Association of GCKR and MBOAT7 genetic polymorphisms with non-alcoholic fatty liver disease.

Aim of the study: Non-alcoholic fatty liver disease (NAFLD) is one of the most important causes of chronic liver disease (CLD) in both Western and Asian populations. There is wide inter-individual variability in the occurrence of NAFLD and progression to non-alcoholic steatohepatitis (NASH) even after correcting environmental factors, and its true explanation can be provided by heritability. Two such genetic variations, the glucokinase regulator (GCKR) and membrane bound O-acyltransferase domain containing 7 (MBOAT7) genes, in NAFLD patients were studied in the Indian population. Material and methods: A cross sectional analytical study was conducted in the Department of Gastroenterology at a tertiary care centre. In total 100 subjects in the age range of 18-65 years were included in the study; 50 were patients with NAFLD including fatty liver, NASH and NASH related cirrhosis, and 50 were healthy subjects (No NAFLD). The polymorphisms rs780094 and rs1260326 for GCKR and rs641738 for MBOAT7 were determined using PCR followed by the PCR-RFLP. Results: GCKR rs780094 minor allele A was more common in NAFLD patients (p = 0.00001). Within the spectrum of NAFLD, the A allele was present frequently among cirrhotics as compared to NASH and fatty liver (p = 0.00001). Morbidly obese individuals showed significant association with the homozygous A allele (p = 0.028). These results were not seen with GCKR rs1260326 across all alleles. In MBOAT7 (rs641738) the frequency of the minor allele T for NAFLD was 84% vs. 80% in healthy subjects (p = 0.79). The association of the T allele among the spectrum of NAFLD was not statistically significant (p = 0.79). Conclusions: GCKR genetic variant rs780094 was found to be significantly associated with NAFLD. The MBOAT7 (rs641738) genetic variant was not found to be significantly associated with NAFLD.

Neurocognitive Disorders in HIV-positive Patients.

Human immunodeficiency viruses (HIV) associated neurocognitive disorders (HAND) encompasses a group of syndromes of various degrees of impairment in cognition and daily functioning of HIV positive individuals. Although the widespread use of highly active antiretroviral therapy (HAART) has drastically reduced the prevalence of severe form of HAND, like HIV associated dementia (HAD), the prevalence of HAND and associated morbidity remains high. OBJECTIVES: (1) To know the prevalence of HAND in HIV-infected patients of a multi-ethnic population. (2) To describe various types of neurocognitive impairment among patients of HAND and study the factors affecting HAND. STUDY DESIGN: This study was a cross-sectional descriptive study conducted on 250 HIV-positive patients in outpatient department (OPD) of a tertiary care center in Mumbai, conducted over a period of 12 months. Patients with HIV-1 attending the OPD and having a minimal formal education of 4 years were included. Patients with concomitant delirium, any known central nervous system (CNS) disorder, any psychiatric disorder, and pregnant females were excluded. Outcome measures-the test batteries used were (1) International HIV Dementia Scale (IHDS) and (2) Addenbrookes cognitive examination-revised (ACE-R) scale. RESULTS: Of 250 subjects studied, 55.6% (139) were males and 44.4 % (111) were females. The mean age of study population was 39.42 years. The mean years of education were 8.32 years. The mean duration of infection (diagnosis of HIV-positive state) was 64.49 months and the mean duration of HAART intake in our patients was 52.30 months. The mean cluster of differentiation 4 (CD4) counts of our subjects were 527.13 per cumm [standard deviation (SD) of 234.13]. The mean nadir CD4 counts were 224.35 per cumm (SD of 115.09). Using the ACE-R scale, the prevalence of HAND was 71.60%, of which 37.20% had an asymptomatic neurological impairment, 29.60% had mild cognitive dysfunction, and 4.80% had HAD. Memory, verbal fluency and visuospatial abilities were the most affected domains on the ACE-R and memory recall and psychomotor speed were affected more on the IHDS. The prevalence of HAND was more with increasing age (p = 0.020), lesser education (p < 0.00) and lesser nadir CD4 counts (p < 0.00). However, it was not affected by the duration of the disease and the current CD4 counts (p > 0.05). CONCLUSION: Human immunodeficiency viruses (HIV) associated neurocognitive disorders HAND is common in HIV-positive patients, most of whom are asymptomatic. Older patients with less education and severe disease, having lower nadir counts are at the highest risk of HAND. Memory, verbal fluency, and visuospatial abilities were the most commonly affected domains.

