Virological and clinical cure in COVID-19 patients treated with hydroxychloroquine: A systematic review and meta-analysis.

Following the demonstration of the efficacy of hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 in vitro, many trials started to evaluate its efficacy in clinical settings. However, no systematic review and meta-analysis have addressed the issue of the safety and efficacy of hydroxychloroquine (HCQ) in coronavirus disease 2019. We conducted a systematic review and meta-analysis with the objectives of evaluation of safety and efficacy of HCQ alone or in combination in terms of "time to clinical cure," "virological cure," "death or clinical worsening of disease," "radiological progression," and safety. RevMan was used for meta-analysis. We searched 16 literature databases out of which seven studies (n = 1358) were included in the systematic review. In terms of clinical cure, two studies reported possible benefit in "time to body temperature normalization" and one study reported less "cough days" in the HCQ arm. Treatment with HCQ resulted in less number of cases showing the radiological progression of lung disease (odds ratio [OR], 0.31, 95% confidence interval [CI], 0.11-0.9). No difference was observed in virological cure (OR, 2.37, 95% CI, 0.13-44.53), death or clinical worsening of disease (OR, 1.37, 95% CI, 1.37-21.97), and safety (OR, 2.19, 95% CI, 0.59-8.18), when compared with the control/conventional treatment. Five studies reported either the safety or efficacy of HCQ + azithromycin. Although seems safe and effective, more data are required for a definitive conclusion. HCQ seems to be promising in terms of less number of cases with radiological progression with a comparable safety profile to control/conventional treatment. We need more data to come to a definite conclusion.

Renal doppler changes in patients with acute pancreatitis: A prospective study.

BACKGROUND: Renal Doppler to assess renal resistive index (RRI) is an attractive option to prognosticate acute kidney injury (AKI) in acute pancreatitis (AP) as it is feasible within scope of point-of-care ultrasound. However, RRI has been infrequently evaluated in AP. OBJECTIVE: Prospectively study diagnostic and prognostic performance of RRI in patients with AP. METHODOLOGY: 75 patients with AP were prospectively enrolled and followed till recovery/death. All patients were subjected to renal Doppler and RRI was compared between patients with and without AKI. RESULTS: Thirty six patients developed AKI and 39 patients did not develop AKI. AKI network stage 1, 2 and 3 AKI was seen in 7(19.4%), 12(33.3%) and 17 (47.2%) patients respectively. Prognostic scoring done at admission by SIRS, modified marshal score, and BISAP scores, as well as duration of hospitalization and mortality rates were significantly higher in patients with AKI. Mean peak systolic velocity and RRI at upper, middle and lower poles of bilateral kidneys were comparable between patients with and without AKI. The RRI was abnormal in 46 (66.6%) patients and it was <0.6 in 35/46 (76%) and >0.7 in 11/46 (24%) patients respectively. RRI <0.6 was observed in 16 (53.3%) and 19 (48.7%) patients with and without AKI respectively (p = 0.80). RRI >0.7 was observed in 4 (53.3%) and 7 (48.7%) patients with and without AKI respectively (p = 0.74). CONCLUSIONS: AKI is associated with poor prognosis in AP. RRI on renal Doppler at admission seems to have poor diagnostic as well as prognostic performance for AKI in patients with AP.

Retino-choroidal changes in patients with acute pancreatitis: A prospective analysis of a novel biomarker.

