessorLevel 4, D Block, Department of General Medicine, GMCH, ChandigarhEmail: [email protected]

substantial cases of biliary obstruction and cholangitis. This condition is known as recurrent pyogenic cholangitis or Oriental cholangiohepatitis and is a progressive disease characterized by recurrent episodes of bacterial cholangitis. It is related to biliary ductal ectasia, focal strictures, and development of intrahepatic

10pigment stones. The causal parasites are Ascaris lumbricoides, Clonorchis sinensis, Opisthorchis viverrini, Opisthorchis felineus, and Dicrocoelium

11dendriticum. Occasionally, Echinococcus granulosus and Echinococcus multilocularis cysts may rupture or fistulize into biliary system with resultant cholangitis.

Other uncommon etiologies are AIDS cholangiopathy characterized by sclerosing chongitis like picture, Mirizzi syndrome characterized by CBD stenosis caused by stone impacted at the gall bladder neck or in the cystic duct and Lemmel syndrome distinguished by presence of cholestatic jaundice, cholangitis and pancreatitis secondary to duodenal pancreatic diverticulum compressing or displacing distal biliary opening. Table I shows the common etiologies of acute cholangitis.

Causative agents

The infecting organisms are usually those of gut flora. Bile cultures are often polymicrobial in 30-80% of patients and gram-negative bacilli are seen in 88% of

12these cases. The common gram-negative bacilli cultured from the bile in acute suppurative cholagitis are Escherichia coli, Klebsiella species, Enterococcus species, Streptococcus species, Enterobacter species,

13and Pseudomonas aeruginosa. Anaerobes consisting of Bacteroides and Clostridium species are detected in roughly 25% of patients. Hospital acquired cholangitis is frequently caused by multiple resistant organisms, such as Pseudomonas, methicillin resistant Staphylococcus aureus, and vancomycin-resistant enterococci, whereas infection in community-acquired cases are typically associated with intestinal microorganism, such as Escherichia coli, Klebsiella, or Enterococcus. Many cases with culture positive cholangitis have the same species of bacteria in blood as isolated from bile

14cultures. The rates of blood culture-positivity in acute

15cholangitis are reported to fluctuate between 21-71%. In AIDS -related cholangitis the causative agents may be Cytomegalovirus or Cryptosporidium and is characterized by extrahepatic biliary edema, ulceration, and obstruction.

Clinical features

To suspect cholangitis, it is important to elicit the history of gallstones or CBD stones, recent cholecystectomy or biliary surgery, recent endoscopic procedures or invasive radiological interventions. The presenting features may be classical as Charcot's triad consisting of fever, right upper quadrant (RUQ) pain, and jaundice. But a classical presentation is usually not the case; although if present it is very specific to the diagnosis of acute cholangitis. Similarly the Reynold's pentad is much rarer. Fever and abdominal pain are the core symptoms, with similar incidence of 80% or more, whereas jaundice is observed

16,17in 60–70% of cases. Other patients may present with altered mental status (10-20%), hypotension (30%), acute renal failure or cholestasis. Physical examination may reveal fever, RUQ tenderness, mild hepatomegaly, jaundice, disturbed consciousness, septic shock, tachycardia and rarely peritonitis. The classic clinical symptoms of fever and abdominal pain are often absent

18or more difficult to recognize in elderly patients. Symptoms in elderly may not correlate with disease severity therefore many with severe cholangitis present with deceptively mild symptoms leading to delayed or

19misdiagnosis. Moreover, elderly have relatively higher prevalence of severe cholangitis, hypotension, altered sensorium, peritonism and renal failure.

Laboratory studies

Laboratory data may indicate evidence of inflammation in the form of abnormal WBC count (leucocytosis or leucopenia), increase of serum C-reactive protein, and erythrocyte sedimentation rate. There may be also indication of biliary stasis (hyperbilirubinemia) and raised liver enzymes (Increased alkaline phosphatase, gamma-glutamyltranspeptidase, aspartate amino-transferase and alanine aminotransferase). Electrolyte panel with renal function should be performed. A prolonged prothrombin time helps to assess severity of disease. Both aerobic and anerobic blood cultures should be done to detect bacteremia and antibiotic susceptibility. Biliary cultures must be sent if a biliary drainage procedure is considered. Hyperamylasemia is a helpful parameter to identify complications such as

20choledocholithiasis resulting in biliary pancreatitis.

Imaging findings

Imaging plays a pivotal role in diagnosis of cholangitis,

Gupta and Sachdev

2Journal of Medical College Chandigarh, 2016, Vol. 6, No.2

identifying predisposing factors, and revealing complications. Ultrasonography (USG) is the most frequently used first-line imaging modality. USG is highly sensitive and specific for imaging gallbladder and assessing bile duct dilatation. As compared to with USG, computed tomography (CT) is more effective in demonstrating the cause and site of biliary obstruction (in particular distal common bile duct) and biliary

21 morphology. CT cholangiography is a novel modality that utilizes contrast which is taken up by hepatocytes and secreted into biliary system and its accuracy is equ iva len t to ERCP. Magne t i c r esonance cholangiopancreatography (MRCP) is a noninvasive technique that detects dilatation and enhancement of intrahepatic biliary ducts in majority (92%) of cholangitis cases. The distribution can be segmental (46%), central (38%) or diffuse (16%). In 85%, there is associated smooth and symmetric wall thickening. Pneumobilia can also be present in cases of acute bacterial cholangitis, similarly complications include liver abscesses and portal vein thrombosis which can

22 also be detected. Oriental cholangiohepatitis is distinguished by stenosis or strictures of peripheral ducts, with decreased branching and abrupt tapering (“arrowhead appearance”) and disproportionate

23dilatation of extrahepatic bile ducts. Diagnostic direct cholangiography methods like percutaneous transhepatic cholangiography (PTC) or ERCP can

demonstrate detailed biliary anatomy. Since they can exacerbate cholangitis, whenever contemplated, these procedures should always be accompanied by therapeutic biliary drainage.

Diagnosis

In Tokyo April 2006, Evidence-Based Practice Guidelines for Management of Acute Cholangitis and Cholecystitis were developed and published by the International Consensus Meeting for Management of

24Acute Cholecystitis and Cholangitis. Based on extensive review of large studies and consensus of World experts, these guidelines have been established as benchmark for the diagnosis, severity assessment and management of acute cholangitis. Before these guidelines were available, there were no standard diagnostic criteria for acute cholangitis. Acute cholangitis was defined by some authors based on clinical signs such as Charcot's triad (fever and/or chills, abdominal pain, and jaundice) while others emphasized the properties of bile or presence of biliary obstruction (acute suppurative cholangitis, acute obstructive

16,25suppurative cholangitis. In 2013, these guidelines were further updated to improve the diagnostic accuracy

26 and reliability in the assessment of severity of disease.Table II shows the diagnostic criteria for acute

27cholangitis that were adopted in 2013. Diseases which need to be differentiated from acute cholangitis are acute cholecystitis, peptic ulcer, acute pancreatitis, acute hepatitis, diverticulitis, mesenteric ischemia and septicemia from other sources.

Table I

1Etiology of acute cholangitis

sCholelithiasissBenign biliary stricturesCongenital factorssPostoperative factors (damaged bile duct, strictured

choledojejunostomy, etc.)sInflammatory factors (oriental cholangitis, etc.)sMalignant occlusion

wBile duct tumorwGallbladder tumorwAmpullary tumorwPancreatic tumorwDuodenal tumor

sPancreatitissEntry of parasites into the bile ductssExternal pressuresFibrosis of the papillasDuodenal diverticulumsBlood clotsSump syndrome after biliary enteric anastomosissIatrogenic factors

Table II 27Diagnostic criteria for acute cholangitis

Acute Cholangitis


A. Systemic inflammation

A-1. Fever and/or shaking chills

A-2. Laboratory data: evidence of inflammatory response

B. Cholestasis

B-1. Jaundice

B-2. Laboratory data: abnormal liver function tests

C. Imaging

C-1. Biliary dilatation

C-2. Evidence of the etiology on imaging (stricture, stone, stent etc.)

Suspected diagnosis: At least one item in A plus one item in either B or C

Definite diagnosis: At least one item in A, one item in B and one item in C

High risk patients

Certain subgroups of patients are at high risk to succumb to acute cholangitis. These include patients with higher disease severity in the form of organ dysfunction, shock, mental confusion, elevated serum creatinine, prolonged prothrombin time, hyperbilirubinemia, cirrhosis and

7,15,28,29reduced platelet count. Other risk factors include high fever, leukocytosis, bacteremia, endotoxemia, hypoalbuminemia, liver abscess, medical comorbidity, female gender, elderly and patients with malignancies. Based on new evidence, five predictive factors for poor prognosis have been identified; these include hyperbilirubinemia, high fever, leucocytosis, elderly

27patient and hypoalbuminemia.

Complications

Acute cholangitis may get complicated with development of septicemia, liver abscesses, portal vein thrombosis, and biliary peritonitis or may become indolent and lead to biliary stricture, sclerosing cholangitis, and cholangiocarcinoma. The mortality in

28,30acute cholangitis varies from 2.5-65%. The mortality rate has declined dramatically from over 60% in 1970's to less than 7% by 1980s with newer antibiotics and

29,31,32prompt biliary drainage. However, mortality may escalate to 11- 27% in high risk group. Even today severe cholangitis may prove fatal unless appropriately managed.

Severity of cholangitis

Assessment of disease severity at presentation is an essential component of management of acute cholangitis. As already emphasized, acute cholangitis may manifest itself from a localized self -limited disease to overwhelming sepsis. Although most cases respond to initial medical management, it is important to recognize those which may prove hazardous. Two factors that are important in grading severity are the 'onset of organ

33dysfunction'and 'response to initial medical treatment'. Even after initial medical treatment, frequent re-evaluations are necessary, so as to re-stratify patients as per their parameters.

Definitions of severity assessment criteria for acute 27

cholangitis

Grade III (Severe) acute cholangitis

''Grade III'' acute cholangitis is defined as acute

cholangitis that is associated with the onset of dysfunction in at least one of any of the following organs/systems:

1. Cardiovascular dysfunction: Hypotension requiring

dopamine ≥ 5 ug/kg per min, or any dose of

norepinephrine

2. Neurological dysfunction: Disturbance of consciousness

3. Respiratory dysfunction: PaO2/FiO2 ratio < 300

4. Renal dysfunction: Oliguria, serum creatinine > 2.0 mg/dl

5. Hepatic dysfunction: PT-INR > 1.5

6. Hematological dysfunction Platelet count < 3100,000/mm

Grade II (moderate) acute cholangitis

''Grade II'' acute cholangitis is associated with any two of the following conditions:

3 31. Abnormal WBC count (>12,000/mm , < 4,000/mm )

2. High fever (≥39°C)

3. Age (≥75 years old)

4. Hyperbilirubinemia (total bilirubin ≥5 mg/dL)

5. Hypoalbuminemia

Grade I (mild) acute cholangitis

''Grade I'' acute cholangitis does not meet the criteria of ''Grade III (severe)'' or ''Grade II (moderate)'' acute cholangitis at initial diagnosis.

Goals of management

The International Guidelines developed based on best clinical evidence and discussions at the International Consensus Meeting (Tokyo 2006) have provided the

34management approach for acute cholangitis. Management is focused towards correction of the most important components of disease: biliary infection and obstruction and approach should be directed by grade of severity of disease. However, early empirical broad-spectrum antibiotics, parenteral fluids and appropriate supportive and resuscitative procedures are mandatory for all these patients.

Antibiotic regimen: The antimicrobial therapy should be administered as soon as diagnosis of acute cholangitis

35is suspected or established. Various comparative trials have not shown the superiority of any one antimicrobial

Gupta and Sachdev


agent. The choice of parenteral antibiotics is based on the pathogenic bacteria, severity of cholangitis, and presence of hepatic or renal disease, setting of infection, patient allergies and local sensitivity patterns and biliary

36penetration of antimicrobial. In the past, ampicillin and gentamicin were commonly used as first-line drugs, but with widespread resistance, they have limited role now. Currently, a combination of ureidopenicillin with metronidazole and an aminoglycoside or a combination of penicillin/ß-lactamase inhibitor or third or fourth-generation cephalosporins/ß-lactamase inhibitor (piperacillin plus tazobactam or ticarcillin plus clavulanante; ceftriaxine plus tazobactam) is the

34,35preferred treatment. If these drugs are not useful, fluorquinolones and carbapenems (imipenem, meropenem) can be substituted. In severe cholangitis or hospital acquired infections, antimicrobials efficacious against methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant enterococcus (VRE) and pseudomonas are recommended. The presumptive antibiotic regimen should be modified based on culture and sensitivity reports.

About 90% of patients respond to antibiotics and 37

supportive measures within 24-48 hours. Response is in the form of improvement of clinical signs and resolution of fever, normalization of white blood cell count, C-reactive protein and liver function tests, and subjective well being. In moderate (grade II) or severe (grade III) acute cholangitis, antimicrobials should be administered for a minimum of 5–7 days. Prolonged therapy may be planned, depending on patient's clinical response and presence of bacteremia. In mild (grade I) acute cholangitis, duration of antimicrobial therapy could be

35shorter (2 or 3 days).

Mild cases are often caused by a single pathogen, such as E. coli, and single antibiotic, for instance, first or second generation cephalosporin, penicillin/beta-lactamase inhibitor is usually adequate. The disease is usually managed by conservative medical management and a good response is expected in more than 70%–80% patients, permitting biliary decompression procedure to be carried out electively.

Moderate cases are often infected with multiple and/or resistant organisms. They should be treated with broad spectrum third- and fourth generation cephalosporins or penicillins with beta-lactamase inhibitors or fluoroquinolones / carbapenems with metronidazole.

Once stable, patient should undergo appropriate endoscopic or percutaneous drainage or even definite operative drainage.

Severe cases usually require resuscitation, such as ventilatory or circulatory support in addition to empirical medical management. The antibiotic therapy is analogous to that used for moderate cholangitis, however piperacillin/tazobactam is strongly suggested when Pseudomonas is expected. Since relief of biliary obstruction can significantly improve antimicrobial penetration and survival, such patients should have immediate endoscopic or percutaneous transhepatic biliary decompression or an emergent operation with decompression of bile duct with a T-tube as soon as they

35are stabilized.

