Colchicine to reduce coronavirus disease-19-related inflammation and cardiovascular complications in high-risk patients post-acute infection with SARS-COV-2-a study protocol for a randomized controlled trial.

BACKGROUND: There is no known effective pharmacological therapy for long COVID, which is characterized by wide-ranging, multisystemic, fluctuating, or relapsing symptoms in a large proportion of survivors of acute COVID. This randomized controlled trial aims to assess the safety and efficacy of an anti-inflammatory agent colchicine, to reduce symptoms among those at high risk of developing long COVID. METHODS: This multi-centre, parallel arm, 1:1 individual randomized, placebo-controlled, double-blind superiority trial will enrol 350 individuals with persistent post-COVID symptoms. Participants will be randomized to either colchicine 0.5 mg once daily (< 70 kg) or twice daily (≥ 70 kg) or matched placebo for 26 weeks and will be followed up until 52 weeks after randomization. The primary trial objective is to demonstrate the superiority of colchicine over a placebo in improving distance walked in 6 min at 52 weeks from baseline. The secondary objectives are to assess the efficacy of colchicine compared to placebo with respect to lung function, inflammatory markers, constitutional symptoms, and mental health state. In a sub-sample of 100 participants, cardiac biomarkers of myocardial injury and myocardial oedema using MRI will be compared. DISCUSSION: Persistent inflammatory response following SARS-CoV-19 is one of the postulated pathophysiological mechanisms of long COVID. Colchicine, a low-cost anti-inflammatory agent, acts via multiple inflammatory pathways and has an established safety profile. This trial will generate evidence for an important health priority that can rapidly translate into practice. TRIAL REGISTRATION: This clinical trial has been registered prospectively on www. CLINICALTRIALS: gov with registration CTRI/2021/11/038234 dated November 24, 2021.

A multicentre, double-blind, placebo-controlled randomized trial of Mycobacterium w in critically ill patients with COVID-19 (ARMY-2).

BACKGROUND: Mycobacterium w (Mw), an immunomodulator, resulted in better clinical status in severe coronavirus infectious disease 19 (COVID-19) but no survival benefit in a previous study. Herein, we investigate whether Mw could improve clinical outcomes and survival in COVID-19. MATERIALS AND METHODS: In a multicentric, randomized, double-blind, parallel-group, placebo-controlled trial, we randomized hospitalized subjects with severe COVID-19 to receive either 0.3 mL/day of Mw intradermally or a matching placebo for three consecutive days. The primary outcome was 28-day mortality. The co-primary outcome was the distribution of clinical status assessed on a seven-point ordinal scale ranging from discharged (category 1) to death (category 7) on study days 14, 21, and 28. The key secondary outcomes were the change in sequential organ failure assessment (SOFA) score on days 7 and 14 compared to the baseline, treatment-emergent adverse events, and others. RESULTS: We included 273 subjects (136 Mw, 137 placebo). The use of Mw did not improve 28-day survival (Mw vs. placebo, 18 [13.2%] vs. 12 [8.8%], P = 0.259) or the clinical status on days 14 (odds ratio [OR], 1.33; 95% confidence intervals [CI], 0.79-2.3), 21 (OR, 1.49; 95% CI, 0.83-2.7) or 28 (OR, 1.49; 95% CI, 0.79-2.8) between the two study arms. There was no difference in the delta SOFA score or other secondary outcomes between the two groups. We observed higher injection site reactions with Mw. CONCLUSION: Mw did not reduce 28-day mortality or improve clinical status on days 14, 21 and 28 compared to placebo in patients with severe COVID-19. [Trial identifier: CTRI/2020/04/024846].

A case series of post-infectious chikungunya myeloradiculoneuropathy.

Chikungunya fever is an arboviral illness caused by chikungunya virus (CHIKV) and transmitted by the bite of Aedes aegypti and Aedes albopictus. It is an RNA virus belonging to the genus Alphavirus and family Togaviridae. We present a case series of three patients with chikungunya illness developing para/post-infectious myeloradiculoneuropathy.These patients developed neurological symptoms in the form of bilateral lower limb weakness with sensory and bowel involvement after the recovery from the initial acute episode of chikungunya fever. Clinical examination findings suggested myeloradiculoneuropathy with normal Magnetic Resonance Imaging of the Spine, with the nerve conduction study showing sensorimotor axonal polyneuropathy. All the patients were treated with 1 g of methylprednisolone once a day for five days, and case 2 was given intravenous immunoglobulin also. In the follow-up, cases 1 and 2 showed complete recovery without recurrence, and case 3 did not show improvement at one month.

Efficacy of a low dose of antivenom for severe neuroparalysis in Bungarus caeruleus (common krait) envenomation: a pilot study.