BACKGROUND: There is paucity of data on ocular changes in acute Pancreatitis (AP). Moreover, subclinical alterations in retina & choroid have not been studied in AP. OBJECTIVE: To prospectively study retino-choroidal changes in AP. METHODS: Sixty patients (mean age 39.07 years; 41 males) with AP were followed up till recovery/death. Baseline slit-lamp examination, choroidal thickness (CT), retinal thickness (RT), choroidal vascularity index (CVI), retinal capillary density index (CDI) and arteriovenous ratio (AVR) were recorded. The patients were divided into two groups - mild (Group A; 5 patients) and moderately severe/severe (Group B; 55 patients) as per revised Atlanta classification. RESULTS: Fundus examination showed mild optic disc edema with retinal hemorrhages in 6 (10%) patients in group B as compared to none in group A (p = 1.00). None of the patients had Purtscher retinopathy. Mean CT (317 ± 56.29 µm) was increased as compared to normal subjects (278.90 ± 57.84 µm, p = 0.003). The mean CVI (0.62 ± 0.04) was decreased as compared to normal (0.66 ± 0.01, p < 0.0001) as was the mean AVR (0.67 ± 0.03 vs. 0.7 ± 0.02, p < 0.0001). However, the mean RT of subjects with AP (239.68 ± 33.76 µm) was not significantly different compared to the normal subjects 253.17 ± 33.67 µm (p=NS). The mean CDI of superficial and deep plexus were comparable between normal and patients with AP. CT, RT, CVI, AVR and CDI were comparable between group A and group B as well as survivors and non-survivors. CONCLUSIONS: Clinically significant ocular changes are seen infrequently in AP. However, subclinical changes in CT, CVI and AVR are observed in patients with AP compared to normal individuals.

Methemoglobinemia in a Case of Paint Thinner Intoxication, Treated Successfully with Vitamin C.

BACKGROUND: Methemoglobin (MetHb) is an oxidized form of hemoglobin. It is a poor transporter of oxygen and is unable to deliver oxygen to the tissue. Globally, drug & toxin induced methemoglobinemia is more common as compared with the congenital form. Methemoglobinemia caused by paint thinner intoxication is rare. Methylene blue is well established as the first-line therapy for severe methemoglobinemia. CASE REPORT: A 25-year old man was brought to the Emergency Department after accidental consumption of paint thinner. On clinical examination, he had cyanosis and there were discrepancies in his pulse oximetry and arterial blood gas (ABG) analysis results. With this clue and supporting laboratory investigations, the diagnosis of toxin-induced methemoglobinemia was made. Due to the unavailability of methylene blue, alternative treatment with high-dose vitamin C was attempted, to which the patient responded. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The role of vitamin C in the treatment of methemoglobinemia has not been well established, with only a few published case reports. This patient had severe methemoglobinemia, with MetHb of 46.4%, which responded dramatically to vitamin C therapy, with no side effects. This case shows that high-dose vitamin C is safe and has the potential to be an effective alternative for the treatment of severe methemoglobinemia. In the presence of cyanosis, mismatch of pulse-oximetry and ABG-analysis are the key for the physician to suspect methemoglobinemia.

Tubercular Mycobacterial Spindle Cell Pseudotumour: A Case Report.

Pseudotumour is a benign inflammatory lesion. Mycobacterial spindle cell pseudotumour (MSP) is a rare pseudotumour. It is a benign proliferation of spindle-shaped histiocytes containing acid-fast mycobacterium, commonly reported in immunocompromised patients. MSP is usually associated with mycobacterium avium complex (MAC). Here, we present the case of a 38-year-old gentleman with acquired immune deficiency syndrome (AIDS) who presented with low-grade fever for 1-month duration. Clinically, he had generalised lymphadenopathy. Chest X-ray showed miliary infiltration in bilateral lung fields. Lymph nodal biopsy showed spindle-shaped histiocytes filled with acid-fast bacilli on Ziehl-Neelsen (ZN) stain, suggestive of MSP. Immunohistochemical (IHC) stains were positive for CD68, S-100 and negative for CD31, which are consistent with MSP. Polymerase chain reaction (PCR) of the biopsy tissue was positive for MTB. Highly active antiretroviral therapy (HAART) was continued and anti-tubercular therapy (ATT) was started. The fever resolved within two weeks and there was a resolution of lymph nodal swelling by 6 weeks. The diagnosis of MSP associated with mycobacterium tuberculosis (MTB) makes our case interesting. It is of utmost importance to differentiate MSP from Kaposi's sarcoma (KS) and other pseudotumours and to know whether it is of tubercular or non-tubercular origin, as the treatment is entirely different.