Biliary drainage

Biliary drainage is central to the management of acute cholangitis. Biliary drainage can be achieved by three different mechanisms: open surgical drainage, ERCP or endoscopic ultrasound (EUS)-guided drainage or, percutaneous transhepatic biliary drainage (PTBD). Open drainage is more invasive and has obvious drawbacks compared to endoscopic and percutaneous routes; thus the latter have become the preferred methods for urgent biliary drainage. Further, endoscopic drainage is advocated as it is associated with a lesser discomfort, lower morbidity rate, and shorter duration of

38hospitalization. Choices for endoscopic drainage during ERCP consists of biliary stent placement and nasobiliary drain placement (ENBD), with or without endoscopic sphincterotomy (EST). Studies have scrutinized whether or not EST should be added to

39,40ENBD or biliary tube stenting. However, no significant difference was observed in the success rate or effectiveness of drainage between the two techniques. Complications in particular hemorrhage were higher in

39,40 patients who underwent EST. Table III shows the data from various studies utilizing endoscopic techniques for biliary drainage in acute cholangitis.

Surgical treatment

Open surgical drainage of biliary tree was the last resort for patients with severe cholangitis before the advent of interventional radiology and therapeutic endoscopy. Surgical interventions consist primarily of stone extraction, T-tube insertion, trans-hepatic intubation of bile duct or bilio-enteric bypass. Open surgery for acute

Acute Cholangitis


cholangitis has traditionally been associated with high morbidity and mortality. Emergency surgery mortality

46 varied from 20-60%. Age, medical co morbidities, organ dysfunction, and malignant diseases are known risk factors linked with higher peri-operative mortality. Open drainage is thus reserved for patients who have contraindications for endoscopic or percutaneous transhepatic drainage or those in whom it has been

38unsuccessful.

Percutaneous transhepatic biliary drainage (PTBD)

PTBD is the favored approach in cases of high biliary obstruction, intrahepatic stones, previous biliary-enteric

47surgery, or failed endoscopic decompression. PTBD aims at establishing drainage in the acute emergency phase of cholangitis, and in a recently reported series, it could achieve successful biliary drainage close to 100%, complications in less than 10% and mortality around

41,42 5%. However, puncturing the liver in severe sepsis is unsafe considering clotting derangement and thrombocytopenia with resul t ing bleeding, hemoperitoneum and hemobilia. Biliary peritonitis and external catheter related issues add to the morbidity. If skilled interventionalist's expertise is available, this procedure's success may be comparable to endoscopic

38,48drainage, although no head to head trials are existing.

Endoscopic drainage

Endoscopic management has grown to be the best possible mode of treatment for patients with acute cholangitis. Numerous studies have documented and established that endoscopy is far superior to surgery in management of acute cholangitis. Lai et al in a retrospective study, found that endoscopic drainage using nasobiliary catheter resulted in lower morbidity (40% vs 65%) and mortality (6.7% vs 20%) compared to

49 surgery. In another prospective randomized trial, the same author observed that patients who were treated surgically had notably higher complications (64% vs 34%) and hospital deaths (32% vs 10%) compared to

43endoscopic treatment.

Options for endoscopic drainage during ERCP consist of biliary stent placement and nasobiliary drain placement, with or without sphincterotomy. Three prospective studies comparing ENBD and biliary tube stent placement showed no significant difference in success

19,44,50rate, effectiveness or morbidity. However, there tube related problems such as inadvertent removal of nasobiliary tube by patients and appreciably higher

50patient discomfort in ENBD group. Thus, in patients who are likely to remove ENBD tube by themselves, biliary stent placement is preferable. Table III shows the

Gupta and Sachdev


Table III

Comparison of various biliary drainage techniques in acute cholangitis

Authors Type of technique No. of patients

Chen et al 41 PTBD 56

Pessa et al 42 PTBD 42

Lai et al 43 Endoscopic drainage 41

Open (laparotomy with T-tube drainage)

41

Sugiyama and Atomi

39

ENBD without EST

93

ENBD without EST

73

Hui et al 40 Stent without EST

37

Stent with EST

37

Sharma et al

44

ENBD

75

Stent

75

Goenka et al

45

ENBD

143

Agarwal et al

19

ENBD

80

Stent

92

Success rate of drainage

Incidence of complications

Mortality Conclusion

82.1%

100% 7% 5%

100% 34% 10% Endoscopy much more safe 100% 66% 32%

96%

2%

95%

11%

86%

3%

89%

11%

97.3%

2.7%

Equally safe and effective

97.3%

2.7%

90.2%

3.5%

ENBD is safe and effective

100

3%

Both equally effective

100

comparison of various biliary drainage techniques used by various research groups. Another area of debate is whether or not EST should be added to ENBD or biliary tube stent placement. Two case-series have indicated and concluded that it does not increase the effectiveness of drainage in any of the techniques, rather it increases

39,40 complications like hemorrhage. Pancreatitis, bowel perforation, and bleeding are the main complications of ERCP.

Conclusions

Acute cholangitis is a bacterial infection superimposed on an obstructed biliary tree and is a potentially life threatening condition. Prompt clinical recognition of this entity and accurate diagnostic imaging are critical steps in the optimal management of cholangitis. Treatment needs to focus simultaneously on managing sepsis with immediate and appropriate antimicrobial therapy and emergent biliary drainage. Endoscopic biliary drainage with stent placement and nasobiliary drainage are established modes of biliary decompression that are equally superior and efficacious.

References

1. Kimura Y, Takada T, Kawarada Y, Nimura Y, Hirata K, Sekimoto M, et al. Definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg 2007;14:15-26.

2. Lipsett PA, Pitt HA. Acute cholangitis. Surg Clin North Am 1990;70:1297-312.

3. Charcot M. De la fi evre hepatique symptomatique. Comparaison avec la fi evre uroseptique. Lecons sur les maladies du foie des voies biliares et des reins. Paris: Bourneville et Sevestre; 1877. p.176–85.

4. Reynolds BM, Dragan EL. Acute obstructive cholangitis. A distinct syndrome. Ann Surg 1959;150:299–303.

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32. Tai DI, Shen FH, Liaw YF. Abnormal pre-drainage serum creatinine as a prognostic indicator in acute cholangitis. Hepatogastroenterology1992;39:47–50.

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36. Leung J, Ling T, Chan R, Cheung S, Lai C, Sung J, et al. Antibiotics, biliary sepsis, and bile duct stones. Gastrointest Endosc 1994; 40:716–721.

37. Mosler P. Diagnosis and management of acute cholangitis. Curr Gastroenterol Rep 2011;13: 166. doi:10.1007/s11894-010-0171-7

38. Nagino M, Takada T, Kawarada Y, Nimura Y, Yamashita Y,

Tsuyuguchi T, et al. Methods and timing of biliary drainage for acute cholangitis: Tokyo Guidelines J Hepatobiliary Pancreat Surg 2007;14:68–77.

39. Sugiyama M, Atomi M. Risk factors predictive of late complications after endoscopic sphincterotomy for bile duct stones: long term (more than 10 years) follow-up study. Am J Gastroenterol 2002;97:2763–2767

40. Hui CK, Lai KC, Yuen MF, Ng M, Chan CK, Hu W, et al. Does the addition of endoscopic sphincterotomy to stent insertion improve drainage of the bile duct in acute suppurative cholangitis. Gastrointest Endosc 2003;58:500–504.

41. Chen MF, Jan YY, Lee TY. Percutaneous transhepatic biliary drainage for acute cholangitis. Int Surg 1987;72:131–133.

42. Pessa ME, Hawkins IF, Vogel SB. The treatment of acute cholangitis: percutaneous transhepatic biliary drainage before definitive therapy. Ann Surg 1987;205:389–392.

43. Lai EC, Mok FP, Tan ES, Lo CM, Fan ST, You KT, et al. Endoscopic biliary drainage for severe acute cholangitis. N Engl J Med 1992;24:1582–1586.

44. Sharma BC, Kumar R, Agarwal N, Sarin SK. Endoscopic biliary drainage by nasobiliary drain or by stent placement in patients with acute cholangitis. Endoscopy. 2005 May;37(5):439-443.

45. Goenka MK, Bhasin DK, Kochhar R, Nagi B, Rungta U, Das K et al . Endoscopic nasobiliary drainage in the management of acute cholangitis: An experience in 143 patients. Diagn Ther Endosc 1997;3:161-170

46. Lai EC, Tam P C, Paterson IA. Ng MM, Fan ST, Choi TK, et al. Emergency surgery for severe acute cholangitis. The high-risk patients. Ann Surg 1990;211:55–59.

47. Yusoff IF, Barkun JS, Barkun AN. Diagnosis and management of cholecystitis and cholangitis. Gastroenterol Clin North Am 2003;32:1145–1168.

48. Tsujino T, Sugita R, Yoshida H, et al. Risk factors for acute suppurative cholangitis caused by bile duct stones. Eur J Gastroenterol Hepatol 2007;19: 585–588.

49. Lai E C, Paterson I A, Tam P C. et al. Severe acute cholangitis: the role of emergency nasobiliary drainage. Surgery 1990;107:268–272.

50. Lee DW, Chan AC, Lam YH, Ng EK, Lau JY, Law BK, et al. Biliary decompression by nasobiliary catheter or biliary stent in acute suppurative cholangitis: a prospective randomized trial. Gastrointest Endosc 2002;56:361–365.


Gupta and Sachdev


INTRODUCTION

Despite number of efforts to fight sepsis, it continues to 1 kill millions of people worldwide annually. With the

increase in usage of invasive procedures, chemothera-peutic agents, prosthetic devices, immunosuppressive conditions and emerging antimicrobial resistance, sepsis is a common and serious problem amongst patients especially being treated in intensive care units (ICUs). Sepsis is defined as probable or documented infection together with systemic manifestations of infection, severe sepsis is defined as sepsis plus sepsis-induced acute organ failure, and septic shock is defined as severe sepsis with hypotension which may or may not be

2 reversed by fluid resuscitation. The current consensus statement defines sepsis as a “Life-threatening organ dysfunction caused by a dysregulated host response to

3infection”.

Bacteria are the most common cause of sepsis; however, systemic viral and fungal infections may also be responsible. Rapid and accurate determination of the presence or absence of bacterial infection is important to guide appropriate therapy and to reduce unnecessary exposure to antibiotics. Empirical antimicrobial therapy

4 should be started upon suspicion of sepsis. Sepsis is more common in elderly and is more likely to increase in aged population. It is very rightly called as a hidden public health disaster. Even with the advancement, sepsis is still defined and diagnosed by non-specific alterations in physiology based on temperature, respiratory rate, heart rate and leucocyte counts and not by specific cellular processes which bring about the inflammation process. It has been said that “it makes no sense to use twenty-first century technology to develop drugs targeted at specific infections whose diagnosis is

5delayed by nineteenth century methods”. So with the aim of early and accurate sepsis detection, to shorten the time of administration of antibiotics and to distinguish sepsis from sepsis like situations, risk stratification of the patient and also in monitoring the prognosis and outcome of the patient, about 100 molecules have been mentioned in the literature and we

Review Article

Role of Biomarkers in Diagnosis of Sepsis1 2

Varsha Gupta , Vibha Mehta1 2Professor , PG Student

Department of Microbiology, Government Medical College Hospital, Sector 32, Chandigarh- 160030

ABSTRACT

Sepsis is a common and serious problem amongst patients being treated in intensive care units. The current consensus statement defines sepsis as a “Life-threatening organ dysfunction caused by a dysregulated host response to infection.” Bacteria are the most common cause of sepsis. Rapid and accurate determination of the presence or absence of bacterial infection is important to guide appropriate therapy. To have early and accurate sepsis detection, to shorten the time of administration of antibiotics and to distinguish sepsis from sepsis like situations various biomarkers have been mentioned. These are defined as “a characteristic that is objectively measured and evaluated as an indicator of normal biological process, pathogenic process, or pharmacologic response to a therapeutic intervention”. Recently they have been classified as diagnostic, monitoring, surrogate, and for stratification. The two most widely used biomarkers are procalcitonin and C-reactive protein. The others are- lipopolysaccharide binding protein, pentraxin, cytokines/chemokines, lactate, soluble triggering receptor expressed on myeloid cells-1, soluble form of urokinase-type plasminogen activator receptor, mid regional proadrenomedullin, neutrophil CD 64, presepsin, interleukin 27, miRNA, cfDNA and copeptin. The focus now is on using combination of the biomarkers than using individually to increase sensitivity and specificity; however further prospective testing of these biomarkers by the use of appropriate statistical methods is required. Finally interpretation in the clinical context of the patient with serial measurements provides more useful information.

Corresponding Author :Prof. Varsha Gupta Department of Microbiology,Government Medical College Hospital,Sector 32, Chandigarh, India 160030Email: [email protected]

are discussing a few clinically important ones which aid in diagnosis of sepsis and extensive work is being done on them. Biomarkers might represent key aides to guide

2 the diagnosis and management of sepsis.

Biomarker is defined as “a characteristic that is objectively measured and evaluated as an indicator of normal biological process, pathogenic process, or

6pharmacologic response to a therapeutic intervention”. They are further classified into two distinct categories of biomarkers: that which denotes the natural history of a disease, and that which demonstrates the effect of a

7therapeutic intervention. Recently four broad classes of biomarkers have been identified: based on the purpose for which they are used as diagnostic, monitoring,

8 surrogate, and stratification. Biomarkers can be classified as acute phase protein biomarkers; chemokine/ cytokine biomarkers and soluble receptor/cell surface

9and other biomarkers .

Procalcitonin (PCT)

Procalcitonin was first described as a biomarker of sepsis 10 in 1993. It is a 116 amino acid peptide with a molecular

weight of 13 kDa. It is a prohormone of calcitonin and is 11secreted by the C cells in the thyroid gland. It is

produced in response to bacterial endotoxin or to inflammatory mediators released in response to bacterial

12infections (IL-1b, IL-6, and TNF-alpha). Normal serum

or plasma levels of PCT in healthy adults are ≤0.05ng/ml 13which is usually not detectable. It is one of the most

widely used and studied biomarker in the management of sepsis. Procalcitonin is also produced by the neuroendocrine cells of the lung and intestine and is released as an acute-phase reactant in response to inflammatory stimuli, especially those of bacterial origin. The physiological importance and regulation of procalcitonin production is not well understood. No enzymes in the plasma break down procalcitonin. Therefore, if procalcitonin enters the circulation, it remains unchanged, with a half-life of around 30 hours, and there is no evidence that in serum procalcitonin binds to cellular receptors of calcitonin or any specific

11procalcitonin receptors.

