Background & objectives: In December 2019, a novel coronavirus (SARS-CoV-2) emerged in China and rapidly spread globally including India. The characteristic clinical observations and outcomes of this disease (COVID-19) have been reported from different countries. The present study was aimed to describe the clinico-demographic characteristics and in-hospital outcomes of a group of COVID-19 patients in north India. Methods: This was a prospective, single-centre collection of data regarding epidemiological, demographic, clinical and laboratory parameters, management and outcome of COVID-19 patients admitted in a tertiary care facility in north India. Patient outcomes were recorded as death, discharge and still admitted. Results: Data of 144 patients with COVID-19 were recorded and analyzed. The mean age of the patients was 40.1±13.1 yr, with 93.1 per cent males, and included 10 (6.9%) foreign nationals. Domestic travel to or from affected States (77.1%) and close contact with COVID-19 patients in congregations (82.6%) constituted the most commonly documented exposure. Nine (6.3%) patients were smokers, with a median smoking index of 200. Comorbidities were present in 23 (15.9%) patients, of which diabetes mellitus (n=16; 11.1%) was the most common. A significant proportion of patients had no symptoms (n=64; 44.4%); among the symptomatic, cough (34.7%) was the most common symptom followed by fever (17.4%) and nasal symptoms (2.15%). Majority of the patients were managed with supportive treatment with hydroxychloroquine and azithromycin given on a case-to-case basis. Only five (3.5%) patients required oxygen supplementation, four (2.8%) patients had severe disease requiring intensive care, one required mechanical ventilation and mortality occurred in two (1.4%) patients. The time to reverse transcription-polymerase chain reaction (RT-PCR) negativity was 16-18 days. Interpretation & conclusions: In this single-centre study of 144 hospitalized patients with confirmed COVID-19 in north India, the characteristic findings included younger age, high proportion of asymptomatic patients, long time to PCR negativity and low need for intensive care unit care.

After 8 years, an update of central nervous system (CNS) tumors was published in 2016 after 2007. First time ever, molecular markers along with histology have been used in classification of any tumor. Major changes are seen in glioma and medulloblastoma groups. Few entities have been added such as diffuse midline glioma, H3 K27M-mutant, RELA fusion-positive ependymoma, embryonal tumor with multilayered rosettes, C19MC-altered, and hybrid nerve sheath tumors. Few variants and patterns that no longer have diagnostic and/or biological relevance and have been deleted such as glioblastoma cerebri, protoplasmic and fibrillary astrocytoma, and cellular ependymoma. Other changes include deletion of term “primitive neuroectodermal tumor,” addition of criterion of brain invasion in atypical meningioma, separation of melanotic schwannoma from other schwannoma, and combination of solitary fibrous tumors and hemangiopericytoma as one entity. There is also expansion of entities in nerve sheath tumors and hematopoietic/lymphoid tumors of the CNS. In this review article, we tried to review CNS tumors 2016 classification update in a simplified manner; comparing the differences between 2016 and 2007 CNS tumors classifications with brief description of important molecular markers and finally utility as well as challenges of this classification.

