Efficacy and safety of hydroxychloroquine/chloroquine against SARS-CoV-2 infection: A systematic review and meta-analysis

IntroductionHydroxychloroquine (HCQ)/Chloroquine (CQ) has been evaluated for treatment and prophylaxis against SARS-CoV-2 infection in various studies with conflicting results. We performed a systematic review to synthesize the currently available evidence over the efficacy and safety of HCQ/CQ therapy alone against SARS-CoV-2 infection.MethodsWe searched Embase, PubMed, Web of Science, and Cochrane central for randomized controlled trials (RCTs) and prospective cohort studies published until October 15, 2020 and assessing the efficacy of HCQ alone against SARS-CoV-2 infection. We included studies evaluating HCQ/CQ alone as intervention and placebo/standard care as a control group. Retrospective studies and studies using other drugs (namely azithromycin, corticosteroids, immunomodulators, etc.) we excluded. Thirteen RCTs and three prospective cohort studies were included in this review. We pooled data using a random-effect model.ResultsPooled data from 12 studies (9917 participants) showed that HCQs increase mortality as compared to placebo/standard of care (RR 1.10; 95% CI:1.00–1.20). Hydroxychloroquine did not reduce the need for hospitalization in out-patients (RR 0.57; 95% CI 0.31–1.02). HCQ group has a significantly higher rate of any adverse event (RR 2.68; 95% CI 1.55–4.64), as compared to the control group. Also, using HCQ for prophylaxis against SARS-CoV-2 infection did not reduce the risk of acquiring SARS-CoV-2 infection (RR 1.04; 95% CI 0.58–1.88).ConclusionsHCQ therapy for COVID-19 is associated with an increase in mortality and other adverse events. The negative effects are more pronounced in hospitalized patients. Therefore, with the available evidence, HCQ should not be used in prophylaxis or treatment of patients with COVID-19.     

Transient versus surgically managed small bowel intussusception in children: Role of ultrasound

Background:

To evaluate and compare the ultrasound (US) features of transient small bowel intussusception (SBI) with those which required surgical management.

Materials and Methods:

US features of 26 children with 32 intussusceptions from January 2014 to August 2014 were recorded and compared with follow-up imaging or surgical findings.

Results:

Transient SBI when compared to surgically managed intussusception has shorter length of intussusception (mean 2.25 cm, range 1.8-4.5 cm vs. mean 5.6 cm, range, 2.3-7.8 cm), smaller transverse diameter (mean, 1.2 cm, range 0.8-2.3 cm vs. mean, 3.3 cm, range 2.9-5.4 cm) and thin wall (mean, 3.3 mm, 2.3-4.9 mm vs. mean, 6.8 mm, range, 4.3-11.2 mm). Four out of five surgically managed intussusceptions were associated with the lead point while none of the transient SBI had any lead point. Peristalsis was absent in all surgically managed intussusceptions.

Conclusion:

Transient SBI is associated with a shorter length of intussusception, smaller transverse diameter, thin walls, absence of the lead point and visible peristalsis. All these findings may help in distinguishing it from those requiring surgical management.Key words: Children, surgically managed small bowel intussusception, transient small bowel intussusception, ultrasound     

Acute toxicity and first clinical results of intensive postinduction therapy using a modified busulfan and cyclophosphamide regimen with autologous bone marrow rescue in first remission of acute myeloid leukemia [see comments]

The combination of high-dose busulfan (16 mg/kg) and 200 mg/kg cyclophosphamide is gaining increasing significance as a preparative regimen prior to autologous, syngeneic, or allogeneic marrow transplantation. A new regimen of high-dose busulfan in conjunction with a reduced dose of 120 mg/kg cyclophosphamide has recently been described as a preparative regimen prior to allogeneic transplantation. To determine the drug-related nonhematologic toxic effects of this new regimen without confounding factors associated with allogeneic transplantation, we conducted a pilot study using this new regimen in 20 patients with acute myeloid leukemia (AML) in first remission prior to autologous unpurged marrow transplantation. All patients experienced transient non-life-threatening acute drug-related toxicity with skin reactions in 20 (100%), nausea and vomiting in 20 (100%), oral mucositis in 18 (90%), hepatic functional impairment in 17 (85%), hemorrhagic cystitis in three (15%), and generalized seizures in two (10%) of these patients, respectively. Two procedural, fatal complications resulted from infectious causes that were not directly related to the speed of hematopoietic reconstitution or the toxicity of the preparative regimen. The 3-year event-free survival estimate (55% +/- 11%) and probability of leukemic recurrence (38% +/- 11%) attained with this new regimen in recipients of autografts in first remission of AML are promising and challenge comparisons with preparative regimens employing combinations of cytotoxic agents or total body irradiation (TBI).     

Co-administration of rIpaB domain of Shigella with rGroEL of S. Typhi enhances the immune responses and protective efficacy against Shigella infection

Shigella species cause severe bacillary dysentery in humans and are associated with high morbidity and mortality. The Invasion plasmid antigen (IpaB) protein, which is conserved across all Shigella spp., induces macrophage cell death and is required to invade host cells. The present study evaluates the immunogenicity and protective efficacy of the recombinant (r) domain region of IpaB (rIpaB) of S. flexneri. rIpaB was administered either alone or was co-administered with the rGroEL (heat shock protein 60) protein from S. Typhi as an adjuvant in a mouse model of intranasal immunization. The IpaB domain region (37 kDa) of S. flexneri was amplified from an invasion plasmid, cloned, expressed in BL21 Escherichia coli cells and purified. Immunization with the rIpaB domain alone stimulated both humoral and cell-mediated immune responses. Furthermore, robust antibody (IgG, IgA) and T-cell responses were induced when the rIpaB domain was co-administered with rGroEL. Antibody isotyping revealed higher IgG1 and IgG2a antibody titers and increased interferon-gamma (IFN-γ) secretion in the co-administered group. Immunization of mice with the rIpaB domain alone protected 60%–70% of the mice from lethal infection by S. flexneri, S. boydii and S. sonnei, whereas co-administration with rGroEL increased the protective efficacy to 80%–85%. Organ burden and histopathological studies also revealed a significant reduction in lung infection in the co-immunized mice compared with mice immunized with the rIpaB domain alone. This study emphasizes that the co-administration of the rIpaB domain and rGroEL protein improves immune responses in mice and increases protective efficacy against Shigella infection. This is also the first report to evaluate the potential of the GroEL (Hsp 60) protein of S. Typhi as an adjuvant molecule, thereby overcoming the need for commercial adjuvants.