PCT has the highest sensitivity and specificity for predicting systemic bacterial inflammation. It has high positive predictive value for severe sepsis and septic

14shock. It helps us in distinguishing between viral and bacterial infections. Serum levels of PCT correlate with

15the severity of bacterial infection and bacterial load.

PCT levels are the earliest to rise within 4-12 hours upon initiation of inflammatory response but high PCT levels are also seen in conditions like first 2 days of life, heat stroke, multiple trauma, some surgical and burns

16patients. Procalcitonin levels may also be elevated in medullary thyroid carcinoma and small-cell lung carcinoma, paralytic/vascular ileus exhibiting

17paraneoplastic production, and renal failure. So these conditions must be kept in mind when evaluating the values of PCT in sepsis.

Further PCT has no value in the assessment of fungal or viral infections and shows no response to intracellular microorganisms or in local infections with no systemic

18 response. Since, it does not usually rise significantly with non-infectious inflammatory conditions it has the potential to be used as a marker of bacterial infection.

Highest levels of PCT are seen in gram negative bacteria (GN), followed by Candida and least raised levels are seen in gram positive bacteria (GP). It is due to difference in which inflammatory responses occurs in all

18the three entities.

PCT appears to be a useful early marker for discriminating between non infectious Systemic

15 Inflammatory Response Syndrome (SIRS) and sepsis.PCT is useful in early diagnosis of respiratory infections and bloodstream infections, but the specificity of PCT in diagnosing bloodstream infections is higher as

19-21 compared to respiratory infections. These days the emphasis is on combining PCT along with CRP however in clinical practice PCT has proven to be the superior biomarker and has largely replaced C-reactive protein as the adjunctive biomarker of choice when

22-24evaluating presumed septic patients.

The role of PCT has been studied widely in antibiotic stewardship as for initiation and the discontinuation of antibiotic therapy in patients with bacterial infections. This will lead to shorter duration of antibiotic administration and thus also in cost cutting in

25,26hospitalized patients.

C-reactive protein (CRP)

It is an acute phase protein synthesized in liver in response to inflammation and tissue damage. Tillet and Francis (1930) discovered the presence of CRP in the serum of patients with pneumonia. The name

Gupta and Mehta


is derived due to the ability of the CRP to react with C-polysaccharide isolated from pneumococcal cell

27walls.

It is a member of pentraxin family of proteins because 28

they form a cyclic pentamer. It has both pro and anti-inflammatory effects. IL-6 is the most effective stimulus for the induction of CRP amongst others (IL-1, TNF-alpha). The serum concentration of CRP in the normal human population has a median of 0.8 mg/l (interquartile range 0.3–1.7 mg/l) and is below 10 mg/l in 99% of normal samples. Levels above these values are abnormal

29and indicate the presence of a disease process. CRP level unlike PCT and IL-6 levels do not decrease up to day 14. So the determination of CRP levels during the later course of the disease process may not be of significance as the levels remain elevated for a long period if the cause is still there. But single high value will still be significant, sometimes 1000 times the reference

28limits. Limitations for the conclusive role of CRP is due to the following reasons - plasma levels of CRP increase with a delay of up to 24 hours, secondly levels of CRP may increase during minor infections and lastly

28plasma levels remain elevated for up to several days. The levels of CRP are raised in many conditions like trauma, surgery, burns, rheumatological disease, systemic lupus erythromatosus, systemic sclerosis, dermatomyositis, Sjogren's disease, inflammatory bowel disease, hematological disease, graft-versus-host

9 disease, neutropenic patients, and Gram positive sepsis.Low specificity is due to persistently elevated levels throughout the course of sepsis. The course of PCT shows a closer correlation than that of CRP with the

30severity of infection and organ dysfunction. Studies show that both markers used together are good indicators

31of sepsis in critically ill patients. The advantage of using CRP as biomarker is that it is a cheap investigation and is easily available as compared to other tests in resource limited countries.

Lipopolysaccharide binding protein

Lipopolysaccharide (LPS)-binding protein (LBP) was initially discovered as an acute-phase reactant binding with the LPS of Gram-negative bacteria cell walls to form a complex and was later found to be elevated in

32,33 gram-positive bacteremia. This complex binds to CD14 and to the Toll-like receptor 4/MD2-complex and results in transcription of cytokines and other pro-

34inflammatory mediators. This marker has been found to be normally present in healthy human serum at a

35concentration of 5 to10 µg/ml. During sepsis, LBP levels were found to increase to median peak levels of 30–40 µg/ml within 24h, almost seven times higher than

35 normal levels. These properties made LBP a promising tool for the diagnosis of sepsis, and suitable to discriminate between SIRS due to infectious or non

36infectious aetiology.

Pentraxin

They are pattern recognition receptors (PRRs). The classic “short” pentraxins include serum amyloid P component (SAP) and C-reactive protein (CRP),

9produced in the liver following inflammatory stimulus. Pentraxin 3 (PTX3) is the prototype of the long pentraxin

37family. CRP is produced in the liver, whereas PTX3 is an inflammatory mediator produced by various cells including leukocytes and endothelial cells in peripheral tissues. It is an acute-phase protein whose plasma concentrations increases rapidly in response to various

38inflammatory conditions, including sepsis. The “long” pentraxin 3 (PTX3) binds to specific patterns of fungi, bacteria, and viruses and induces phagocytosis by its

39binding to complement component C1q. Various other acute phase reactants under consideration are ceruloplasmin, alpha 1 acid glycoprotein and

40,41hepcidin.

Cytokines/Chemokines

They are released from virtually all nucleated cells, mainly from endothelial, epithelial and macrophages

42 and are proinflammatory and anti-inflammatory both.Their presence is not specific as they can be induced in

9 many non-infectious situations also. In a small observational study, a combined cytokine score that comprised IL-6, IL-8, and the anti-in?ammatory cytokine IL-10 was associated with a worse outcome for patients with sepsis and the predictive value of the combined score for mortality was highly superior to

43those of CRP and PCT. Another chemokine Interleukin-8 (IL-8) is produced by macrophages for the purpose of mobilizing and activating other pro-

44inflammatory cells, primarily neutrophils. Some work has been done regarding the use of IL-8 and its prognostic significance. By using specified cutoff levels higher than 220 pg/ml, it had a sensitivity of 78%, specificity of 64% and positive predictive value of only

Role of Biomarkers in Diagnosis of Sepsis


25% for predicting mortality. The negative predictive value for serum concentrations less than 220 pg/ml was

4595%.

Lactate

Lactate is normally found in the human tissues. Lactate levels are raised (>4mmol/L ) in severe sepsis and septic shock, hypoperfusion secondary to anaerobic metabolism, cellular metabolic failure and decreased

46clearance by the liver. Numerous studies have established that lactate is a good marker of global tissue

47hypoxia in circulatory shock. 'Serial' lactate level monitoring is recommended . Two parameters have been studied in this regard increased production, decreased clearance, or a combination of both. There are numerous non-infectious causes of raised levels like gluconeogenesis (biguanides, alcohol intoxication), imbalance between ATP supply and demand (severe exercise, carbon monoxide poisoning), metabolic problems (thiamine deficiency, pyruvate carboxylase)

46and malignancies.

Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1).

These are triggering receptors expressed on myeloid cells 1 (TREM-1) which have been recently discovered

48as a member of the immunoglobulin superfamily. There expression is greatly upregulated in the presence of bacteria or fungi in cell culture, peritoneal lavage ?uid, and tissue samples from patients infected with these microorganisms. TREM-1 expression is associated with the release of soluble form called as TREM-

91(sTREM-1).

They can be found in body fluids, such as plasma, pleural fluid, bronchoalveolar lavage fluid, urine, and cerebrospinal fluid, where assay can be done by ELISA

48using commercial immunoassay kits. The clinical application of sTREM-1 as a diagnostic and prognostic marker still requires larger studies for further

49elucidation”.

Soluble form of urokinase-type plasminogen activator receptor (SUPAR)

The urokinase-type plasminogen activator (uPA) system 50consists of a protease, a receptor and inhibitors. In

1991, the soluble form of uPAR (suPAR) was 51 identi?ed. uPAR is expressed on various cell types,

including neutrophils, lymphocytes, monocytes/

macrophages, and endothelial and tumor cells. After cleavage from the cell surface, suPAR can be found in

9the blood and other organic ?uids in all individuals.

Levels of suPAR are increased in acutely ill patients, but this increase is not specific for sepsis. Serial serum suPAR concentrations were found to be higher in adult ICU patients with endorgan dysfunction and significantly higher admission suPAR levels in nonsurvivors with the best admission cutoff value to predict ICU and 28-day mortality as 6.2 ng/ml in the total

52population and 10.2 ng/ml in patients with sepsis.

Mid regional proadrenomedullin

Serum adrenomedullin (ADM), a 52-amino-acid peptide, is modulated by the complement system and has potent vasodilating as well as bactericidal effects. Since it is rapidly broken down and masked by a binding protein (complement factor H), the mid regional fragment of proadrenomedullin Pro-ADM consisting of

9aminoacids 45 to 92 is measured for diagnosis. Pro-ADM level measured at admission was found to be a good predictor of the severity and outcome of

53 community acquired pneumonia. Normal values of the few important biomarkers are depicted in Table –I.

Neutrophil CD64 (nCD64)

Cluster of differentiation 64 (CD64) is an immunoglobulin Fc-γ receptor I found ubiquitously on

54monocytes and sparingly on neutrophils. However, neutrophil CD64 (nCD64) expression markedly increases manifold after infection as the innate immune

Table I

Serum Level of Biomarkers

Biomarkers Normal values Cut off values

Procalcitonin Reference range is below

the level of detection

0.1-3.0ng/ml

CRP

0.0-0.8mg/dl

>1.0 -10 or higher mg /dl

LPS 5-10 µg/ml 200µg/ml

PENTRAXIN <2ng/ml >14-16ng/ml

LACTATE 0.5-1mmol/L >2 mmol/L

STREM

-

3.5µg/L

SuPAR - 2.7µg/L

Mid regional PAM - 4.86 mmol/L


Gupta and Mehta

55system tries to optimize phagocytosis. The levels rise within two hours of pathogen exposure, and return to their normal low level within a few days after the

56 clearance of the infectious agent. Thus, nCD64 could be a promising diagnostic and monitoring tool.

Presepsin

CD14 is a glycoprotein expressed on monocytes and macrophages, serving as a receptor for lipopoly-saccharides. Upon coming in contact with microbes activation of pro inflammatory signalling cascade occurs. During inflammatory stress, soluble CD14 fragments are cleaved, one of which has been identified

57 as presepsin (sCD14-ST). Presepsin has potential both as a diagnostic and prognostic sepsis biomarker. It has been demonstrated that presepsin levels correlated with the severity of sepsis when compared with other common sepsis biomarkers (IL-6, C-reactive protein,

58,59 PCT).

nCD64 and Presepsin are thought to play role in antibiotic stewardship also as discontinuation of antibiotics if levels are showing downtrends and thus leading to saving on hospital costs may be accomplished.

Interleukin-27 (IL-27)

IL-27 is a hetero-dimeric cytokine composed of the IL-27p28 and Epstein-Barr virus induced gene 3 (EBI3)

60,61 subunits. These two subunits originate primarily from antigen presenting cells upon exposure to either microbial product or inflammatory stimulus. It has been demonstrated that an IL-27 serum concentration of >5 ng/ml had >90% specificity and positive predictive value for identifying critically ill children with laboratory-confirmed bacterial infection but further

62work needs to be done to confirm the findings .

miRNA

miRNAs are a newly identified class of biomarkers that may serve a diagnostic or prognostic role in various human pathologic conditions, including sepsis. miRNAs are short sequences of endogenous RNAs that are

63involved in translational gene regulation. The methods of detection of miRNAs are different as they can be detected directly or the proteins coded by the genes of previously identified miRNA which can be measured in serum .

Cell Free DNA (cfDNA)

cfDNA is comprised of short-lived fragments of DNA produced secondary to cellular necrosis and

64,65 apoptosis. cfDNA is present in healthy people, at minimal levels, as clearance of apoptotic cells is readily accomplished by phagocytes while in sepsis there is increased apoptosis but dying cells are not cleared

66 leading to accumulation of cf DNA. Most of the work on cfDNA has focused on its use as a stratification marker for patients with higher risk of mortality .

Copeptin

Copeptin is a 39-amino acid glycopeptide derived from precursor provasopressin and normal values in healthy individuals of copeptin range between 1.70 and

6711.25pmol/L . In sepsis, there is endocrine dysfunction which is characterized by inappropriately low levels of vasopressin and sepsis-induced hypotension is one of the main stimuli of vasopressin secretion, causing an increase in the hormone serum levels which

68,69 contributes to the maintenance of arterial pressure.Copeptin which is released in an equimolar ratio with vasopressin is a stable peptide in EDTA plasma and can be used as a surrogate biomarker of arginine

70vasopressin. Copeptin thus has a role in suspected sepsis in three different areas of application: diagnosis, prognosis and monitoring.

Single biomarker associated with clinical signs when used is a simple, rapid, cheap, sensitive though usually not very specific, whereas multiple biomarkers when used are less rapid, more expensive but have increased specificity. A panel called the “bioscore,” proved highly diagnostic for sepsis having a combination of various

71 biomarkers. Similarly other combinations showed improved predictive power for mortality in patients with septic shock compared with the individual markers

72 alone. In children with septic shock a Pediatric Sepsis Biomarker Risk Model (PERSEVERE) has been studied and recently, the prognostic accuracy of the model was

73,74 prospectively validated in an independent cohort.

CONCLUSION

Thus, the combination of several biomarkers holds some promise to increase sensitivity and specificity; however, the clinical utility and cost-effectiveness regarding the management of septic patients need further prospective testing of these biomarkers by the use of appropriate



statistical methods that can be applied to high-dimensional data . None of the biomarkers is perfect so interpretation in the clinical context of the patient with serial measurements is preferred and provides more useful information. Further it is essential to consider the dynamics of the disease and to always keep in mind the other conditions which may affect these biomarker levels like that of PCT. Last but not the least good clinical judgment should always be applied.

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17

INTRODUCTION

Diminished balance and mobility in elderly population can be a limiting factor in the maintenance of an independent lifestyle and can increase the risk of falls and fractures. Understanding the changes in functional mobility is becoming more important because of a longer

life expectancy and an increasing elderly population. We need prognostic tools that help identify individuals with an increased risk of falling in order to take preventive action. The Timed Get Up and Go test (TGUG) is a screening tool that determines timed performance of getting up from a chair, walking 3 metres (m), turning around, and walking back to sit down again.