Introduction: Despite the widespread use of antivenom for the treatment of snakebite envenoming in the Indian subcontinent, the ideal dose of antivenom has been a point of contention. Low-dose regimens can economize on a scarce resource in low- and middle-income countries. This study assessed the effectiveness of a low-dose (10 vials) antivenom regimen compared to the usual 20 vials in patients with krait bite neuroparalysis requiring mechanical ventilation. Methods: This study was a prospective controlled pilot study conducted in a tertiary-care hospital in north India. Participants were eligible if they were ≥12 years old, had krait bite neurotoxicity, showed severe paralysis requiring mechanical ventilation, and had access to antivenom therapy within 24 h of the bite. The primary outcome was the duration of mechanical ventilation, and the secondary outcomes were the length of hospital stay and in-hospital survival. Results: Fifteen patients received 10 vials of antivenom, and 25 received 20 vials. The two treatment groups had similar baseline demographics, clinical and laboratory features, snakebite severity scores, and median time from snakebite to initiation of antivenom therapy. The low-dose regimen was as effective as the standard dose concerning the median duration of mechanical ventilation (41 h vs. 55 h, P = 0.094), the median length of stay (78 h vs. 85.5 h, P = 0.360), and in-hospital deaths (1 vs. 3, P = 1.000). The incidence of ventilator-associated pneumonia was similar between the two groups (1 vs 3, P = 1.000). Conclusion: A low dose of antivenom effectively treats patients with severe krait bite neuroparalysis.

Knuckle hyperpigmentation in a young male: A clinical sign of B12 deficiency not to be missed.

Vitamin B12 and folate deficiency are reversible causes of megaloblastic anemia. Strict vegetarians are at risk of megaloblastic anemia due to low cobalamin in their diet. Knuckle hyperpigmentation in patients with megaloblastic anemia is due to excess melanin synthesis in skin. Here we present a case of a young vegetarian male with megaloblastic anemia with knuckle hyperpigmentation managed successfully with intravenous followed by oral vitamin b12 and folate supplementation.

Cycle threshold values of SARS-CoV-2 RNA in conjunctival swabs and nasopharyngeal secretions: a comparative study from a tertiary care center in India.

PURPOSE: To detect the viral RNA load of SARS-CoV-2 in conjunctival swabs of COVID-19 patients, and compare with nasopharyngeal swabs. METHODS: Conjunctival swabs of COVID-19 patients (with PCR positive nasopharyngeal swabs) were subjected to quantitative reverse transcription-polymerase chain reaction (RT-PCR) for detection of SARS-CoV-2 RNA. The cycle threshold (Ct) values of Open Reading Frame 1 (ORF 1 Ab gene) and nucleoprotein (N gene) PCRs were used to assess the viral RNA load, and compare them with the baseline values of nasopharyngeal swabs. RESULTS: Of 93 patients, 17 (18.27%) demonstrated SARS-CoV-2 RNA in conjunctival swabs. Baseline nasopharyngeal swabs were collected at a median of 2 days; while, the conjunctival swabs were collected at median 7 days, from onset of illness (p < 0.001). Despite a significant delay in conjunctival swab collection than nasopharyngeal swabs, the Ct values (ORF or N gene PCRs) were comparable between nasopharyngeal swab and conjunctival swab samples. Subsequently, during the recovery period, in four of these 17 patients (with conjunctival swab positivity), when the second nasopharyngeal swab was 'negative', the conjunctival swab was 'positive'. CONCLUSION: The conjunctival swabs demonstrated SARS-CoV-2 RNA in 17 (18.27%) of 93 COVID-19 patients. Our results may suggest a delayed or a prolonged shedding of the virus/viral RNA on the ocular surface than in nasopharyngeal mucosa.

Case Report: A Case of Complicated Typhoid Fever with Rhabdomyolysis and Hemophagocytic Lymphohistiocytosis.

Typhoid fever can have diverse extra-intestinal complications including encephalitis, Guillain-Barré syndrome, endocarditis, myocarditis, osteomyelitis, renal abscess, and splenic abscesses. Secondary hemophagocytic lymphohistiocytosis with rhabdomyolysis is a rare complication of typhoid fever. Here, we present the case of an adolescent with typhoid fever complicated by rhabdomyolysis and hemophagocytic lymphohistiocytosis.