ANABOLIC BONE WINDOW WITH WEEKLY TERIPARATIDE THERAPY IN POSTMENOPAUSAL OSTEOPOROSIS: A PILOT STUDY.

OBJECTIVE: Osteoporosis is a major public health problem that reduces bone strength and increases fracture risk. Teriparatide is an established and the only currently available anabolic therapy for the treatment of postmenopausal osteoporosis (PMO) with a recommended daily dose of 20 µg given subcutaneously. However, there are limited data regarding the long-term effect of once-weekly teriparatide therapy on bone mineral density (BMD), bone turnover markers (BTMs), and anabolic bone window. METHODS: In this prospective observational study, 26 patients with PMO were treated with weekly teriparatide therapy (60 µg) for 2 years. BMD was measured at baseline, 12 months, and 24 months. The bone formation marker type 1 collagen C-terminal propeptide (P1NP) and the bone resorption marker C-terminal telopeptide of type 1 collagen (CTx) were measured at baseline; 6 weeks; and 6, 12, 18, and 24 months. RESULTS: BMDs at the lumbar spine increased by 3.1% and 10.8% after 1 and 2 years of weekly teriparatide therapy, respectively. The T-score increased significantly at the lumbar spine compared to baseline after 2 years of therapy (P = .015). Serum P1NP levels increased significantly at 6 months (P = .024), peaked at 1 year, and remained above the baseline even after 2 years. Serum CTx levels decreased significantly at 6 months (P = .025) and remained below baseline after 2 years of teriparatide therapy. CONCLUSION: Weekly teriparatide therapy (60 µg) appears to be as effective as daily teriparatide for the treatment of PMO by extending the anabolic bone window. ABBREVIATIONS: AE = adverse event; BMD = bone mineral density; BTM = bone turnover marker; CTx = C-terminal telopeptide of type 1 collagen; DXA = dual-energy X-ray absorptiometry; iPTH = intact parathyroid hormone; P1NP = type 1 collagen C-terminal propeptide; PMO = postmenopausal osteoporosis.

Efficacy of tranexamic acid in haemoptysis: A randomized, controlled pilot study.

BACK GROUND: Haemoptysis is a life threatening condition irrespective of aetiology. Tranexamic acid (TA), a potent anti-fibrinolytic agent, has been shown to control bleeding, decrease transfusion requirement in knee & hip arthroplasty, coronary artery bypass grafting and heavy menstrual bleeding. TA also has mortality benefit in bleeding from surgical and trauma patients. But the studies, regarding efficacy and safety of TA in controlling haemoptysis are conflicting. METHOD: In this single blinded, prospective study, total 66 patients with sub-massive haemoptysis were randomized into treatment (T) and placebo control (C) groups. Group-T received intravenous (IV) TA in a loading dose of 1 g, followed by 1 g TA over 8 h infusion and group-C received IV 0.9% normal saline. The severity of haemoptysis was assessed by quantity, frequency and visual analogue scale (VAS) score. RESULTS: On day 2, frequency, quantity and VAS score of haemoptysis were 2.23 ± 2.11/day, 34.19 ± 67.0 ml and 14.72 ± 15.7 respectively in Group-T and 2.29 ± 2.0/day, 90.4 ± 79.0 ml and 31.33 ± 22.12 respectively in group-C. In group-T 16.27% patients needed intervention as compared to 38.1% in group-C (p 0.053). The mean blood transfusion (1.58 ± 0.88 & 1.67 ± 0.669 units) and hospital stay (4.14 ± 3.18 & 5.48 ± 3.26 days) was also lower in group-T as compared to group-C. Group-T had better outcomes as compared to group-C, but statistically significant only for VAS score (p 0.001). During study no adverse event of the drug was noted. CONCLUSION: TA decreases severity of haemoptysis and can be used as a bridging therapy in acute haemoptysis before definitive intervention can be under taken.