Gallbladder Polyp: Review and Proposed Algorithm for Management.

Gall bladder polyp is a lesion which is often an incidentally reported finding on ultrasonography. Such patients may or may not have symptoms of gall bladder disease. Although majority of polyps are cholesterol polyps, some are malignant. The challenge is early detection of malignant polyp and cholecystectomy before it becomes invasive or if invasive to carry out adequately wide surgical excision; while avoiding surgery in asymptomatic patients with benign disease. Following are the characteristics suggestive of malignancy in polyp: - size more than 10 mm, solitary lesions, increase in size over time, adenomatous polyps, sessile lesions and associated gallbladder wall thickening. Incidence of malignancy is higher in patients with Indian ethnicity, age more than 50 years, associated primary sclerosing cholangitis or gall stone disease. Pre-operative tissue diagnosis is difficult to obtain and review ultrasonography, contrast enhanced CT scan, endo sonography and a regular follow-up can help the surgeon take the appropriate decision.

COVID-19 Associated Stroke-A Single Centre Experience.

BACKGROUND AND PURPOSE: Various neurological complications have been reported in association with COVID-19. We report our experience of COVID-19 with stroke at a single center over a period of eight months spanning 1 March to 31 October 2020. METHODS: We recruited all patients admitted to Internal Medicine with an acute stroke, who also tested positive for COVID-19 on RTPCR. We included all stroke cases in our analysis for prediction of in-hospital mortality, and separately analyzed arterial infarcts for vascular territory of ischemic strokes. RESULTS: There were 62 stroke cases among 3923 COVID-19 admissions (incidence 1.6%). Data was available for 58 patients {mean age 52.6 years; age range 17-91; F/M=20/38; 24% (14/58) aged ≤40; 51% (30/58) hypertensive; 36% (21/58) diabetic; 41% (24/58) with O2 saturation <95% at admission; 32/58 (55.17 %) in-hospital mortality}. Among 58 strokes, there were 44 arterial infarcts, seven bleeds, three arterial infarcts with associated cerebral venous sinus thrombosis, two combined infarct and bleed, and two of indeterminate type. Among the total 49 infarcts, Carotid territory was the commonest affected (36/49; 73.5%), followed by vertebrobasilar (7/49; 14.3%) and both (6/49; 12.2%). Concordant arterial block was seen in 61% (19 of 31 infarcts with angiography done). 'Early stroke' (within 48 hours of respiratory symptoms) was seen in 82.7% (48/58) patients. Patients with poor saturation at admission were older (58 vs 49 years) and had more comorbidities and higher mortality (79% vs 38%). Mortality was similar in young strokes and older patients, although the latter required more intense respiratory support. Logistic regression analysis showed that low Glasgow coma score (GCS) and requirement for increasing intensity of respiratory support predicted in-hospital mortality. CONCLUSIONS: We had a 1.6% incidence of COVID-19 related stroke of which the majority were carotid territory infarcts. In-hospital mortality was 55.17%, predicted by low GCS at admission.

Tocilizumab improves survival in severe COVID-19 pneumonia with persistent hypoxia: a retrospective cohort study with follow-up from Mumbai, India.

