ABSTRACT
To quantify the clinical unmet need of r/r MCL patients who progress on a covalent Bruton tyrosine kinase inhibitor (BTKi), we conducted a systematic review to identify studies that reported overall survival (OS), progression-free survival (PFS), or response outcomes of patients who received a chemo(immunotherapy) ± targeted agent standard therapy (STx) or brexucabtagene autoleucel (brexu-cel) in the post-BTKi setting. Twenty-six studies (23 observational; three trials) reporting outcomes from 2005 to 2022 were included. Using two-stage frequentist meta-analyses, the estimated median PFS/OS for patients treated with an STx was 7.6 months (95% CI: 3.9-14.6) and 9.1 months (95% CI: 7.3-11.3), respectively. The estimated objective response rate (ORR) was 45% (95% CI: 34-57%). For patients treated with brexu-cel, the estimated median PFS/OS was 14.9 months (95% CI: 10.5-21.0) and 32.1 months (95% CI: 25.2-41.2), with a pooled ORR of 89% (95% CI: 86-91%). Our findings highlight a significant unmet need for patients whose disease progresses on a covalent BTKi.
ABSTRACT
Travel destinations, particularly large resorts in otherwise small communities, risk infectious disease outbreaks from an influx of visitors who may import infections during peak seasons. The COVID-19 pandemic highlighted this risk in the context of global travel and has raised questions about appropriate interventions to curb the potential spread of infectious disease at tourist destinations. In Colorado, the initial outbreaks of SARS-CoV-2 in the state occurred in ski communities, leading to large economic losses from closures and visitor restrictions. In this study, we modeled SARS-CoV-2 transmission during the 2020-21 season in a ski region of Colorado to determine optimal combinations of intervention strategies that would keep the region below a predetermined threshold of SARS-CoV-2 infection density. This analysis used an age-stratified, deterministic SEIR compartmental model of disease transmission, calibrated to cellphone-based mobility data, to simulate infection trajectories during the winter ski season. Under three national infection levels corresponding to high, medium, and low viral importation risk, we estimated the potential impact of interventions including policy and behavior changes, visitor restriction strategies, and case investigation/contact tracing, in order to quantify the relative and absolute impacts of these interventions in the context of the COVID-19 pandemic. Our results suggest that, in the context of low viral importation risk, case investigation/contact tracing and policy and behavior changes may be sufficient to stay below predetermined infection thresholds without visitor restrictions. However, if viral importation risk is high, visitor restrictions and/or screening for infected visitors would be needed to avoid lockdown-like control scenarios and large outbreaks in tourist communities. These findings provide important guidance to tourist destinations for balancing policy impact in future infectious disease outbreaks.
ABSTRACT
Sperm identification and selection is an essential task when processing human testicular samples for in vitro fertilization. Locating and identifying sperm cell(s) in human testicular biopsy samples is labor intensive and time consuming. We developed a new computer-aided sperm analysis (CASA) system, which utilizes deep learning for near human-level performance on testicular sperm extraction (TESE), trained on a custom dataset. The system automates the identification of sperm in testicular biopsy samples. A dataset of 702 de-identified images from testicular biopsy samples of 30 patients was collected. Each image was normalized and passed through glare filters and diffraction correction. The data were split 80%, 10%, and 10% into training, validation, and test sets, respectively. Then, a deep object detection network, composed of a feature extraction network and object detection network, was trained on this dataset. The model was benchmarked against embryologists' performance on the detection task. Our deep learning CASA system achieved a mean average precision (mAP) of 0.741, with an average recall (AR) of 0.376 on our dataset. Our proposed method can work in real time; its speed is effectively limited only by the imaging speed of the microscope. Our results indicate that deep learning-based technologies can improve the efficiency of finding sperm in testicular biopsy samples.
ABSTRACT
As coronavirus disease 2019 (COVID-19) outbreak, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), started in China in January, 2020, repurposing approved drugs is emerging as important therapeutic options. We reported here the first clinical study using hepatitis C virus (HCV) protease inhibitor, danoprevir, to treat COVID-19 patients. Danoprevir (Ganovo(R)) is a potent HCV protease (NS3/4A) inhibitor (IC50 = 0.29 nM), which was approved and marketed in China since 2018 to treat chronic hepatitis C patients. Ritonavir is a CYP3A4 inhibitor to enhance plasma concentration of danoprevir while it also acts as a human immunodeficiency virus (HIV) protease inhibitor at high doses. The chymotrypsin-like protease of SARS-CoV-2 shares structure similarity with HCV and HIV proteases. In the current clinical study (NCT04291729) conducted at the Nineth Hospital of Nanchang, we evaluated therapeutic effects of danoprevir, boosted by ritonavir, on treatment naive and experienced COVID-19 patients. The data from this small-sample clinical study showed that danoprevir boosted by ritonavir is safe and well tolerated in all patients. After 4 to 12-day treatment of danoprevir boosted by ritonavir, all eleven patients enrolled, two naive and nine experienced, were discharged from the hospital as they met all four conditions as follows: (1) normal body temperature for at least 3 days; (2) significantly improved respiratory symptoms; (3) lung imaging shows obvious absorption and recovery of acute exudative lesion; and (4) two consecutive RT-PCR negative tests of SARS-CoV-2 nucleotide acid (respiratory track sampling with interval at least one day). Our findings suggest that repurposing danoprevir for COVID-19 is a promising therapeutic option.
ABSTRACT
BACKGROUND: In 2018, diagnosis-related group-based prospective payment system (DRG-PPS) was implemented nationwide by China that did not fully consider the additional costs caused by healthcare-associated infections (HAIs). HAIs can increase hospitalization costs, but only a few studies have been conducted in China. We aimed to assess the additional costs caused by HAIs. METHODS: A retrospective matched case-control (1:1) study was performed in one of the largest tertiary hospitals in Sichuan Province, China. A multiple linear regression was used to identify confounding factors, and the propensity score matching (PSM) method was used to balance confounding factors between cases and controls. On this basis, we estimated the additional costs caused by HAIs. RESULTS: Of the 109,294 inpatients observed, 1912 had HAI. After the PSM method was implemented, 1686 cases were successfully matched. Median hospitalization costs were 5613.03 for patients with HAIs and 3414.83 for patients without HAIs (P < 0.001), resulting in an absolute difference of 2198.19. With the exception of pathological diagnosis costs, surgical treatment costs and disposable medical material costs for surgery, all other types of costs for the cases with HAIs were larger. CONCLUSIONS: Patients with HAIs incurred greater hospitalization costs than non-HAI patients, which warrants closer attention if we are to reform the payment method of medical insurance in China.
Subject(s)
Cross Infection/economics , Hospital Costs , Hospitalization/economics , Adult , Aged , Aged, 80 and over , Case-Control Studies , China , Cross Infection/diagnosis , Female , Health Expenditures , Hospitalization/statistics & numerical data , Humans , Length of Stay , Male , Middle Aged , Propensity Score , Retrospective Studies , Tertiary Care CentersABSTRACT
There is no national referral criteria for burns in China till now, which brings inconvenience and confusion. Based on the oversea experiences and the actual situation in China, many famous experts on burns discussed and developed this Chinese burn referral criteria (2018 version). We hope these referral criteria will be helpful in clinical practice in burn field and can be improved continuously during application.
