Multiple Electrolytes Solution Versus Saline as Bolus Fluid for Resuscitation in Pediatric Septic Shock: A Multicenter Randomized Clinical Trial.

OBJECTIVE: To determine if initial fluid resuscitation with balanced crystalloid (e.g., multiple electrolytes solution [MES]) or 0.9% saline adversely affects kidney function in children with septic shock. DESIGN: Parallel-group, blinded multicenter trial. SETTING: PICUs of four tertiary care centers in India from 2017 to 2020. PATIENTS: Children up to 15 years of age with septic shock. METHODS: Children were randomized to receive fluid boluses of either MES (PlasmaLyte A) or 0.9% saline at the time of identification of shock. All children were managed as per standard protocols and monitored until discharge/death. The primary outcome was new and/or progressive acute kidney injury (AKI), at any time within the first 7 days of fluid resuscitation. Key secondary outcomes included hyperchloremia, any adverse event (AE), at 24, 48, and 72 hours, and all-cause ICU mortality. INTERVENTIONS: MES solution ( n = 351) versus 0.9% saline ( n = 357) for bolus fluid resuscitation during the first 7 days. MEASUREMENTS AND MAIN RESULTS: The median age was 5 years (interquartile range, 1.3-9); 302 (43%) were girls. The relative risk (RR) for meeting the criteria for new and/or progressive AKI was 0.62 (95% CI, 0.49-0.80; p < 0.001), favoring the MES (21%) versus the saline (33%) group. The proportions of children with hyperchloremia were lower in the MES versus the saline group at 24, 48, and 72 hours. There was no difference in the ICU mortality (33% in the MES vs 34% in the saline group). There was no difference with regard to infusion-related AEs such as fever, thrombophlebitis, or fluid overload between the groups. CONCLUSIONS: Among children presenting with septic shock, fluid resuscitation with MES (balanced crystalloid) as compared with 0.9% saline resulted in a significantly lower incidence of new and/or progressive AKI during the first 7 days of hospitalization.

Effect of COVID-19 vaccination status on outcome of adult patients admitted at a tertiary care centre in India.

COVID-19 vaccination was initially started in India on 16th January 2021 after approval from national authorities. This study was carried out to assess the effect of vaccination status on the severity and clinical outcome among patients infected with COVID-19. The study included all adult COVID-19 patients admitted to our hospital from 1st April to 30th June 2021. A total of 819 patients were enrolled in the study out of which only 183 (22.3%) were vaccinated. The study documented a statistically significant reduction in the severity of illness among the vaccinated (single/double dose) (33% severe COVID-19) against the unvaccinated (43% severe COVID-19) groups; along with a reduction in mortality. On univariate and multivariate analysis, age, severity of illness and lack of COVID-19 vaccination status were associated with a statistically significant increased mortality. To conclude, this study demonstrates the role of vaccination in decreasing the severity and mortality of COVID-19 infection.

Risk factors and frequency of COVID-19 among healthcare workers at a tertiary care centre in India: a case-control study.

BACKGROUND: There is a paucity of data on risk factors for infection among healthcare workers (HCWs) from India. Our objective was to evaluate the risk factors and frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among HCWs. METHODS: We conducted this retrospective case-control study of 3100 HCWs between May and July 2020. HCWs positive for SARS-CoV-2 infection were the cases (n=506) and those negative for SARS-CoV-2 were the controls (n=253). Univariate analysis was followed by multivariate analysis of key demographic, clinical and infection control variables. RESULTS: SARS-CoV-2 infection was found in 16.32% of HCWs. Nearly 45% of infected HCWs were asymptomatic. The proportions of sanitation workers (24% vs 8%; p<0.0001) and technicians (10% vs 4%; p=0.0002) were higher and that of doctors was lower among cases as compared with controls (23% vs 43%; p<0.0001). On univariate analysis, the type of HCW, smoking, lack of training, inadequate personal protective equipment (PPE) use and taking no or fewer doses of hydroxychloroquine (HCQ) were found to be significant. On multivariate analysis, the type of HCW (risk ratio [RR] 1.67 [95% confidence interval {CI} 1.34 to 2.08], p<0.0001), inappropriate PPE use (RR 0.63 [95% CI 0.44 to 0.89], p=0.01) and taking fewer doses of HCQ (RR 0.92 [95% CI 0.86 to 0.99], p=0.03) were significant. CONCLUSIONS: The frequency of SARS-CoV-2 infection was 16% among HCWs. Being a sanitation worker, inappropriate PPE use and lack of HCQ prophylaxis predisposed HCWs to SARS-CoV-2 infection.

