Clinical Evaluation of a Novel Intrarectal Device for Management of Fecal Incontinence in Bedridden Patients.

PURPOSE: The primary objective of the study was to evaluate the safety and efficacy of a stool management kit (SMK) for containment of fecal incontinence in hospitalized bedridden patients. DESIGN: A single-group quasi-experimental study. SUBJECTS AND SETTING: Twenty bedridden adults who had at least 1 episode of fecal incontinence in the prior 24 hours participated in the study. The study setting was the neurological unit of the All India Institute of Medical Sciences in New Delhi, India. METHODS: The study was carried out in 2 phases. The device was placed in situ for up to 24 hours in 10 patients during phase I of the study and up to 120 hours in an additional 10 patients during phase II. Participants were assessed for anorectal injury and peripheral device leakage on a 4- to 6-hourly basis. Sigmoidoscopy was performed to evaluate for any mucosal trauma or alteration of anorectal pathology after retrieval of the device. RESULTS: The device was successfully placed in all patients following the first attempt to place the device; 80% of patients retained the device until planned removal. The SMK diverted fecal matter without anal leakage in 174 (93.5%) out of 186 assessment points in a group of 20 patients. The devices remained in situ for 21 ± 0.2 and 84.5 ± 38.9 hours during phase I and phase II, respectively. None experienced anorectal bleeding, sphincter injury, or mucosal ulceration with device usage. Post-device sigmoidoscopy revealed erythema at the site of diverter placement in 2 participants. CONCLUSION: Study findings suggest that the SMK successfully diverted liquid to semiformed fecal exudate without peripheral device leakage in 93.5% of bedridden patients. No serious adverse events occurred. Additional research is needed to compare its effectiveness with that of currently available intrarectal balloon devices.

Predictors of infection in viral-hepatitis related acute liver failure.

OBJECTIVE: Infections are common and associated with complications and mortality in acute liver failure (ALF). The temporal relationship between ammonia and infection in ALF patients is unclear. We aimed to evaluate the predictors of infection and its relationship with arterial ammonia levels. MATERIALS AND METHODS: Consecutive ALF patients hospitalized between January 2004 and December 2015, without signs of infection at/within 48 h of admission, were included. Occurrence of infection after 48 h was documented and ammonia levels were estimated for five consecutive days. Multivariate logistic regression analysis was used to assess factors associated with development of infection. Generalized estimating equations (GEE) were used to evaluate five-day time trend of ammonia in patients with and without infection. RESULTS: Of 540 consecutive patients, 120 were infected at admission/within 48 h and were excluded. Of the rest 420 patients, 144 (34.3%) developed infection after 48 h and 276 (65.7%) remained non-infected. Infected patients had higher mortality than non-infected patients (61.8% vs 40.0%, p < .001). On multivariate analysis, presence of cerebral edema(HR 2.049; 95%CI, 1.30-3.23), ammonia level on day 3 of admission (HR 1.006; 95%CI, 1.003-1.008), and model for end stage liver disease (MELD) score (HR 1.051; 95%CI, 1.026-1.078) were associated with development of infection. GEE showed group difference in serial ammonia values between infected and non-infected patients indicating lack of ammonia decline in infected patients. CONCLUSIONS: Cerebral edema, elevated ammonia on day 3, and higher MELD score predict the development of infection in ALF. Ammonia persists at high levels in infected patients, and elevated ammonia on day 3 is associated with complications and death.

Issues associated with the emergence of coeliac disease in the Asia­Pacific region: a working party report of the World Gastroenterology Organization and the Asian Pacific Association of Gastroenterology.