AIM AND OBJECTIVES

To measure the timed 'get up and go' score in ambulatory elderly patients. To assess if there was any difference in the TGUG score in relation to the age, sex, body mass index (BMI), number of chronic illnesses and polypharmacy.

Original Article

Balance and functional assessment in ambulatory elderly patients using Timed Get Up and Go test

1 2 2Aakanksha Sharma , Monica Gupta , Sarabmeet Singh Lehl1 2MBBS student ProfessorDepartment of Medicine, Government Medical College and Hospital, Chandigarh

ABSTRACT

Introduction: Falls are a foremost cause of injury and activity limitation in older adults. Falls result in significant personal, social and economic burden. The Timed Get Up and Go test is a commonly used screening tool to assist clinicians to identify elderly patients at risk of falling.

Aim and objectives: To measure the timed 'get up and go' score in ambulatory elderly patients. To assess if there was any difference in the TGUG score in relation to the age, sex, body mass index (BMI), number of chronic illnesses and polypharmacy.

Materials and Methods: 120 randomly selected ambulatory elderly patients who visited the outpatient geriatric clinic at our centre were categorised into 3 groups on the basis of their age; 60-69 years (Group A), 70-79 years (Group B) and > 80 years (Group C). History pertaining to the number of co-morbidities and polypharmacy, history of falls and/or fractures (hip and lower limb) in the past 1 year, and use of walking aid, alcohol use and smoking were noted. Barthel Index was used to assess the functional independence. Functional mobility was assessed by doing a timed 'get up and go' (TGUG) test.

Statistical Analysis: The TGUG score was analysed with respect to age, gender, body mass index, number of comorbidities and polypharmacy.

Results: The TGUG score was highest in Group C (>80 years) and statistically significant when compared to other 2 groups. Females overall had a statistically significant higher TGUG score as compared to the males. In comparison to other two groups, Group B females fared worse in their scores when compared to corresponding males. The body mass index, larger number of comorbid illnesses and presence of polypharmacy did not significantly influence the TGUG score.

Conclusion: The TGUG test is a good screening tool to identify elderly at high risk of falls and fractures and therefore should be part of routine geriatric assessment.

Keywords: Timed Get Up and Go Test, Elderly, Falls


Dr. Monica GuptaM. D., D.N.B. MedicineDepartment of General Medicine,Government Medical College and Hospital, ChandigarhEmail: [email protected]

Journal of Medical College Chandigarh, 2016, Vol. 6, No.2

MATERIALS AND METHODS

A cross sectional analytical study was carried out on 120 randomly selected ambulatory elderly patients who visited the outpatient geriatric clinic at our centre. Patients with hearing or visual loss, with Mini Mental State examination (MMSE) score <10 and those refusing to participate were excluded. After obtaining their written consent, patients were categorised into 3 groups on the basis of their age; 60-69 years (Group A), 70-79 years (Group B) and > 80 years (Group C). Demographic data and medical history especially pertaining to the number of co-morbidities and polypharmacy and history of falls and/or fractures (hip and lower limb) in the past 1 year were recorded. Personal history relating to use of walking aid, alcohol use and smoking were noted. Weight and height were measured as per standard guidelines. The body mass index (BMI) was calculated

2as body weight (kg)/height (m ).

Barthel Index (Table I) was used to assess the functional 1

independence. The index is used as a record of what a patient does or not as a record of what a patient could do with the main aim of establishing degree of independence from any help, physical or verbal, however minor and for whatever reason.

Timed 'get up and go' test

We assessed functional mobility quantitatively by doing a timed 'get up and go' (TGUG) test as recommended by the American Geriatrics Society, and the score was recorded. The patient was made to sit correctly in a stable chair with arms, with his/her back resting on the back of the chair. A piece of tape or other marker was placed on the floor 3 meters away from the chair so that it is easily seen by the subject. The area for the TGUG test was set up by measuring 3 m from the front legs of a straight-backed armchair with a seat height of ~46 cm. The subject was instructed to: "Sit with your back against the chair and your arms on the arm rests. On the word 'go,' stand upright, then walk at your normal pace to the line on the floor, turn around, return to the chair, and sit down." Timing began when the person started to rise from the chair and ended when he or she returned to the chair and sat down. The person was given 1 practice trial and then 3 actual trials. The times from the three actual trials were averaged. The person was allowed to wear their usual footwear and use any assistive device they

2-4normally use. The reference values are provided in Table II.


Sharma et al

Table I1

The Barthel index

Activity

Score

0

5

10

15

FEEDING:

Unable

Needs help

Independent

BATHING: Dependent Independent

GROOMING: Needs help Independent

DRESSING:

Dependent

Needs help

Independent

BOWELS:

Incontinent

Occasional accidents

Continent

BLADDER:

Incontinent

Occasional accidents

Continent

TOILET USE:

Dependent

Needs some help

Independent

TRANSFER:

Unable

Major help

Minor help

Independent

MOBILITY:

Immobile

Wheelchair independent

Person's help

Independent

STAIRS:

Unable

Needs help

Independent

Total Score (out of 100) :

Statistical analysis: The TGUG score was analysed with respect to age, gender, body mass index, number of comorbidities and polypharmacy. The values were compared using the t-test and p-value <0.05 was considered as significant.

RESULTS

The demographic data and personal details pertaining to the body mass index, Barthel index, number of falls and fractures in past, use of walking aids, number of medical comorbidities and number of prescription drugs is highlighted in Table III.


Balance and functional assessment in ambulatory elderly patients using TGUG test

Table IIReference values for TGUG

Normative Reference Values by Age2

Age Group

Time in Seconds (95% Confidence Interval)

60 – 69 years

8.1

(7.1 –

9.0)

70 –

79 years

9.2

(8.2 –

10.2)

80 –

99 years

11.3

(10.0 –

12.7)

Cut-off Values Predictive of Falls3

Group

Time in Seconds

Community Dwelling Frail Older

>

14 associated with high fall risk

Post-op hip fracture patients at time

of discharge4

> 24 predictive of falls within 6 months after hip

fracture

Frail older adults > 30 predictive of requiring assistive device for

ambulation and being dependent in ADLs

Table IIIDemographic and clinical data of the study population

GROUPS Sex No. Mean Presence of Fall

Fractures

Walking

aid

No. of

comorbidities

No. of

drugsAge BMI Barthel Index

Group A

60-69 yrs

F 19

63.1 ±

3.13

33.04 ±

4.50

96.25 ± 3.46

6

1

0

≤ 2 : 16

<5 : 15

> 2 : 03

≥5 : 04

M 21

64.2 ±

2.72

28.32 ±

5.78

99.76 ± 1.09

2

0

0

≤ 2 : 17

<5 : 12

> 2 : 04

≥5 : 09

Group B

70-79 yrs

F 20

74.05 ±

3.10 31.12 ±

8.08 97.25 ± 4.72

7

1

3

≤ 2 : 11

<5 : 13

> 2 : 09 ≥5 : 17

M 20 74.1 ±

2.79

26.45 ±

5.49

99.75 ± 1.12 2 0 2 ≤ 2 : 14 <5 : 10

> 2 : 16

≥5 : 10

Group C

>80 yrs

F 18

83.81 ±

2.64

26.66 ±

7.05

92.77 ± 20.64

5

2

6

≤ 2 : 09

<5 : 09

> 2 : 09

≥5 : 09

M 22 83.31 ±

2.38

26.05 ±

5.05

95.00 ± 7.40 3 1 7 ≤ 2 : 12 <5 : 10

> 2 : 10 ≥5 : 12

As shown in the Figure 1, the mean TGUG values in our 3 groups were as follows: Group A: 12.57± 5.71, Group B: 14.7± 4.92 and Group C: 19.62± 7.60 seconds. The two tailed p-value for Group A vs. Group B TGUG score equals 0.062, which is not statistically significant. For Group B vs. Group C, p = 0.0006, therefore statistically significant. For Group A vs. Group C, p = 0.0001, this comparison was thus extremely statistically significant. This led us to infer that TGUG score worsens as the age advances and senior elderly are more prone to gait instability and functional limitations.

As shown in Table IV, among the total males the mean TGUG score was 14.25 ± 6.50 as compared to the total females who had a mean TGUG score of 17.15 ± 6.30 seconds. The p-value for male versus female TGUG scores equals 0.0147 and is statistically significant. The p-value for male vs. female TGUG score in Group A equals 0.1106, thus not statistically significant. However in Group B, p value = 0.0022, therefore statistically significant difference in males vs females

was observed. In Group C, p = 0.414, so no significant difference was obtained between the male and female subgroups.

As is obvious from the Table V, the body mass index, larger number of comorbid illnesses and presence of polypharmacy did not significantly influence the TGUG score.


Table IV

Comparison of TGUG score on the basis of Gender

Age Group Number TGUG Score P value

Group A

(60 –

69 years)

M = 21

13.36 ± 3.35

0.1106

F = 19

11.85 ± 2.35

Group B

(70 –

79 years)

M = 20

11.85 ± 2.48

0.0022

F = 20

17.55 ± 7.37

Group C

(>80 years)

M = 22

18.72 ± 8.97

0.414

F = 18

20.72 ± 5.54

Total Males= 63 14.25 ± 6.50 0.0147

Females= 57 17.15 ± 6.30

Table V

Comparison of TGUG score on basis of BMI, number of chronic illnesses and Polypharmacy

Variable Number of Pts. Mean TGUG score P value

BMI (Kg/ m2)

< 25

41 (34.16%)

16.04 ± 1.66 0.249

25 -

30

33 (27.5%)

16.33 ± 1.41

> 30

46 (38.33%)

14.76 ± 4.29

No. of comorbidities

≤ 2

41 (34.16%) 16.64 ± 5.64 0.217

> 2

79 (65.84%) 15.10 ± 6.88

Number of drugs < 5 68 (56.66%) 15.43 ± 6.10 0.733

≥ 5 52 (43.33%) 15.82 ± 6.35

0

5

10

15

20

25

(60 -69 yrs) (70 - 79 yrs) (>80 yrs)

TUG Score

Group A Group B Group C

Fig. 1. Comparison of TGUG score in different age groups

Sharma et al

DISCUSSION

Thirty percent of individuals over 65 years old, and almost 50% of individuals over 80 years old, experience

5at least one fall each year. Although most falls do not end in death or result in significant physical injury, the psychological impact of a fall often results in an increasing self-restriction of activities and a decrease in

6quality of life. Gait instability has been identified as a relatively consistent risk factor for falls and the majority of screening programmes to identify those at risk of falls comprise an assessment of gait and balance. There are a number of performance orientated mobility assessment and falls risk screening tools that assess aspects of balance and gait involved in normal daily activities. One such initial subjective instrument was the "Get-up-and-Go" (GUG) test that graded the performance on a 5-point

7scale. The test was later modified to include the time taken to complete the test: the "Timed Get-up-and-Go" (TGUG) test. The TGUG was adapted by Podsiadlo and Richardson from the Get Up and Go Test of Mathias et

8al. The original purpose of the TGUG was to test basic mobility skills of frail elderly persons. The test has been used in other populations, including people with arthritis, stroke, and vertigo.

Performance on the TGUG is related to multiple factors. There is a tendency for TGUG times to increase with

2age. A history of arthritis increases the risk of falling as measured by balance tests such as the TGUG. As a test of balance, the TGUG may be most useful for patients with rheumatoid arthritis in functional class IV. Scores also differ based on type of footwear worn. They were longest with dress shoes and shortest with walking shoes. Cognitively impaired subjects take longer to perform the TGUG than unimpaired subjects. Including a cognitive or manual task concurrent with the TGUG increases the times. The type of an assistive device increases the TGUG times. A cane increased the time the least,

2followed by a rolling walker and then a pick up walker. Chair type (standard arm chair, armless chair and easy chair) does not affect speeds.

TUG is recommended as a routine screening test for falls in guidelines published by the American Geriatric

9Society and the British Geriatric Society. The National Institute of Clinical Evidence (NICE) guidelines also advocate the use the TUG for assessment of gait and

10balance in the prevention of falls in older people. To date three systematic reviews have examined the clinical utility of the TUG to discriminate between those at low

11-13and high risk of falling. Low scores correlate with good functional independence while high scores correlate with poor functional independence and higher

3risk of falls.

The ssensitivity of TGUG for predicting falls is close 2

0.80 and specificity 0.934. Thus the TGUG test has a high prognostic validity and is used to assess the functional independence and postural instability of the subject. Also it can be easily performed in a short period of time and is highly cost effective. It helps to assess other components such as gait and stride length of the patient as well. Very few types of equipment, namely arm chair, measuring tape, colored tape, stop watch are required to carry out this test. It has been found that a sample of adults without balance problems could complete this test in less than 10 s, whereas a sample of those dependent in most activities of daily living and mobility skills, according to the Barthel Index, took more than 30 s.

A major feature of the test is that it incorporates a series of tasks: standing up from a seated position, walking, turning, stopping, and sitting down, all of which are critical for independent mobility. However, by only measuring the time to complete the entire series of tasks, the problems a subject may be having with any particular one of them may be masked. If one could measure the times for each of the tasks separately, then the test would provide useful clinical information. It would better isolate the areas of functional deficit, thereby aiding the clinician in devising prevention strategies and in guiding both treatment and further testing. A recent metaanalysis has concluded that The Timed Up and Go test has limited ability to predict falls in community dwelling elderly and should not be used in isolation to identify individuals at

14high risk of falls in this setting. The limited predictive value of the TUG may be explained by the fact that the TUG is a single test which reflects strength balance and mobility nonetheless, the risk of falling has been shown

15,16to depend on multiple intrinsic and extrinsic factors. The TUG does not appear to adequately encompass these risk factors. More sensitive and clinically useful risk assessment tools have been designed to assess multiple components of gait instability. Recent literature has focused on the addition of a second manual or cognitive

17,18 task. These include the expanded timed get up and go test(ETGUG), TGUG Cognitive complete the task while counting backwards from a randomly selected number between 20 and 100, TGUG manual-complete the task while carrying a full cup of water. The time taken to


Balance and functional assessment in ambulatory elderly patients using TGUG test

complete the task is strongly correlated to level of functional mobility, (i.e. the more time taken, the more dependent in activities of daily living). The cutoff levels for TGUG is 13.5 seconds or longer with an overall correct prediction rate of 90%; for TGUG manual is 14.5 seconds or longer with a 90% correct prediction rate; and TGUG cognitive is 15 seconds or longer with an overall correct prediction rate of 87%. In addition, all these tests have very high inter rater reliability.

