Search

Background: Immune checkpoint inhibitors (ICIs) are currently the primary approach for managing NSCLC. However, numerous combination therapies are currently under investigation. Our goal is to investigate the overall efficacy and safety of ICIs and taxane-based chemotherapy., Methods: We conducted a systematic review and meta-analysis, searching web databases for relevant literature. We limited our eligibility to phase II/III randomized clinical trials involving advanced/metastatic NSCLC patients., Results: We performed a meta-analysis encompassing nineteen studies derived from sixteen RCTs. For patients with sq-NSCLC PD-L1 ≥ 50%, using ICIs plus taxane significantly improve PFS and OS with HR of 0.58 (95% CI, 0.45-0.74, p  < 0.0001) and 0.41 (95% CI, 0.33-0.50, p  < 0.00001), respectively. For patients with non-sq NSCLC PD-L1 1-49%, the analysis revealed significant improvement of OS and PFS with HR of 0.64 (95% CI, 0.47-0.88, p  = 0.005) and 0.62 (95% CI, 0.47-0.81, p  = 0.0004), respectively. For TRAEs of all grades, ICIs plus taxane resulted with no significant difference compared to control group with risk ratio (RR) 1.00 (95% CI 0.99-1.02)., Conclusion: The analysis revealed significant improvement in efficacy of ICIs with taxane in advanced/metastatic NSCLC patients compared with ICI/taxane monotherapy. Registration: PROSPERO (CRD42023447532).

Introduction: Our systematic review and meta-analysis aimed to evaluate the clinical efficacy and safety of Rucaparib, a PARP inhibitor (PARPi), in patients with ovarian cancer and BRCA mutation., Methods: Online databases were comprehensively searched for all phase III Randomized trials that used Rucaparib therapy for ovarian cancer patients and patients having BRCA mutation. Efficacy results are progression-free survival and overall response rate in addition to addressing its safety concerns., Results: After pooling data from 4 clinical trials, the analysis showed a significant improvement in PFS among ovarian cancer patients and for the maintenance therapy with a hazard ratio (HR) of 0.49 (95% CI 0.34-0.73, p  = 0.0003) and 0.42 (95% CI 0.29-0.62, p  < 0.0001), respectively. For patients with BRCA mutations, the PFS showed significant improvement with a (HR) of 0.42 (95% CI 0.25-0.71, p < 0.001). A difference was observed in the risk of grade ≥ 3 TEAEs between the two groups (RR = 2.48; 95% CI 1.40-4.37)., Conclusion: Rucaparib demonstrated significant efficacy in improving PFS and ORR in ovarian cancer patients, particularly those having BRCA mutations. However, they should be closely monitored due to the greater risk of various adverse effects.

Objective: To evaluate the clinical efficacy and safety of Capivasertib on patients with solid tumors., Methods: Data from four RCTs were pooled to create a systematic review and meta-analysis focusing on Capivasertib-treated patients with solid tumor. Progression-free survival (PFS) and adverse events (AE) were the primary outcomes., Results: A total of 540 individuals from four RCTs were included. The analysis showed that Capivasertib improved PFS for the ITT population with an HR of 0.75 (95% CI = 0.62-0.90, p = 0.002), whereas it did not show improvement in PFS of the PI3K/AKT/PTEN-altered group with an HR = 0.61 (95% CI = 0.32-1.16, p = 0.13). The analysis also showed that Capivasertib improved OS for the ITT population with an HR = 0.61 (95% CI = 0.47-0.78, p = 0.0001). For safety, four studies were included; statistical differences between Capivasertib and placebo were found in discontinuation of Capivasertib due to toxicity or AE (RR = 2.37, 95% CI = 1.37-4.10, p = 0.002)., Conclusion: Capivasertib plus chemotherapy or hormonal therapy combination has shown promising antitumor efficacy and promising safety profile in the treatment of individuals with solid tumor.

Introduction: We aimed to describe the clinical efficacy and safety of tislelizumab, a new (PD-1) inhibitor, in patients with malignant solid tumors., Methods: We searched relevant databases for phase III randomized controlled trials, including patients with solid tumors. The following outcomes are of interest: overall response rate (OS), overall survival (ORR), progression-free survival (PFS), disease control rate (DCR), and treatment-related adverse events (TRAE). We conducted subgroup analyses based on the line of therapy, type of solid tumor, and tislelizumab alone or combined with chemotherapy., Results: Seven phase III RCTs with 3478 were included in the meta-analysis. Pooled analysis demonstrated that tislelizumab significantly improved ORR and DCR with (OR) of 2.59 (95% (CI) = 2.15-3.12, p < 0.00001) and 1.78 (95% CI = 1.43-2.21, p > 0.00001), respectively. Pooled HRs for OS and PFS were 0.71 (95% CI = 0.65-0.78, p > 0.00001) and 0.68 (95% CI = 0.54-0.84, p = 0.0005), respectively., Conclusion: Overall, based on this meta-analysis, the available data strongly supports the utilization of tislelizumab in the treatment of malignant solid tumors., Prospero Registration Number: CRD42023408815.

