Construction of prognostic markers for pancreatic adenocarcinoma based on mitochondrial fusion-related genes.

Early detection of pancreatic adenocarcinoma (PAAD) remains a pressing clinical problem. Information on the clinical prognostic value of mitochondrial fusion-related genes in PAAD remains limited. In this study, we investigated mitochondrial fusion-related genes of PAAD to establish an optimal signature plate for the early diagnosis and prognosis of PAAD. The cancer genome atlas database was used to integrate the Fragments Per Kilobase Million data and related clinical data for patients with PAAD. Least absolute shrinkage and selection operator regression, cox regression, operating characteristic curves, and cBioPortal database was used to evaluate model performance, assess the prognostic ability and sensitivity. The levels of immune infiltration were compared by CIBERSORT, QUANTISEQ, and EPIC. Chemotherapy sensitivity between the different risk groups was compared by the Genomics of Drug Sensitivity in Cancer database and the "pRRophetic" R package. At last, a total of 4 genes were enrolled in multivariate Cox regression analysis. The risk-predictive signature was constructed as: (0.5438 × BAK1) + (-1.0259 × MIGA2) + (1.1140 × PARL) + (-0.4300 × PLD6). The area under curve of these 4 genes was 0.89. Cox regression analyses indicates the signature was an independent prognostic indicator (P < .001, hazard ratio [HR] = 1.870, 95% CI = 1.568-2.232). Different levels of immune cell infiltration in the 2 risk groups were observed using the 3 algorithms, with tumor mutation load (P = .0063), tumor microenvironment score (P = .01), and Tumor Immune Dysfunction and Exclusion score (P = .0012). The chemotherapeutic sensitivity analysis also revealed that the half-maximal inhibitory concentration of 5-fluorouracil (P = .0127), cisplatin (P = .0099), docetaxel (P < .0001), gemcitabine (P = .0047), and pacilataxel (P < .0001) were lower in the high-risk groups, indicating that the high-risk group patients had a greater sensitivity to chemotherapy. In conclude, we established a gene signature plate comprised of 4 mitochondrial fusion related genes to facilitate early diagnosis and prognostic prediction of PAAD.

Pharmacovigilance study of GLP-1 receptor agonists for metabolic and nutritional adverse events.

Aims: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are employed extensively in the management of type 2 diabetes and obesity. However, there is a paucity of real-world data on their safety and tolerability for metabolic and nutritional adverse events in large sample populations. This study aimed to analyse the metabolic and nutritional safety signatures of different GLP-1 RAs by exploring the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Methods: AEs data were extracted from the FDA Adverse Event Reporting System database for each GLP-1 RA from the time of its launch until the second quarter of 2023. The reported odds ratio (ROR), proportional reporting ratio (PRR), Empirical Bayesian Geometric Mean and Bayesian Confidence Propagation Neural Network were employed to identify AE signals. Results: A system organ class of metabolism and nutrition disorders was employed to filter AE reports, resulting in the identification of 10,450 reports for exenatide, 2,860 reports for liraglutide, 240 reports for albiglutide, 4,847 reports for dulaglutide, 2,905 reports for semaglutide, 1,089 reports for tirzepatide, and 13 reports for lixisenatide. Semaglutide (ROR, 3.34; 95%CI, 3.22), liraglutide (ROR, 2.78; 95%CI, 2.69), and exenatide (ROR, 2.15; 95%CI, 2.11) were associated with metabolism and nutrition disorders. The number of AE signals detected were as follows: albiglutide (n = 1), lixisenatide (n = 2), tirzepatide (n = 11), exenatide (n = 12), liraglutide (n = 16), semaglutide (n = 20), dulaglutide (n = 22). Dehydration was the most frequent AE contributing to serious outcomes for liraglutide (n = 318, 23.93%), dulaglutide (n = 434, 20.90%), semaglutide (n = 370, 25.10%) and tirzepatide (n = 70, 32.86%). The time to onset (TTO) of AE was statistically different between exenatide and the other GLP-1 RAs (p < 0.001), and the Weibull parameters for dehydration for liraglutide, dulaglutide, and semaglutide analyses all showed an early failure-type profile. Conclusion: Our study suggests that exenatide, liraglutide, and semaglutide are more susceptible to metabolic and nutritional AEs than other GLP-1 RAs. Liraglutide, dulaglutide, semaglutide, and tirzepaptide's potential to induce dehydration, necessitates special attention. Despite certain deficiencies, GLP-1 RAs have considerable potential for the treatment of eating disorders.