COVID-19 with and without anosmia or dysgeusia: A case-control study.

Various new clinical signs and symptoms, such as dysfunction of smell (anosmia) and taste (dysgeusia) have emerged ever since the coronavirus disease 2019 (COVID-19) pandemic begun. The objective of this study was to identify the clinical presentation and factors associated with 'new loss/change of smell (anosmia) or taste (dysgeusia)' at admission in patients positive by real time polymerase chain reaction for SARS-CoV-2 infection. All adult COVID-19 patients with new onset anosmia or dysgeusia at admission were included in study group. Equal number of age and gender matched COVID-19 patients without anosmia or dysgeusia at admission were included in the control group. A total of 261 COVID-19 patients were admitted during the study period of which 55 (21%) had anosmia and or dysgeusia. The mean (SD) age was 36 (13) years and majority were males (58%, n = 32). Comorbidity was present in 38% of cases (n = 21). Anosmia and dysgeusia were noted in more than 1/5th of the cases. Anosmia (96%, n = 53) was more common than dysgeusia (75%, n = 41). Presence of both ansomia and dysgeusia was noted in 71% of patients (n = 39). On comparing the cases with the controls, on univariate analysis, fever (higher in cases), rhinitis (lower in cases), thrombocytopenia, elevated creatinine and bilirubin (all higher in cases) were significantly associated with anosmia or dysgeusia. On multivariate analysis, only rhinitis (odds ratio [OR]: 0.28; 95% confidence interval [CI]: 0.09-0.83; p = .02) thrombocytopenia (OR: 0.99; 95% CI: 0.99-0.99; p = .01) and elevated creatinine (OR: 7.6; 95% CI: 1.5-37.6; p = .01) remained significant. In this retrospective study of COVID-19 patients, we found anosmia and dysgeusia in more than 1/5th of the cases. Absence of rhinitis, low platelet counts and elevated creatinine were associated with anosmia or dysgeusia in these patients.

Evaluation of the clinical profile, laboratory parameters and outcome of two hundred COVID-19 patients from a tertiary centre in India.

COVID-19 is a pandemic with over 5 million cases worldwide. The disease has imposed a huge burden on health resources. Evaluation of clinical and epidemiological profiles of such patients can help in understanding and managing the outbreak more efficiently. This study was a prospective observational analysis of 200 diagnosed COVID-19 patients admitted to a tertiary care center from 20th march to 8th May 2020. All these patients were positive for COVID-19 by an oro-nasopharyngeal swab-rtPCR based testing. Analyses of demographic factors, clinical characteristics, comorbidities, laboratory parameters, and the outcomes were performed. The mean age of the population was 40 years with a slight male predominance (116 patients out of 200, 58%). A majority of the patients (147, 73.5 %) were symptomatic, with fever being the most common symptom (109, 54.5%), followed by cough (91, 45.5%). An older age, presence of symptoms and their duration, leukocytosis, a high quick SOFA score, a high modified SOFA score, need for ventilator support, an AST level more than 3 times the upper limit of normal (ULN), and a serum creatinine level of 2 mg/dl or greater were at a significantly higher risk of ICU admission and mortality. Presence of diabetes mellitus, AST > three times ULN, serum creatinine 2 mg/dl or higher, and a qSOFA score of 1 or higher were all associated with significantly greater odds of critical care requirement. Triage and severity assessment helps in deciding the requirement for a hospital stay and ICU admission for COVID-19 which can easily be done using clinical and laboratory parameters. A mild, moderate and severe category approach with defined criteria and treatment guidelines will help in judicious utilization of health-care resources, especially for developing countries like India.   *Other members of the Safdarjung Hospital COVID-19 working group: Balvinder Singh (Microbiology), MK Sen (Pulmonary Medicine), Shibdas Chakrabarti (Pulmonary Medicine), NK Gupta (Pulmonary medicine), AJ Mahendran (Pulmonary Medicine), Ramesh Meena (Medicine), G Usha (Anaesthesiology), Santvana Kohli (Anaesthesiology), Sahil Diwan (Anaesthesiology), Rushika Saksena (Microbiology), Vikramjeet Dutta (Microbiology), Anupam Kr Anveshi (Microbiology).

