The effect of antifibrotic agents on acute respiratory failure in COVID-19 patients: a retrospective cohort study from TriNetX US collaborative networks.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on global health and economies, resulting in millions of infections and deaths. This retrospective cohort study aimed to investigate the effect of antifibrotic agents (nintedanib and pirfenidone) on 1-year mortality in COVID-19 patients with acute respiratory failure. METHODS: Data from 61 healthcare organizations in the TriNetX database were analyzed. Adult patients with COVID-19 and acute respiratory failure were included. Patients with a pre-existing diagnosis of idiopathic pulmonary fibrosis before their COVID-19 diagnosis were excluded. The study population was divided into an antifibrotic group and a control group. Propensity score matching was used to compare outcomes, and hazard ratios (HR) for 1-year mortality were calculated. RESULTS: The antifibrotic group exhibited a significantly lower 1-year mortality rate compared to the control group. The survival probability at the end of the study was 84.42% in the antifibrotic group and 69.87% in the control group. The Log-Rank test yielded a p-value of less than 0.001. The hazard ratio was 0.434 (95% CI: 0.264-0.712), indicating a significant reduction in 1-year mortality in the antifibrotic group. Subgroup analysis demonstrated significantly improved 1-year survival in patients receiving nintedanib treatment and during periods when the Wuhan strain was predominant. DISCUSSION: This study is the first to demonstrate a survival benefit of antifibrotic agents in COVID-19 patients with acute respiratory failure. Further research and clinical trials are needed to confirm the efficacy of these antifibrotic agents in the context of COVID-19 and acute respiratory failure.

HPLC/ESI-MS and NMR Analysis of Chemical Constitutes in Bioactive Extract from the Root Nodule of Vaccinium emarginatum.

Vaccinium emarginatum Hayata is a medicinal plant that has been historically used in ethnopharmacy to treat diseases in Taiwan. The objective of this study is to evaluate the anti-cancer and anti-bacterial constitutes from the root nodule extract of V. emarginatum. The chemical composition of V. emarginatum fractions was analyzed by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) and the chemical constitutes were isolated and structurally identified by nuclear magnetic resonance (NMR) spectroscopy. Bioassay-guided chromatography showed that the ethyl acetate (EA) fraction was bioactive on the hepatocellular carcinoma (HepG2). By LC-ESI-MS/MS analysis, twenty peaks of EA fraction were partially identified and the phytochemical investigation of the fractions led to the isolation and identification of protocatuchuic acid (1), epicatechin (2), catechin (3), procyanidin B3 (4), procyanidin A1 (5), hyperin (6), isoquercetin (7), quercetin (8), lupeol (9), beta-amyrin (10), and alpha-amyrin (11). Both procyanidin B3 and A1 exhibited anti-proliferative activity against HepG2 and gastric adenocarcinoma (AGS) cells at IC50 values between 38.4 and 41.1 µM and 79.4 and 83.8 µM, respectively. In addition, isoquercetin displayed the strongest anti-proliferative activity against the HepG2, lung carcinoma (A549), and AGS cell at 18.7, 24.6 and 68.5 µM, respectively. Among the triterpenoids, only lupeol showed the inhibitory activity against all tested tumor cell lines at IC50 values between 72.9 and 146.8 µM. Furthermore, procyanidins B3, A1 and isoquercetin displayed moderate anti-bacterial activity against Staphylococcus aureus. In conclusion, this study provides background information on the exploitation of V. emarginatum as a potential natural anti-cancer and anti-bacterial agent in pharmaceutical research.

Occult cancer and thromboembolism: current epidemiology and its practical implications.

Venous thromboembolism (VTE) may be the first presentation of malignancy. Up to 10% of patients with unprovoked VTE are diagnosed with occult cancer within 1 year. Cancer patients with concomitant VTE have a worse outcome. While limited screening strategy (thorough medical history, physical examination, basic laboratory tests, and chest X­ray) and extensive screening strategy (limited screening plus computed tomography scan of the abdomen/pelvis or 18F-fluorodeoxyglucose positron emission tomography-computed tomography) have a similar ability to detect early-stage cancer and improve morbidity and mortality of cancer patients with unprovoked VTE, the extensive screening strategy has been shown to diagnose occult cancer earlier. Among the risk factors for occult cancer in patients with unprovoked VTE, age is the most promising one. The risk of occult cancer detection increases with age. The newly developed RIETE score helps identify risk of occult cancer and might decrease unnecessary diagnostic procedures in lower-risk patients. Current guidelines suggest that patients with first unprovoked VTE undergo limited screening, with age- and sex-specific cancer screening, including colon, breast, cervical, and prostate cancers.

