Background and aims: Currently there is limited knowledge on medical comorbidities and COVID-19; we conducted a systematic review and meta-analysis to evaluate the impact of various morbidities on serious events in COVID 19. Methods: PubMed, Cochrane Central Register of Clinical Trials were searched on April 28, 2020, to extract published articles that reported the outcomes of COVID-19 patients. The search terms were "coronavirus" and "clinical characteristics". ICU admission, mechanical ventilation, ARDS, Pneumonia, death was considered serious events. The comorbidities assessed in the study were Hypertension (HTN), Diabetes mellitus (DM), Cardiovascular diseases (CVD), Chronic obstructive pulmonary disease (COPD) and Chronic Kidney disease (CKD). Subsequently, comparisons between comorbidity patient group and the non-comorbidity patient groups, in terms of serious events were made using the pooled estimates of odd's ratio (OR) Results: We identified 688 published results and 16 studies with 3994 patients were included in the systematic review. Serious events were seen in 526(13.16%) patients. Presence of hypertension with OR 2.95, diabetes mellitus with OR 3.07, Cardio vascular disease with OR 4.58, COPD with OR 6.66 and Chronic kidney disease with OR 5.32 had significant association in patients with COVID 19 on having serious events. Presence of diabetes mellitus (OR 2.78)) had a significant impact on death in COVID 19 patients with a p-value 0.004. Conclusions: Presence of medical comorbidities in COVID-19 leads to higher risk of developing serious events i.e. ICU admission, mechanical intubation and mortality. The presence of Diabetes mellitus has a significant impact on mortality rate in COVID-19 patients.
Pathogenic bacteria scavenge ferric iron from the host for survival and proliferation using smallmolecular chelators, siderophores. Here, we introduce and assess the gallium(III) complex of ciprofloxacin-functionalized desferrichrome (D2) as a potential therapeutic for bacterial infection using an in vitro assay and radiochemical, tracer-based approach. Ga-D2 exhibits a minimum inhibitory concentration of 0.23 μM in Escherichia coli, in line with the parent fluoroquinolone antibiotic. Competitive and mutant strain assays show that Ga-D2 relies on FhuA-mediated transport for internalization. Ga-D2 is potent against Pseudomonas aeruginosa (3.8 μM), Staphylococcus aureus (0.94 μM), and Klebsiella pneumoniae (12.5 μM), while Fe-D2 is inactive in these strains. Radiochemical experiments with E. coli reveal that 67 Ga-D2 is taken up more efficiently than 67 Ga-citrate. In naive mice, 67 Ga-D2 clears renally and is excreted 13% intact in the urine. These pharmacokinetic and bacterial growth inhibitory properties qualify Ga-D2 for future investigations as a diagnosis and treatment tool for infection.
Background and aimsbackground Currently there is limited knowledge on cancer and COVID-19; we conducted a systematic review and meta-analysis to evaluate the impact of cancer on serious events including ICU admission rate and mortality in COVID 19. Methods PubMed, Cochrane Central Register of Clinical Trials were searched on April 16, 2020, to extract published articles that reported the outcomes of cancer in COVID-19 patients. The search terms were “coronavirus” and “clinical characteristics” with no language or time restrictions. We identified 512 published results and 13 studies were included in the analysis. Results There were 3775 patients, of whom 63 (1·66%) had a cancer. The pooled estimates of ICU admission in COVID 19 patients with and without cancer were 40% versus 8·42%.The odds ratio of ICU admission rates between the cancer and non-cancer groups was 2.88 with a 95% CI of 1·18 to 7·01 (p = 0·026). The pooled estimates of death rate in COVID -19 patients with and without cancer were 20·83% versus 7·82%. The odds ratio of death rates between the cancer and non-cancer groups was 2.25 with a 95% CI ranging from 0·71 to 7·10 with p value of 0·166. The pooled prevalence of cancer patients was 2% (95 CI 1–4). Conclusions Presence of cancer in COVID-19 leads to higher risk of developing serious events i.e. ICU admission, mechanical ventilation and mortality. The presence of cancer has a significant impact on mortality rate in COVID-19 patients.
Background: Inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6i) are widely used as first-line therapy for hormone receptor–positive metastatic breast cancer (HR+ MBC). Although abemaciclib monotherapy is also FDA-approved for treatment of disease progression on endocrine therapy, there is limited insight into the clinical activity of abemaciclib after progression on prior CDK4/6i. Patients and Methods: We identified patients with HR+ MBC from 6 cancer centers in the United States who received abemaciclib after disease progression on prior CDK4/6i, and abstracted clinical features, outcomes, toxicity, and predictive biomarkers. Results: In the multicenter cohort, abemaciclib was well tolerated after a prior course of CDK4/6i (palbociclib)-based therapy; a minority of patients discontinued abemaciclib because of toxicity without progression (9.2%). After progression on palbociclib, most patients (71.3%) received nonsequential therapy with abemaciclib (with ≥1 intervening non-CDK4/6i regimens), with most receiving abemaciclib with an antiestrogen agent (fulvestrant, 47.1%; aromatase inhibitor, 27.6%), and the remainder receiving abemaciclib monotherapy (19.5%). Median progression-free survival for abemaciclib in this population was 5.3 months and median overall survival was 17.2 months, notably similar to results obtained in the MONARCH-1 study of abemaciclib monotherapy in heavily pretreated HR+/HER2-negative CDK4/6i-naïve patients. A total of 36.8% of patients received abemaciclib for ≥6 months. There was no relationship between the duration of clinical benefit while on palbociclib and the subsequent duration of treatment with abemaciclib. RB1, ERBB2, and CCNE1 alterations were noted among patients with rapid progression on abemaciclib. Conclusions: A subset of patients with HR+ MBC continue to derive clinical benefit from abemaciclib after progression on prior palbociclib. These results highlight the need for future studies to confirm molecular predictors of cross-resistance to CDK4/6i therapy and to better characterize the utility of abemaciclib after disease progression on prior CDK4/6i.
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