CONCLUSION

The reasons why the elderly fall continues to be explored in the literature, and further research is required to develop a comprehensive falls risk tool that can accurately identify the common risk factors that predict falls. The Expanded TGUG test is a practical, objective, assessment tool that can be used in almost any clinical setting with minimal equipment, professional expertise, or training. Additionally, it has the capacity to give the clinician more information than the TGUG test, since it measures each of the component parts of the test. Additional research is needed to determine correlations between increased component times and specific functional deficits. Once these relationships have been established, the scope of application of the test might be enlarged to include implications for prevention strategies in the high-risk geriatric population and in guiding treatment more specifically.

REFERENCES

1. Mahoney FI, Barthel D. “Functional evaluation: the Barthel Index.”Maryland State Medical Journal 1965;14:56-61.

2. Bohannon RW. Reference values for the Timed Up and Go Test: A Descriptive Meta-Analysis. Journal of Geriatric Physical Therapy, 2006;29(2):64-8.

3. Shumway-Cook A, Brauer S, Woollacott M. Predicting the probability for falls in community-dwelling older adults using the timed up & go test. Phys Ther 2000;80:896-903.

4. Kristensen MT, Foss NB, Kehlet H. Timed "Up and Go" Test as a predictor of falls within 6 months after hip fracture surgery. Phys Ther. 2007.87(1):24-30.

5. Tinetti ME, Speechley M, Ginter SF. Risk factors for falls among elderly persons living in the community. N Engl J Med 1988; 319: 1701–7.

6. King MB, Tinetti ME. A multifactorial approach to reducing

injurious falls. Clin Geriatr Med 1996; 12: 745–592.

7. Mathias S, Nayak USL, Isaacs B. Balance in the elderly patient: The "Get-up and Go" test. Arch Phys Med Rehabil 1986; 67:387-89.

8. Podsiadlo D, Richardson S. The Timed Up & Go: A test of basic functional mobility for frail elderly persons. J Am Geriatr Soc 1991; 39:142-8.

9. Panel on Prevention of Falls in Older Persons. American Geriatrics Society and British Geriatrics Society: Summary of the Updated American Geriatrics Society/British Geriatrics Society clinical practice guideline for prevention of falls in older persons. J Am Geriatr Soc 2011, 59(1):148–157.

10. NICE: The assessment and prevention of falls in older people. 2013. http://www.nice.org.uk/CG161.

11. Rydwik E, Bergland A, Forséén L, Fräändin K: Psychometric properties of Timed Up and Go in elderly people: a systematic review. Physical & Occupational Therapy in Geriatrics 2011, 29(2):102–25.

12. Beauchet O, Fantino B, Allali G, Muir SW, Montero-Odasso M, Annweiler C. Timed Up and Go test and risk of falls in older adults: a systematic review. J Nutr Health Aging 2011, 15(10):933–8.

13. Schoene D, Wu SM, Mikolaizak AS, Menant JC, Smith ST, Delbaere K, et al. Discriminative ability and predictive validity of the timed up and go test in identifying older people who fall: systematic review and meta-analysis. J Am Geriatr Soc 2013, 61(2):202–8.

14. Barry E, Galvin R, Keogh C, Horgan F, Fahey T. Is the Timed Up and Go test a useful predictor of risk of falls in community dwelling older adults: a systematic review and meta- analysis. BMC Geriatrics 2014 14:14.

15. Stenhagen M, Nordell E, Elmstahl S. Falls in elderly people: a multifactorial analysis of risk markers using data from the Swedish general population study 'Good Ageing in Skane'. Aging Clin Exp Res 2013, 25(1):59–67.

16. Rossat A, Fantino B, Nitenberg C, Annweiler C, Poujol L, Herrmann FR, et al: Risk factors for falling in community-dwelling older adults: which of them are associated with the recurrence of falls? J Nutr Health Aging 2010, 14(9):787–91.

17. Yamada M, Aoyama T, Nakamura M, Tanaka B, Nagai K, Tatematsu N, et al: The reliability and preliminary validity of game-based fall risk assessment in community-dwelling older adults. Geriatr Nurs 2011, 32(3):188–94.

18. Vaillant J, Martigné P, Vuillerme N, Caillat-Miousse JL, Parisot J, Juvin R, et al: Prediction of falls with performance on Timed “Up-and-Go” and one-leg-balance tests and additional cognitive tasks. Ann Réadapt Méd Phys 2006, 49(1):1–7.


Sharma et al


INTRODUCTION

Abdominal trauma is frequently encountered, but the pancreas remains one of the uncommonly injured organs; as per Western data, pancreatic injuries are seen in only about 0.09% of blunt abdominal trauma, usually in conjunction with other injuries -

1,2isolated pancreatic injuries are even rarer. The deep, central and retroperitoneal location of the pancreas is believed to protect it from injury, and it is this particular reason that is also thought to be responsible for the delay in diagnosis and treatment of the pancreatic trauma, with

3a consequent high mortality rate of around 23.4%.

The mechanism of pancreatic injury in blunt trauma abdomen is the transmission of blunt force to the retroperitoneum leading to crushing of the pancreatic substance between rigid structures such as a steering wheel / seatbelt and the patient's vertebral column. This causes injury to the gland that can range from mild contusion to complete transaction with or without main

pancreatic duct disruption. The patient can present with a wide variety of non-specific acute abdominal symptoms that not only depend upon the severity of pancreatic injury, but also, on associated injuries to other organs that might confound or hide the diagnosis of a pancreatic injury. Given these facts, accurate diagnosis of pancreatic injuries requires a high degree of suspicion, especially for patients who have sustained upper

2,4abdominal trauma. Although serum amylase levels can be elevated in such patients, little is known about their specificity, hence limiting their value as an indicator of

2,5pancreatic injury. Contrast enhanced computerized tomogram (CECT) scan is the investigation of choice, and the findings of may be direct (parenchymal hematomas or disruption) or indirect (malperfusion, surrounding fluid or hematoma, adjacent soft tissue

6stranding).

The management of pancreatic trauma depends upon ductal integrity, and stable patients with intact pancreatic

5ducts can be successfully managed conservatively. Ductal injuries usually need some form of intervention, although there have been reports of such cases also being managed successfully conservatively – the incidence of sepsis, pancreatic fistula, prolonged recovery, and

7,8mortality is higher in this subset of patients. By and large, patients with ductal injuries need surgical intervention, and one such case managed successfully recently in our department is hereby reported.

Case Report

Splenic Preservation in Blunt Pancreatic Trauma – Report of a Case1 2 3

Gaurav Shanker Pandey , Simrandeep Singh , Robin Kaushik 1 2 3Postgraduate Resident, Assistant Professor, Professor

Department of SurgeryGovernment Medical College and Hospital, Sector 32, Chandigarh, India

ABSTRACT

The management of pancreatic trauma is challenging and is essentially dictated by the status of the main pancreatic duct. Lesser grades of injuries without ductal involvement usually respond to conservative management, but once the main duct is involved, patients usually need some form of intervention. For patients with injuries to the body and tail of the pancreas, the classical operation has been distal pancreatectomy (with splenectomy). With a better understanding of splenic functions and an awareness of the dangers of the asplenic state over the last few decades, the concept of splenic conservation has led to a change in surgical strategy, with spleen preserving distal pancreatectomy (SPDP) being offered in the setting of pancreatic trauma in hemodynamically stable patients. One such patient of pancreatic trauma who underwent SPDP at our hospital is reported and the relevant details on SPDP are discussed.

Keywords: Laparotomy, pancreatectomy, resection, fistula, splenectomy


Dr. Robin KaushikDepartment of SurgeryGovernment Medical College and HospitalChandigarh 160 030Emil: [email protected]

CASE REPORT

A 38 year old patient presented to the emergency after a traffic accident in which his motorcycle was hit from behind by a car. He sustained a blow to his upper abdomen by the handle of the motorcycle. On presentation, he had stable vitals, and he was managed conservatively. A decision was taken to get a CECT abdomen done the next day and it showed a complete transaction of the pancreatic body, with minimal free fluid and no other organ injury.

The patient was taken up for exploration under general anesthesia. A generous midline abdominal incision was given and approximately 500 ml of blood came out on opening the peritoneum. There were patches of saponification all over the omentum. Once the blood was drained and all other organs inspected for any injuries that might have been missed on imaging, the lesser sac was opened by dividing the gastro-colic omentum, right up to the fundus of the stomach to expose the pancreas. A complete transection of distal body of pancreas was visualized (Fig. 1). Since the patient was hemodynamically stable, a decision was taken to perform a spleen preserving distal pancreatectomy (SPDP). The pancreas was mobilized along its inferior border and lifted up to identify the splenic artery and vein. These main vessels were looped to gain proximal control and gradually, the distal portion of the pancreas was mobilized by carefully separating it after dividing multiple pancreatic vessels from them using a combination blunt and sharp dissection, ligation and cautery upto the splenic hilum. Once distal pancreatectomy was completed, an attempt was made to identify the main pancreatic duct in the proximal

pancreatic body, but it could not be identified. The proximal stump of the pancreas was closed sutured using 000 polydioxanone mattress sutures and after reconfirming hemostasis, the abdomen was closed after placing a drain in the pancreatic bed.

The patient remained well in the post operative period and although he developed wound infection and a controlled pancreatic fistula that settled on conservative management, he had a fairly uneventful course and was

th 3,5,8discharged on the 7 post operative day.

DISCUSSION

Surgery for pancreatic trauma is challenging, not only because it is infrequent, but also because of its anatomical location in the retroperitoneum, complex blood supply and close anatomical relationship with the duodenum, inferior vena cava, aorta, mesenteric vessels, spleen and other upper abdominal organs. The site of injury and the status of the main pancreatic duct are the main determinants of what kind of surgery is to be performed – most patients without ductal injuries can be managed with a conservative approach but, by and large, ductal disruption needs surgery that can range from classical pancreaticoduodenectomy or duodenal preserving pancreatic head resections (pancreatic head injuries) to distal pancreatectomy (injuries in the pancreatic body and tail) that should only be considered in hemodynamically stable patients and in centres where adequate surgical expertise is available.

Distal pancreatectomy usually entails removal of the spleen also, but a better understanding of the functions of the spleen has lead to a concept of splenic preservation to avoid the complications of splenic removal, especially OPSI (overwhelming post splenectomy infection) which is caused by S. pneumonia and can occur any time after splenectomy and carries a very high mortality rate (as

3,9 high as 70%). Spleen preserving distal pancreatectomy (SPDP) preserves the spleen while performing a distal pancreatic resection, thus protecting the patient from lifelong consequences of splenic removal. This procedure was first described in the 1940s by the French

7surgeon Mallet-Guy, and in addition to the benefits of splenic preservation, the proponents of SPDP have also reported that it is associated with significantly lesser incidence of blood loss, intra-abdominal infections, post-operative infections, pancreatic fistula, and shorter hospital stay. However, the flip side is that performing

Fig. 1 : Intra-operative photograph showing transection of the body of pancreas.

Pandey et al


SPDP is technically demanding and requires a greater understanding of the anatomy of the pancreas and its blood supply, since multiple small vessels from the splenic artery and vein need to be carefully divided to mobilize the pancreas, as was done in our patient. This technique is based on the work of Dawson and Scott-

9Conner who demonstrated that approximately 22 tributaries drain into the splenic vein from the pancreas, with about 8 arterial branches arising from the splenic artery to the pancreas. Each of these needs to be individually ligated along the pancreatic substance being resected, and as is obvious, needs patience and time as well as knowledge of the anatomy of this region. Another technique of performing SPDP is by the technique as

10 described by Warshaw in which the splenic vessels are ligated at the level of pancreatic transaction and the spleen is left to survive on the blood supply through the short gastric and left gastroepiploic vessels.

CONCLUSION

In conclusion, a high index of suspicion is the key in early recognition of pancreatic injuries. Although there are series of successful conservative management, pancreatic duct disruption usually needs surgery, the nature of which is dictated by the site of injury; distal pancreatectomy with splenic conservation remains a suitable procedure for hemodynamically stable patients.

REFERENCES

1. O'Hanlon DM, Shaw C, Fenlon HM, McEntee GP. Traumatic transection of the pancreas. Am J Surg 2002 ;183:191.

2. Ahmed N, Vernick JJ. Pancreatic injury. South Med J 2009 ; 102: 1253-6.

3. Towensend CMTJ, Beauchamp RD, Evers BM, Mattox KL. Sabiston Textbook of Surgery: The Biological Basis of Modern Surgical Practice, 19 edition. Philadelphia, PA: Saunders; 2012; 2152

4. Cirillo RL, Koniaris LG. Detecting blunt pancreatic injuries. J Gastrointest Surg 2002; 6: 587-98.

5. Debi U, Kaur R, Prasad KK, Sinha SK, Sinha A, Singh K. Pancreatic trauma: A concise review. WJG. 2013; 19: 9003-11.

6. Fischer JH, Carpenter KD, O'Keefe GE. CT diagnosis of an isolated blunt pancreatic injury. AJR Am J Roentgenol. 1996; 167: 1152.

7. Wales PW, Shuckett B, Kim PCW. Long-term outcome after nonoperative management of complete traumatic pancreatic transection in children. J Pediatr Surg. 2001; 36: 823-7.

8. Meier DE, Coln CD, Hicks BA, Guzzetta PC. Early operation in children with pancreas transection. J Pediatr Surg. 2001; 36: 341-4.

9. Dawson DL, Scott-Conner CE. Distal pancreatectomy with splenic preservation: the anatomic basis for a meticulous operation. J Trauma 1986; 26: 1142-5

10. Warshaw AL. Conservation of the spleen with distal pancreatectomy. Arch Surg. 1988; 123: 550-553

Splenic Preservation in Blunt Pancreatic Trauma



INTRODUCTION

Each unit of blood or blood component transfused is associated with the possibility that patient may experience an adverse reaction to the product transfused. These reactions may range from mild febrile non hemolytic transfusion reaction or allergic reaction to hemolytic transfusion reaction. However, hypotensive

1,2transfusion reactions are less well recognised. We hereby report a case of hypotensive transfusion reaction.