18F-FDG PET/CT in detection of gynecomastia in patients with hepatocellular carcinoma.

OBJECTIVE: We retrospectively investigate the prevalence of gynecomastia as false-positive 2-[18F]fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) imaging in patients with hepatocellular carcinoma (HCC). METHODS: Among the 127 male HCC patients who underwent 18F-FDG PET/CT scan, the 18FDG uptakes at the bilateral breasts in 9 patients with gynecomastia were recorded as standard uptake value (SUVmax) and the visual interpretation in both early and delayed images. RESULTS: The mean early SUVmax was 1.58/1.57 (right/left breast) in nine gynecomastia patients. The three patients with early visual score of 3 had higher early SUVmaxs. CONCLUSION: Gynecomastia is a possible cause of false-positive uptake on 18F-FDG PET/CT images.

Inhibitory effects of Rhenium-188-labeled Herceptin on prostate cancer cell growth: a possible radioimmunotherapy to prostate carcinoma.

PURPOSE: Herceptin is widely used in treating Her2-overexpressing breast cancer. However, the application of Herceptin in prostate cancer is still controversial. Our previous results have indicated the relevance of Her2 in the transition of the androgen requirement in prostate cancer cells. In this study, the effects of radioimmunotherapy against Her2 in prostate cancer were investigated. MATERIALS AND METHODS: DU145, an androgen receptor-negative prostate cancer cell line, was used in vitro and in vivo to evaluate the effects of Herceptin labeled with a beta emitter, Rhenium-188 (Re-188). Its effects on cell growth, extent of apoptosis, the bio-distribution of Re-188 labeled Herceptin (Re-H), and protein levels were determined. RESULTS: Treatments with Re-188 and Re-H reduced the proliferation of DU145 cells in dose- and time-dependent manners compared to the Herceptin-treated group. Growth inhibition and apoptosis were induced after Re-H treatment; growth inhibition was more distinct in cells with high Her2/p-Her2 levels. Our in vivo xenograft studies revealed that Re-H treatment significantly retarded tumor growth and altered the levels of apoptosis-related proteins. The bio-distribution of Re-H in mice demonstrated a tissue-specific pattern. Importantly, the levels of p35 protein, which is related to cancer cell survival and invasion, dramatically decreased after Re-H treatment. CONCLUSIONS: Our data demonstrate that Re-188-labeled Herceptin effectively inhibited the growth of DU145 cells compared to the Herceptin- and Re-188-treated cohorts. This implies that targeting Her2 by both radio- and immuno- therapy might be a potential strategy for treating patients with androgen-independent prostate cancer.

Meta-analysis of the diagnostic performance of [18F]FDG-PET and PET/CT in renal cell carcinoma.

OBJECTIVES: Positron emission tomography (PET) using fluorodeoxyglucose (FDG) is useful for restaging renal cell carcinoma (RCC) and detecting metastatic diseases but is less satisfactory for detecting primary disease. We evaluated whether the integration of computed tomography (CT) scans with the PET system could increase the applicability of FDG-PET for RCC. METHODS: The MEDLINE databases were searched for relevant studies published since 2001. Two reviewers independently assessed the methodological quality of each study identified. We then performed a meta-analysis of the sensitivity and specificity of FDG-PET findings as reported in all the selected studies. RESULTS: Fourteen studies were eligible for inclusion. The pooled sensitivity and specificity of FDG-PET were 62% and 88% respectively, for renal lesions. For detecting extra-renal lesions, the pooled sensitivity and specificity of FDG-PET were 79% and 90%, respectively, based on the scans, and 84% and 91% based on the lesions. The use of a hybrid FDG-PET/CT to detect extra-renal lesions increased the pooled sensitivity and specificity to 91% and 88%, respectively, with good consistency. CONCLUSIONS: For RCC, combining the FDG-PET and CT systems is helpful for detecting extra-renal metastasis rather than renal lesions. The hybrid PET/CT system has comparable sensitivity and specificity with PET in detecting extra-renal lesions of RCC. ADVANCES IN KNOWLEDGE: The FDG-PET and PET/CT systems are both useful for detecting extra-renal metastasis in renal cell carcinoma.