Delhi Model: A New Tool for Predicting Response to Terlipressin in Hepatorenal Syndrome-Acute Kidney Injury.

Background and objectives: International club of ascites (ICA) has introduced revised criteria for hepatorenal syndrome-acute kidney injury (HRS-AKI) with an aim to improve the response rate to treatment. We lack prospective trials to assess its positive impact on the response rate and factors influencing response rate. Thus, we conducted this study with the primary aim of identifying independent factors that predict treatment response to terlipressin. Methods: We prospectively included patients of HRS-AKI as per the revised ICA criteria. All were treated with terlipressin and albumin according to the defined protocol and were followed for 90 days, death or liver transplantation. Baseline parameters, as well as delta serum creatinine (sCr) at day 4 (DCD4), were investigated as predictive factors influencing response to terlipressin (primary endpoint). Secondary endpoints were the overall response rate to terlipressin, response in various subgroups of acute-on-chronic liver failure (ACLF) patients, need for readmission, and 90 days survival. Results: The study included 114 patients with a median age of 52 years (83% males). 70 (61%) patients responded to terlipressin. Response rate among ACLF1, ACLF2, and ACLF3 were 62%, 48%, and 35%, respectively. On multivariate analysis, baseline creatinine (odds ratio [OR] 7.889, 95% confidence interval [CI] 3.335, 18.664), Child Turcotte Pugh (CTP) score (OR 1.470, 95% CI 1.026, 2.106), and the DCD4 (OR 0.048, 95% CI 0.015, 0.158) were independently predicting response. We also created a Delhi Model (DM) with an excellent predictive ability for response prediction at day 4 with an AUROC of 0.940 (95% CI 0.897, 0.982). Among responder group, 50% of patients required readmission within three months. The 90-days survival among responder and non-responder groups were 68.5% and 9% (P value < 0.01), respectively. Conclusions: Baseline creatinine, CTP score, and DCD4 independently predict response to terlipressin in HRS-AKI. The DM may guide terlipressin treatment in HRS-AKI but need further validation.

Transplant endocrinology.

Solid organ transplants and stem cell transplants are becoming more common but a significant proportion of patients are still on waiting lists, awaiting transplants. When endocrinologists treat transplant recipients who have underlying endocrine problems, which might include endocrine emergencies, there are special clinical care considerations to be aware of. The stage of the transplant (pre-transplant, early post-transplant, and chronic post-transplant) must be taken into account. Additionally, it's crucial to be knowledgeable about immunosuppressive medications, their typical adverse effects and drug interactions. The review article addresses a number of endocrine and metabolic abnormalities that are reported after transplantation.

Public Knowledge, Awareness, and Vaccination Rates for Hepatitis B in India: A Cross-Sectional Survey.

BACKGROUND: Hepatitis B virus (HBV) is a considerable public health concern in India, characterized by a significant number of chronically infected individuals. India falls into the category of an intermediate HBV endemic country, with approximately 40 million people chronically infected. Public awareness and knowledge about HBV are crucial for prevention, diagnosis, and treatment. This study aimed to assess the knowledge and vaccination status of the general public regarding hepatitis B in India. METHODS: An online cross-sectional survey was conducted with 3,545 participants, excluding healthcare workers and individuals below 18 years old. The survey evaluated knowledge in four domains: cause and spread of the disease (Domain A), organ affected and consequences (Domain B), treatment (Domain C), and vaccination (Domain D). The survey used a scoring scale from -20 to +22 points. Vaccination status was also assessed. RESULTS: The mean knowledge score of the respondents was 6.89 (±5.88). Only 25% of the respondents demonstrated good knowledge (score ≥12), while 31% had fair knowledge (score 6-11), 40% had poor knowledge (score 0-5), and 4% had incorrect knowledge (score <0). Males, individuals aged 18-60 years, respondents with higher education levels, and urban residents had significantly higher mean knowledge scores (p < 0.01). In the domain-specific analysis, 47% of the respondents had good knowledge in Domain B, while 43% of the respondents had good knowledge in Domains C and D. Only 17% of the respondents had good knowledge in Domain A. Overall, 22.7% of the respondents had received all three doses of the HBV vaccine, with higher vaccination rates among males, individuals aged 18-60 years, those with higher education levels, and urban residents. CONCLUSION: The study revealed limited knowledge about HBV among the general public in India. Vaccination rates were also suboptimal. Public health interventions, including educational campaigns and targeted vaccination programs, are needed to improve awareness and vaccination coverage, ultimately reducing the burden of HBV infection.