BACKGROUND AND AIM: Once thought to be uncommon in Asia, coeliac disease (CD) is now being increasingly recognized in Asia­Pacific region. In many Asian nations, CD is still considered to be either nonexistent or very rare. In recognition of such heterogeneity of knowledge and awareness, the World Gastroenterology Organization and the Asian Pacific Association of Gastroenterology commissioned a working party to address the key issues in emergence of CD in Asia. METHODS: A working group consisting of members from Asia­Pacific region, Europe, North America, and South America reviewed relevant existing literature with focus on those issues specific to Asia­Pacific region both in terms of what exists and what needs to be done. RESULTS: The working group identified the gaps in epidemiology, diagnosis, and management of CD in Asian­Pacific region and recommended the following: to establish prevalence of CD across region, increase in awareness about CD among physicians and patients, and recognition of atypical manifestations of CD. The challenges such as variability in performance of serological tests, lack of population-specific cut-offs values for a positive test, need for expert dietitians for proper counseling and supervision of patients, need for gluten-free infrastructure in food supply and creation of patient advocacy organizations were also emphasized. CONCLUSIONS: Although absolute number of patients with CD at present is not very large, this number is expected to increase over the next few years or decades. It is thus appropriate that medical community across the Asia­Pacific region define extent of problem and get prepared to handle impending epidemic of CD.

Fibroscan can avoid liver biopsy in Indian patients with chronic hepatitis B.

BACKGROUND AND AIM: Liver fibrosis is an established determinant of prognosis and therapy in chronic hepatitis B (CHB). The role of fibroscan in assessing fibrosis in CHB remains unclear. Present study was designed to correlate fibroscan with liver biopsy and determine whether fibroscan can avoid liver biopsy in patients with CHB. METHODS: Fibroscan and liver biopsy were performed in 382 consecutive patients with CHB. Biopsies were reviewed by pathologist blinded to the fibroscan value. Discriminant values of liver stiffness measurement (LSM) to reasonably exclude and predict significant fibrosis were calculated from receiver operating characteristic (ROC) curves. The factors affecting LSM independent of fibrosis were assessed. RESULTS: Three hundred fifty-seven patients were included (mean age 30.1 ± 9.7 years, male : female 17 : 3). There was significant correlation between LSM and histological fibrosis (r = 0.58, P < 0.001). The area under ROC curve of LSM for significant fibrosis (F0-1 vs. F2-4), bridging fibrosis (F0-2 vs. F3-4), and cirrhosis (F0-3 vs. F4) was 0.84 (95% CI: 0.78-0.89), 0.94 (95% CI: 0.89-0.99), and 0.93 (95% CI: 0.85-1.00), respectively. LSM < 6.0 KPa could exclude significant (F ≥ 2) and bridging fibrosis (F ≥ 3) with a negative predictive value (NPV) of 92.4% and 99.5%, respectively. Cut-off of 9 KPa could detect significant (F ≥ 2) and bridging fibrosis (F ≥ 3) with specificity of 95% and 97%, respectively, and had a positive predictive value (PPV) of 84.3% in predicting significant fibrosis. LSM < 6 KPa and > 9 KPa matched with histological fibrosis in 227/250 (91%) patients. Therefore, fibroscan could avoid liver biopsy in 70% (250/357) patients with an accuracy > 90%. Histological fibrosis, ALT > 5 times, and age > 40 years were independent determinants of increased liver stiffness. CONCLUSIONS: Fibroscan accurately assessed fibrosis and could avoid liver biopsy in more than two-thirds of patients with CHB.

Prospective derivation and validation of early dynamic model for predicting outcome in patients with acute liver failure.

OBJECTIVE: It is difficult to predict the outcome in patients with acute liver failure (ALF) using existing prognostic models. This study investigated whether early changes in the levels of dynamic variables can predict outcome better than models based on static baseline variables. DESIGN: 380 patients with ALF (derivation cohort n=244, validation cohort n=136) participated in a prospective observational study. The derivation cohort was used to identify predictors of mortality. The ALF early dynamic (ALFED) model was constructed based on whether the levels of predictive variables remained persistently high or increased over 3 days above the discriminatory cut-off values identified in this study. The model had four variables: arterial ammonia, serum bilirubin, international normalised ratio and hepatic encephalopathy >grade II. The model was validated in a cohort of 136 patients with ALF. RESULTS: The ALFED model demonstrated excellent discrimination with an area under the receiver operator characteristic curve of 0.91 in the derivation cohort and of 0.92 in the validation cohort. The model was well calibrated in both cohorts and showed a similar increase in mortality with increasing risk scores from 0 to 6. The performance of the ALFED model was superior to the King's College Hospital criteria and the Model for End stage Liver Disease score, even when their 3-day serial values were taken into consideration. An ALFED score of ≥4 had a high positive predictive value (85%) and negative predictive value (87%) in the validation cohort. CONCLUSION: The ALFED model accurately predicted outcome in patients with ALF, which may be useful in clinical decision-making.