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.

Efficacy of empirical Ciprofloxacin or Cefixime plus Metronidazole therapy for the treatment of liver abscess: a randomized control clinical trial.

Liver abscess is a potentially life-threatening medical emergency. Prompt empirical antimicrobial with or without percutaneous aspiration or drainage is therapeutic. The rational for using empirical intravenous broad-spectrum antimicrobials upfront instead of oral Fluoroquinolone or Cephalosporin is contentious. In this double blind randomized control clinical trial 69 participants received Ciprofloxacin (500 mg q 12 hourly) and 71 participants received Cefixime (200 mg q 12 hourly) orally for 2 weeks. Both the group received oral Metronidazole (800 mg q 8 hourly) for 2 weeks and percutaneous drainage or aspiration of the abscess was done as per indication and followed-up for 8 weeks. Out of 140 participants, 89.3% (N = 125) achieved clinical cure, 59 (85.5%) in Ciprofloxacin group and 66 (93%) in Cefixime group (p = 0.154). Mean duration of antimicrobial therapy was 16.2 ± 4.3 days, 15.1 ± 4.5 days in Ciprofloxacin group and 16.0 ± 4.2 days in Cefixime group (p = 0.223). Total 15 (10.7%) participants had treatment failure, 10 (14.5%) in Ciprofloxacin group and 5 (7.0%) in Cefixime group (p = 0.154). The most common reason for treatment failure was need of prolong (> 4 weeks) antimicrobial therapy due to persistent hepatic collection requiring drainage, which was significantly (p = 0.036) higher in Ciprofloxacin (14.5%, N = 10) group, compared to the Cefixime (4.2%, N = 3) group. In conclusion, both, the Ciprofloxacin or Cefixime plus Metronidazole for duration of 2-3 weeks were efficacious as empirical oral antimicrobial regimen along with prompt percutaneous drainage or aspiration for the treatment of uncomplicated liver abscess with similar efficacy. Oral Cefixime was better than Ciprofloxacin in term of lesser chance of treatment failure due to persistent collection which is required to be investigated further in larger clinical trial.Trial registration: clinicaltrials.gov PRS ID: NCT03969758, 31/05/2019.

Prognostic significance of poison-related factors and consumption patterns in acute aluminum phosphide poisoning.

OBJECTIVES: The prognosis of acute aluminum phosphide poisoning is usually based on toxidrome features, with little focus on poison-related factors. We aimed to study the prognostic significance of poison-related factors, consumption patterns, and time delays to treatment. METHODS: We performed a prospective cohort study in an academic hospital in North India in patients aged ≥ 13 with aluminum phosphide poisoning from July 2019 to December 2020. During data collection, a particular emphasis was made on the poison formulation, the ingested dose, the reconstitution of poison, vomiting, and time intervals to initiate various treatments. The primary outcome was inhospital mortality. RESULTS: Fifty-eight patients were enrolled (median age, 32 years; 37 males). The mean dose of the ingested poison was 6.56 (±5.42) g. The predominant formulation of poison was pellet (n = 41), followed by powder (n = 16). Twenty patients performed reconstitution of poison before consumption, and 13 stirred the poison while reconstituting. All patients but three developed vomiting after consumption. Inhospital mortality (n = 23, 39%) was significantly high with a higher ingested dose (P < 0.001), nonstirred reconstitution before consumption (P = 0.042), fewer vomiting episodes (P = 0.010), a delay in detection of the victim by someone (P = 0.001), and delayed initiation of intravenous fluids (P = 0.043). The secondary outcomes (shock and requirement of vasopressor or ventilation) remained unaffected by the stirring in the reconstitution group. CONCLUSIONS: Poison-related factors and time intervals determine early risk stratification at admission in aluminum phosphide poisoning.