Clinical profile and molecular typing of viral etiological agents associated with Hand, Foot and Mouth Disease (HFMD): A study from Udhampur, Northern India.

PURPOSE: Hand, Foot and Mouth disease (HFMD) is a contagious pediatric viral disease caused due to enteroviruses (EV) of the family Picornaviridae. Cases of HFMD were reported from a tertiary care health centre, Udhampur, (Jammu and Kashmir), Northern India. The present study highlights the clinical and molecular virological aspects of HFMD cases. MATERIAL AND METHODS: Cases reported during August 2016-September 2017, and clinically diagnosed as HFMD of all age groups were included. Clinical, Biochemical and molecular virology aspects were compared. Clinical samples (n â€‹= â€‹50) such as vesicle swab, buccal and throat swabs were collected for enterovirus detection. EV-RNA was detected by 5'NCR based RT-PCR and genotyping by VP1 gene amplification and cycle sequencing. RESULTS: Of the cases of HFMD enrolled (n â€‹= â€‹50), highest (84%) were of children aged <5 years, presented either or both anathemas and exanthemas with prodromal symptoms (fever, irritability). Clinical presentations involved mainly oral ulcers on lips and tongue (48%). Oral erosions were either single or multiple in numbers. Exanthemas were seen on hand and palm, widely spread up to buttocks, legs, arms and trunk. Of these, six patients were found anemic. Complete blood count (CBC) indicated lymphocytosis and C-reactive protein (n â€‹= â€‹10) in children aged <5 years. EV-RNA was detected in 78% (39/50) of the clinical samples. VP1 gene based typing indicated the presence of CV-A16, CVA6 and EV-A71 types. CONCLUSIONS: The study highlights association of EVs in HFMD cases in the reported region. CV-A16, CV-A6 and EV-A71 types were reported for the first time from Udhampur (J&K), Northern India. No differences were observed in the clinical profile of EV strains detected. Circulation of the strains warrant and alarm outbreaks. More focused studies on HFMD and monitoring of viral strains is mandatory.

Hungry bone syndrome like presentation following single-dose denosumab for hypercalcaemia secondary to sarcoidosis with IgA nephropathy.

A woman in her mid-50s with IgA nephropathy, sarcoidosis and steroid-induced diabetes mellitus presented with generalised paraesthesia and spontaneous tetany. She had received denosumab 60 mg subcutaneously 8 weeks previously for parathyroid hormone independent hypercalcaemia.At admission, she had severe hypocalcaemia (5 mg/dL), hypophosphataemia (1.9 mg/dL), hypomagnesaemia (1.4 mg/dL) and elevated serum creatinine (1.48 mg/dL) with prolonged QTc (corrected QT interval) on electrocardiograph. She initially received intravenous calcium and magnesium followed by oral calcium carbonate and calcitriol. Her prednisolone dose was tapered to 5 mg/day. Evaluation showed secondary hyperparathyroidism (1474 pg/mL) and elevated 1,25-dihydroxy vitamin D (195 pg/mL). After 1 week of oral calcium carbonate (3000 mg/day) and calcitriol (1.5 µg/day), she achieved normocalcaemia (8.1 mg/dL).To conclude, denosumab for hypercalcaemia with renal insufficiency causes prolonged severe symptomatic hypocalcaemia and hypophosphataemia mimicking hungry bone syndrome. It is important to periodically monitor for hypocalcaemia after denosumab.