BNIP3-mediated mitophagy boosts the competitive growth of Lenvatinib-resistant cells via energy metabolism reprogramming in HCC.

An increasing evidence supports that cell competition, a vital selection and quality control mechanism in multicellular organisms, is involved in tumorigenesis and development; however, the mechanistic contributions to the association between cell competition and tumor drug resistance remain ill-defined. In our study, based on a contructed lenvitinib-resistant hepatocellular carcinoma (HCC) cells display obvious competitive growth dominance over sensitive cells through reprogramming energy metabolism. Mechanistically, the hyperactivation of BCL2 interacting protein3 (BNIP3) -mediated mitophagy in lenvatinib-resistant HCC cells promotes glycolytic flux via shifting energy production from mitochondrial oxidative phosphorylation to glycolysis, by regulating AMP-activated protein kinase (AMPK) -enolase 2 (ENO2) signaling, which perpetually maintaining lenvatinib-resistant HCC cells' competitive advantage over sensitive HCC cells. Of note, BNIP3 inhibition significantly sensitized the anti-tumor efficacy of lenvatinib in HCC. Our findings emphasize a vital role for BNIP3-AMPK-ENO2 signaling in maintaining the competitive outcome of lenvitinib-resistant HCC cells via regulating energy metabolism reprogramming; meanwhile, this work recognizes BNIP3 as a promising target to overcome HCC drug resistance.

Mendelian randomization supports causality between COVID-19 and glaucoma.

To determine whether there is a causal relationship between Corona Virus Disease 2019 (COVID-19) and glaucoma, a 2-sample Mendelian Randomization (MR) design was applied with the main analysis method of inverse-variance-weighted. The reliability of the results was checked using the heterogeneity test, pleiotropy test, and leave-one-out method. Four sets of instrumental variables (IVs) were used to investigate the causality between COVID-19 and glaucoma risk according to data from the IEU Genome Wide Association Study (GWAS). The results showed that 2 sets of COVID-19(RELEASE) were significantly associated with the risk of glaucoma [ID: ebi-a-GCST011071, OR (95% CI) = 1.227 (1.076-1.400), P = .002259; ID: ebi-a-GCST011073: OR (95% CI) = 1.164 (1.022-1.327), P = .022450; 2 sets of COVID-19 hospitalizations were significantly associated with the risk of glaucoma (ID: ebi-a-GCST011081, OR (95% CI) = 1.156 (1.033-1.292), P = .011342; ID: ebi-a-GCST011082: OR (95% CI) = 1.097 (1.007-1.196), P = .034908)]. The sensitivity of the results was acceptable (P > .05) for the 3 test methods. In conclusion, this MR analysis provides preliminary evidence of a potential causal relationship between COVID-19 and glaucoma.

Association between the gut microbiota and diabetic nephropathy: a two-sample Mendelian randomization study.

Numerous studies have revealed a correlation between the risk of developing diabetic nephropathy (DN) and the gut microbiota (GM) composition. However, it remains uncertain whether the GM composition causes DN. We aimed to explore any potential causal links between the GM composition and the risk of developing DN. A meta-analysis conducted by the MiBioGen consortium of the largest genome-wide association study (GWAS) provided aggregated data on the GM. DN data were obtained from the IEU database. The inverse-variance weighting (IVW) method was employed as the primary analytical approach. The IVW analysis indicated that genus Dialister (OR = 0.51, 95% CI: 0.34-0.77, p = 0.00118) was protective against DN. In addition, class Gammaproteobacteria (OR = 0.47, 95% CI: 0.27-0.83, p = 0.0096), class Lentisphaeria (OR =0.76, 95% CI: 0.68-0.99, p = 0.04), order Victivallales (OR = 0.76, 95% CI: 0.58-0.99, p = 0.04), and phylum Proteobacteria (OR = 0.53, 95% CI: 0.33-0.85, p = 0.00872) were negatively associated with the risk of developing DN. Genus LachnospiraceaeUCG008 (OR =1.45, 95% CI: 1.08-1.95, p = 0.01), order Bacteroidales (OR = 1.59, 95% CI: 1.02-2.49, p = 0.04), and genus Terrisporobacter (OR = 1.98, 95% CI: 1.14-3.45, p = 0.015) were positively associated with the risk of developing DN. In this study, we established a causal relationship between the genus Dialister and the risk of developing DN. Further trials are required to confirm the protective effects of probiotics on DN and to elucidate the precise protective mechanisms involving genus Dialister and DN.