CASE REPORT

A 48 year old female was admitted in the emergency medicine ward with the chief complaint of increased shortness of breath since 2 weeks. She had hypothyroidism and was a patient of chronic kidney disease since four years. On physical examination, clubbing, pallor and bilateral wheeze were present. There was no pedal edema and heart sounds were normal on auscultation. On laboratory investigation, her hemoglobin was 7.5 g/dl, total leucocyte count (TLC) was 18,500/µl and differential leucocyte count (DLC) showed predominantly neutrophilia (84%). Her renal

function tests were deranged with blood urea of 136 mg/dl and serum creatinine of 5.4 mg/dl. Her chest X-ray showed non homogenous opacity in left lower zone. Patient was shifted to intensive care unit (ICU) after 10 hours of admission and dialysis was planned. A request for 2 units of packed red blood cells (PRBCs) was received in the department.

On forward and reverse grouping, her blood group was found to be A Rh D positive. Two units of A Rh D positive packed red cells were cross-matched for the patient using tube technique and were found to be incompatible in anti-human globulin (AHG) phase. Antibody screen and identification was performed using microcolumn gel technique (BioRad, Switzerland) and anti E and anti c antibodies were identified. Antigen negative units were cross-matched and found compatible for the patient using microcolumn gel technique.

The treating physician demanded one unit of packed red cells which was issued to the patient. Before starting the transfusion, her vitals were within normal range. However, after about 80-90 ml of blood transfusion, patient experienced hypotension (90/60 mmHg) and tachycardia (160/min). The patient was afebrile and there were no rigors or chills. Blood transfusion was stopped and symptoms subsided. Blood unit along with post transfusion sample was sent to the department for transfusion reaction work up.

On reaction work up, blood group was confirmed to be A Rh D positive, cross-match was found to be compatible in AHG phase with both pre and post transfusion sample

Case Report

Hypotensive transfusion reaction – a case report2 3 4 4 5

Kshitija Kumar Kaur Kaur Sood Kaur1 2 3 4Senior Blood bank officer cum Lecturer, Demonstrator, Associate Professor, Assistant Professor,

Department of Transfusion Medicine,Government Medical College and Hospital, Chandigarh 160030

1Mittal , Rakesh , Gagandeep , Paramjit , Tanvi , Ravneet

5Professor

ABSTRACT

Transfusions reactions can be caused by the toxicity of chemicals that leach in blood components from blood storage containers or by endogenous mediators generated in the blood during filtration, processing and storage, such as bradykinin mediated hypotensive reactions. Such transfusion reactions are characterized by early and abrupt onset of hypotension as the predominant clinical manifestation and subside once transfusion is stopped. We report a case who presented with hypotension on blood transfusion and its management.

Keywords: blood transfusion, hypotension, adverse reactions


Dr Gagandeep KaurDepartment of Transfusion MedicineGovernment Medical College, Sector 32Chandigarh.160030Phone: 9646121576E mail: [email protected]

and direct anti-globulin test (DAT) was negative. Second unit of blood was issued the subsequent day and patient experienced similar symptoms. Transfusion reaction work up again revealed no discrepancy. Hence, a diagnosis of acute hypotensive transfusion reaction (AHTR) was made. Patient was provided with washed red blood cells on three different occasions and all the transfusions were uneventful.

Acute hypotension can occur as a part of constellation of symptoms resulting from bacterial contamination of blood products, acute hemolysis, and transfusion related

3acute lung injury and anaphylaxis. Recently, acute hypotensive transfusion reactions have been characterized by early and abrupt onset of hypotension as the predominant and sole clinical manifestation which

4resolves quickly once the transfusion is stopped. Similarly in our case, patient experienced only hypotension and tachycardia with absence of fever, chills, urticaria, laryngeal edema or flank pain. Symptoms resolved within half an hour once transfusion was stopped.

Hypotensive reactions occur due to disturbances in the production and metabolism of bradykinin. Bradykinin is generated as a result of Factor XII activation due to contact with negatively charged surfaces such as tubing systems, dialysis membranes and leukoreduction filters. Bradykinin is primarily metabolized by the angiotensin converting enzyme (ACE) and is a vasoactive peptide that binds to receptors on the endothelium causing hypotension. An increase in the recognition of such reactions has been due to the growing use of ACE inhibitors, the use of negatively charged leukoreduction filters and both genetic and induced alterations in

4bradykinin kinetics. In our case, patient was a known case of chronic kidney disease and was undergoing dialysis for it.

In 1978, first report of hypotensive reactions resulting from the use of plasma derivatives was published. However, the authors failed to identify kallikrein or

5bradykinin in the samples. Subsequently, correlation of the generation of bradykinin in plasma derivatives to the development of hypotensive transfusion reactions was

6recognized. Usually, such reactions are self limiting and

symptoms subside once the transfusion is stopped. However, if repeated transfusions are required, then use of washed cellular blood products, discontinuation of leuco-reduction filters or ACE inhibitors, use of

4,7 kallikrein blockade drugs has been reported. Similarly in our case, patient did not experience any transfusion reaction symptoms with washed packed red blood cells suggesting the likely role of plasma protein fraction in causing symptoms probably activated after contact with negatively charged dialysis membrane. Anaphylaxis was ruled out as patient had only hypotension and tachycardia without any urticaria, flushing or edema. However, bradykinin or kallikrein levels could not be performed due to financial constraints.

CONCLUSION

The exact pathophysiology of hypotensive transfusion reactions is probably multifactorial. Therefore, further research needs to be done in understanding and identifying the etiology and factors involved in causing these transfusion reactions for the optimum management of the patient.

REFERENCES

1. Hume HA, Popovsky MA, Benson K, Glassman AB, Hines D, et al. Hypotensive reactions: a previously uncharacterized complication of platelet transfusion? Transfusion 1996; 36:904-909.

2. Sweeney JD, Dupuis M, Mega AJ. Hypotensive reactions to red cells filtered at the bedside, but not to those filtered before storage, in patients taking ACE inhibitors. Transfusion 1998; 38:410-411.

3. Popovsky MA. Transfusion reactions. Bethesda, MD: AABB Press; 2001: 222.

4. Bruno DS, Herman JH. Acute Hypotensive Transfusion Reactions. Lab Medicine 2006; 37: 542-545.

5. Alving BM, Hojima Y, Pisano JJ, Mason BL, Buckingham RE Jr, et al. Hypotension associated with prekallikrein activator (Hageman factor fragments) in plasma protein fraction. N Engl J Med 1978;299:66-70.

6. Van Roosevelt RF, Bakker JC, Sinclair DM, Damen J, Van Mourik JA. Bradykinin mediated hypotension after infusion of plasma protein fractions. J Lab Clin Med 1982;100:288-295.

7. Quillen K. Hypotensive transfusion reactions in patients taking Angiotensin-converting-enzyme inhibitors. N Eng J Med 2000; 343: 1422-1423.

Hypotensive transfusion reaction


28Journal of Medical College Chandigarh, 2016, Vol.6, No.2

INTRODUCTION

Lichen scrofulosorum was first described in 1868 by Hebra. It was believed to be a rare tuberculid usually affecting children and adolescents with tuberculosis. The lesions are usually asymptomatic, tiny, closely grouped, skin-colored to reddish-brown papules, often perifollicular and are mainly found on the abdomen,

1,2chest, back, and proximal parts of the limbs. Lichen scrofulosorum is

and is usually associated with a 3

strongly positive tuberculin reaction.

CASE REPORT

A 25-year-old woman presented with mildly itchy generalized papular rash on the trunk and proximal parts of the upper and lower extremities since 15 days. It was not associated with fever, cough, anorexia, weight loss or any other systemic symptoms. There was history of a swelling on right side of neck 2 years ago, which was incised and drained by a local practitioner and healed with a scar. There was no history of similar complaints,

thought to result from an immune response to haematological spread from an underlying

1tuberculous focus

diabetes mellitus, tuberculosis and atopy in the family.

General physical examination revealed a moderately built and nourished female with mild pallor. No significant lymphadenopathy or organomegaly was detected. Systemic examination did not reveal any abnormalities. Cutaneous examination showed multiple, grouped, skin-colored to reddish-brown, follicular and extra follicular lichenoid papules with mild scaling on the front and back of the trunk, upper arms and thighs (Figure 1). A scar was present on right side of neck. BCG scar was found. Examination of hair, nails and mucosae were normal.

Case Report

Lichen scrofulosorum associated with active pulmonary tuberculosis in an adult1 2 2

Manjit Kaur , Mala Bhalla , Gurvinder P. Thami1 2 Senior Resident, Professor

Department of Dermatology and VenereologyGovernment Medical College and Hospital, Sector 32 B, Chandigarh, India

ABSTRACT

Lichen scrofulosorum is an increasingly diagnosed tuberculid, usually seen in children or young adults with strong immune sensitivity to Mycobacterium tuberculosis and an active focus of tuberculosis elsewhere in the body. The eruption is characterized by asymptomatic, closely grouped, tiny follicular papules, mainly confined to the trunk, which involute with conventional anti-tubercular therapy. Correct diagnosis of lichen scrofulosorum is frequently delayed because of its clinical similarity to other skin conditions and asymptomatic nature. We report a case of lichen scrofulosorum in an adult female associated with active pulmonary tuberculosis.

Keywords: Lichen scrofulosorum, tuberculid


Dr. Mala Bhalla, ProfessorDepartment of Dermatology and VenereologyGovernment Medical College and HospitalSector 32 B, Chandigarh, 160 030, IndiaE-mail: [email protected]

Fig. 1 : Lichenoid, follicular and perifollicular papular eruption on back.

Histopathological examination of a papule from the trunk revealed non-caseating, epitheloid cell granulomas in the upper dermis surrounding a hair follicle (Figure 2). No tubercular bacilli were detected on acid-fast staining. Laboratory examination revealed anemia (hemoglobin 8 g%), raised erythrocyte sedimentation rate of 50 mm in the first hour and a reactive Mantoux test with an induration of 18 × 14 mm. Serum for VDRL and ELISA for HIV were non-reactive. Hepatic and renal function tests were normal. Chest radiography revealed patchy consolidation and infiltrate in lung parenchyma. Sputum examination showed 2+ acid fast bacilli/field on 3 consecutive days. Culture for Mycobacterium tuberculosis was negative.

A diagnosis of Lichen Scrofulosorum associated with active pulmonary tuberculosis was made and antituberculosis therapy (ATT) was started with four drugs- Rifampicin, Isoniazid, Ethambutol and Pyrazinamide for the first two months, followed by rifampicin and isoniazid for four months. There was complete resolution of the lesions with ATT.

DISCUSSION

Hebra first described lichen scrofulosorum in 1868. Lichen scrofulosorum (LS) earlier believed to be a rare tuberculid is usually seen in children or young adults with strong immune sensitivity to Mycobacterium tuberculosis and an active focus of tuberculosis

1elsewhere in the body. The eruption is characterized by asymptomatic, closely grouped, tiny, skin-colored to reddish-brown papules, often perifollicular, mainly confined to the trunk and proximal parts of the limbs.

Correct diagnosis of lichen scrofulosorum is frequently delayed because of its clinical similarity to other skin

2conditions and asymptomatic nature. The lesions usually involute with conventional Anti-tubercular treatment.

LS is

and is usually associated with a strongly positive 1,3

tuberculin reaction. Lichen scrofulosorum is being increasingly diagnosed especially in endemic countries like India and is now believed to be the commonest

4tuberculide seen in children. This hypersensitivity reaction is no longer limited to children and has been

5,6recently reported in adults as well, as in our patient.

LS is rarely associated with active pulmonary 2

tuberculosis. In our patient also, it may have started with cervical lymphadenopathy that was drained. Failure to start anti-tubercular treatment at that time may have lead to its progression and haematogenous spread resulting in pulmonary tuberculosis and lichen scrofulosorum. Though LS is an asymptomatic condition, it can act as a cutaneous marker for detection of an underlying systemic tubercular infection even in adults as in this

4case.

CONCLUSION

It is imperative that dermatologists have a high index of suspicion in order to quickly diagnose this treatable condition and substantial morbidity can be prevented by the timely effective conventional ATT.

REFERENCES

1. Yates VM. Mycobacterial infections. In: Burns T, Breatnach S, thCox N, Griffiths C, editors. Rook's Textbook of Dermatology. 8

ed. Oxford: Blackwell Science; 2010.p. 31.21-2.

2. Singhal A, Bhattacharya SN. Lichen scrofulosorum: A prospective study of 39 patients. Int J Dermatol 2005; 44:489-493.

3. Sing G, Kaur V, Singh S. Bacterial infections. In: Valia RG, Valia ndAR, Siddappa K, editors. Textbook and atlas of dermatology. 2

ed. Mumbai: Bhalani Publishing House; 2003. p. 190–214.

4. Singhal P, Patel PH, Marfatia YS. Lichen scrofulosorum: A diagnosis overlooked. Indian Dermatol Online J 2012;3(3):190-192.

5. Thami GP, Kaur S, Kanwar AJ, Mohan H. Lichen scrofulosorum: A rare manifestation of a common disease. Pediatr Dermatol 2002; 9:22–26.

6. Joshi HS, Zacharia A, Warrier A. Lichen scrofulosorum. BMJ Case Rep 2014; pii: bcr2013200858. doi: 10.1136/bcr-2013-200858.

thought to result from an immune response to haematological spread from an underlying tuberculous focus

Fig. 2 : Photomicrograph showing epitheloid cell granulomas in upper dermis

Lichen scrofulosorum associated with active pulmonary tuberculosis



INTRODUCTION

The parapharyngeal space tumors are only 0.5% of all 1

the head and neck tumors. Approximately 50% of the tumors have a salivary origin, 20% are neurogenic and the remaining 30% are benign and malignant lymphoreticular lesions, carotid body tumors and

2metastatic lesions.

Schwannomas are also known as neurilemoma or neurinomas. They are benign tumors arising from Schwann cells of nerve sheath. The Schwann cell originates from neural crest and surrounds peripheral nerve tissue. They are typically solitary, well-encapsulated, benign tumors characteristically running or attached along the course of cranial, peripheral or sympathetic nerves. Schwannoma undergoing malignant conversion is rare.

About 25% to 45% of schwannomas are located in the head and neck and may involve the cranial nerves such as IV, V, VII, X, XI, XII or the sympathetic and peripheral

3nerves. About 10% of schwannomas that occur in the neck region originate from the vagus or sympathetic

4nervous system. In the parapharyngeal space, the prevalent location is vagus, though it may arise from any of the last four cranial nerves and autonomic nerve.

