医学最新文献

Purpose: Neoadjuvant chemotherapy (NAC) has proven valuable in treating locally advanced colon cancer (LACC) and is included as a treatment option for patients with clinical T4b colon cancer by the National Comprehensive Cancer Network. However, the long-term survival benefit of NAC in LACC remains debated, due to a lack of conclusive clinical trial results identifying the patients who would benefit most from NAC. This study aimed to assess the efficacy of NAC in patients with LACC based on histological subtype.

Patients and methods: This retrospective study analyzed 3,709 patients with LACC who underwent curative resection at Harbin Medical University Cancer Hospital between 2014 and 2018. Patients were grouped into two groups: neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC) groups. Propensity score matching (PSM) was used to adjust for confounders, and survival outcomes of the two groups across different histological subtypes were evaluated using Kaplan-Meier (K-M) curves and log-rank tests.

Results: Patients with non-mucinous adenocarcinoma (NMAC) treated with NAC had a significantly improved 5-year OS rate (76.3% vs. 69.2%, p = .039) and DFS rate (67.2% vs. 60.1%, p = .041) compared with patients treated with AC. However, there was no significant difference in OS and DFS between the two treatment groups among patients with mucinous adenocarcinoma (MAC) and signet ring cell carcinoma (SRCC).

Conclusion: In patients with LACC, the prognostic value of NAC varied by histology. NMAC may serve as a predictor of improved long-term survival benefit from NAC in these patients.

Indigenous food sovereignty (IFS) has the potential to reconnect Indigenous peoples in Canada to their food systems, reduce health problems and improve food security. Using PRISMA-ScR guidelines to search Medline, Web of Science, Embase and Cabi databases, this review sought to explore the characteristics of IFS promotion and the food environments involved through food and nutrition interventions in Indigenous communities in Canada. Data from 30 relevant studies published between 2004 and 2022 were included, analysed and synthesised using a thematic approach based on key IFS principles and a food environment typology. Most studies were conducted in urban contexts, mainly in provinces with the largest Indigenous populations. Local descriptions of IFS showed conceptual and operational similarities. Among the four key principles of IFS, the principle of participation was the most reported. Gardening, farming, hunting, fishing and gathering were the main food activities used to operationalise IFS in traditional and cultivated food environments. Several IFS facilitators and barriers were identified. The IFS movement that emerged from the literature in Canada advocates for a healthy and sustainable food system based on traditional beliefs and controlled by communities to ensure wellbeing and food security. This review provides evidence of converging visions for food autonomy despite the heterogeneity of Indigenous nations in Canada.

Therapeutic option for treating methicillin-resistant Staphylococcus aureus (MRSA) infection is urgently required since its resistance to a broad spectrum of currently available antibiotics. Here, we report that isoniazid is able to potentiate the killing efficacy of tigecycline to MRSA. The combination of isoniazid and tigecycline reduces the minimal inhibitory concentration of clinic MRSA strains to tigecycline. The killing activity of tigecycline is further confirmed by killing experiments and murine infection model. We further demonstrate the mechanism that isoniazid increases intracellular accumulation of tigecycline by promoting the influx but limiting the efflux of tigecycline through proton motive force. We also show that isoniazid and tigecycline synergize to increase the abundance of isoniazid-NAD adduct, which in turn damage cell membrane, possibly contributing to the disruption of PMF. Whereas phosphatidylethanolamine and cardiolipin are able to abrogate the synergistic effect of isoniazid plus tigecycline. Thus our study provides a new perspective that antibiotics, e.g. isoniazid, once recognized only to target Mycobacterium tuberculosis, can be repurposed as antibiotic adjuvant to tigecycline, expanding our choice of antibiotic-antibiotic combinations in treating bacterial infectious diseases.