Molecular Basis of the Granular Characteristics of Small-Granule Starch: A Comparative Study.

Small-granule starches (SGSs) have technological advantages over starches of conventional sizes for many applications. The study compared the granular characteristics of three SGSs (from amaranth, quinoa, and taro) with those of maize and potato starches and revealed their molecular basis. The results indicated that the supramolecular architecture of starch granules was not necessarily correlated with granule size. Acid hydrolysis of amaranth and quinoa starches was fast due to not only their small granule sizes but also the defects in the supramolecular structure, to which short external and internal chain lengths of amaranth and quinoa amylopectins contributed. By comparison, the granular architecture of taro starch granules was more stable partly due to the longer external chain length of taro amylopectin. Comparison of the molecular composition of branched subunits (released by using α-amylase of Bacillus amyloliquefaciens) in amylopectins and that in lintnerized starches suggested a significant heterogeneous degradation of amaranth and quinoa starches at supramolecular levels.

Emerging therapies: Potential roles of SGLT2 inhibitors in the management of pulmonary hypertension.

Pulmonary hypertension (PH) is a pathophysiological disorder that may involve multiple clinical conditions and may be associated with a variety of cardiovascular and respiratory diseases. Pulmonary hypertension due to left heart disease (PH-LHD) currently lacks targeted therapies, while Pulmonary arterial hypertension (PAH), despite approved treatments, carries considerable residual risk. Metabolic dysfunction has been linked to the pathogenesis and prognosis of PH through various studies, with emerging metabolic agents offering a potential avenue for improving patient outcomes. Sodium-glucose cotransporter 2 inhibitor (SGLT-2i), a novel hypoglycemic agent, could ameliorate metabolic dysfunction and exert cardioprotective effects. Recent small-scale studies suggest SGLT-2i treatment may improve pulmonary artery pressure in patients with PH-LHD, and the PAH animal model shows that SGLT-2i can reduce pulmonary vascular remodeling and prevent progression in PAH, suggesting potential benefits for patients with PH-LHD and perhaps PAH. This review aims to succinctly review PH's pathophysiology, and the connection between metabolic dysfunction and PH, and investigate the prospective mechanisms of action of SGLT-2i in PH-LHD and PAH management.

Identification of Fasudil as a collaborator to promote the anti-tumor effect of lenvatinib in hepatocellular carcinoma by inhibiting GLI2-mediated hedgehog signaling pathway.

Lenvatinib is a frontline tyrosine kinase inhibitor for patients with advanced hepatocellular carcinoma (HCC). However, just 25% of patients benefit from the treatment, and acquired resistance always develops. To date, there are neither effective medications to combat lenvatinib resistance nor accurate markers that might predict how well a patient would respond to the lenvatinib treatment. Thus, novel strategies to recognize and deal with lenvatinib resistance are desperately needed. In the current study, a robust Lenvatinib Resistance index (LRi) model to predict lenvatinib response status in HCC was first established. Subsequently, five candidate drugs (Mercaptopurine, AACOCF3, NU1025, Fasudil, and Exisulind) that were capable of reversing lenvatinib resistance signature were initially selected by performing the connectivity map (CMap) analysis, and fasudil finally stood out by conducting a series of cellular functional assays in vitro and xenograft mouse model. Transcriptomics revealed that the co-administration of lenvatinib and fasudil overcame lenvatinib resistance by remodeling the hedgehog signaling pathway. Mechanistically, the feedback activation of EGFR by lenvatinib led to the activation of the GLI2-ABCC1 pathway, which supported the HCC cell's survival and proliferation. Notably, co-administration of lenvatinib and fasudil significantly inhibited IHH, the upstream switch of the hedgehog pathway, to counteract GLI2 activation and finally enhance the effectiveness of lenvatinib. These findings elucidated a novel EGFR-mediated mechanism of lenvatinib resistance and provided a practical approach to overcoming drug resistance in HCC through meaningful drug repurposing strategies.