Diagnostic accuracy of transient elastography in diagnosing clinically significant portal hypertension in patients with chronic liver disease: a systematic review and meta-analysis.

PURPOSE: Liver stiffness measurement using transient elastography (TE-LSM) is a promising noninvasive alternative to hepatic venous pressure gradient (HVPG) for diagnosing clinically significant portal hypertension (CSPH). However, previous studies have yielded conflicting results. We evaluated the correlation between TE-LSM and HVPG and the performance of TE-LSM in diagnosing CSPH (HVPG ≥ 10 mmHg). METHODS: We conducted a systematic review and meta-analysis by searching PubMed and Scopus databases for relevant literature evaluating the clinical usefulness of TE for diagnosing CSPH in patients with chronic liver disease. RESULTS: Twenty-six studies (4337 patients with valid TE and HVPG) met our inclusion criteria. The median correlation coefficient of TE with HVPG was 0.70 (range 0.36-0.86). The weighted mean of optimal cut-off of liver stiffness value for diagnosing CSPH was 22.8 kPa (95% CI 22.7-23.0 kPa). The summary sensitivity and specificity were 79% (95% CI 74-84%) and 88% (95% CI 84-91%), respectively. The area under the hierarchical summary receiver operating characteristic (HSROC) curve was 0.91 (95% CI 0.88-0.93) according to the bivariate model. One limitation of the study was significant heterogeneity in the results of summary sensitivity and specificity (I2 83 and 74%, respectively). The heterogeneity could be explained by the variable liver stiffness cut-offs used in studies. The meta-regression plot revealed that as the optimal cut-off increased, the sensitivity decreased, the specificity increased, and vice versa. CONCLUSIONS: Liver stiffness measurement using TE correlates well with HVPG, and a liver stiffness cut-off value of 22.8 kPa shows a high accuracy for diagnosing CSPH. Thus, use of TE should be integrated into clinical practice for noninvasive diagnosis of CSPH.

Clinical Profile and Prevalence of H Pylori, Iga-Ttg, and Spectrum of Duodenal Abnormalities in Non Ulcer Dyspepsia.

The Rome IV criterion for a diagnosis of NUD is chronic or recurrent epigastric pain within the last 3 months and an onset of symptoms at least 6 months prior to presentation. The term functional Dyspepsia and idiopathic dyspepsia are often used as well. Symptoms include ulcer-like dyspepsia; gastroparetic-like (nausea, early satiety, and post-prandial pain), and undifferentiated. Pathogenesis of NUD is not completely known yet. Several mechanisms have been proposed to be responsible for these symptoms. Although there is strong evidence of an association between H. pylori infection and NUD, Celiac Disease and NUD. Being a tropical country, the prevalence of infections is parasitic cause. Dyspepsia is likely to be more in India. However, the present data from India as scares in literature. Hence the present study was planned to decipher the clinical profile, prevalence of H. pylori, IgA tTG, spectrum of duodenal biopsy abnormalities in NUD patients. MATERIAL: This Descriptive Observational study was carried out in the Gastro Enterology center in GOI research institute from August 2020 to March 2021. Initially, 200 dyspepsia patients were selected. 50 patients were excluded due to various reasons. Finally, 150 patients who met the Rome 4 criteria for NUD/Functional Dyspepsia were recruited. The inclusion criteria were patients above 18 years of age, dyspepsia for >/- 6 months, and no evidence of underlying malignancy, pan gastritis, previous gastric ulcers, and pancreatitis. The patients underwent routine blood investigations like haemogram and biochemistry, Rapid Urease Test (RUT), Upper Gastro-Intestinal Endoscopy, Duodenal Biopsy, and Serum IgA-tTG antibody. OBSERVATION: The mean age was 46.3 yrs. +/- 14.12 yrs, of which 49.3% were females and 50.70% were males. The prevalence of Epigastric Pain Syndrome (EPS) was found in 37.3%, Post Prandial Distress Syndrome (PDS) in 30.7%, and 32% had both EPS+PDS. 38% of the NUD patients were positive on Rapid Urease Test (RUT) suggesting H. pylori infection. 88.7% of NUD patients were IgA-tTG antibody negative and 11.3% serologically positive. The Duodenal biopsy was normal in 48% of patients, 21.3% had mild inflammation/duodenitis, 8% chronic duodenitis and 22.7% had various grades of Celiac Disease (as per Marsh Grading). These 22.7% showing evidence of Celiac Disease on histopathological examination showed Marsh Grade 1 in 12.7%, Grade-2 in 2%, Grade 3A in 6.7%, and Grade 3B in 1.3%. Only 17.6% of biopsy positive had IgA-tTG antibody positivity but only 4% of total cases were positive for both biopsy and IgA-tTG antibody (p-value 0.05). Eosinophilic infiltration in duodenum common in NUD patients. It was observed that 17.33% (26/150) NUD patients had duodenal eosinophilia. Further, look for the association of duodenal eosinophilia with various diseases. 33.33% (19/57) H. pylori patients had duodenal eosinophilia with p-value < 0.001. It was also observed that 7.52% (7/93) others like normal individual, Chronic duodenitis, mild inflammation/ duodenitis had Duodenal eosinophilia. CONCLUSION: The prevalence of H. pylori and IgA-tTG antibodies in non-ulcer dyspepsia patients was 38% and 11.3% respectively. The spectrum of Duodenum biopsy abnormalities in NUD patients included mild inflammation/ duodenitis, Chronic duodenitis, and Celiac Disease. 22.7% of NUD patients had various degrees of celiac disease morphology on D2 biopsy and only 17.6% of these biopsy positive patients were positive for IgA-tTG. Only 4% of total NUD patients were positive for both biopsy and IgA-tTG antibody labeled as Celiac Disease (CeD). There is a significant association between H. pylori and duodenal eosinophilia.