Comparação dos escores não endoscópicos para a previsão de resultados em doentes com sangramento gastrointestinal alto na emergência de um hospital de referência em cuidados terciários: um estudo de coorte prospectivo / Comparison of non-endoscopic scores for the prediction of outcomes in patients of upper gastrointestinal bleed in an emergency of a tertiary care referral hospital: a prospective cohort study

ABSTRACT BACKGROUND: Traditionally peptic ulcer disease was the most common cause of upper gastrointestinal (UGI) bleed but with the changing epidemiology; other etiologies of UGI bleed are emerging. Many scores have been described for predicting outcomes and the need for intervention in UGI bleed but prospective comparison among them is scarce. OBJECTIVE: This study was planned to determine the etiological pattern of UGI bleed and to compare Glasgow Blatchford score, Pre-Endoscopy Rockall score, AIMS65, and Modified Early Warning Score (MEWS) as predictors of outcome. METHODS: In this prospective cohort study 268 patients of UGI bleed were enrolled and followed up for 8 weeks. Glasgow Blatchford score, Endoscopy Rockall score, AIMS65, and MEWS were calculated for each patient, and the area under the receiver operating characteristic (AUC-ROC) curve for each score was compared. RESULTS: The most common etiology for UGI bleed were gastroesophageal varices 150 (63.55%) followed by peptic ulcer disease 29 (12.28%) and mucosal erosive disease 27 (11.44%). Total 38 (15.26%) patients had re-bleed and 71 (28.5%) patients died. Overall, 126 (47%) patients required blood component transfusion, 25 (9.3%) patients required mechanical ventilation and 2 (0.74%) patients required surgical intervention. Glasgow Blatchford score was the best in predicting the need for transfusion (cut off - 10, AUC-ROC= 0.678). Whereas AIMS65 with a score of ≥2 was best in predicting re-bleed (AUC-ROC=0.626) and mortality (AUC-ROC=0.725). CONCLUSION: Gastrointestinal bleed was most commonly of variceal origin at our tertiary referral center in Northern India. AIMS65 was the best & simplest score with a score of ≥2 for predicting re-bleed and mortality.

RESUMO CONTEXTO: Tradicionalmente, a doença úlcera péptica era a causa mais comum de sangramento digestivo alto, mas com a mudança da epidemiologia, outras etiologias do sangramento do trato digestivo alto estão emergindo. Muitas pontuações têm sido descritas para prever resultados e a necessidade de intervenção na hemorragia gastrointestinal superior, mas a comparação prospectiva entre elas é escassa. OBJETIVO: Este estudo foi planeado para determinar o padrão etiológico de pacientes com hemorragia digestiva alta e comparar os escores de Glasgow Blatchford, o Rockall pré-endoscopia, o AIMS65 e o Early Warning modificado (MEWS) como preditores do resultado. MÉTODOS: Neste estudo prospetivo de coorte, 268 pacientes com sangramento digestivo alto foram acompanhados durante 8 semanas. Os escores Glasgow Blatchford, Rockall pré-endoscopia, AIMS65 e MEWS foram calculados para cada paciente, e a área sob a curva (AUC-ROC) para cada pontuação foi comparada. RESULTADOS: A etiologia mais comum para a hemorragia gastrointestinal alta foi varizes gastroesofágicas 150 (63,55%), seguida de úlcera péptica 29 (12,28%) e de doença erosiva de mucosa 27 (11,44%). No total, 38 (15,26%) doentes voltaram a sangrar e 71 (28,5%) doentes morreram. No total, 126 (47%) doentes necessitaram de transfusão de componentes sanguíneos, 25 (9,3%) necessitaram de ventilação mecânica e 2 (0,74%) destes doentes necessitaram de intervenção cirúrgica. O escore de Glasgow Blatchford foi o melhor na previsão da necessidade de transfusão (corte - 10, AUC-ROC =0,678). Enquanto o AIMS65 com uma pontuação de ≥2 foi o melhor na previsão de ressangramento (AUC-ROC =0,626) e mortalidade (AUC-ROC =0,725). CONCLUSÃO: O sangramento gastrointestinal alto mais comum é de origem varicosa em centro de referência terciária. O AIMS65 é o melhor escore simples, com uma pontuação de ≥2 para prever o ressangramento e a mortalidade.

Chronic brucellosis with hepatic brucelloma and AA amyloidosis in a patient with autosomal dominant polycystic kidney disease

We describe an autopsy case of a 45-year-old male diagnosed with autosomal dominant polycystic kidney disease who presented with complaints of altered sensorium. The autopsy revealed multiple tumor-like masses in the liver, which on histological examination depicted multiple large suppurative granulomas with the presence of variable acid-fast coccobacilli (consistent with Brucella spp.). Interestingly, extensive amyloid deposition in multiple organs was noted. To the best of our knowledge, this is the first case of chronic brucellosis causing tumor-like abscesses in the liver accompanied by secondary systemic amyloidosis in a patient with underlying autosomal dominant polycystic kidney disease.