HSP90a promotes the resistance to oxaliplatin in HCC through regulating IDH1-induced cell competition.

Though burgeoning research manifests that cell competition, an essential selection and quality control mechanism for maintaining tissue or organ growth and homeostasis in multicellular organisms, is closely related to tumorigenesis and development, the mechanism of cell competition associated with tumor drug resistance remains elusive. In the study, we uncovered that oxaliplatin-resistant hepatocellular carcinoma (HCC) cells exhibit a pronounced competitive advantage against their sensitive counterparts, which is related to lipid takeover of resistant cells from sensitive cells. Of note, such lipid takeover is dependent on the existence of isocitrate dehydrogenase 1 (IDH1) in resistant HCC cells. Mechanistically, IDH1 activity is regulated by heat shock protein 90 alpha (HSP90α) through binding with each other, which orchestrates the expressions of lipid metabolic enzymes and lipid accumulation in resistant HCC cells. Our results suggest that HCC cell competition-driven chemoresistance can be regulated by HSP90α/IDH1-mediated lipid metabolism, which may serve as a promising target for overcoming drug resistance in HCC.

Senescence risk score: a multifaceted prognostic tool predicting outcomes, stemness, and immune responses in colorectal cancer.

Colorectal cancer (CRC) remains a primary cause of cancer mortality globally, necessitating precise prognostic indicators for effective clinical management. Our study introduces the Senescence Risk Score (SRRS), based on several senescence-related genes (SRGs), a potent prognostic tool designed to measure cellular senescence in CRC. The higher SRRS predicts a poorer prognosis, providing a novel and efficient approach to patient stratification. Notably, we found that SRRS correlates with methylation and mutation variations, and increased immune infiltration in the tumor microenvironment, thus revealing potential therapeutic targets. We also discovered an inverse relationship between SRRS and cell stemness, which could have significant implications for cancer treatment strategies. Utilizing bioinformatics resources and machine learning, we identified LIMK1 and WRN as key genes associated with SRRS, further enhancing its prognostic value. Importantly, the modulation of these genes significantly impacts cellular senescence, proliferation, and stemness in CRC cells. In summary, our development of SRRS offers a powerful tool for CRC prognosis and paves the way for novel therapeutic strategies, underscoring its potential in transforming CRC patient management.

Clinical features and risk factors analysis for poor outcomes of severe community-acquired pneumonia in children: a nomogram prediction model.

Background: Pneumonia remains the leading cause of death among children aged 1-59 months. The early prediction of poor outcomes (PO) is of critical concern. This study aimed to explore the risk factors relating to PO in severe community-acquired pneumonia (SCAP) and build a PO-predictive nomogram model for children with SCAP. Methods: We retrospectively identified 300 Chinese pediatric patients diagnosed with SCAP who were hospitalized in the Affiliated Hospital of Southwest Medical University from August 1, 2018, to October 31, 2021. Children were divided into the PO and the non-PO groups. The occurrence of PO was designated as the dependent variable. Univariate and multivariate logistic regression analyses were used to identify the risk factors of PO. A nomogram model was constructed from the multivariate logistic regression analysis and internally validated for model discrimination and calibration. The performance of the nomogram was estimated using the concordance index (C-index). Results: According to the efficacy evaluation criteria, 56 of 300 children demonstrated PO. The multivariate logistic regression analysis resulted in the following independent risk factors for PO: co-morbidity (OR: 8.032, 95% CI: 3.556-18.140, P < 0.0001), requiring invasive mechanical ventilation (IMV) (OR: 7.081, 95% CI: 2.250-22.282, P = 0.001), and ALB < 35 g/L (OR: 3.203, 95% CI: 1.151-8.912, P = 0.026). Results of the internal validation confirmed that the model provided good discrimination (concordance index [C-index], 0.876 [95% CI: 0.828-0.925]). The calibration plots in the nomogram model were of high quality. Conclusion: The nomogram facilitated accurate prediction of PO in children diagnosed with SCAP and could be helpful for clinical decision-making.

Adherence to Antiretrovirals and HIV Viral Suppression Under COVID-19 Pandemic Interruption - Findings from a Randomized Clinical Trial Using Ingestible Sensors to Monitor Adherence.