Schwannomas arising from cervical sympathetic chain are rare. They usually begin and present as gradually progressive, without symptoms, lone neck swelling; Horner's syndrome is rarely apparent on physical examination. For preoperative evaluation and confirmation of diagnosis of neurilemmoma, contrast-enhancing computed tomography (CECT) and

5ultrasound are considered useful, while open biopsy is not recommended due to correlated complications such as infection, haemorrhage and

4cranial nerve damage.

In this article, a patient with schwannoma arising from the right cervical sympathetic chain is described.

Case Report

Intracapsular dissection in cervical sympathetic chain schwannoma: a case report

1 2Naiya Rao , Manish Gupta1 2Post Graduate Student , Professor

Department of ENTMaharishi Markandeshwar Institute of Medical Sciences and Research, MMU, Mullana, Ambala.

ABSTRACT

Cervical sympathetic chain schwannoma often presents as an asymptomatic single neck mass, which generally grows slowly and rarely undergoes malignant change. Definitive pre-operative diagnosis at times may become difficult and investigations are not usually helpful. CT may show displaced major vessels anterolaterally. Diagnosis mainly relies on clinical suspicion and is confirmed by histopathological examination after surgical excision which is also the treatment of choice. Recurrence rate is low for this tumor. Horner's syndrome is a common post-operative neurological consequence and may be asymptomatic.

The case described here is of a 45-year-old female who presented with an asymptomatic right neck mass. Diagnostic studies included computed tomography and ultrasound which confirmed a circumscribed mass in the upper right portion of the neck next to the thyroid gland. The mass was excised through a horizontal right cervical skin incision. Post-operatively the patient showed no clinical signs of Horner's syndrome. The detailed assessment with regard to histopathology, radiology presentation, treatment options and post-operative complications of this neoplasm is being discussed.

Keywords: Cervical sympathetic chain, Schwannoma, Surgical treatment, Horner's syndrome


Dr. Manish GuptaDepartment of ENT, MMIMSR, MMU, Ambala, India.Email: [email protected]

CASE REPORT

A 45-year-old female presented with an asymptomatic right upper lateral neck mass found on routine physical examination 5 months back. The mass, measuring approximately 3 X 2 cm, was located anterior to the upper portion of the sternocleidomastoid muscle. It was mobile, non-tender, and non-pulsatile, with no associated bruit. Though the mass was gradually increasing in size but was not associated with dysphonia, dysphagia, and pain or weight loss. Other cranial nerve examination was found to be normal.

The routine blood and urine investigations were normal. A fine needle aspiration cytology (FNAC) was performed via the neck and it was suggestive of schwannoma. FNAC revealed spindle-shaped cells with irregular fusiform nuclei in a vague interwoven pattern.

It is important to identify the nerve of origin preoperatively using radiological tools. It helps in making surgeon aware of and explaining the patient possible complications. Contrast enhanced computed tomogram (CECT) of neck region showed large well defined non enhancing lesion on right side of neck measuring 5.4cm x 2.4 cm extending from base of skull superiorly till carotid bifurcation inferiorly (Figure 1, 2 and 3).

The pre-operative differentials were cervical sympathetic chain schwannoma, vagal schwannoma, metastatic or reactive lymphadenopathy, branchial cleft cyst and paraganglioma.

Patient was taken up for excision via cervical approach under general anaesthesia. The tumor was identified

arising from cervical sympathetic chain and intracapsular blunt dissection was done all around the tumor to separate the mass preserving the nerve (Figure 4 and 5).

The histopathology confirmed a schwannoma with Antoni A (highly cellular) and Antoni B (sparsely

Fig. 2 : Axial section CECT Neck Showing mass pushing major vessels antero-laterally.

Fig. 1 : Axial Section of Non-Contrast CT, Showing Mass In Right Para-Pharyngeal Space.

Fig. 3: Coronal section of CECT neck showing vertical and horizontal extensions of the mass in right parapharyngeal space.

Fig. 4 : Intraoperative clinical picture of mass with its capsule.


Intracapsular dissection in cervical sympathetic chain schwannoma

cellular) areas. In between compact rows of well aligned nuclei, the Verocay body formation by the cell processes was also seen with areas of necrosis (Figure 6). There was no nerve deficit or recurrence in one year follow-up.

DISCUSSION

Schwannomas are seen most frequently between fourth 3

and sixth decade of life, with female preponderance. Clinically they often present as an asymptomatic mass. As per the criteria suggested for identification of the nerve of origin, the cervical sympathetic chain is placed posterior to major vessels of neck and thus

6displaces them anteriorly. It can also be identified intraoperatively by tracing the nerve of origin & correlating anatomically.

The conservative approach of observation and follow-up may be tried in some cases because of slow growth and non-invasive nature of these tumors, but they may increase in size and apply pressure over adjoining

7tissues, compromising the aero-digestive tract. Thus, surgery is the treatment of choice. Total removal of the

tumor, with preservation of nerve fibers, is always the aim for surgical treatment of nerve sheath tumors.

Recently intracapsular enucleation has been popularized 7

to safeguard the neurological function. This preserves more than 30% nerve fibers function, when compared to

8tumor resection with primary anastomosis. The neurological function can also be checked using a nerve stimulator or performing the surgery under microscopic magnification for intracapsular enucleation. If it is futile to find working plane and is difficult to preserve the physical integrity of the nerve, the tangled segment is cut-off and an end-to-end anastomosis performed using microscope.

Post-operative complications following tumor resection with involved nerve, depends on the nerve of origin. It may be vocal cord palsy, pharyngeal or laryngeal loss of sensation leading to aspiration or Horner's syndrome,

8which is often permanent. Some controversy exists regarding higher recurrence rate with enucleation/ intracapsular dissection, but it is mainly the partial resection which is associated with high recurrence. However, further long term follow-up analysis is needed to correlate the benefit/ loss ratio of the enucleation procedure.

REFERENCES

1. Saito DM, Glastonbury CM, El-Sayed IH, Eisele DW. Parapharyngeal space schwannomas: preoperative imaging determination of the nerve origin. Arch Otolaryngol Head Neck Surg 2007;133(7):662-7.

2. Kim SH, Kim NH, Kim KR. Schwannoma in head and neck: preoperative imaging study and intracapsular enucleation for functional nerve preservation. Yonsei Med J 2010;51(6):938-42.

3. Kang GC, Soo KC, Lim DT. Extracranial nonvestibular head and neck schwannoma: a ten year experience. Ann Acad Med Singapore 2007;36(4):233-8.

4. Biswas D, Marnane C, Mal R, Baldwin D. Benign extracranial nerve sheath tumor of the skull base: postoperative morbidity and management. Skull Base 2008;18(2):99-106.

5. Rao AB, Koeller KK, Adair CF. Paragangliomas of the head and neck: radiologic-pathologic correlation. Radiographics 1999;19:1605-32.

6. Furukawa M, Furukawa MK, Katoh K, Tsukuda M. Differentiation between schwannoma of the vagus nerve and schwannoma of the cervical sympathetic chain by imaging diagnosis. Laryngoscope 1996;106:1548-52.

7. Gupta M, Singh S, Gupta M, Kaur R. A cervical sympathetic chain schwannoma of the left parapharyngeal space, presenting in the prestyloid region. Int J Otorhinolaryngol Head Neck Surg 2016;2:95-8.

8. Valentino J, Boggess MA, Ellis JL, Hester TO, Jones RO. Expected neurologic outcomes for surgical treatment of cervical neurilemomas. Laryngoscope 1998;108:1009-13.

Fig. 5 : Picture showing complete excised mass.

Fig. 6 : Picture of histopathology slide under magnification (40X) showing spindle shaped cells in Antoni A and B pattern.


Rao and Gupta


INTRODUCTION

Dermatomyositis/polymyositis (DM/PM) and Rheumatoid arthritis (RA) are independent rheumatic diseases that may have a variety of overlapping clinical, radiological, and pathological manifestations according to different accepted criteria. The occurrence of myositis in RA and the appearance of inflammatory arthropathy in DM/PM have been mentioned previously in the literature. The association of well defined DM/PM with RA in the same patient, however, appears to be infrequent. Since the specific coincidence of DM and RA has received a scant attention in the literature, this case report is intended to describe a patient diagnosed with definite RA who also had overlapping DM.

CASE REPORT

A 46 year male presented with history of myalgias since 8 months associated with history of joint pains and early morning stiffness. Patient had also developed erythematous rash on face since 8 months which gradually worsened. Joint complaints started as monoarticular arthralgia involving right metacarpo-phalangeal joint of index finger which over period of 4 months turned into symmetrical polyarthralgia

involving both metacarpophalangeal joints and proximal interphalangeal joint. Over period of time arthralgia worsened and there was swelling of PIP joints of index and middle fingers of both hands. Patient also started feeling worsening of myalgias with difficulty in climbing stairs and brushing his teeth and even in wearing turban. His weakness progressively worsened over a period of 6-8 months. Now he had difficulty in standing and walking and he needed help for doing basic daily activities. His rash on face also worsened and became more hyperpigmented.

On examination there was no wasting of any muscle and deep tendon reflexes were normal. There was generalized tenderness over small joints of both hands and there was swelling of proximal interphalangeal joints involving index finger, ring finger and middle finger of both hands.

His investigation revealed normal hemogram except for ESR which was 150mm in first hour. His rheumatoid factor was 56 IU/ml. His C-reactive protein (CRP) was 30mg/l and anti-CCP (Anti-cyclic citrullinated peptide antibody) was 70 units. His ANA and dsDNA were negative, his CPK was 22,000 u/l, and his LDH was 332u/l. MRI of muscles revealed hyper intense signals in bilateral gluteal muscles. Electromyogram revealed denervation along with myopathic changes characteristic of dermatomyositis. As his ACR (American college of Rheumatology) score was more than 8, he was diagnosed as case of rheumatoid arthritis

Case Report

Dermatomyositis overlapping with Rheumatoid arthritis: a rare clinical entity 1 2 3

Mandip Singh Bhatia , Ritu Attri , Monica Gupta 1 2 3Senior consultant, SGHS Mohali, Senior resident, Govt Medical College Patiala, Professor,

Department of MedicineGovernment Medical College and Hospital, Sector 32 B, Chandigarh, India

ABSTRACT

The association of dermatomyositis with rheumatoid arthritis (RA) is described in a 46 year old patient who was studied over a period of one year. Our patient had both diseases simultaneously overlapping with each other. His ACR score was 8 confirming diagnosis of RA and his classical rash on face, proximal muscle weakness, significantly elevated creatinine phosphokinase (CPK) levels and electromyography (EMG) and magnetic resonance imaging (MRI) findings confirmed the diagnosis of Dermatomyositis. A review of literature revealed few specific reports of coexistence of both diseases.

Keywords: Dermatomyositis, Rheumatoid arthritis


Dr. Mandip Singh BhatiaSenior consultant, SGHS Mohali,E-mail: [email protected]

with dermatomyositis and treated with oral prednisolone 1mg/kg/day along with other DMARDs (disease-modifying antirheumatic drugs) including methotrexate 10mg once weekly and sulfasalazine 500mg twice daily whose dose over 8 weeks was increased to 1000mg twice daily and tablet leflunamide was added 10mg once daily. Patient was kept on close follow up. After 4 weeks he started showing improvement and after 8 weeks there was significant decreases in rash, there were no swollen or tender joints and significant improvement in muscle power with resumption of normal day to day activities.

DISCUSSION

Dermatomyositis (DM) is one of the idiopathic 1-3

inflammatory myopathies. In 1975, Bohan and Peter published classic article that suggested a set of criteria to aid in the diagnosis and classification of DM and

2polymyositis (PM). Of the 5 criteria, 4 related to the muscle disease: progressive proximal symmetrical weakness, elevated muscles enzymes, an abnormal electromyogram, an abnormal muscle biopsy, while the fifth was the presence of compatible cutaneous disease. It was felt that DM differed from PM only by the presence of cutaneous disease. Recent studies of the pathogenesis

of the myopathy have been controversial, some suggesting that the myopathies in DM and PM are pathogenetically different with DM being due to a vascular inflammation, whereas other studies of

3cytokines suggest that the processes are similar. There has been a renewed interest in the pathogenetic mechanisms involved in the myopathy with recent studies revealing abnormal levels of nitric oxide, elevation of circulating tumor necrosis factor (TNF) receptors, elevated soluble CD 40 expression, and increased expression of major histocompatibility

3complex class I and interleukin 1a within the muscle. The pathogenesis of the cutaneous disease is poorly understood.

The etiology of these disorders is not known. There appear to be immunogenetic markers that are correlated with DM, PM, and additionally, these patients often

4possess TNF-a polymorphisms. It is possible that DM, PM, and/or juvenile DM are due to an interaction of environmental factors including infections in an individual with an immunogenetic predisposition to

5,6develop disease. The association of DM/PM and RA is well defined and independent rheumatic diseases have

Bhatia et al


Fig 1 and 2. Clinical pictures before treatment and 8 weeks after treatment

been recorded infrequent in literature.

Since the appearance of the diagnostic criteria for RA in 1959 there has been only few cases reports of actual coexistence of DM/PM and RA. Three cases of PM patients with undoubted erosive RA were described in

71966 in Great Britain. In 1977, Bohan et al reported overlap of one DM and three PM patients with RA in

8study of 153 American DM/PM patients. The report on 92 patients studied for over 20 years in Israel disclosed 12 cases with overlapping syndrome, including six with

9RA. A study of 105 DM/PM patients in Australia revealed that 14 from group of 43 who satisfied criteria for the association with other connective tissue diseases also met the diagnostic criteria for RA (11 with PM and

10three with DM). A study of 75 DM/PM patients in Singapore revealed 15 cases in overlap group, including

11four with coincidental RA.

Our patient had both diseases simultaneously overlapping with each other. His ACR score was 8 confirming diagnosis of RA and his classical rash on face, proximal muscle weakness, significantly elevated CPK levels and EMG and MRI findings confirmed the diagnosis of dermatomyositis. As stated above he responded very well to both diseases with steroids and DMARDs.

