Presence of diarrhea associated with better outcomes in patients with COVID-19 – A prospective evaluation

Purpose: Gastrointestinal (GI) manifestations have been well documented in patients with coronavirus disease 2019 (COVID-19), but its clinical impact on the course of the disease is debatable. Majority of the available data is retrospective, and hence this prospective study was planned to study the impact of GI symptoms on COVID-19 outcome. Methods: All COVID-19 patients admitted in a tertiary care centre from August–October 2020 were screened and patients without pre-existing GI diseases were included. A detailed history of the various symptoms including duration was documented. Various baseline laboratory investigations and inflammatory markers were conducted as per the protocol. Patients with and without diarrhea were compared for the various disease outcome parameters. Results: Of the 244 patients screened, 203 patients (128 males; 63.1%) were included. Respiratory symptoms alone were present in 49 (24.1%), GI symptoms alone in 20 (9.9%) and 117 (57.6%) had both. Overall GI symptoms was noted in 137 (67.5%) cases with the commonest being diarrhea (61; 30.0%). Patients with both respiratory and any GI symptoms showed a lower trend towards need for mechanical ventilation (12.2% vs 7.7%; p ¼ 0.35) and mortality (10.2% vs 4.3%; p ¼ 0.14) compared to respiratory symptoms alone, although not statistically significant. Patients with diarrhea (n ¼ 61) had no mortality (0% vs 7.7%; p ¼ 0.036) or need for mechanical ventilation and shorter hospital stay compared to those who did not have diarrhea. Conclusion: GI symptoms are frequent in patients with SARS-CoV-2 infection and the commonest is diarrhea. Diarrhea is a harbinger of better outcome with lower mortality among COVID-19 positive patients.

ALK+ Anaplastic large cell lymphoma with extensive cardiac involvement: A rare case report and review of the literature

Cardiac lymphoma is a rare entity. In this setting, the secondary involvement of the heart is far more frequent than the primary cardiac lymphoma. Herein, we present an autopsy case of a disseminated anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma with a dominant mediastinal involvement. Extensive cardiac infiltration with the near replacement of the myocardial wall by the neoplastic cells was observed. A total of nine isolated case reports of anaplastic large cell lymphoma with cardiac involvement were found in the English-language literature, and a widespread cardiac and thymic infiltration by the systemic ALK-positive anaplastic large cell lymphoma has not been documented. An incidental regenerative nodule was also identified in the liver. The patient died of pulmonary thromboembolism and cardiac arrest.

Effect of zoledronic acid on bone mineral density in patients of celiac disease: A prospective, randomized, pilot study.

Background & objectives: The symptoms of celiac disease (CD) are varied and metabolic bone disease (MBD) is less recognized amongst all manifestations in CD patients. Bone disease in CD is attributed to secondary hyperparathyroidism, which in turn is associated with increased bone remodelling. Improvement in bone mineral density (BMD) with gluten free diet (GFD) is known, but the data on efficacy of bisphosphonates in CD patients are limited. Bisphosphonates being a potent inhibitor of bone resorption may be useful in patients with CD having low BMD. The aim of the present investigation was to study the effect of zoledronic acid on BMD in CD patients. Methods: A total of 28 CD patients were randomized to receive GFD, calcium and cholecalciferol (group A), and zoledronic acid (group B). Baseline biochemical tests and T-score by dual energy x-ray absorptiometer were done and repeated after 12 months. Results: The T-score showed improvement in the control arm (group A) from -3.31 ± 1.46 to -2.12 ± 1.44, a gain of 35.9 per cent (P<0.05) and in drug arm (group B) -2.82 ± 1.27 to -1.06 ± 1.84, registering a gain of 62.4 per cent (P<0.001). However, there was no difference in improvement of T-score in zoledronic acid group as compared to the control group. Interpretation & conclusions: Administration of zoledronic acid was not found to be better than GFD alone in increasing BMD in CD patients with low BMD in this pilot study.

Increased accumulation of dendritic cells in celiac disease associates with increased expression of autophagy protein LC3.