Nivolumab plus ipilimumab (aCTLA-4/aPD-1) combination therapy has significantly improved clinical outcomes in patients with metastatic melanoma, with 50%-60% of patients responding to treatment, but predictors of response are poorly characterized. We hypothesized that circulating cytokines and peripheral white blood cells may predict response to therapy and evaluated 15 cytokines and complete blood counts (CBC with differentials) from 89 patients with advanced melanoma treated with combination therapy from three points in time: pre-treatment, one month and approximately three months after starting therapy. Clinical endpoints evaluated included durable clinical benefit (DCB), progression-free survival (PFS), and overall survival (OS). A parsimonious predictive model was developed to identify cytokines predictors of response to combination therapy. In this study, we found that pre-treatment, patients with DCB had higher IL-23, lower CXCL6, and lower IL-10 levels. Lower NLR one month after starting therapy predicted better PFS and OS, primarily driven by an increase in absolute lymphocytes. A multivariate model demonstrated that baseline CXCL6, IL-10, IL-23 were independent predictors of therapy response, and the combined model has reached an area under the curve (AUC) of 0.79 in prediction of response to combination therapy. Our study identified baseline CXCL6, IL-23, and IL-10 as predictors of response to aCTLA4/aPD1 combination therapy among patients with metastatic melanoma. This study also provides a framework for identifying patients who are likely to respond to combination ICB, as well as a subset of patients with high risk of developing resistance and are thus in need of alternative therapeutic options, such as clinical trials.

We aim to identify Libyans' knowledge, attitudes, and acceptance regarding the COVID-19 vaccine. A cross-sectional survey was electronically distributed to the Libyan population aged 18 and older between May and September 2023. The questionnaire had three sections: socio-demographics, COVID-19 vaccination and infection, and knowledge and attitudes toward the COVID-19 vaccine. The chi-square test was used to assess the associations. A total of 1,043 respondents completed the questionnaire. Of these, 590 (56.6%) were vaccinated, and 453 (43.4%) were unvaccinated. Only age, educational level, employment status, history of COVID-19 infection, and source of information had a significant association with vaccination status; all shared a p-value <.05. However, Monthly income did not. Regarding knowledge, 63.7% agreed that vaccines in general are an effective way to prevent and control infectious diseases, and 76.6% agreed that they can prevent disease and mortality. However, regarding COVID-19 vaccine, 48.4% agreed that the benefits outweigh the risks. Regarding COVID-19 safety, 40.8% responded that COVID-19 vaccines are only slightly safe or not safe at all. COVID-19 vaccine acceptance was at 57.2%, and only age and source of information were significantly associated. Those who held favorable views were more likely to accept the vaccine, while those who had concerns about safety were more vaccine hesitant. There is a gap between the perception of the COVID-19 vaccine compared to other vaccines among Libyans. Our study revealed that 57.2% of Libyans accept the COVID-19 vaccine. However, only 34% of the Libyan population is vaccinated. A comprehensive health policy is needed.

Preeclampsia is a complex condition characterized by elevated blood pressure and organ damage involving kidneys or liver, resulting in significant morbidity and mortality for both the mother and the fetus. Increasing evidence suggests that oxidative stress, often caused by mitochondrial dysfunction within fetal trophoblast cells may play a major role in the development and progression of preeclampsia. Oxidative stress occurs as a result of an imbalance between the production of reactive oxygen species (ROS) and the capacity of antioxidant defenses, which can lead to placental cellular damage and endothelial cell dysfunction. Targeting oxidative stress appears to be a promising therapeutic approach that has the potential to improve both short- and long-term maternal and fetal outcomes, thus reducing the global burden of preeclampsia. The purpose of this review is to provide a comprehensive account of the mechanisms of oxidative stress in preeclampsia. Furthermore, it also examines potential interventions for reducing oxidative stress in preeclampsia, including natural antioxidant supplements, lifestyle modifications, mitochondrial targeting antioxidants, and pharmacological agents.A better understanding of the mechanism of action of proposed therapeutic strategies targeting oxidative stress is essential for the identification of companion biomarkers and personalized medicine approaches for the development of effective treatments of preeclampsia.

Aims: Empagliflozin confers cardioprotective benefits among patients with heart failure, across the range of ejection fraction (EF), regardless of type 2 diabetes status. The long-term cost-effectiveness of empagliflozin for the treatment of heart failure (HF) in the Philippines remains unclear. This study aims to determine the economic benefit of adding empagliflozin to the standard of care (SoC) vs the SoC alone for HF in the Philippines.

Methods: Using a Markov model, we predicted lifetime costs and clinical outcomes associated with treating HF in the Philippine setting. We used estimates of treatment efficacy, event probabilities, and derivations of utilities from the EMPEROR trials. Costs were derived from hospital tariffs and expert consensus. Separate analyses were performed for patients with left ventricular EF > 40%, categorized under mid-range ejection fraction or preserved ejection fraction (HFmrEF/HFpEF), and patients with left EF ≤ 40%, categorized under HF with reduced ejection fraction (HFrEF).