Alcoholic foamy degeneration: an unusual presentation of the alcoholic liver disease diagnosed on autopsy.

Alcoholic foamy degeneration (AFD) is an uncommon presentation of alcoholic liver disease (ALD) with characteristic histologic findings of foamy-looking hepatocytes due to the presence of abundant microvesicles of fat within the cytoplasm predominantly in perivenular and midzonal regions without inflammation and fibrosis. It is underdiagnosed as the patients quickly recover after alcoholic abstinence and are rarely caught on biopsies. AFD has better prognosis than alcoholic hepatitis, and the injury mechanism is different, warranting a different diagnosis. We present an uncommon case of AFD incidentally diagnosed during autopsy in a chronic alcoholic and diabetic man.

The 'myth of Hydroxychloroquine (HCQ) as post-exposure prophylaxis (PEP) for the prevention of COVID-19' is far from reality.

The efficacy of Hydroxychloroquine (HCQ) as post-exposure prophylaxis (PEP) for the prevention of COVID-19 was contentious. In this randomized control double-blind clinical trial, asymptomatic individuals with direct contact with laboratory-confirmed COVID-19 cases were randomized into PEP/HCQ (N = 574) and control/placebo (N = 594) group. The PEP/HCQ group received tablet HCQ 400 mg q 12 hourly on day one followed by 400 mg once weekly for 3 weeks, and the control/Placebo group received matching Placebo. The incidence of COVID-19 was similar (p = 0.761) in PEP [N = 24 out of 574, (4.2%)] and control [N = 27 out of 594, (4.5%)] groups. Total absolute risk reduction for the incidence of new-onset COVID-19 was -0.3% points with an overall relative risk of 0.91 (95% confidence interval, 0.52 to 1.60) and the number needed to treat (NNT) was 333 to prevent the incident of one case of COVID-19. The study found that, PEP with HCQ was not advantageous for the prevention of COVID-19 in asymptomatic individuals with high risk for SARS-CoV-2 infection. Though HCQ is a safer drug, the practice of irrational and indiscriminate use of HCQ for COVID-19 should be restrained with better pharmacovigilance.

Comparison of two doses of leucovorin in severe low-dose methotrexate toxicity - a randomized controlled trial.

BACKGROUND: Leucovorin (folinic acid) is a commonly used antidote for severe toxicity with low-dose methotrexate, but its optimum dose is unclear, varying from 15 to 25 mg every 6-h. METHODS: Open-label RCT included patients with severe low-dose (≤ 50 mg/week) methotrexate toxicity defined as WBC ≤ 2 × 10^9/L or platelet ≤ 50 × 10^9/L and randomized them to receive either usual (15 mg) or high-dose (25 mg) intravenous leucovorin given every 6-h. Primary outcome was mortality at 30-days and secondary outcomes were hematological recovery and mucositis recovery. TRIAL REGISTRATION NUMBER: CTRI/2019/09/021152. RESULTS: Thirty-eight patients were included, most with underlying RA who had inadvertently overdosed MTX (taken daily instead of weekly). At randomization, the median white blood and platelet count were 0.8 × 10^9/L and 23.5 × 10^9/L. 19 patients each were randomized to receive either usual or high-dose leucovorin. Number (%) of deaths over 30-days was 8 (42) and 9 (47) in usual and high-dose leucovorin groups (Odds ratio 1.2, 95% CI 0.3 to 4.5, p = 0.74). On Kaplan-Meier, there was no significant difference in survival between the groups (hazard ratio 1.1, 95% CI 0.4 to 2.9, p = 0.84). On multivariable cox-regression, serum albumin was the only predictor of survival (hazard ratio 0.3, 95% CI 0.1 to 0.9, p = 0.02). There was no significant difference in hematological or mucositis recovery between the two groups. CONCLUSION: There was no significant difference in survival or time-to hematological recovery between the two doses of leucovorin. Severe low-dose methotrexate toxicity carried a significant mortality.