Persistent hyperammonemia is associated with complications and poor outcomes in patients with acute liver failure.

BACKGROUND & AIMS: Patients admitted to the hospital with acute liver failure (ALF) and high arterial levels of ammonia are more likely to have complications and poor outcomes than patients with lower levels of ammonia. ALF is a dynamic process; ammonia levels can change over time. We investigated whether early changes (first 3 days after admission) in arterial levels of ammonia were associated with complications and outcomes and identified factors associated with persistent hyperammonemia. METHODS: We performed a prospective observational study that measured arterial ammonia levels each day for 5 days in 295 consecutive patients with ALF. We analyzed associations of changes in ammonia levels during the first 3 days with complications and outcomes. RESULTS: Patients with persistent arterial hyperammonemia (≥122 µmol/L for 3 consecutive days), compared with those with decreasing levels, had lower rates of survival (23% vs 72%; P < .001) and higher percentages of cerebral edema (71% vs 37%; P < .001), infection (67% vs 28%; P = .003), and seizures (41% vs 7.7%; P < .001). Patients with persistent hyperammonemia had greater mortality, with an odds ratio (OR) of 10.7, compared with patients with baseline levels of ammonia ≥122 µmol/L (OR, 2.4). Patients with persistent hyperammonemia were more likely to progress to and maintain advanced hepatic encephalopathy than those with decreasing levels. Patients with persistent, mild hyperammonemia (≥85 µmol/L for 3 days) were also more likely to have complications or die (P < .001) than patients with serial ammonia levels <85 µmol/L. Infections (OR, 4.17), renal failure (OR, 2.20), and decreased arterial pH (OR, 0.003) were independent predictors of persistent hyperammonemia. CONCLUSIONS: Patients with ALF and persistent arterial hyperammonemia for 3 days after admission are more likely to develop complications and have greater mortality than patients with decreasing levels or high baseline levels. Infection, renal failure, and decreased arterial pH are independent predictors of persistent hyperammonemia.

POEMS Syndrome: Skin Lesions Bringing the Jigsaw Puzzle Together.

A 47-year-old man presented to the outpatient department with multiple asymptomatic, erythematous and violaceous, soft, dome-shaped papulonodular lesions that had been present for 3 years. The lesions were vascular and were about 1 cm in diameter. They were present over the face, trunk, arms and legs (Figures 1 and 2). The patient gave history of recurrent ascites and progressive difficulty in walking for last two years.

Pattern & correlates of neurocognitive dysfunction in Asian Indian adults with severe obstructive sleep apnoea.

BACKGROUND & OBJECTIVES: No published data are available on neurocognitive dysfunction in Asian Indians with obstructive sleep apnoea (OSA). We therefore, studied the pattern and correlates of neurocognitive dysfunction in Indian adults with severe OSA. METHODS: Fifty patients aged 25-65 yr with severe OSA (apnoea-hypopnoea index>30) and 25 age, sex, and education level-matched normal controls were studied. Both groups were administered a standardized battery of neurocognitive tests. RESULTS: Patients with severe OSA had significantly impaired performance on tests of alertness, working memory, response inhibition, problem solving, and executive function. However, the difference in executive function between the groups disappeared after adjusting for delayed information processing. The test scores did not correlate with apnoea-hypopnoea index, arousal index, or Epworth sleepiness score. However, the percentage of time spent at <90 per cent oxygen saturation had a weak correlation with the number of stroop errors (Spearman's rho=0.64; P=0.033), number of trials required (rho=0.05; P=0.02), and perseverative errors on Wisconsin card sorting test (rho=0.36; P=0.02). INTERPRETATION & CONCLUSIONS: Our results suggested that delayed information processing rather than impaired abstract thinking was probably the cause of impaired performance on composite tests of neurocognitive function in patients with severe OSA.