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Objectives To assess the impact of adding statin (atorvastatin) and/or aspirin on clinical deterioration in patients infected with SARS-CoV-2 who require hospitalisation. The safety of these drugs in COVID-19 patients will also be evaluated. Trial design This is a single-centre, prospective, four-arm parallel design, open-label, randomized control trial. Participants The study will be conducted at National Cancer Institute (NCI), Jhajjar, Haryana, which is a part of All India Institute of Medical Sciences (AIIMS), New Delhi, and has been converted into a dedicated COVID-19 management centre since the outbreak of the pandemic. All RT-PCR confirmed cases of SARS-CoV-2 infection with age ≥ 40 years and < 75 years requiring hospital admission (patients with WHO clinical improvement ordinal score 3 to 5) will be included in the trial. Written informed consent will be taken for all recruited patients. Patients with a critical illness (WHO clinical improvement ordinal score > 5), documented significant liver disease/dysfunction (aspartate transaminase [AST] / alanine aminotransferase [ALT] > 240), myopathy and rhabdomyolysis (creatine phosphokinase [CPK] > 5x normal), allergy or intolerance to statins or aspirin, prior statin or aspirin use within 30 days, history of active gastrointestinal bleeding in past three months, coagulopathy, thrombocytopenia (platelet count < 100000/ dl), pregnancy, active breastfeeding, or inability to take oral or nasogastric medications will be excluded. Patients refusing to give written consent and taking drugs that are known to have a significant drug interaction with statin or aspirin [including cyclosporine, HIV protease inhibitors, hepatitis C protease inhibitor, telaprevir, fibric acid derivatives (gemfibrozil), niacin, azole antifungals (itraconazole, ketoconazole), clarithromycin and colchicine] will also be excluded from the trial. Intervention and comparator In this study, the benefit and safety of atorvastatin (statin) and/or aspirin as adjuvant therapy will be compared with the control group receiving usual care for management of COVID-19. Atorvastatin will be prescribed as 40 mg oral tablets once daily for ten days or until discharge, whichever is earlier. The dose of aspirin will be 75 mg once daily for ten days or until discharge, whichever is earlier. All other therapies will be administered according to the institute’s COVID-19 treatment protocol and the treating physician’s clinical judgment. Main outcomes All study participants will be prospectively followed up for ten days or until hospital discharge, whichever is longer for outcomes. The primary outcome will be clinical deterioration characterized by progression to WHO clinical improvement ordinal score ≥ 6 (i.e., endotracheal intubation, non-invasive mechanical ventilation, pressor agents, renal replacement therapy, ECMO requirement, and mortality). The secondary outcomes will be change in serum inflammatory markers (C-reactive protein and Interleukin-6), Troponin I, and creatine phosphokinase (CPK) from time zero to 5th day of study enrolment or 7th day after symptom onset, whichever is later. Other clinical outcomes that will be assessed include progression to Acute Respiratory Distress Syndrome (ARDS), shock, ICU admission, length of ICU admission, length of hospital admission, and in-hospital mortality. Adverse drug effects like myalgia, myopathy, rhabdomyolysis, hepatotoxicity, and bleeding will also be examined in the trial to assess the safety of the interventions. Randomisation The study will use a four-arm parallel-group design. A computer-generated permuted block randomization with mixed block size will be used to randomize the participants in a 1:1:1:1 ratio to group A (atorvastatin with conventional therapy), group B (aspirin with conventional therapy), group C (aspirin + atorvastatin with conventional therapy), and group D (control; only conventional therapy). Blinding (masking) The study will be an open-label trial. Numbers to be randomised (sample size) As there is no existing study that has evaluated the role of aspirin and atorvastatin in COVID-19 patients, formal sample size calculation has not been done. Patients satisfying the inclusion and exclusion criteria will be recruited during six months of study period. Once the first 200 patients are included in each arm (i.e., total 800 patients), the final sample size calculation will be done on the basis of the interim analysis of the collected data. Trial Status The institutional ethical committee has approved the study protocol (Protocol version 3.0 [June 2020]). Participant recruitment starting date: 28th July 2020 Participant recruitment ending date: 27th January 2021 Trial duration: 6 months Trial registration The trial has been prospectively registered in Clinical Trial Registry – India (ICMR- NIMS): Reference no. CTRI/2020/07/026791 (registered on 25 July 2020)]. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Background Statins and aspirin have been proposed for treatment of COVID-19 because of their anti-inflammatory and anti-thrombotic properties. Several observational studies have shown favourable results. There is a need for a randomised controlled trial. Methods In this single-center, open-label, randomised controlled trial, 900 RT-PCR positive COVID-19 patients requiring hospitalisation, were randomly assigned to receive either atorvastatin 40 mg (Group A, n = 224), aspirin 75 mg (Group B, n = 225), or both (Group C, n = 225) in addition to standard of care for 10 days or until discharge whichever was earlier or only standard of care (Group D, n = 226). The primary outcome variable was clinical deterioration to WHO Ordinal Scale for Clinical Improvement ≥ 6. The secondary outcome was change in serum C-reactive protein, interleukin-6, and troponin I. Results The primary outcome occurred in 25 (2.8%) patients: 7 (3.2%) in Group A, 3 (1.4%) in Group B, 8 (3.6%) in Group C, and 7 (3.2%) in Group D. There was no difference in primary outcome across the study groups (P = 0.463). Comparison of all patients who received atorvastatin or aspirin with the control group (Group D) also did not show any benefit [Atorvastatin: HR 1.0 (95% CI 0.41–2.46) P = 0.99; Aspirin: HR 0.7 (95% CI 0.27–1.81) P = 0.46]. The secondary outcomes revealed lower serum interleukin-6 levels among patients in Groups B and C. There was no excess of adverse events. Conclusions Among patients admitted with mild to moderate COVID-19 infection, additional treatment with aspirin, atorvastatin, or a combination of the two does not prevent clinical deterioration. Trial Registry Number CTRI/2020/07/026791 (http://ctri.nic.in; registered on 25/07/2020)