Safety and efficacy of laparoscopic sleeve gastrectomy in patients with portal hypertension with liver function of Childs A.

INTRODUCTION: Advanced liver disease and portal hypertension (PH) are seen as a relative contraindication for bariatric and metabolic surgery. Several studies have shown significant improvement in liver function and liver histology after bariatric surgery. There are very few studies describing bariatric surgery in patients with PH. The purpose of this retrospective study is to evaluate the feasibility and results of laparoscopic sleeve gastrectomy (SG) in patients with PH. MATERIAL AND METHODS: We present our experience of performing laparoscopic SG in 15 patients with evidence of PH. All the patients were Childs Pugh Criteria A. PH was confirmed by the presence of dilated esophageal varices on endoscopy. RESULTS: The mean operative time was 77.33 ± 15.22 min and mean blood loss was 80.67 ± 37.12 ml. The mean length of stay was 2.73 ± 0.59 days. There were no intraoperative or immediate postoperative complications. None of the patients required blood transfusion in the postoperative period. The weight, BMI, Excess body weight loss% (EBWL%), Total weight loss (TWL) and TWL% at 1 year were 86.05 ± 14.40 kg, 31.16 kg/m2 ± 3.82, 63.84% ± 15.24, 31.49 ± 9.54 kg and 26.50 ± 5.42%, respectively. Diabetes and hypertension resolution at 1 year was 80% and 72.72%, respectively. All the patients were followed up for mean 3 ± 1.5 years. There were no immediate or long-term morbidity and mortality noted. CONCLUSION: SG is a feasible and safe option for the treatment of obesity in carefully selected patients with PH with good weight loss and comorbidity resolution.

Multifocal colorectal non-Hodgkin's lymphoma in a patient with ulcerative colitis: A case report.

A case of multifocal non-Hodgkin's (Diffuse large B cell type) lymphoma of colon in a patient with ulcerative colitis is described. The patient was a 69-year old male treated with azathioprine and methotrexate for ulcerative colitis for 2 years. He was admitted with loose stools and hematochezia. Colonoscopy revealed two deep ulcers in ascending colon and a large ulcer in rectum. Biopsy from both the sites revealed atypical large lymphoid cells, which were CD20 positive. A whole body PET-CT scan showed disease localized to colon with bone marrow examination showing no evidence of lymphoma. The patient was given chemotherapy cycles and recovered well.