Efficacy and Safety of Anti-malarial Drugs (Chloroquine and Hydroxy-Chloroquine) in Treatment of COVID-19 Infection: A Systematic Review and Meta-Analysis.

Background: Anti-malarial drugs inhibit coronaviruses in-vitro. Few published studies have evaluated the safety and efficacy of these drugs in the treatment of COVID-19 infection. Materials and Methods: This is a systematic review and meta-analysis of clinical trials and observational studies. Major database searches were carried out up until June 5, 2020. Participants admitted with RT-PCR-confirmed SARS Cov-2 (COVID-19) infection were included. The "Intervention group" received anti-malarial drugs with or without other drugs (Azithromycin) administered as an adjunct to the standard treatment/care. The "Control group" received treatment except anti-malarial drugs. The primary outcome is "all-cause mortality." Secondary outcome measures were effects on clinical and laboratory parameters and adverse events. Results: Of 3,472 citations, 17 (six clinical trials and 11 observational studies) studies provided data of 8,071 participants. Compared to the control, Hydroxy-chloroquine (HCQ) has no significant effect on mortality [(OR 0.87; 95% CI 0.46-1.64); eight observational studies; N = 5,944]. Data from a single, small non-randomized trial (N = 42) also reached a similar conclusion (OR 1.94; 95% CI 0.07-50.57; p = 0.69). Compared to the control, HCQ plus Azithromycin (AZM) significantly increased mortality [(OR 2.84; 95% CI 2.19-3.69); four observational studies; N = 2,310]. Compared to the control, risk of any adverse event was significantly increased in HCQ group [(OR 3.35; 95% CI 1.58-7.13); four clinical trials; N = 263]. Compared to control, risk of adverse cardiac events (abnormal ECG, arrhythmia, or QT prolongation) were not significantly increased in HCQ group (but significantly increased in the HCQ plus AZM group). The GRADE evidence generated for all the outcomes was of "very low-quality." Conclusions: As very low quality evidence suggests an increased risk of mortality and adverse event with HCQ plus Azithromycin combination (not HCQ alone), caution should be exercised while prescribing this combination for treatment of hospitalized adults with COVID-19 infection. Good quality, multi-centric RCTs (including both hospitalized and non-hospitalized patients) are required for any firm recommendation to be made during the ongoing pandemic. OSF Protocol Registration Link: https://osf.io/6zxsu.

COVID-19 infection outbreak among health care workers: perspective from a low-middle income country.

To the Editor, The new pandemic COVID -19 caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) is a global threat. So far, more than 11 million infections and more than five hundred thousand deaths have been reported worldwide. In India the number of cases as of 5th July, 2020 is 6,73,165 with 19,268 deaths. Health care workers (HCWs) have been the backbone of this pandemic since the very beginning...

Scleroedema of Buschke in conjunction with ovarian carcinoma: rare association of a rare disease.

Scleroedema is a rare clinical condition characterised by diffuse woody induration of skin commonly associated with diabetes mellitus, infections and monoclonal gammopathy. Its association with ovarian malignancy has not been reported. We report a case of a 56-year-old female with rapidly progressing skin thickening of limbs, face and trunk for 1 year and abdominal distension for 3 months. Patient had thickened skin, mask-like facies and ascites on examination. Atypical cells were seen in ascitic fluid. Contrast-enhanced computerised axial tomography scan of abdomen was suggestive of ovarian malignancy. Markers for autoimmune disorders were negative. CA 125 was elevated. Other causes of sclerodermiform-like syndrome were ruled out. Histopathology of skin biopsy was definitive of scleroedema. Diagnosis of scleroedema associated with ovarian malignancy was made based on temporal association, exclusion of other causes and histopathological findings. To our knowledge this is the first reported case of scleroedema associated with ovarian tumour.

Serum 25-hydroxyvitamin D level in patients with chronic liver disease and its correlation with hepatic encephalopathy: A cross-sectional study.