Tuberculous mycotic aneurysm of aortic root: an unusual cause of cardiac tamponade.

We describe a young male who presented to the emergency room with sudden onset dyspnea, and was found to have aortic root aneurysm with aortic regurgitation and cardiac tamponade. He underwent a Bentall procedure, and excised aortic root tissue showed epithelioid cell granulomas with panaortitis. He was started on anti-tubercular therapy, with which he improved. Although tubercular aortitis is fairly common, tuberculous mycotic aneurysm of the aorta is rare, with involvement of the aortic root being exceedingly uncommon. We report only the fifth case in English literature of tuberculous mycotic aneurysm of the aortic root.

Obesity, and not obstructive sleep apnea, is responsible for increased serum hs-CRP levels in patients with sleep-disordered breathing in Delhi.

OBJECTIVE: The present study was conducted to evaluate serum levels of high-sensitivity C-reactive protein (hs-CRP) in newly diagnosed patients with obstructive sleep apnea (OSA). SUBJECTS AND METHODS: Between April 2005 and March 2006, a total of 231 consecutive adult habitual snorers underwent polysomnography (PSG) in the sleep laboratory. Ninety-seven subjects were found suitable for hs-CRP measurement after application of the following exclusion criteria: patients with diabetes mellitus, hypertension, coronary artery disease, acromegaly, hypothyroidism, chronic renal failure, congestive cardiac failure, or smoking history, patients who were pregnant, on steroid treatment, on hormone replacement therapy, or with chronic use of drugs such as non-steroidal anti-inflammatory drugs, oral anticoagulants and lipid-lowering drugs and patients having undergone upper airway surgery. Patients were classified as apneic [apnea-hypopnea index (AHI)>5], obese non-apneic [body mass index (BMI)>25, AHI<5] and non-obese non-apneic (BMI<25, AHI<5). C-reactive protein levels were measured in stored sera by high-sensitivity enzyme immunoassay (Biocheck, Inc. Foster City, CA, USA). After checking normality with the Kolmogorov-Smirnov test and using a square-root transformation, Pearson's and partial correlation coefficients were calculated for identified risk factors and confounders. A multiple linear regression model was used to identify variables that were independently associated with hs-CRP. RESULTS: The mean serum levels of hs-CRP were found to be 0.25+/-0.23, 0.58+/-0.55, and 0.51+/-0.37 mg/dl in non-obese non-apneics (n=23), obese non-apneics (n=45) and apneics (obese and non-obese, n=29), respectively. Pearson's correlation coefficient of hs-CRP with BMI was found to be 0.25 (p=0.01), and with AHI 0.16 (p=0.12). Partial correlation analysis showed that hs-CRP levels correlated significantly with BMI after adjustment for AHI and age (r=0.22, p=0.03), while correlation with disease severity as assessed by AHI after adjustment for BMI and age was not significant (r=0.10, p=0.33). After stepwise multiple linear regression, only BMI was found to be significantly associated with serum hs-CRP levels (beta=0.02, p=0.01). CONCLUSIONS: In this first comprehensive cross-sectional study on Indian subjects, we found that obesity, and not obstructive sleep apnea, is associated with elevated serum levels of hs-CRP. No independent correlation was found between severity of OSA and hs-CRP in the present study.

Overview and implications of obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is a leading public health problem both in the developed and developing nations. However, awareness regarding diagnostic options, management and consequences of untreated OSA remains inadequate. In developing nations, the resources for adequate sleep medicine facilities are scarce. Therefore, there is a need for low cost, simple and accurate diagnostic and therapeutic modalities exists. Untreated OSA leads to excessive daytime sleepiness, diminished performance and an overall poor quality of life. The role of OSA in promoting insulin resistance, atherosclerosis, hypertension and a procoagulant state has now been established. Newer insights into the biochemical and genetic mediators of OSA have raised hopes regarding the development of a "cure". However, as of now, continuous positive airway pressure (CPAP) therapy remains the first-line treatment. Though its use improves the quality of life as well as metabolic derangements observed in OSA, patients' acceptance remains low. Its high cost and long-term use are also cumbersome. Newer modes of delivering CPAP, oral appliances and upper airway surgery are the other options available. It is hoped that their appropriate use to increase patients' compliance may improve the quality of life as well as provide a survival benefit.