Midodrine and albumin versus albumin alone for the secondary prophylaxis of acute kidney injury in a patient with cirrhosis and ascites.

BACKGROUND: Acute kidney injury (AKI) in a patient with cirrhosis has high short-term mortality. Midodrine has shown promising results in the treatment of AKI-hepatorenal syndrome (HRS-AKI). AIMS: To compare midodrine and albumin versus albumin alone for the secondary prophylaxis of HRS-AKI. PATIENTS AND METHOD: Open labeled, nonrandomized, pilot study. Patients with a diagnosis of HRS-AKI were recruited after complete recovery. Patients were given midodrine daily (15 mg) and injection albumin infusion 20 g weekly in group-A (Gp-A) and injection albumin 20 g weekly with no midodrine in group-B (Gp-B). The primary endpoint was the recurrence of AKI-HRS, and the secondary endpoint was ascites tap in 2-month period. RESULTS: A total of 42 patients were enrolled in Gp-A, n = 22, and Gp-B, n = 20. There was no significant difference between the groups (Gp-A vs. Gp-B) in terms of age, model stage liver disease, Child-Turcotte-Pugh score and serum creatinine at inclusion (1.27 ± 0.1 vs. 1.22 ± 0.2 mg/dL). During follow up ten patients (50%) in Gp-B and four patients (18%) in Gp-A develop HRS-AKI (P = 0.04). The mean number of ascites tap was significantly higher in Gp-B compared to Gp-A (2.6 ± 0.5 vs. 1.9 ± 0.5) in 2 months. There was a significant increase in mean arterial pressure in Gp-A compared to Gp-B on days 7, 15, 30, 45 and 60. There was a significant difference in mean arterial pressure at day 7 in patients who developed HRS-AKI versus those who did not develop HRS-AKI [(n = 14, 65.5 ± 5.5) vs. (n = 28,74.6 ± 9.2 mm Hg), P = 0.02]. CONCLUSIONS: Midodrine along with albumin infusion, is helpful in the secondary prophylaxis of HRS-AKI and reduces the number of ascites tap. However, a large randomized study is required for further validation.

Effect of COVID-19 on Pre-existing Liver disease: What Hepatologist Should Know?

COVID-19 is characterized by predominant respiratory and gastrointestinal symptoms. Liver enzymes derangement is seen in 15-55% of the patients. Advanced age, hypertension, diabetes, obesity, malignancy, and cardiovascular disease predispose them to severe disease and the need for hospitalization. Data on pre-existing liver disease in patients with COVID-19 is limited, and most studies had only 3-8% of these patients. Patients with metabolic dysfunction-associated fatty liver (MAFLD) had shown a 4-6 fold increase in severity of COVID-19, and its severity and mortality increased in patients with higher fibrosis scores. Patients with chronic liver disease had shown that cirrhosis is an independent predictor of severity of COVID-19 with increased hospitalization and mortality. Increase in Child Turcotte Pugh (CTP) score and model for end-stage liver disease (MELD) score increases the mortality in these patients. Few case reports had shown SARS-CoV-2 as an acute event in the decompensation of underlying chronic liver disease. Immunosuppression should be reduced prophylactically in patients with autoimmune liver disease and post-transplantation with no COVID-19. Hydroxychloroquine and remdesivir is found to be safe in limited studies in a patient with cirrhosis and COVID-19. For hepatologists, cirrhosis with COVID-19 is a pertinent issue as the present pandemic will have severe disease in patients with chronic liver disease leading to more hospitalization and decompensation.

Nutritional assessment and factors affecting dietary intake in patients with cirrhosis: A single-center observational study.