BACKGROUND: Cytokine storm triggered by Severe Coronavirus Disease 2019 (COVID-19) is associated with high mortality. With high Interleukin -6 (IL-6) levels reported in COVID-19 related deaths in China, IL-6 is considered to be the key player in COVID-19 cytokine storm. Tocilizumab, a monoclonal antibody against IL-6 receptor, is used on compassionate grounds for treatment of COVID-19 cytokine storm. The aim of this study was to assess effect of tocilizumab on mortality due to COVID-19 cytokine storm. METHOD: This retrospective, observational study included patients of severe COVID-19 pneumonia with persistent hypoxia (defined as saturation 94% or less on supplemental Oxygen of 15 L per minute through non-rebreathing mask or PaO2/FiO2 ratio of less than 200) who were admitted to a tertiary care center in Mumbai, India, between 31st March to 5th July 2020. In addition to standard care, single Inj. Tocilizumab 400 mg was given intravenously to 151 consecutive COVID-19 patients with persistent hypoxia, from 13th May to 5th July 2020. These 151 patients were retrospectively analysed and compared with historic controls, ie consecutive COVID-19 patients with persistent hypoxia, defined as stated above (N = 118, from our first COVID-19 admission on 31st March to 12th May 2020 i.e., till tocilizumab was available in hospital). Univariate and multivariate Cox regression analysis was performed for identifying predictors of survival. Statistical analysis was performed using IBM SPSS version 26. RESULTS: Out of 269 (151 in tocilizumab group and 118 historic controls) patients studied from 31st March to 5th July 2020, median survival in the tocilizumab group was significantly longer than in the control group; 18 days (95% CI, 11.3 to 24.7) versus 9 days (95% CI, 5.7 to 12.3); log rank p 0.007. On multivariate Cox regression analysis, independent predictors of survival were use of tocilizumab (HR 0.621, 95% CI 0.427-0.903, P 0.013) and higher oxygen saturation. CONCLUSION: Tocilizumab may improve survival in severe COVID-19 pneumonia with persistent hypoxia. Randomised controlled trials on use of tocilizumab as rescue therapy in patients of severe COVID-19 pneumonia with hypoxia (PaO2/FiO2 less than 200) due to hyperinflammatory state, are warranted.

Snake Bite Envenomation in a Tertiary Care Centre.

Background: In India, it is estimated that up to 20,000 people die annually from snake bites. The present study was carried to out to estimate the snake bite related epidemiology, predictors of severity, relationship between type of snake, clinical severity, complications, outcome and usage pattern of polyvalent anti snake venom (ASV) in a tertiary care center. Methods: All indoor patients admitted in our institute with definitive history of bite by a snake, with or without presence of fang marks, Evidence of cellulitis, acute onset of neurotoxicity or bleeding diathesis were serially recruited in the study. Results: The majority of cases were in the range of 21- 40 years (54.7%). There were 82.8% males (53/64), 17.2% females (11/64) and 60.9% (39/64) bites were during day time. Upper limb bites were seen in 34% (22/64) of the patients and lower limb bites in 54% (35/64), and axial body bites in 6%. There were 43.8% (28/64) vasculotoxic bites, 34.4% (22/64) neurotoxic bites and 20.3% (14/64) non-poisonous bites. Viper was the most common (9%) identified snake, followed by krait (5%). References from Rural Health Centers were 57.8% (57/64), 11% were from Primary health centers and rest from private sector. Anti snake venom (ASV) was received by 68.75% (44/64) patients before reaching tertiary care. Local swelling was present in 90.6% (58/64) patients, Systemic bleeding was seen in 35.9% (23/64), and Neuromuscular weakness in 35.9% (23/64) patients. Complications like Respiratory paralysis developed in 18.75% (12/64), Acute kidney injury in 12% (8/64), DIC in 9% (6/64), and hepatic involvement in 7% (5/64) of snake bite patients. Blood transfusion was required in 20.3% (13/64) p<0.001), 18.75% (12/64) required Mechanical ventilation (p=0.001), 4 received hemodailysis and 4 required ionotropic support (p<0.001). Improvement was seen in 57.8% (37/64), morbidity during hospital stay was seen in 39% (25/64) and 2 patients expired (3%). ASV was received within 4 hours in 67% (42/64) patients, 22.5% (14/64) received ASV between 4 to 24 hours and remaining after 24 hours (p=0.016). Total ASV requierment was 24.05 vials in patients who improved and 34.4vials in patients in Morbid group and 29.0 vials in mortality group (p>0.05). The SSS score amongst improved was 4.76 ± 2.46 whereas among morbid, it was 8.48 ± 1.75 and amongst expired, it was 8.5 ± 0.707 (p<0.05). Conclusions: Patients requiring various supportive treatments like blood transfusion, Inotropes, Haemodialysis and Mechanical ventilation, had a statistically significant correlation with poor outcome. Early administration of ASV that is within 4 hours was, associated with better outcome. The total amount of ASV (in vials) had no a significant correlation with outcome. Snakebite Severity Score correlates significantly with early recovery in vasculotoxic snake bites (p=0.03).