The COVID-19 pandemic had a significant impact on vulnerable populations, including people living with HIV. California implemented a coronavirus lockdown (stay-at-home order) in March 2020, which ended in January 2021. We evaluated the pandemic's impact on both clinical outcomes of HIV RNA viral load (VL) and retention rate in a randomized clinical trial conducted from May 2018 to October 2020. The intervention group took co-encapsulated antiretrovirals (ARVs) with ingestible sensor (IS) pills from baseline through week 16. The IS system has the capacity to monitor adherence in real-time using a sensor patch, a mobile device, and supporting software. Both the IS and usual care (UC) groups were followed monthly for 28 weeks. Longitudinal mixed-effects models with random intercept and slope (RIAS) were used to fit log VL and self-reported adherence. The sample size of the study was 112 (54 in IS). Overall, the retention rate at week 28 was 86%, with 90% before the lockdown and 83% after the lockdown. The lockdown strengthened the associations between adherence and VL. Before the lockdown, a 10% increase in adherence was associated with a 0.2 unit decrease in log VL (ß = -1.88, p = 0.004), while during the lockdown, the association was a 0.41-unit decrease (ß = -2.27, p = 0.03). The pandemic did not have a significant impact on our adherence-focused intervention. Our findings regarding the intervention effect remain valid. TRIAL REGISTRATION NUMBER: NCT02797262. Date registration: September 2015.

A profile of SGLT-2 inhibitors in hyponatremia: The evidence to date.

Hyponatremia is the most common electrolyte disorder in clinical practice, which may lead to life-threatening complications. Several lines of evidence suggest that hyponatremia is associated not only with significant increases in length of stay, cost, and financial burden, but also with increased morbidity and mortality. Hyponatremia is also considered to be a negative prognostic factor in patients with heart failure and cancer. Although multiple therapeutic methods are available for treating hyponatremia, most have some limitations, such as poor compliance, rapid correction of serum Na+, other negative side effects and high cost. Given these limitations, identifying novel therapies for hyponatremia is essential. Recent clinical studies have shown that SGLT-2 inhibitors (SGLT 2i) significantly increased serum Na+ levels and were well tolerated by patients who underwent this treatment. Therefore, oral administration of SGLT 2i appears to be an effective treatment for hyponatremia. This article will briefly review the etiology of hyponatremia and integrated control of sodium within the kidney, current therapies for hyponatremia, potential mechanisms and efficacy of SGLT 2i for hyponatremia, and the benefits in cardiovascular, cancer, and kidney disease by regulating sodium and water balance.

Butyrate and obesity: Current research status and future prospect.

Over the past few decades, increasing prevalence of obesity caused an enormous medical, social, and economic burden. As the sixth most important risk factor contributing to the overall burden of disease worldwide, obesity not only directly harms the human body, but also leads to many chronic diseases such as diabetes, cardiovascular diseases (CVD), nonalcoholic fatty liver disease (NAFLD), and mental illness. Weight loss is still one of the most effective strategies against obesity and related disorders. Recently, the link between intestinal microflora and metabolic health has been constantly established. Butyrate, a four-carbon short-chain fatty acid, is a major metabolite of the gut microbiota that has many beneficial effects on metabolic health. The anti-obesity activity of butyrate has been demonstrated, but its mechanisms of action have not been fully described. This review summarizes current knowledge of butyrate, including its production, absorption, distribution, metabolism, and the effect and mechanisms involved in weight loss and obesity-related diseases. The aim was to contribute to and advance our understanding of butyrate and its role in obesity. Further exploration of butyrate and its pathway may help to identify new anti-obesity.

Chemical analysis of selected harmful and potentially harmful constituents and in vitro toxicological evaluation of leading flavoured e-cigarette aerosols in the Chinese market.