OBJECTIVES: Malnutrition is predictor of morbidity and mortality in patients with cirrhosis. We investigated prevalence of malnutrition and factors affecting dietary intake in patients with cirrhosis. METHODS: Single-center cross-sectional observational study. A total of 251 patients with cirrhosis underwent dietary and nutritional assessment by subjective global assessment (SGA) and anthropometric measurement (dry body mass index, midarm circumference, midarm muscle circumference, triceps skinfold thickness, handgrip strength). Dietary intake was assessed in terms of total calories and protein intake, percentage of recommended intake, and per kilogram body weight per day. Factors influencing dietary intake were also assessed. RESULTS: Of 251 patients 199 (79%) were male and 52 (21%) were female (mean age, 51 ± 14 y, Child's A:B:C: 83:116:52). In SGA analysis 87 (35%) were well nourished (SGA-A), 106 (42%) were moderately nourished (SGA-B), and 58 (23%) were severely malnourished (SGA-C). Patients with Child's C score were severely malnourished compared with patients with Child's B and A scores. Midarm circumference, midarm muscle circumference, triceps skinfold thickness, and handgrip strength were significantly higher in SGA-A than SGA-B and SGA-C. Patients in SGA-A (1939 ± 479 kcal/d) consumed significantly higher calories than SGA-B (1494 ± 216 kcal/d) and SGA-C (1321 ± 213 kcal/d). Percentage of recommended calories intake (SGA-A [76%], SGA-B [61%], SGA-C [59%], P = 0.001) and calories/kg/d is also higher in SGA-A than SGA-B and SGA-C. The results with protein intake were similar (SGA-A [61 ± 14 gm/d], SGA-B [56 ± 7 gm/d], SGA-C [51 ± 9 gm/d], P = 0.001). Protein intake in g/kg/d is significantly lower in SGA-C (0.76 ± 0.22) than SGA-B (0.85 ± 0.2) and SGA-A (0.93 ± 0.2). A total of 61% patients were vegetarian, and 84% did not take evening snacks. Poor appetite (n = 68, 27%), early satiety (n = 75, 30%), abdominal fullness (n = 62, 25%), low-salt diet (n = 52, 21%), and social myth about diet 43(17%) were the common reasons for poor intake. Distension of abdomen, social myth about diet, and low sodium in diet were key factors affecting dietary intake in patients with cirrhosis and malnutrition. CONCLUSIONS: Malnutrition seen in 65% of patients. Total calories and protein intake was significantly low compared with recommendation even in well-nourished patients. Distension of abdomen, social myth about diet, and low sodium in diet were key factors affecting dietary intake in patients with cirrhosis and malnutrition.

Performance of Non-invasive Blood Parameters for Ruling Out Significant Liver Fibrosis in Patients with Chronic Hepatitis B.

Background and Aims: Evaluation of significant liver fibrosis is important for treatment decision and treatment response evaluation in patients with chronic hepatitis B. Since liver biopsy is invasive and transient elastography (TE) has limited availability, various non-invasive blood parameters need evaluation for their capabilities for detection of significant fibrosis. Methods: In this retrospective study, records of patients who had undergone liver biopsy for treatment-naïve chronic hepatitis B were evaluated to obtain various non-invasive blood parameters (aspartate aminotransferase-to-platelet ratio index [referred to as APRI], Fibrosis-4 score [referred to as FIB-4], gamma-glutamyl transpeptidase-to-platelet ratio [referred to as GPR], and gamma-glutamyl transpeptidase-to-albumin ratio [referred to as GAR]), in addition to TE, to assess significant liver fibrosis and compare these to fibrosis stage in liver biopsy. Results: A total of 113 patients were included in the study (median age 33 [interquartile range: 11-82 years], 74% males). Most (75%) patients were HBeAg-negative. The liver biopsy revealed significant fibrosis (Ishak ≥3) in 13% of the patients and nil or mild fibrosis (Ishak <3) in 87% of the patients. TE findings were available for 85 patients, APRI and FIB-4 for 95 patients, GPR for 79 patients, and GAR for 78 patients. The median values of all the parameters were significantly higher in patients with significant fibrosis, as compared to patients with non-significant fibrosis, and all the blood parameters as well as TE were able to identify patients with significant fibrosis significantly well (p<0.05). All non-invasive parameters had low positive predictive value but negative predictive value above 92%. Compared to TE, all the non-invasive blood parameters had similar area under the curve for detecting significant fibrosis, with excellent negative predictive value (≥93%). Conclusions: Non-invasive blood parameters (APRI, FIB-4, GPR, and GAR) with negative predictive values above 93% are excellent parameters for ruling-out significant fibrosis in patients with chronic hepatitis B. These can be used at bedside in place of TE.