BACKGROUND: Hepatic encephalopathy (HE) is an established clinical manifestation in chronic liver disease (CLD). It is associated with various factors including gastrointestinal bleed, constipation, and dyselectrolemia. Recently 25-hydroxyvitamin D (25-OHD) deficiency has been identified as one of the factors associated with the development of HE. The current study was aimed to assess the level of 25-OHD in patients with CLD and hepatic encephalopathy and the relationship between 25-OHD deficiency and hepatic encephalopathy. MATERIALS AND METHODS: This cross-sectional study included 100 subjects of either sex between 18 and 60 years of age, diagnosed as CLD on the basis of ultrasonography with hepatic encephalopathy and 50 age, sex-matched CLD subjects without encephalopathy. Hemogram, hepatic and renal functions, serum electrolytes, coagulation profile, and serum 25-hydroxyvitamin D levels were recorded. RESULTS: The baseline variables were matched for age, sex, hepatic and kidney function, and coagulation profiles. The hemoglobin (P = 0.002) and platelet count (P = 0.0003) were significantly lower in subjects with HE. The mean level of 25-OHD was significantly lower in subjects with HE as compared to the control group (25.62 ± 21.94 nmol/L vs 37.44 ± 18.61 nmol/L, P < 0.001). The mean 25-OHD level was 30.64 ± 21.64 nmol/L in grade 1 HE, 12.03 ± 11.05 nmol/L in grade 3 with P < 0.0001, and 18.8 ± 16.88 nmol/L in grade 4 with P < 0.0001 when compared to grade 1. Moderate and severe deficiency of 25-OHD level was significantly associated with higher grades of HE, i.e. grades 3 and 4 (P < 0.0001). There was a significant negative correlation between 25-OHD levels and worsening grades of hepatic encephalopathy (person's correlation coefficient r = -0.354; P = 0.0003). CONCLUSION: In this cohort of North Indian population, serum 25-OHD level was significantly lower in patients with CLD and HE. The levels of 25-OHD showed a significant negative correlation with hepatic encephalopathy.

Association of high-sensitivity C-reactive protein (hs-CRP) with non-alcoholic fatty liver disease (NAFLD) in Asian Indians: A cross-sectional study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is an important etiology for the development of chronic liver disease worldwide. Its pathophysiology includes chronic low-grade inflammation. There are limited studies on the association of inflammatory markers with NAFLD. Hence, in the present research, we aimed to study the association of one such inflammatory marker hs-CRP with NAFLD in north Indian population. MATERIALS AND METHODS: For this cross-sectional study, 100 subjects of either sex above 18 years of age, being diagnosed as a case of NAFLD on the basis of ultrasonography and age, sex and BMI matched subjects fulfilling the inclusion and exclusion criteria were included. Anthropometric profile, high-sensitivity C-reactive protein (hs-CRP), HbA1c, and hepatic function tests were recorded. RESULTS: The baseline variables were matched for age, weight, BMI, waist-hip circumference ratio, and blood pressure. The HbA1c (P < 0.001), alanine aminotransferase (P = 0.002), alkaline phosphatase (0.002), and hs-CRP (P < 0.001) were elevated in subjects with NAFLD. The mean level of hs-CRP was significantly higher in subjects with NAFLD as compared to the control group (3.12 ± 1.42 mg/L vs 1.05 ± 0.44 mg/L, P < 0.001). The mean hs-CRP level was 1.42 ± 0.55 mg/L in grade 1, 0.98 ± 0.72 mg/L in grade 2 with P < 0.001, and 4.5 ± 1.11 mg/L in grade 3 with P < 0.001 when compared to grade 1.The comparative value of hs-CRP in the control group was found to be 1.05 ± 0.44 mg/L. On univariate analysis waist-hip circumference ratio (P = 0.035), HbA1c (P < 0.001), and hs-CRP (P < 0.001), showed a significant association with NAFLD. On logistic regression hs-CRP was found to have significant association with NAFLD even after adjusting waist-hip circumference ratio and HbA1C (odds ratio 1.311, 95% confidence interval 1.146-1.488, P < 0.001). CONCLUSION: In this cohort of north Indian population, hs-CRP showed independent relationships with NAFLD. Thus, hs-CRP may be used as a surrogate marker for the disease severity in NAFLD.

Tuberculous encephalopathy without meningitis: A rare manifestation of disseminated tuberculosis.