Randomized Controlled Trial Comparing the Efficacy of Terlipressin and Albumin with a Combination of Concurrent Dopamine, Furosemide, and Albumin in Hepatorenal Syndrome.

BACKGROUND: Terlipressin with albumin is recommended in hepatorenal syndrome (HRS). Terlipressin is expensive and not licensed in many countries. Alternative therapy is necessary. We compared the efficacy of terlipressin and albumin with concurrent low-dose dopamine, furosemide, and albumin in HRS. METHODS: In an open-label, randomized trial, forty consecutive patients each with HRS type I and HRS type II received either concurrent infusion of terlipressin 0.5 mg for every 6 hr and albumin 20 g/day for 5 days (n = 20) or a combination of dopamine 2 µg/kg/min, furosemide 0.01 mg/kg/hr, and albumin 20 g/day (triple therapy), in one of two therapeutic arms. Twenty-four-hour urine output, urinary sodium, and plasma renin activity (PRA) were assessed before and after treatment. RESULTS: The two groups were comparable at baseline in both HRS-I and II. In HRS-I, 24 hr urine output and urine sodium at the end of 5 days increased in both treatment groups (terlipressin, urine output 278 ± 136 to 765 ± 699 ml/day, P < 0.01; urine sodium 28 ± 25.1 to 39 ± 32.1 meq/l, P = 0.05. Triple therapy: urine output 219 ± 134 to 706 ± 595 ml/day, P < 0.01; urine sodium 25 ± 18.3 to 41 ± 27.5 meq/l, P < 0.01). PRA (ng/ml/hr) decreased from 28.1 ± 9.76 to 24.2 ± 9.5 (P = 0.01) and from 29.5 ± 15.8 to 27.3 ± 17.1 (P = 0.02) in the terlipressin and triple therapy groups, respectively. In HRS-II, similar significant improvement (P < 0.01) was seen in 24 hr urine output and urine sodium; decrease in PRA (P < 0.05) was documented after treatment in both the arms. Post-treatment changes in parameters were comparable between the two arms, in both HRS-I and HRS-II cases. CONCLUSIONS: Concurrent triple therapy improved renal function in HRS and was less expensive than terlipressin (Registration: CTRI/2011/07/001860; www.ctri.nic.in).

Prevalence of celiac disease in Indian patients with irritable bowel syndrome and uninvestigated dyspepsia.

OBJECTIVE: The clinical spectrum of celiac disease (CeD) is wide and its symptoms overlap with those of functional bowel diseases. This study aimed to investigate the relationship among gluten-related disorders, irritable bowel syndrome (IBS) and uninvestigated dyspepsia in Indian patients. METHODS: Patients with IBS and uninvestigated dyspepsia (using Rome III criteria) were tested for immunoglobulin A (IgA) anti-tissue transglutaminase (anti-tTG) antibody and anti-gliadin antibody (AGA). Those with positive anti-tTG antibody were evaluated for the presence of villous abnormalities. Patients who were only IgA AGA-positive were considered to have gluten sensitivity and those with positive anti-tTG antibody and villous atrophy were considered to have CeD. RESULTS: Of 362 patients with IBS, 22 (6.1%) had positive anti-tTG antibody, among whom 3 (0.8%) had CeD and 19 had potential CeD. Of 358 patients with uninvestigated dyspepsia, 18 (5.0%) were anti-tTG antibody-positive and among them 4 (1.1%) had CeD and 14 had potential CeD. AGA was positive in 104 (28.7%) patients with IBS and 68 (19.0%) with uninvestigated dyspepsia, suggesting the presence of gluten sensitivity. CONCLUSION: This study highlights the relationship between IBS or dyspepsia and CeD or gluten sensitivity.