Gastrointestinal and hepatic manifestations of Corona Virus Disease-19 and their relationship to severe clinical course: A systematic review and meta-analysis.

BACKGROUND: Many case series on Corona Virus Disease (COVID-19) have reported gastrointestinal (GI) and hepatic manifestations in a proportion of cases; however, the data is conflicting. The relationship of GI and hepatic involvement with severe clinical course of COVID-19 has also not been explored. OBJECTIVES: The main objectives were to determine the frequency of GI and hepatic manifestations of COVID-19 and to explore their relationship with severe clinical course. METHODS: We searched PubMed for studies published between January 1, 2020, and March 25, 2020, with data on GI and hepatic manifestations in adult patients with COVID-19. These data were compared between patients with severe and good clinical course using the random-effects model and odds ratio (OR) as the effect size. If the heterogeneity among studies was high, sensitivity analysis was performed for each outcome. RESULTS: We included 62 studies (8301 patients) in the systematic review and 26 studies (4676 patients) in the meta-analysis. Diarrhea was the most common GI symptom (9%), followed by nausea/vomiting (5%) and abdominal pain (4%). Transaminases were abnormal in approximately 25%, bilirubin in 9%, prothrombin time (PT) in 7%, and low albumin in 60%. Up to 20% patients developed severe clinical course, and GI and hepatic factors associated with severe clinical course were as follows: diarrhea (OR 2), high aspartate aminotransferase (OR 1.4), high alanine aminotransferase (OR 1.6), high bilirubin (OR 2.4), low albumin (OR 3.4), and high PT (OR 3). CONCLUSIONS: GI and hepatic involvement should be sought in patients with COVID-19 since it portends severe clinical course. The pathogenesis of GI and hepatic involvement needs to be explored in future studies.

Clinical Features of COVID-19 and Factors Associated with Severe Clinical Course: A Systematic Review and Meta-analysis.