REFERENCES

1. Callen JP. Dermatomyositis. Lancet 2000;355:53-7.

2. Bohan A, Peter JB. Polymyositis and dermatomyositis. N Engl J Med 1975;292:344-7.

3. Sugugiura T, Kawaguchi Y, Harigai M, Takagi K, Ohta S, Fukasawa C, et al. Increased CD40 expression on muscle cells of polymyositis and dermatomyositis: role of CD40-CD40 ligand interaction in IL-6, IL-8, IL-5, and monocyte chemoattractant protein–1 production. J Immunol 2000;164:6593-600.

4. Werth VP, Callen JP, Ang G, Sullivan KE. Associations of tumor necrosis factor alpha and HLA polymorphisms with adult dermatomyositis: implications for a unique pathogenesis. J Invest Dermatol 2002;119:617-20.

5. Sarkar K, Weinberg CR, Oddis CV, Medsger TA Jr, Plotz PH, Reveille JD, et al. Seasonal influence on the onset of idiopathic inflammatory myopathies in serologically defined groups. Arthritis Rheum 2005;52:2433-8.

6. Pachman LM, Lipton R, Ransey-Goldman R, Shamiyeh E, Abbott K, Mendez EP, et al. History of infection before the onset of juvenile dermatomyositis: results from the National Institute of Arthritis and Musculoskeletal and Skin Diseases Research Registry. Arthritis Rheum 2005;53:166-72.

7. Pitkeathly DA, Coomes EN. Polymyositis in rheumatoid arthritis. Ann Rheum Dis 1966;25:127-132

8. Bohan A, Peter JB, Bowman RL, Pearson CM. A computer assisted analysis of 153 patients with polymyositis and dermatomyositis. Medicine 1977;56:255-86.

9. Benbassat J, Gefel D, Larholt K, Sukenik S, Morgestern V, Zlotnik A. Prognostic factors in polymyositis/dermatomyositis. A computer assisted analysis of ninety-two cases. Arthritis Rheum 1985;28:249-55.

10. Thymms KE, Weeb J. Dermatomyositis and other connective tissue disease: a review of 105 cases. J Rheumatol 1985;12:1140-48.

11. Koh ET, Seow A, Ong B. Adult onset polymyositis/ dermatomyositis; clinical and laboratory response in 75 patients. Ann Rheum Dis 1993;52:857-861.

Dermatomyositis overlapping with Rheumatoid arthritis



INTRODUCTION

Plantar fasciitis (PF) is the most common cause of heel 1

pain. It is a chronic degenerative process which occurs as a result of repeated micro trauma mainly occurring at the insertion of aponeurosis into the medial tubercle of

the calcaneus.PF impacts the health of millions of people around the world both with sedentary and active

1,2 population.

The peak incidence of PF is between 45 and 64 years and 3 occurs more commonly in women. Obesity, flat foot,

reduced ankle dorsiflexion, prolonged weight bearing, poor footwear are the main risk factors associated with

1PF. Approximately, 33% of patients experience bilateral

3 PF pain. Majority of patients are improved by the conservative treatment, but a few may require more

invasive options. So far, none of these modalities have

4 proven their efficacy alone.

The basis of chronic pain management involves interruption of nociceptive transmission from the involved site to produce pain relief with minimal risk. We published a case series in which a diagnostic medial calcaneal nerve (MCN) block was performed in three

patients following which they had significant reduction 5 in PF pain. To validate the results of our previous

5published study, we report a case series of seven patients with chronic PF in which MCN block was performed from 2011 to 2016 at pain management centre of our institute.

METHODS

The most common complaint of patients was pain in the heel on getting up in the morning and on prolonged walking. On examination, patients reported agonising tenderness on applying pressure over the medial side of the heel and discomfort on dorsiflexion of the foot. The other possible causes of heel pain were ruled out by taking detailed history and clinical examination. The chronic heel pain was refractory to conservative and pharmacological management. All seven patients received diagnostic MCN block of the affected foot under ultrasound guidance (USG) and nerve locator guidance. During follow up, two patients out of these received repeat MCN block with pulsed radiofrequency (PRF) application. (Table I)

Procedure

The MCN in the foot was identified near its origin by transcutaneous nerve stimulation (NM-20©, Inmed Equipments Pvt. Ltd., Vadodara, India). This site was marked as 'X' on skin for MCN block. Under aseptic precautions, 1.0 ml solution (0.5 ml of 2% lignocaine and 0.5 ml of 0.2% ropivacaine) of local anaesthetic was injected under ultrasound guidance. The pain relief was recorded using verbal numerical rating scale (VNRS). Patient 1 and Patient 2 received PRF (Cosman

Case Report

Medial Calcaneal Nerve block for plantar fasciitis pain: A case series1 2 3 3

Deepak Thapa , Vanita Ahuja , Ankita Mittal , Manjot Singh1 2 3Professor, Associate Professor, Junior Resident

Department of Anaesthesia and Intensive care, Government Medical College and Hospital, Chandigarh, India.

ABSTRACT

Plantar fasciitis (PF) is a chronic degenerative process involving plantar aponeurosis in foot. Chronic heel pain can have detrimental effect on health-related quality of life. In the present case series, seven patients diagnosed with PF received medial calcaneal nerve (MCN) block under ultrasound and nerve locator guidance. During follow up, two patients received repeat MCN block with pulsed radiofrequency (PRF) application. Patient reported 80-100 % pain relief during a follow up period of three months to five years. To conclude, blocking MCN at its origin provided pain relief in patients with chronic PF refractory to medical management.

Keywords: Planter fasciitis, visual analogue scale, pulsed radiofrequency


Dr. Vanita AhujaAssociate ProfessorDepartment of Anaesthesia and Intensive care, Government Medical College and Hospital, Chandigarh, Indiaemail: [email protected]

Medical Inc.,Burlington, MA, USA) application for two minutes at 42.5º (three cycles) along with repeat MCN lock.

RESULTS

The patients with PF in the present case series aged between 25-75 years. All the patients received diagnostic MCN block after a failed trial of medical management. Patients were followed up for a period of three months to five years. The MCN block resulted in 80-100% pain relief in VNRS both on getting up from the bed and on prolonged walking. Cases 1 and 2 had relapse of PF pain which was successfully managed with repeat MCN

block and PRF. During follow up, case 2 still reported mild pain on walking which was managed with occasional analgesics (Table I).

DISCUSSION

The diagnosis of PF is mostly clinical and the differential diagnosis which were considered included calcaneal trauma, systemic arthritides (ankylosing spondylitis, Reiter's syndrome and osteoarthritis), neuropathies, achilles tendonitis, heel contusion and

6plantar fascia rupture. PF usually improves within one year regardless of the treatment. Prior to reporting to Pain management centre of our Institute, patients had


TABLE I

Baseline characteristics of patient with Planter fasciitis and follow up

S no.

Age(yrs)

sex

Chief complaints

MCN Block

Pre

block

VNRS

Post block VNRS

Follow up

1.

27

M

Bilateral PF pain

Left heel

9/10

0/10

After 3 months, pain on

prolonged walking

PF pain left heel during

walking

at 3 months

Followed by PRF

5/10

0/10

Pain free for 4 years and 10

months

Right heel

6/10

0/10

Pain free 4 years and 10 months

2. 40 F Recalcitrant PF pain in

right heel

Right heel 8/10 1/10 (on getting up

in the morning)

After 10 days, persistent pain

during prolonged walking

At two weeks Followed by PRF 5/10 0/10 Pain free for 4 years but

complained of pain of VNRS 3/10

during prolonged walking

3. 50 M Pain in the right medial

heel

Right heel 7/10 2/10 Pain free for 4 years

4. 33 F Pain in the right medial

heel


5. 38 M Pain in the right medial

heel


6.

36 M Pain in the left medial heel Left heel 7/10

0/10

Pain free for 7 months

7. 73 F Pain in the right medial

heel

Right heel 8/10 1/10 Pain free for 5 months

PF: Plantar fasciitis, PRF: Pulsed Radiofrequency , MCN: Medial calcaneal nerve, VNRS: Verbal numeric rating scale, M: male, F: female

Medial Calcaneal Nerve block for plantar fasciitis pain

undergone physiotherapy and pharmacological management. In the present case series, MCN block provided analgesia in the sensory supply to the inferior and medial heel of the foot (first order neurons). MCN is a sensory nerve which usually arises from the tibial nerve, proximal to the tarsal tunnel, approximately 4–10 cm above the ankle joint. Further it courses outside the tarsal tunnel toward the medial aspect of the heel and

7calcaneus. MCN can have variable origin points from 8,9tibial nerve or lateral plantar nerve. During follow up,

Patient 2 still had mild pain on walking, which was managed with occasional analgesics. This could be explained due to the anatomical variability of the branching points of MCN which was spared during the nerve block.

Currently, use of corticosteroid needs justification as it may lead to skin and fat pad atrophy, infection and

3,10 plantar fascia rupture. Recently, multiple clinical trials have supported the efficacy of extracorporeal shock wave therapy (ESWT) but none has proved to be

6,11 clinically significant. Although, it is an office based

11 procedure but requires special equipment and may cause pain, ecchymosis and numbness with dysesthesia

6 at the involved site. We did not use ESWT as it requires additional infrastructure.

The other modalities for management of PF includes rest, nonsteroidal anti-inflammatory drugs (NSAIDs), stretching, counter strain technique, orthoses, corticosteroid injections, ESWT, platelet rich plasma

12 12 (PRP) and ultrasound therapy.

The novelty of use of MCN block includes that it is less invasive, requires low volume of local anaesthetic, USG and nerve locator allows accurate placement and low risk of infection as compared to heel pad injections. Two patients had relapse of PF pain which was managed with repeat MCN block and PRF. PRF prolonged the analgesic effect as the radiofrequency current used in short; high-voltage bursts, keeps the temperature of the target tissue below 42° C without causing significant

13damage to nervous tissue. It has also been found to be an effective modality for chronic pain treatment in

13various other clinical conditions also.

CONCLUSION

The present case series provides evidence for benefit of MCN block as pain relieving modality in patients with chronic PF refractory to medical management.

REFERENCES

1. Roxas M. Plantar fasciitis: diagnosis and therapeutic considerations. Altern Med Rev 2005;10:83-93.

2. Schwartz EN, Su J. Plantar fasciitis: a concise review. Perm J 2014;18:e105-7.

3. Thompson JV, Saini SS, Reb CW, Daniel JN. Diagnosis and management of plantar fasciitis. J Am Osteopath Assoc 2014;114:900-6.

4. Johnson RE, Haas K, Lindow K, Shields R. Plantar fasciitis: what is the diagnosis and treatment? Orthop Nurs 2014;33:198-204.

5. Thapa D, Ahuja V. Combination of diagnostic medial calcaneal nerve block followed by pulsed radiofrequency for plantar fascitis pain: A new modality. Indian J Anaesth 2014;58:183-5.

6. Goff JD, Crawford R. Diagnosis and treatment of plantar fasciitis. Am Fam Physician 2011;84:676-82.

7. De Maeseneer M, Madani H, Lenchik L, Kalume Brigido M, Shahabpour M, Marcelis S, et al. Normal anatomy and compression areas of nerves of the foot and ankle: US and MR imaging with anatomic correlation. Radiographics 2015;35:1469-82.

8. Kim BS, Choung PW, Kwon SW, Rhyu IJ, Kim DH. Branching patterns of medial and inferior calcaneal nerves around the tarsal tunnel. Ann Rehabil Med 2015;39:52-5.

9. Torres AL, Ferreira MC. Study of the anatomy of the tibial nerve and its branches in the distal medial leg. Acta Ortop Bras 2012;20:157-64.

10. Lareau CR, Sawyer GA, Wang JH, DiGiovanni CW. Plantar and medial heel pain: diagnosis and management. J Am Acad Orthop Surg 2014;22:372-80.

11. Eslamian F, Shakouri SK, Jahanjoo F, Hajialiloo M, Notghi F. Extra corporeal shock wave therapy versus local corticosteroid injection in the treatment of chronic plantar fasciitis, a single blinded randomized clinical trial. Pain Med 2016;17:1722-31.

12. Franceschi F, Papalia R, Franceschetti E, Paciotti M, Maffulli N, Denaro V. Platelet-rich plasma injections for chronic plantar fasciopathy: a systematic review. Br Med Bull 2014;112:83-95.

13. Byrd D, Mackey S. Pulsed Radiofrequency for chronic Pain. Curr Pain Headache Rep 2008;12:37-41.

Journal of Medical College Chandigarh, 2016, Vol. 6, No.2 38

Thapa et al

JOURNAL OF MEDICAL COLLEGE CHANDIGARH

VOLUME 6, NUMBER 2 SEPT., 2016

CONTENTS

Printed and Published by Director Principal, Govt. Medical College & Hospital, Sector 32, Chandigarh at Sanjay Printers, Plot No. 404, Indl. Area, Phase-II, Chandigarh.

E-mail: [email protected] Phone : Off.: 2665253 Fax : 2609360

EDITORIAL i-ii

Acute cholangitis: The “scope” of treatment iAtul Sachdev

REVIEW ARTICLES

Acute cholangitis- An overview of diagnosis and medical management 1-8Monica Gupta, Atul Sachdev

Role of Biomarkers in Diagnosis of Sepsis 9-16Varsha Gupta, Vibha Mehta

ORIGINAL ARTICLE

Balance and functional assessment in ambulatory elderly patients using Timed Get Up and Go test 17-22Aakanksha Sharma, Monica Gupta, Sarabmeet Singh Lehl

CASE REPORTS

Splenic Preservation in Blunt Pancreatic Trauma – Report of a Case 23-25Gaurav Shanker Pandey, Simrandeep Singh, Robin Kaushik

Hypotensive transfusion reaction – a case report 26-27Kshitija Mittal, Rakesh Kumar, Gagandeep Kaur, Paramjit Kaur, Tanvi Sood, Ravneet Kaur

Lichen scrofulosorum associated with active pulmonary tuberculosis in an adult 28-29Manjit Kaur, Mala Bhalla, Gurvinder P. Thami

Intracapsular dissection in cervical sympathetic chain schwannoma: a case report 30-32Naiya Rao, Manish Gupta

Dermatomyositis overlapping with Rheumatoid arthritis: a rare clinical entity 33-35Mandip Singh Bhatia, Ritu Attri, Monica Gupta

Medial Calcaneal Nerve block for plantar fasciitis pain: A case series 36-38Deepak Thapa, Vanita Ahuja, Ankita Mittal, Manjot Singh

INSTRUCTIONS TO AUTHOR

Guidelines to Contributors 39-40

journal of medical college c h a n d i g a r h · cholangitis and cholecystitis: tokyo guidelines....

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