There is an urgent need for an oral drug for the treatment of mild to moderate outpatient SARS-CoV-2. Our preclinical and clinical study’s aim was to determine the safety and preliminary efficacy of oral TQ Formula (TQF), in the treatment of outpatient SARS-CoV-2. In a double-blind, placebo-controlled phase 2 trial, we randomly assigned (1:1 ratio) non-hospitalized, adult (>18 years), symptomatic SARS-CoV-2 patients to receive oral TQF or placebo. The primary endpoints were safety and the median time-to-sustained-clinical-response (SCR). SCR was 6 days in the TQF arm vs. 8 days in the placebo arm (p = 0.77), and 5 days in the TQF arm vs. 7.5 days in the placebo arm in the high-risk cohort, HR 1.55 (95% CI: 0.70, 3.43, p = 0.25). No significant difference was found in the rate of AEs (p = 0.16). TQF led to a significantly faster decline in the total symptom burden (TSB) (p < 0.001), and a significant increase in cytotoxic CD8+ (p = 0.042) and helper CD4+ (p = 0.042) central memory T lymphocytes. TQF exhibited an in vitro inhibitory effect on the entry of five SARS-CoV-2 variants. TQF was well-tolerated. While the median time-to-SCR did not reach statistical significance; it was shorter in the TQF arm and preclinical/clinical signals of TQF activity across multiple endpoints were significant. Therefore, a confirmatory study is planned.
Background and Aims:
Endoscopic full-thickness resection (eFTR) is a field of increasing interest that offers a minimally invasive resection modality for lesions that are not amenable for resection by conventional methods. Full-thickness resection device (FTRD) is a new device that was developed for a single-step eFTR using an over-the scope-clip. In this meta-analysis, we aim to assess the efficacy and safety of FTRD for eFTR of colorectal lesions.
Methods:
A Comprehensive literature review of different databases to identify studies reporting FTRD with outcomes of interest was performed. Studies with <10 cases were excluded. Rates of histologic complete resection (R0), technical success, and complications were extracted. Efficacy was assessed by using the technical and the R0 rates whereas safety was assessed by using the complications rates. Weighted pooled rates (WPRs) and the 95% confidence interval (CI) were calculated depending on the heterogeneity (I
2 statistics).
Results:
Nine studies including 551 patients with 555 lesions were included in this study. The WPR for overall R0 was 82.4% (95% CI: 79.0%-85.5%),with moderate heterogeneity (I
2=34.8%). The WPR rate for technical success was 89.25% (95% CI: 86.4%-91.7%), with low heterogeneity (I
2=23.7%). The WPR for total complications rate was 10.2% (7.8, 12.8%) with no heterogeneity. The pooled rate for minor bleeding, major bleeding, postpolypectomy syndrome, and perforation were 3.2%, 0.97%, 2.2%, and 1.2%, respectively. Of 44 periappendicular lesions, the pooled rate for acute appendicitis was 19.7%.
Conclusions:
FTRD seems to be effective and safe for eFTR of difficult colorectal lesions. Large prospective studies comparing FTRD with conventional resection techniques are warranted.
Pseudozyma spp are amorphic yeasts. They are commonly plant pathogens, but rarely cause invasive fungal disease in humans. Only three cases of central venous catheter (CVC)-associated blood stream infections due to this organism have been reported in the literature. Main underlying risk factors for Pseudozyma spp infection are bowel surgery, CVC and total parenteral nutrition. We present a rare case of Pseudozyma spp catheter-associated blood stream infection that was successfully treated with antifungal therapy and removal of CVC. It is important to recognise and differentiate this species from other yeasts as it may require the use of amphotericin B or voriconazole instead of fluconazole, to which the organism is variably resistant.
The life span of persons with HIV has been greatly extended over the past 30 years due to novel therapies. In the developed world and urban settings, this results in a lifespan rivaling the lifespan of a person without HIV. A retrospective study was conducted on 459 patients of an urban, academic medical center who died between 2005 and 2013 in a medium-sized US city. Using the established Cause of Death Project (CoDe) protocol, we measured multiple factors including comorbidities, risk behaviours, contributing and underlying causes of death. This study is one of the few US-based studies using this validated protocol. Among the deaths, 25.9% were sudden and 15.2% were unexpected. Almost one-fifth were related to AIDS-related infections; 47.5% related to non-AIDS causes; with the remainder unknown. Statistically significant increases in CD4 counts and decreasing viral loads were observed over the study period. There were no statistically significant differences observed by HIV risk behaviour, race, gender, age at death, or on antiretrovirals at death. In support of the existing literature, improved HIV management appears to reduce the AIDS-related attributable death among patients observed in this study.
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