Background: COVID-19 is a new disease which has become a global pandemic, and is caused by a novel coronavirus, SARS-CoV-2. The disease is still not very well characterized, and factors associated with severe clinical course are not well known. Methods: The main objectives were to determine the demographic, clinical and laboratory manifestations of COVID-19 and to identify the factors associated with severe clinical course. We searched the PubMed for studies published between Jan 1, 2020 and Mar 17, 2020, and included them if they were in English language, published in full, were retrospective or prospective observational or case control study with data on clinical, laboratory and imaging features of adult patients with COVID-19 disease from single or multiple centers. Studies that included exclusively pediatric patients were excluded. The demographic, clinical and laboratory data was displayed as n (%) or mean (SD). The meta-analysis on factors associated with severe clinical course was performed using the random effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated as the effect sizes. Findings: We included 58 studies (6892 patients) for the systematic review on clinical manifestations and 21 studies (3496 patients) for meta-analysis on factors associated with severe clinical course. The mean age of patients with COVID-19 is 49.7±16.3 years with a male to female ratio of 1.2:1. Common symptoms and their frequency are: fever (83.4%), cough (60.5%), fatigue (33.8%), sputum (28.9%), dyspnea (22.1%), myalgia (20.6%), chest tightness / pain (16.3%), sore throat (13.5%), headache (11.2%), diarhhea (7.5%), nasal congestion / rhinorrhea (6.7%), nausea / vomiting (5.6%), pain abdomen (4.6%), and hemoptysis (1.7%). The comorbidities associated with COVID-19 are: hypertension (18.4%), diabetes mellitus (9.8%), cardiovascular diseases (8.8%), endocrine diseases (5.8%), gastrointestinal diseases (5%), CLD (3%), and COPD (2.8%). Among the laboratory parameters WBC was low in 27%, high in 9%, platelets were low in 22.9%, creatinine was high in 6.5%, AST was high in 25.3%, ALT was high in 22.7%, bilirubin was high in 8.8%, albumin was low 60.1%, CT chest was abnormal in 89%, CRP was high in 67.5%, LDH was high in 52%, D-dimer was high in 34.8%, CK was high in 14.4%, and procalcitonin was high in 15.4%. Factors significantly associated severe clinical course (with their ORs) are as follows: High CRP (5.78), high procalcitonin (5.45), age >60 (4.82), dyspnea (4.66), high LDH (4.59), COPD (4.37), low albumin (4.34), high D-dimer (4.03), cardiac disease (3.88), low lymphocyte count (3.22), any associated comorbidity (3.16), diabetes mellitus (3.11), high WBC count (2.67), high bilirubin level (2.55), high creatinine (2.34), high AST (2.31), hypertension (2.30), low platelets (1.78), High ALT (1.69), high CK (1.66), fever spikes ≥39°C (1.59), diarrhea (1.55), male gender (1.47), and sputum (1.35). Interpretation: Identification of these factors associated with severe COVID-19 will help the physicians working at all levels of healthcare (primary, secondary, tertiary and ICU) in determining which patients need home care, hospital care, HDU care, and ICU admission; and thus, prioritize the scarce healthcare resource use more judiciously. Many of these identified factors can also help the public at large in the current COVID-19 epidemic setting, to judge when they should seek immediate medical care.

Disseminated histoplasmosis in India presenting as addisonian crisis with epiglottis involvement.

Histoplasmosis is caused by Histoplasma capsulatum. Like most fungal infections, histoplasmosis is common in immunocompromised patients. In immunocompetent patient, infection is generally asymptomatic and rarely turns into a disseminated form. Addisonian crisis as presentation of disseminated form has been reported in present. Here, we report a case of disseminated histoplasmosis leading to life threatening adrenal crisis and hypercalcemia in an elderly immunocompetent Indian patient. Appropriate diagnosis and anti fungal and steroid treatment lead to dramatic improvement in patient. Histoplasmosis should be considered in a immunocompetent hosts with adrenal involvement.

Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis.

BACKGROUND: Many studies on COVID-19 have reported diabetes to be associated with severe disease and mortality, however, the data is conflicting. The objectives of this meta-analysis were to explore the relationship between diabetes and COVID-19 mortality and severity, and to determine the prevalence of diabetes in patients with COVID-19. METHODS: We searched the PubMed for case-control studies in English, published between Jan 1 and Apr 22, 2020, that had data on diabetes in patients with COVID-19. The frequency of diabetes was compared between patients with and without the composite endpoint of mortality or severity. Random effects model was used with odds ratio as the effect size. We also determined the pooled prevalence of diabetes in patients with COVID-19. Heterogeneity and publication bias were taken care by meta-regression, sub-group analyses, and trim and fill methods. RESULTS: We included 33 studies (16,003 patients) and found diabetes to be significantly associated with mortality of COVID-19 with a pooled odds ratio of 1.90 (95% CI: 1.37-2.64; p < 0.01). Diabetes was also associated with severe COVID-19 with a pooled odds ratio of 2.75 (95% CI: 2.09-3.62; p < 0.01). The combined corrected pooled odds ratio of mortality or severity was 2.16 (95% CI: 1.74-2.68; p < 0.01). The pooled prevalence of diabetes in patients with COVID-19 was 9.8% (95% CI: 8.7%-10.9%) (after adjusting for heterogeneity). CONCLUSIONS: Diabetes in patients with COVID-19 is associated with a two-fold increase in mortality as well as severity of COVID-19, as compared to non-diabetics. Further studies on the pathogenic mechanisms and therapeutic implications need to be done.