Introduction: Till date, no drug has shown definite benefit in non-severe COVID-19. Ivermectin is an antiparasitic drug which has in-vitro efficacy in reducing coronavirus-2 (SARS-CoV-2) load in severe disease. Objectives: To determine if a single oral administration of Ivermectin to patients with mild and moderate COVID-19 is effective in converting SARS-CoV-2 RT-PCR to negative result and in reducing viral load.Methods: In this double-blind trial, patients were randomized to elixir formulation of Ivermectin in 24 mg, 12 mg or placebo in 1:1:1 ratio. The co-primary outcomes were conversion of RT-PCR to negative result and the decline of viral load at day 5 of enrolment and were assessed in patients with positive RT-PCR at enrolment (modified intention-to-treat population). Safety outcomes included total and serious adverse events and were assessed in all patients who received the trial drug (intention-to-treat population). Results: Among 157 patients randomized, 125 patients were included in mITT analysis. Forty patients each were assigned to Ivermectin 24 mg and 12 mg, and 45 patients to placebo. The RT-PCR negativity at day 5 was higher in the two Ivermectin arms but failed to attain statistical significance (Ivermectin 24 mg, 47.5%; 12 mg, 35.0%; and placebo, 31.1%; p= 0.30). The decline of viral load at day 5 was similar in the three arms. No serious adverse events were encountered.Conclusion: In patients with mild and moderate COVID-19, a single administration of Ivermectin elixir (either 24 mg or 12 mg) demonstrated a trend towards higher proportion of RT-PCR negativity at day 5 of enrolment. The protocol was registered in the Clinical Trial Registry – India (CTRI) vide ref No CTRI/2020/06/026001.

BackgroundThere is limited data on coronavirus disease 2019 (COVID-19) and latent tuberculosis infection (LTBI). MethodologyWe analyzed data of admitted COVID-19 patients evaluated for LTBI to examine the impact of LTBI on severity, laboratory parameters, and COVID-19 outcome. Prospectively collected data were analyzed for 60 patients who were administered the Mantoux tuberculosis skin test (TST) using five tuberculin units of purified protein derivative. All patients were administered TST irrespective of Bacille Calmette-Guérin (BCG) vaccination status. Comorbidities, clinical features, radiologic involvement, laboratory parameters, and clinical course were analyzed concerning LTBI. ResultsThe mean age was 45.9 (±15.2) years, and 35 (58.3%) patients had non-severe disease. The vast majority (n = 56/60; 93.3%) had been vaccinated with single-dose BCG in infancy or early childhood, as per national immunization guidelines. LTBI was diagnosed in 15 (25%) patients. LTBI prevalence was lower in severe (n = 1/25; 4%) than non-severe (n = 14/35; 40%) COVID-19 (p = 0.01) patients. LTBI patients had lower percentage neutrophil count, higher lymphocyte percentage, higher monocyte count, lower neutrophillymphocyte (NL) ratio, lower alanine aminotransferase, lower C-reactive protein, and lesser radiologic involvement compared to those without LTBI (p < 0.05). Similarly, among the mild COVID-19 subgroup, those with LTBI had higher lymphocyte and monocyte counts and lesser radiologic involvement than those without LTBI (p < 0.05). ConclusionsLTBI patients appear to have milder disease, higher lymphocyte and monocyte count, higher NL ratio, and lesser radiographic involvement. This observation needs to be studied in larger studies using interferon release assays.

Time course absorption and desorption of metalaxyl by seeds of pearl millet was analysed by following chemical kinetics equations. Uptake of metalaxyl through roots, leaves and seed, its translocation and distribution in different plant parts and persistence following seed application were studied in pearl millet using '•*C-metalaxyl. Both uptake and efflux of metalaxyl by pearl millet seeds were complex and compartmentalized. Distribution inside the seed was not uniform. A major part of applied fungicide remained within the treated plant part, particularly after seed and foliar applications. Metalaxyl was ambimobile inside the plant and was found to get accumulated at apex and margins of leaf blade. No metalaxyl could be detected in grains harvested from plants grown from metalaxyl treated seeds. ZusammenfassungAufnahme, Translokation, Verteilung und Persistenz von "C-Metalaxyl in Pearlhirse {Pennisetum americanum [L.] Leeke) Der zeitliche Ablauf der Absorption und der Desorption von Metalaxyl in Perlhirsesamen wurde mit chemisch-kinetischen Formeln analysiert. Die Aufnahme von Metalaxyl durch Wurzeln, Blatter und Samen, die Translokation und Verteilung in den verschiedenen Pflanzenteilen und dessen Persistenz wurden mit '*C-Metalaxyl behandelten Perlhirsesamen untersucht. Die Verteilung innerhalb der Samen war nicht einheitlich. Ein grofierer Teil der applizierten Fungizide blieb ' Experiment Station