Recurrent pyogenic meningitis in a 17-year-old: a delayed presentation of X-linked agammaglobulinemia with growth hormone deficiency.

We report an adolescent male with X-linked agammaglobulinemia (XLA) and recurrent episodes of pyogenic meningitis. The workup for proportionate short stature revealed isolated growth hormone deficiency. This patient highlights the delayed presentation of the XLA variant and the need to consider primary immunodeficiency in patients with recurrent serious infections, irrespective of age.

Trauma precipitating thyroid storm.

A 40 year old male victim of a road traffic accident presented to our emergency trauma services with multiple limb injuries and a Glasgow Coma Score (GCS) of 15/15. Soon after admission, he became confused, stuporous, febrile and tachycardic. A clinical diagnosis of thyrotoxic crisis precipitated by trauma was confirmed by relevant investigations, with appropriate therapeutic response. A review of the clinical features and management of this rare medical emergency, with only few cases reported worldwide, is presented.

VACTERL Association.

Here we report a case of VACTERL ASSOCIATION in a twenty three years old married female patient primigravida with 3 months of amenorrhea admitted with history of fever and gastroenteritis along with congenital developmental defects such as scoliosis (V), small ventricular septal defect (C), right sided hemifacial dysmorphic features (right mandibular hypoplasia), small sized right sided kidney (R), bilateral hypoplastic thumb (L). For the diagnosis of VACTERL atleast three out of seven anomalies should be present while our patient had four anomalies.

A case of nephrotic syndrome with Gitelman's syndrome.

Nephrotic syndrome, though common in children, association of it with Gitelman's syndrome (GS) is a rare occurrence. Very few cases have been reported in the medical literature so far. Here we report a case of nephrotic syndrome with frequent relapses and remissions on intermittent steroid and diuretic therapy. Patient was restarted on steroids and frusemide. Puffiness of face, bipedal edema and oliguria improved but patient developed tingling numbness in both limbs, perioral numbness and carpopedal spasm. On investigation she was found to have proteinuria, metabolic alkalosis, hypokalemia, hypocalcemia, hypomagnesemia and hyperreninemia with normal blood pressure.

Kinesin-2 differentially regulates the anterograde axonal transports of acetylcholinesterase and choline acetyltransferase in Drosophila.

Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) are involved in acetylcholine synthesis and degradation at pre- and postsynaptic compartments, respectively. Here we show that their anterograde transport in Drosophila larval ganglion is microtubule-dependent and occurs in two different time profiles. AChE transport is constitutive while that of ChAT occurs in a brief pulse during third instar larva stage. Mutations in the kinesin-2 motor subunit Klp64D and separate siRNA-mediated knock-outs of all the three kinesin-2 subunits disrupt the ChAT and AChE transports, and these antigens accumulate in discrete nonoverlapping punctae in neuronal cell bodies and axons. Quantification analysis further showed that mutations in Klp64D could independently affect the anterograde transport of AChE even before that of ChAT. Finally, ChAT and AChE were coimmunoprecipitated with the kinesin-2 subunits but not with each other. Altogether, these suggest that kinesin-2 independently transports AChE and ChAT within the same axon. It also implies that cargo availability could regulate the rate and frequency of transports by kinesin motors.