Use of electronic cigarettes (e-cigarettes) has increased significantly over the past decade due to consumer perception that these products represent a less risky alternative to combustible cigarettes. E-liquids generally contain a simple mix of vegetable glycerin, propylene glycerol, nicotine, organic acids, and flavourings. Regulators require that harmful and potentially harmful constituents (HPHCs) that might cause harm to the consumer must be monitored in the aerosol generated by e-cigarettes and in cigarette smoke (CS). To quantify HPHCs in aerosols from commercial flavoured e-cigarettes in Chinese market, this study has systematically compared levels of HPHCs, including eight carbonyls, five volatile organic compounds, four tobacco-specific nitrosamines, 16 polycyclic aromatic hydrocarbons, and seven heavy metals, in the aerosols of four market-leading flavoured e-cigarettes and mainstream CS, alongside in vitro cytotoxicity and mutagenicity assays. The vast majority of HPHCs were either undetected or significantly lower in the e-cigarette aerosols than in commercial CS or reference CS (3R4F). Where HPHCs were detected, there were small variations among the different flavoured e-cigarettes. In the neutral red uptake and Ames assays, aqueous extracts of the e-cigarette aerosols did not induce obvious cytotoxicity or mutagenicity, whereas CS aqueous extract showed dose-related cytotoxicity and mutagenicity. Collectively, these results indicate that use of e-cigarettes might potentially lead to a significant reduction in exposure to harmful substances, with fewer cytotoxic and mutagenic effects, as compared with conventional smoking. Further studies based on human puffing conditions and longer evaluation periods will be needed to substantiate this potential.

Ferroptosis and its interaction with tumor immune microenvironment in liver cancer.

Exploring effective systemic treatments for liver cancer is still a great challenge worldwide. As a novel form of regulated cell death, ferroptosis has been paid more and more attention in the cancer research field. In recent years, targeting ferroptosis has become an encouraging strategy for liver cancer treatment. Cancer cells can be directly killed by inducing ferroptosis; in contrast, ferroptosis can also ameliorate the tumor immunosuppressive microenvironment and sensitize cancers to immunotherapy. Here, we summarize fully current progress in the iron homeostasis in the liver, the internal association between imbalanced iron homeostasis and ferroptosis in liver carcinogenesis and development, as well as ferroptosis-related regulators in liver cancer. Furthermore, we discuss thoroughly the interaction between ferroptosis and tumor immune microenvironment. Finally, we provide certainly a future insight on the potential value of ferroptosis in the immunotherapy of liver cancer.

Nucleotide sugar transporter SLC35A2 is involved in promoting hepatocellular carcinoma metastasis by regulating cellular glycosylation.

PURPOSE: Recently, aberrant glycosylation has been recognized to be relate to malignant behaviors of cancer and outcomes of patients with various cancers. SLC35A2 plays an indispensable role on glycosylation as a nucleotide sugar transporter. However, effects of SLC35A2 on malignant behaviors of cancer cells and alteration of cancer cells surface glycosylation profiles are still not fully understood, particularly in hepatocellular carcinoma (HCC). Hence, from a glycosylation perspective, we investigated the effects of SLC35A2 on metastatic behaviors of HCC cells. METHODS: SLC35A2 expression in clinical samples and HCC cells was examined by immunohistochemical staining or Western blot/quantitative PCR and was regulated by RNA interference or vectors-mediated transfection. Effects of SLC35A2 expression alteration on metastatic behaviors and membrane glycan profile of HCC cells were observed by using respectively invasion, migration, cell adhesion assay, in vivo lung metastatic nude mouse model and lectins microarray. Co-location among proteins in HCC cells was observed by fluorescence microscope and detected by an in vitro co-immunoprecipitation assay. RESULTS: SLC35A2 was upregulated in HCC tissues, and is associated with poor prognosis of HCC patients. SLC35A2 expression alteration significantly affected the invasion, adhesion, metastasis and membrane glycan profile and led to the dysregulated expressions or glycosylation of cell adhesion-related molecules in HCC cells. Mechanistically, the maintenance of SLC35A2 activity is critical for the recruitment of the key galactosyltransferase B4GalT1, which is responsible for complex glycoconjugate and lactose biosynthesis, to Golgi apparatus in HCC cells. CONCLUSION: SLC35A2 plays important roles in promoting HCC metastasis by regulating cellular glycosylation modification and inducing the cell adhesive ability of HCC cells.

Real-world Biapenem vs. Meropenem in the treatment of severe community-acquired pneumonia in children: A propensity score matching analysis.

Objective: To compare the real-world efficacy and safety of Biapenem and Meropenem for treating severe community-acquired pneumonia (SCAP) in children. Methods: We retrospectively evaluated 915 children with SCAP who were treated with Biapenem or Meropenem from August 2018 to June 2022. A 1:1 propensity score matching (PSM) analysis was used to reduce the actual baseline difference between groups. Results: 416 patients participated in the analysis after PSM (Biapenem: Meropenem = 1:1). For the Biapenem group and Meropenem group, the effective rates were 90.4% and 90.9%, respectively (p = 1.0) and the incidence of adverse reactions were 7.7% and 7.2%, respectively (p = 1.0). There were no statistical differences between Biapenem and Meropenem. Conclusion: In general, the efficacy and safety of Biapenem are comparable to Meropenem in the treatment of children with SCAP.