Role of external beam radiation therapy in management of hepatocellular carcinoma.

Diagnosis at advanced disease stage and early vascular invasion are the bane of majority of patients with hepatocellular carcinoma (HCC) in India. The currently standardized curative and palliative treatment modalities [surgery, ablative techniques, trans-catheter chemotherapy, systemic chemotherapy] are suboptimal for a significant proportion of disease stages. Interest in radiotherapy for hepatocellular carcinoma has seen a resurgence with revolutionary improvements in targeting radiation doses safely. Encouraging results have been reported with a host of radiation techniques from conformal radiotherapy, stereotactic whole body radiation therapy to charged particle based therapies. The dissemination of this knowledge has been slow across other specialties involved in care of patients with HCC. However the increasing availability of radiotherapy services predicts a hopeful future for wider evaluation of radiotherapy in HCC.

Role of Transcatheter Intra-arterial Therapies for Hepatocellular Carcinoma.

Transcatheter intra-arterial therapies play a vital role in treatment of HCC due to the unique tumor vasculature. Evolution of techniques and newer efficacious modalities of tumor destruction have made these techniques popular. Various types of intra-arterial therapeutic options are currently available. These constitute: bland embolization, trans-arterial chemotherapy, trans-arterial chemo embolization with or without drug-eluting beads and trans-arterial radio embolization, which are elaborated in this review.

Effect of oral glutamine supplementation on gut permeability and endotoxemia in patients with severe acute pancreatitis: a randomized controlled trial.

OBJECTIVE: The aim of this study is to evaluate the effect of oral glutamine (GL) supplementation on gut permeability and endotoxemia (surrogate end point) in patients with severe acute pancreatitis. METHODS: In a randomized controlled trial, patients were randomized to be given placebo or GL for 7 days. The primary outcome measures include the effect on gut permeability (assessed by lactulose/mannitol excretion in urine and endotoxemia assessed by endotoxin core antibodies type IgG and IgM (EndoCab IgG and IgM). The secondary outcome measures include infectious complications, mortality, total hospital/intensive care unit stay, C-reactive protein, and prealbumin levels. RESULTS: Patients were assigned to GL (n = 41) and placebo (n = 39) groups. There was no change in gut permeability after the intervention. However, the EndoCab IgM levels increased significantly (33 [4, 175] to 40 [8, 350] GMU/mL; P = 0.0164) and the C-reactive protein levels decreased significantly (133 [1, 287] to 88 [1, 267] ng/mL; P = 0.0236) in the GL group. No difference was observed in infectious complication, prealbumin value, hospital/intensive care unit stay, and mortality in both groups. CONCLUSIONS: No significant trend was identified for an effect of GL on gut permeability. Decreased inflammation and endotoxemia did not translate into reduced infectious complications in severe acute pancreatitis. However, the study was underpowered to detect the aforementioned difference (trial registration: CTRI/2009/000945).

The Indian National Association for Study of the Liver (INASL) Consensus on Prevention, Diagnosis and Management of Hepatocellular Carcinoma in India: The Puri Recommendations.

Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality and healthcare expenditure in patients with chronic liver disease. There are no consensus guidelines on diagnosis and management of HCC in India. The Indian National Association for Study of the Liver (INASL) set up a Task-Force on HCC in 2011, with a mandate to develop consensus guidelines for diagnosis and management of HCC, relevant to disease patterns and clinical practices in India. The Task-Force first identified various contentious issues on various aspects of HCC and these issues were allotted to individual members of the Task-Force who reviewed them in detail. The Task-Force used the Oxford Center for Evidence Based Medicine-Levels of Evidence of 2009 for developing an evidence-based approach. A 2-day round table discussion was held on 9th and 10th February, 2013 at Puri, Odisha, to discuss, debate, and finalize the consensus statements. The members of the Task-Force reviewed and discussed the existing literature at this meeting and formulated the INASL consensus statements for each of the issues. We present here the INASL consensus guidelines (The Puri Recommendations) on prevention, diagnosis and management of HCC in India.