Background: Celiac disease (CD) an immune-mediated disorder associates with accumulation of dendritic cell (DC) in duodenal mucosa. Autophagy has recently been implicated in autoantigen formation. However, its role in CD is still unknown. Aim: To examine role of autophagic protein LC3 expressed by activated DC in CD. Materials and Methods: Thirty CD patients were analyzed at initial presentation and after 6 months of gluten-free diet (GFD). Duodenal biopsies were studied for histological changes and CD11c, CD86, and MAP1LC3A expressions by double immunohistochemistry (IHC). Masson’s trichrome (MT) staining was used to assess basement membrane (BM) thickness and Oil Red O (ORO) staining for mucosal lipid deposit. Polymerase chain reaction (PCR) was performed for HLA-DQ system. Statistical analysis was done using paired and unpaired t test, chi-square test, Fisher’s exact test, and McNemar-Bowker test. A P-value <0.05 was considered statistically signifi cant. Results: HLA-DQ2 and HLA-DQ8 alleles were present in all studied patients. Increased BM thickness was observed in 63% and 73% had ORO-positive lipid in surface lining epithelium. Pre-treatment biopsies showed increased DCs expressing LC3, which were signifi cantly less in follow-up biopsies. The follow-up biopsies had shown signifi cant reduction in BM thickness and ORO. Conclusion: Histological improvement in duodenal biopsies was associated with reduction in activated DCs expressing autophagic protein, which probably play important role in pathogenesis of an autoimmune disorder like CD.

Celiac disease suspected at endoscopy in patients with chronic liver disease.

Endoscopic findings of celiac disease have high specificity and sensitivity. We evaluated records of 137 consecutive patients who had endotherapy for variceal hemorrhage, and who had features of celiac disease at endoscopy; patients who had such markers at endoscopy had undergone duodenal histology and serology. Thirty-one patients had changes of portal hypertensive vasculopathy in the duodenum, 8 had scalloping, and 6 had mosaic pattern; 3 patients also had decreased fold height or sparse folds in the descending duodenum. Six of these 8 patients had positive serology and histology suggestive of celiac disease. Endoscopic evaluation resulted in diagnosis of CD in 4.37% patients of chronic liver disease undergoing endotherapy.

Effect of Lactobacillus acidophilus & epidermal growth factor on experimentally induced Clostridium difficile infection.

Background & objectives: Clostridium difficile-associated disease (CDAD) remains an important nosocomial ailment. Antimicrobial therapy used for CDAD gives inconsistent results. This experimental study was planned to investigate the beneficial effects of Lactobacillus acidophilus and epidermal growth factor (EGF) for CDAD management. Methods: Among 10 groups of BALB/c mice (6 in each), group 1 served as controls receiving no inoculum. Animals in groups 2-10 received C. difficile, those in groups 3, 6 and 9 received L. acidophilus and those in groups 4, 7 and 10 received EGF after C. difficile inoculation. Animals in groups 5-7 were pre-treated with ampicillin and those in groups 8-10 with lansoprazole prior to C. difficile. The animals were killed and investigated for colonisation by C. difficile and toxin production, myeloperoxidase (MPO) activity and histopathology. Results: Colonisation by C. difficile was found to be significantly different (P<0.001) in the various groups. C. difficile toxin titres and MPO activity were significantly lower in animals given L. acidophilus and EGF after ampicillin (groups 6 and 7) and lansoprazole (groups 9 and 10). The severity of acute inflammation was also significantly less (P<0.05) in caecal and colonic segments of animals in groups 6 and 7 compared to those in group 5. Although the severity of acute inflammation was less in the caecal and colonic segment of animals in groups 9 and 10, the reduction was not significant compared to group 8. Interpretation & conclusions: Our findings showed that the administration of L. acidophilus and EGF reduced the severity of C. difficile infection in the experimental animals.

Pertechnetate SPECT-CT in corrosive gastric injury.

We report a 24-year-old woman with corrosive poisoning who was subjected to pertechnetate scintigraphy to evaluate gastric injury. Fusion imaging (SPECT-CT) provided valuable information regarding viability of gastric mucosa, and it helped guide appropriate management.

Endoscopic jejunal biopsy culture: a simple and effective method to study jejunal microflora.