Tuberculous (TB) encephalopathy is a rare presentation of the central nervous system tuberculosis. Its pathophysiology is believed to have an immune mechanism without any direct invasion by the tubercular bacilli. The clinical presentation is highly variable from mild illness to a potentially fatal one. The characteristic signs of meningitis and cerebrospinal fluid findings are mild or absent. Diffuse white matter edema and demyelination have been noted. This clinical entity has been reported mainly from the pediatric population. In the adult population, it has been reported only in very few case reports. We report here a rare case of TB encephalopathy in a 21-year-old female with disseminated tuberculosis, without meningitis, responding to antitubercular therapy.

Hyperglycemia-induced posterior reversible encephalopathy syndrome: A rare cause of reversible blindness.

Posterior reversible encephalopathy syndrome (PRES) is an amalgam of clinical and radiological entities, which is reversible if diagnosed and treated promptly. It is characterized by varying neurological manifestation of seizure, headache, visual loss with typical magnetic resonance imaging findings of symmetric distribution of changes involving the parietooccipital lobes, which reflects vasogenic edema. The common causes include hypertension, renal failure, eclampsia, preeclampsia, sepsis, diabetic ketoacidosis, sepsis, cytotoxic drugs, and autoimmune disorders. Although it has been reported in association with diabetic ketoacidosis in few cases, its association with hyperglycemia in the absence of any other clinical or metabolic derangements is extremely rare. We report here a case of reversible blindness caused by hyperglycemia-induced PRES in a 21-year-old female.

Effect of Severe Vitamin D Deficiency at Admission on Shock Reversal in Children With Septic Shock: A Prospective Observational Study.

OBJECTIVES:: To evaluate the association of severe vitamin D deficiency with clinically important outcomes in children with septic shock. METHODS:: We enrolled children ≤17 years with septic shock prospectively over a period of 6 months. We estimated 25-hydroxyvitamin D [25 (OH) D] levels at admission and 72 hours. Severe deficiency was defined as serum 25 (OH) <10 ng/mL. We performed univariate and multivariate analysis to evaluate association with clinically important outcomes. RESULTS:: Forty-three children were enrolled in the study. The prevalence of severe vitamin D deficiency was 72% and 69% at admission and 72 hours, respectively. On univariate analysis, severe vitamin D deficiency at admission was associated with lower rates of shock reversal, 74% (23) versus 25% (3); relative risk (95% confidence interval [CI]): 2.9 (1.09-8.08), at 24 hours and greater need for fluid boluses (75 vs 59 mL/kg). On multivariate analysis, nonresolution of shock at 24 hours was significantly associated with severe vitamin D deficiency after adjusting for other key baseline and clinical variables, adjusted odds ratio (95% CI): 12 (2.01-87.01); 0.01. CONCLUSION:: The prevalence of severe vitamin D deficiency is high in children with septic shock admitted to pediatric intensive care unit. Severe vitamin D deficiency at admission seems to be associated with lower rates of shock reversal at 24 hours of ICU stay. Our study provides preliminary data for planning interventional studies in children with septic shock and severe vitamin D deficiency.

An infection cocktail: malaria, dengue, chikungunya and Japanese encephalitis.

Vector-borne diseases cause a significant burden on healthcare facilities. An increasing number of cases reported with multiple co-infections only add to the ordeal. The presence of co-infection may modify clinical and laboratory parameters significantly making diagnosis and treatment a challenge. Cases of malaria and dengue with other infections such as chikungunya, leptospirosis and hepatitis have been reported previously. We report a case of acute febrile illness with altered sensorium which was eventually diagnosed to have quadruple infection with malaria, dengue, chikungunya and Japanese encephalitis. This may be the first case with four concurrent vector-borne infections, all of which are transmitted by mosquitoes.

Chyluria: A rare initial manifestation of disseminated tuberculosis.

Chyluria is described as passage of chyle in the urine. It results from the formation of lymphaticorenal fistulae due to various etiologies. The most common implicated cause is filariasis especially in endemic areas. Other uncommon causes include thoracic duct trauma or anatomical abnormalities, pregnancy, malignancy, and tuberculosis. Although tuberculosis has been included as a cause, there are only a few case reports suggesting it as an etiology. Tuberculosis can present in various ways. However, chyluria as initial presentation of tuberculosis has never been reported in the literature. We present, here, an extremely rare case of disseminated tuberculosis involving lung, lymph nodes, liver, intestine, and spine presenting as chyluria. The patient responded dramatically with antituberculous therapy with complete clearing of urine.