Background: The prevalence of alcohol-associated liver disease (ALD), a subtype of fatty liver disease (FLD), continues to rise. ALD is a major cause of preventable death. Polychlorinated biphenyl (PCB) 126 is an environmentally relevant, dioxin-like pollutant whose negative metabolic effects have been well documented. In human and animal studies, PCB has been associated with the severity of nonalcoholic fatty liver disease (NAFLD). However, few studies have investigated whether exposures to environmental toxicants can worsen ALD. Thus, the objective of the current study was to develop an alcohol-plus-toxicant model to study how an environmental pollutant, PCB 126, impacts rodent ALD pathology., Methods: Briefly, male C57BL/6J mice were exposed to 0.2 mg/kg PCB 126 or corn oil vehicle four days prior to ethanol feeding using the chronic-binge (10-plus-one) model., Results: Concentrations of macromolecules, including hepatic lipids, carbohydrates, and protein (albumin) were impacted. Exposure to PCB 126 exacerbated hepatic steatosis and hepatomegaly in mice exposed to the chemical and fed an ethanol diet. Gene expression and the analysis of blood chemistry showed a potential net increase and retention of hepatic lipids and reductions in lipid oxidation and clearance capabilities. Depletion of glycogen and glucose was evident, which contributes to disease progression by generating systemic malnutrition. Granulocytic immune infiltrates were present but driven solely by ethanol feeding. Hepatic albumin gene expression and plasma levels were decreased by ~50% indicating a potential compromise of liver function. Finally, gene expression analyses indicated that the aryl hydrocarbon receptor and constitutive androstane receptor were activated by PCB 126 and ethanol, respectively., Conclusions: Various environmental toxicants are known to modify or enhance FLD in high-fat diet models. Findings from the present study suggest that they interact with other lifestyle factors such as alcohol consumption to reprogram intermediary metabolism resulting in exacerbated ethanol-associated systemic malnutrition in ALD., (© 2022 Research Society on Alcohol.)

The movement of the ferrous nanoparticles is random in the base fluid, and it will be homogeneous under the enforced magnetic field. This phenomenon shows a significant impact on the energy transmission process. In view of this, we inspected the stream and energy transport in magnetohydrodynamic dissipative ferro and hybrid ferrofluids by considering an uneven heat rise/fall and radiation effects. We studied the Fe 3 O 4 (magnetic oxide) and CoFe 2 O 4 (cobalt iron oxide) ferrous particles embedded in H 2 O-EG (ethylene glycol) (50-50%) mixture. The flow model is converted as ODEs with suitable similarities and resolved them using the 4th order Runge-Kutta scheme. The influence of related constraints on transport phenomena examined through graphical illustrations. Simultaneous solutions explored for both ferro and hybrid ferrofluid cases. It is found that the magnetic oxide and cobalt iron oxide suspended in H 2 O-EG (ethylene glycol) (50-50%) mixture effectively reduces the heat transfer rate under specific conditions.

This report presents the flow and heat transfer characteristics of MHD micropolar fluid due to the stretching of a surface with second order velocity slip. The influence of nonlinear radiation and irregular heat source/sink are anticipated. Simultaneous solutions are presented for first and second-order velocity slips. The PDEs which govern the flow have been transformed as ODEs by the choice of suitable similarity transformations. The transformed nonlinear ODEs are converted into linear by shooting method then solved numerically by fourth-order Runge-Kutta method. Graphs are drowned to discern the effect of varied nondimensional parameters on the flow fields (velocity, microrotation, and temperature). Along with them the coefficients of Skin friction, couple stress, and local Nussel number are also anticipated and portrayed with the support of the table. The results unveil that the non-uniform heat source/sink and non-linear radiation parameters plays a key role in the heat transfer performance. Also, second-order slip velocity causes strengthen in the distribution of velocity but a reduction in the distribution of temperature is perceived.

Theoretical analysis has been carried out to establish the heat transport phenomenon of six different ferromagnetic MnZnFe2O4-C2H6O2 (manganese zinc ferrite-ethylene glycol), NiZnFe2O4-C2H6O2 (Nickel zinc ferrite-ethylene glycol), Fe2O4-C2H6O2 (magnetite ferrite-ethylene glycol), NiZnFe2O4-H2O (Nickel zinc ferrite-water), MnZnFe2O4-H2O (manganese zinc ferrite-water), and Fe2O4-H2O (magnetite ferrite-water) nanofluids containing manganese zinc ferrite, Nickel zinc ferrite, and magnetite ferrite nanoparticles dispersed in a base fluid of ethylene glycol and water mixture. The performance of convective heat transfer is elevated in boundary layer flow region via nanoparticles. Magnetic dipole in presence of ferrites nanoparticles plays a vital role in controlling the thermal and momentum boundary layers. In perspective of this, the impacts of magnetic dipole on the nano boundary layer, steady, and laminar flow of incompressible ferromagnetic nanofluids are analyzed in the present study. Flow is caused by linear stretching of the surface. Fourier's law of heat conduction is used in the evaluation of heat flux. Impacts of emerging parameters on the magneto-thermomechanical coupling are analyzed numerically. Further, it is evident that Newtonian heating has increasing behavior on the rate of heat transfer in the boundary layer. Comparison with available results for specific cases show an excellent agreement.

We discuss a 48-year old, who presented with upper epigastrium pain associated with early satiety and significant weight loss. Physical examination revealed a thickening and darkening of skins around the skin folds, scalp, back and front of abdomen. A diagnosis of gastro-esophageal junction adenocarcinoma was confirmed by oesophagogastroduodenoscopy (OGDS) and biopsy. The biopsy of the skin lesion revealed a diagnosis of acanthosis nigricans, He underwent a total gastrectomy followed by adjuvant chemo-radiotherapy. Recovery is unremarkable. Interestingly, the skin lesions disappear following our therapy. We believe this may be attributed to the treatment of the malignancy. We highlight the interesting association, pathophysiology and therapy.