Background Jejunal fluid culture is the gold standard for assessing jejunal microflora. Aspiration of jejunal fluid is sometime difficult. As the microorganisms rests on the mucosal surface, culture of the mucosal biopsy may be a possible alternative method. Aim To study the role of jejunal mucosal biopsy culture to assess jejunal microflora and to compare it with jejunal fluid culture. Methods Thirty adult subjects with gastroesophageal reflux disease requiring endoscopy underwent enteroscopy. Jejunal fluid aspirate and mucosal biopsy were cultured. The procedure was repeated after omeprazole therapy in 18 patients. Results Forty-eight pairs (30 preomeprazole therapy and 18 postomeprazole therapy) of fluid and mucosal biopsies were cultured. In 45 of the 48 pairs (94%), both the culture of jejunal biopsy and jejunal fluid yielded similar results with respect to the presence (n=27) or absence of growth (n=18). In the remaining 3 pairs, the growth was present either in the biopsy culture (n=2) or in the fluid culture (n=1) only. Among those pairs in which growth was present, microorganisms isolated were identical in 53%, differed by ≤2 organism in 37% and different by >2 organisms in 10%. Ten of the 12 patients who were detected to have small intestinal bacterial overgrowth (SIBO) on fluid culture were also detected to have SIBO on biopsy culture. Sensitivity, specificity, positive and negative predictive value of biopsy culture in diagnosing SIBO was 83.5%, 97.2%, 94.7%, and 91.6%, respectively. Conclusion Culture of unwashed endoscopic jejunal mucosal biopsy is an effective and simple alternative to jejunal fluid culture for assessing jejunal microflora.

Epidemiological and clinical profile of irritable bowel syndrome in India: report of the Indian Society of Gastroenterology Task Force.

AIMS: To study the profile of irritable bowel syndrome (IBS), and the frequency of such symptoms among the general population, in India. METHODS: In this prospective, multi-center study, data were obtained from 2785 patients with chronic lower gastrointestinal symptoms (complainants) with no alarm feature and negative investigations for organic causes visiting physicians at 30 centers, and from 4500 community subjects (non-complainants), using separate questionnaires. RESULTS: Most complainants were middle-aged (mean age 39.4 years) and male (1891; 68%). The common symptoms were: abdominal pain or discomfort (1958; 70%), abdominal fullness (1951; 70%); subjective feeling of constipation (1404 of 2656; 53%), or diarrhea (1252 of 2656, 47%), incomplete evacuation (2134; 77%), mucus with stools (1506; 54%), straining at stools (1271; 46%), epigastric pain (1364; 49%) and milk intolerance (906; 32%). Median stool frequency was similar in patients who felt they had constipation or those who felt they had diarrhea. Information to subtype symptoms using standard criteria was available in 1301 patients; of these, 507 (39%) had constipation-predominant IBS ( 3 <or= stools/week), 50 (4%) had diarrhea-predominant IBS (>3 stools/day) and 744 (57%) had indeterminate symptoms. Among non-complainants, most subjects reported daily defecation frequency of one (2520 [56%]) or two (1535 [34%]). Among non-complainants, 567 (12.6%) reported abdominal pain, 503 (11%) irregular bowel, 1030 (23%) incomplete evacuation, 167 (4%) mucus and 846 (18%) straining at stools; a combination of abdominal pain or discomfort relieved by defecation, and incomplete evacuation was present in 189/4500 (4.2%) community subjects. CONCLUSIONS: Most patients with IBS in India are middle-aged men, and have a sense of incomplete evacuation and mucus with stools. Abdominal pain or discomfort is frequent but not universal. Importantly, stool frequency was similar irrespective of whether the patients felt having constipation or diarrhea. Most (90%) non-complainant subjects had 1 or 2 stools per day; symptoms complex suggestive of IBS was present in 4.2% of community subjects.

Estimation of endotoxin in infected bile from patients with biliary diseases.