Ingestible sensor system for measuring, monitoring and enhancing adherence to antiretroviral therapy: An open-label, usual care-controlled, randomised trial.

BACKGROUND: Co-encapsulated antiretrovirals (ARVs) with ingestible sensor (IS) has the capacity to monitor adherence in real-time using a sensor patch, a mobile device, and supporting software. We evaluated the acceptability, effectiveness, and sustainability of the IS system with real-time text reminders. METHODS: Participants were recruited from HIV clinics in Los Angeles and were randomised 1:1 to IS or usual care (UC) group. Adherence to ARVs (primary outcome) was measured by IS system (IS group only), plasma ARV concentration, and self-report. IS-measured adherence was clustered by group-based trajectory model and was validated by ARV concentration summarized by integrated pharmacokinetic adherence measure (IPAM) score. HIV RNA viral load (VL) was compared between IS and UC group. FINDINGS: A total of 112 (IS = 54, UC = 58) participants who completed baseline with at least one follow-up data collection were included in analyses. Overall satisfaction rate for the IS system was >90%. The IPAM score was higher (0.018, 95% CI: -0.098-0.134, p = 0.75) and VL decayed faster (-0.020, 95% CI: -0.042-0.002, p = 0.08) in the IS group compared with the UC group. The ingestible sensor system was well tolerated by study participants. INTERPRETATION: The IS system was well accepted by participants and its use was associated with improved adherence and lower HIV RNA VL. The findings provide a potentially effective strategy for improving adherence. FUNDING: This work was supported by grant R01-MH110056 from the National Institute of Mental Health (NIMH)/National Institutes of Health (NIH). Y. Wang was in part supported by the NIMH/NIH award T32MH080634. E. Daar was in part supported by the National Center for Advancing Translational Sciences through UCLACTSI Grant UL1TR001881. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

A comprehensive comparison of medication strategies for platinum-sensitive recurrent ovarian cancer: A Bayesian network meta-analysis.

Background: The Platinum-based combination has been proven to have an outstanding effect on patients with platinum-sensitive recurrent ovarian cancer (PSROC), but the best scientific combination has not been established yet. The present study is aimed to seek the best treatment plan for PSROC. Methods: We did a systematic review and Bayesian network meta-analysis, during which lite before March 2022 were retrieved on PubMed, Embase, Web of Science, and Cochrane Central Registry of Controlled databases. We included randomized controlled clinical trials comparing chemotherapy combinations with other treatments for patients with PSROC. The important outcomes concerned were progression-free survival (PFS) (the primary outcome), overall survival (OS), objective response rate (ORR), adverse events (AEs), and AEs-related discontinuation. All outcomes were ranked according to the surface under the cumulative ranking curve. Results: 26 trials involving 10441 patients were retrieved in this study. For the initial treatment of PSROC, carboplatin plus pegylated liposomal doxorubicin (PLD) plus bevacizumab had the best PFS [hazard ratio (HR) 0.59, 95% credible interval (CI) 0.51-0.68]; Carboplatin plus paclitaxel plus bevacizumab resulted in the best OS (HR 1.22, 95% CI 1.09-1.35) and ORR [odds ratio (OR) 1.22, 95% CI 1.09-1.35]. For the maintenance therapy in PSROC, poly (ADP-ribose) polymerase inhibitors (PARPi) following platinum-based chemotherapy provided the best PFS (HR 0.64, 95% CI 0.61-0.68), the highest frequency of adverse events of grade three or higher (OR 0.18, 95% CI 0.07-0.44) but the treatment discontinuation was generally low. Subgroup analysis suggested that trabectedin plus PLD was comparable to single platinum in prolonging PFS in the platinum-free interval (6-12 months). Conclusion: Both platinum-based chemotherapy plus PARPi and platinum-based chemotherapy plus bevacizumab had higher survival benefits than other treatments in PSROC. Trabectedin plus PLD might be a potential alternative treatment strategy for the partially platinum-sensitive subpopulation with intolerance to platinum. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?], identifier [CRD42022326573].