Results: Our model predicted an average of 0.09 quality-adjusted life year (QALY) gains among HFmrEF/HFpEF patients and HFrEF patients when empagliflozin was compared to SoC. The addition of empagliflozin in the treatment results in a discounted incremental lifetime cost of PHP 62,692 (USD 1,129.99) and PHP 17,215 (USD 308.67) for HFmrEF/HFpEF and HFrEF, respectively. The incremental cost-effectiveness ratio (ICER) of empagliflozin is PHP 198,270 (USD 3,570.72)/QALY and PHP 742,604 (USD 13,385.08)/QALY for HFrEF and HFmrEF/HFpEF, respectively.

Limitations: This study employed parameters derived from short-term clinical trial data, alongside metrics representative of Asian populations, which are not specific to the Philippine cohort.

Conclusions: Adding empagliflozin to the SoC in comparison to the SoC is associated with improved clinical outcomes and quality-of-life, at additional costs for both HFrEF and HFmrEF/HFpEF.

Lung cancer, one of the most prevalent tumors, remains a clinical challenge with a poor five-year survival rate. Daurisoline, a bis-benzylisoquinoline alkaloid derived from the traditional Chinese herb Menispermum dauricum, is known to suppress tumor growth effectively. However, its precise mechanism of action remains unclear. In this study, we demonstrate that Daurisoline targets glycolysis and reduces the protein level of HK2, thereby inhibiting lung cancer progression. Mechanistic investigations reveal that Daurisoline directly binds to AKT and antagonizes the AKT-GSK3β-c-Myc-HK2 signaling axis. Furthermore, in an animal model, we validate the in vivo anti-tumor effect of Daurisoline without any observable side effects. Overall, our findings suggest that Daurisoline holds potential as an anti-tumor agent through its targeting of glycolysis.

Healthcare in low- and middle-income countries is becoming problematic due to the emergence of multidrug-resistant bacteria causing serious morbidity and mortality. Klebsiella variicola carrying multiple antimicrobial resistance (AMR) genes were found significantly among sepsis patients in a study done between October 2019 and September 2020 at four Ethiopian hospitals located in the central (Tikur Anbessa and Yekatit 12), southern (Hawassa), and northern (Dessie) parts. Among 1416 sepsis patients, 74 K. variicola isolates were identified using MALDI-TOF, most of them at Dessie (n = 44) and Hawassa (n = 28) hospitals. Whole genome sequencing showed that K. variicola strains identified at Dessie Hospital displayed phylogenetic clonality, carried an IncM1 plasmid and the majority were ST3924. Many K. variicola identified at Hawassa Hospital were clonally clustered and the majority belonged to novel STs and carried IncFIB(K) and IncFII(K) plasmids concurrently. Fifty K. variicola carried ESBL genes while 2 isolates harboured AmpC. Other frequently found genes were aac(3)-lla, bla_CTX-M-15, bla_TEM-1B, bla_LEN2, bla_OXA-1, bla_SCO-1, catB3, dfrA14, QnrB1, aac(6')-lb-cr and sul2. Virulence genes detected at both sites were mrk operons for biofilm formation and siderophore ABC transporter operons for iron uptake. Capsular alleles varied, with wzi 269 at Dessie and wzi 582 at Hawassa. The isolation of multidrug-resistant K. variicola as an emerging sepsis pathogen calls for strong infection prevention strategies and antimicrobial stewardship supported by advanced bacterial identification techniques.

Background: A number of studies have tested the factor structure of the suggested ICD-11 symptom criteria for PTSD and complex PTSD (CPTSD) across various trauma populations, finding support for two different models in line with the ICD-11 theoretical rationale.Objective: Here, we aim to explore the factor structure of the Danish version of the International Trauma Questionnaire (ITQ) by testing two alternative factor models that have previously gained support in a large sample of treatment-seeking veterans.Method: Treatment-seeking Danish soldiers and veterans (N = 599) recruited from the Military Psychology Department in the Danish Defence completed the International Trauma Questionnaire (ITQ). Confirmatory factor analysis (CFA) was used to assess fit of a first-order and a second-order model.Results: Both models fit the data well but displayed latent variable correlations above 1 and negative variances (known as Heywood cases), indicating model misspecification or other problems. The specification problems included the latent variable Affect Dysregulation.Conclusions: Based on our results and results reported in previous CFAs of the ITQ, we suggest consideration of the proposed models. While many previous studies did find support for the models with no indications of misfit, others find Heywood cases concerning the same items and latent variables as our analysis. Hence, models of (C)PTSD based on the ITQ should be carefully evaluated and interpreted.