Diseases of the biliary tract can get complicated by infection. Endotoxin may theoretically be responsible for damage to the gall bladder due to its numerous pathophysiological effects. The aim of the present study was to detect and semi-quantitate the amount of endotoxin present in the bacteriologically positive bile samples and to correlate the endotoxin levels with the clinical profile of the patients. One hundred patients with gall bladder diseases and with infected bile constituted the population for investigation. The clinical profile included presence of fever, jaundice, abdominal pain and gall bladder stones. Endotoxin detection and semi-quantitation in the bile samples were carried out using the Limulus amoebocyte assay: Of 100 infected bile samples investigated, 9 samples (9%) were positive for endotoxin ranging from 1.9 EU/ml to 15 EU/ml. Four of them had Klebsiella pneumoniae, 2 had Acinetobacter anitratus and one each of the remaining 3 samples was positive for (i) Escherichia coli and Serratia marcescens (ii) Pseudomonas aeruginosa and (iii) Salmonella enteritidis. The stool sample of the patient with S. enteritidis in the bile also grew the same microorganism. Statistical analysis showed a significant increase in the presence ofjaundice (p<0.05) and abdominal pain (p<0.01) in the endotoxin positive patients compared to the endotoxin negative ones. Hitherto this is the first report that investigated the endotoxin levels in the bile of patients with gall bladder and biliary tract diseases, along with their biliary bacterial profile. Further research is warranted on the effects of endotoxin on gall stone formation.

Bacteriuria in patients with gallbladder and biliary tract diseases.

Urinary tract infections (UTI) are important hospital acquired entities, resulting in bacteriuria indicated by the presence of significant numbers of bacteria in the urine. This study examined the prevalence of bacteriuria in our patients with gallbladder diseases. Three hundred and forty eight patients with various gallbladder (GB) diseases were enrolled in our study. Routine bacteriological cultures of midstream urine specimens were done. Significant bacteriuria was defined as the growth of 105 or more organisms in pure culture per milliliter of urine. Forty four (12.6%) of the patients (18 symptomatic; 26 asymptomatic) showed bacteriuria. Escherichia coli was the predominant isolate followed by Klebsiella pneumoniae, Enterobacter, Pseudomonas aeruginosa, Enterococci and several others. Thus UTI is also a frequent concomitant of gall bladder diseases and is a sign of the fact that kidneys are in a condition endangered by pyelonephritis.

C-reactive protein in patients with gallbladder and biliary tract diseases.

C-reactive protein (CRP) assay is widely used as a clinical tool for the evaluation of bacterial infections. No study has been undertaken to evaluate the presence of CRP and/or the estimation of this protein in the bile of patients with diseases of the gallbladder (GB). In the present study, we estimated the quantity of CRP in bile (n=358) as well as serum samples (n=186) obtained from patients with GB and biliary tract diseases, using the semiquantitative Avitex CRP kit. Bacteriological study was also done on the bile samples. CRP was positive in the bile of 56 patients, (15.6%) many of who had bacteriobilia. CRP was also present in 49 of the serum samples studied (26.3%). Control serum samples did not show any CRP within detectable limits. Hitherto, this is the first report that investigated the level of CRP in the bile of patients with GB and biliary tract diseases, along with biliary bacterial profile.

Multiple squamous cell carcinomas of esophagus.

Multiple tumors of the esophagus are reported only rarely. We describe three patients with double carcinoma of esophagus. They developed a second squamous cell carcinoma of esophagus more than 4 1/2 years after external radiation for a primary squamous cell carcinoma at a different site in the esophagus.

Simultaneous assays for Clostridium difficile and faecal lactoferrin in ulcerative colitis.

Infectious agents may be one of the important factors in initiating or perpetuating ulcerative colitis. Increasing evidence has accumulated regarding the role of Clostridium difficile (C. difficile) infection in the exacerbation of ulcerative colitis. The present work was undertaken to study the implications of C. difficile toxin (CDT) and faecal lactoferrin (FL) positivity in patients with idiopathic ulcerative colitis (IUC) in a north Indian hospital. Ninety-four faecal samples from patients of IUC were processed for CDT and FL simultaneously. Clinical details of patients, including antibiotic intake in the past 6 weeks, were recorded. Eighty-one of the 94 patients (86.2%) had diarrhoea and 48 (51.1%) had received antibiotics. There was a statistically significant (p < 0.001) increase in the prevalence of diarrhoea among individuals receiving antibiotics. Twelve of the 94 samples (12.8%) were CDT positive while 16 were FL positive. No statistical significance (p > 0.05) was seen while comparing the positivity of CDT and FL in relation to the receipt of antibiotics. A statistically significant (p < 0.001) positive correlation was present between CDT and FL assays. FL positivity in IUC may depend on the intestinal inflammation precipitated by C. difficile infection.