How to prevent Atopic Dermatitis (Eczema) in 2024: theory and evidence.

Atopic dermatitis (AD) or eczema is a chronic inflammatory skin disease characterized by dry, itchy, and inflamed skin. We review emerging concepts and clinical evidence addressing the pathogenesis and prevention of atopic dermatitis. We review several interventions ranging from skin barrier enhancement strategies; probiotics, prebiotics, and synbiotics, and conversely, antimicrobial exposure; vitamin D and omega fatty acid supplementation; breastfeeding and hydrolyzed formula; house dust mite avoidance and immunotherapy. We appraise the available evidence base within the context of the GRADE approach. We also contextualize our findings in relation to concepts relating atopic dermatitis and individual-patient allergic life trajectories versus a linear concept of the atopic march and provide insights into future knowledge gaps and clinical trial design considerations that must be addressed in future research. Finally, we provide implementation considerations to detect population-level differences in AD risk. Major international efforts are required to provide definitive evidence regarding what works, and what does not, for preventing AD.

Safety, Tolerability, and Preliminary Efficacy of Serplulimab, a Novel Anti-PD-1 Antibody, in Patients with Metastatic or Recurrent Solid Tumors: A Phase I Study.

BACKGROUND: Serplulimab is a novel, recombinant, humanized, monoclonal, anti-programmed death 1 antibody with a similar or better affinity and pre-clinical antitumor activity than pembrolizumab and nivolumab. OBJECTIVE: This phase I, open-label, dose-escalation study evaluated serplulimab in patients with advanced solid tumors. The second interim analysis of the dose-finding phase is reported here. METHODS: Adult patients with histologically confirmed metastatic/recurrent solid tumors who had progressed on, or were intolerant to/clinically unsuitable for standard treatment, were enrolled. Four intravenous serplulimab dose levels were evaluated: 0.3, 1.0, 3.0, and 10.0 mg/kg every 2 weeks in 28-day cycles for up to 2 years. Primary endpoints were the incidence of treatment-emergent adverse events and the maximum tolerated dose. RESULTS: By 27 July, 2020 (data cut-off), 29 patients with stage IV disease (34.5% with lung cancer) received one or more doses of serplulimab. One (3.4%) patient had completed treatment and 26 (89.7%) had discontinued from the study. The maximum tolerated dose was not reached. Twenty-two (75.9%) patients experienced treatment-emergent adverse events related to serplulimab, most frequently nausea (24.1%), with no notable differences in incidence between dose cohorts; of these, grade ≥ 3 events occurred in four (13.8%) patients. Pharmacokinetic data demonstrated minimal accumulation of serplulimab after repeated administration. Functional programmed death 1 blockade was observed across dose levels. Objective response and disease control rates were 8.0 and 60.0%, respectively. CONCLUSIONS: Serplulimab was well tolerated and demonstrated antitumor activity. These data support further study of serplulimab in larger patient populations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03468751 (19 March, 2018).

Comparative Effectiveness of Intensity-Modulated Proton Therapy Versus Intensity-Modulated Radiotherapy for Patients With Inoperable Esophageal Squamous Cell Carcinoma Undergoing Curative-Intent Concurrent Chemoradiotherapy.

INTRODUCTION: This study compared outcomes in patients with inoperable esophageal squamous cell carcinoma (ESCC) undergoing curative-intent concurrent chemoradiotherapy (CCRT) with intensity-modulated radiotherapy (IMRT) versus intensity-modulated proton therapy (IMPT). METHODS: The study encompassed a retrospective cohort analysis of patients with inoperable ESCC who underwent curative-intent CCRT from January 1, 2015, to December 31, 2020, with data sourced from the Taiwan Cancer Registry Database. In this study, both IMRT and IMPT delivered a total equivalent effective dose of approximately 5040 cGy in 28 fractions, accompanied by platinum-based chemotherapy administered as per established protocols. Multivariate Cox regression analyses were performed to assess oncologic outcomes, and statistical analyses were conducted, including inverse probability of treatment-weighted and Fine and Gray method for competing risks. RESULTS: The observed risks of ESCC-specific and all-cause mortality were lower in patients treated with IMPT compared with those treated with IMRT, with adjusted hazard ratios (aHRs) of 0.62 (95% confidence interval [CI]: 0.58-0.70) and 0.72 (95% CI: 0.66-0.80), respectively. IMPT also reduced grade 2 radiation-induced side effects, such as pneumonitis, fatigue, and major adverse cardiovascular events, with aHRs (95% CI) of 0.76 (0.66-0.82), 0.10 (0.07-0.14), and 0.70 (0.67-0.73), respectively. However, IMPT was associated with an increased risk of grade 2 radiation dermatitis, with aHR (95% CI) of 1.48 (1.36-1.60). No substantial differences were found in the incidence of radiation esophagitis between IMPT and IMRT when adjusting for covariates. CONCLUSION: IMPT seems to be associated with superiority over IMRT in managing patients with inoperable ESCC undergoing curative-intent CCRT, suggesting improved survival outcomes and reduced toxicity. These findings have significant implications for the treatment of ESCC, particularly when surgery is not an option.

Statin use reduces radiation-induced stroke risk in advanced nasopharyngeal carcinoma patients.

OBJECTIVE: This cohort study aimed to evaluate the impact of statin use on ischemic stroke risk in patients with advanced nasopharyngeal carcinoma (NPC) undergoing standard concurrent chemoradiotherapy (CCRT). METHODS: Using data from the Taiwan Cancer Registry Database, we conducted an inverse probability of treatment-weighted Cox regression analysis to examine the association between statin use during CCRT and ischemic stroke risk. RESULTS: The adjusted hazard ratio (aHR) for ischemic stroke in the statin group compared to the non-statin group was 0.70 (95 % CI: 0.54-0.92; P < 0.0107). This protective effect was observed across different statin classes, with hydrophilic statins such as pravastatin showing an aHR of 0.37 (95 % CI: 0.17-0.85) and lipophilic statins including atorvastatin displaying an aHR of 0.32 (95 % CI: 0.21-0.50) compared to non-statin use. Analysis of cumulative defined daily doses (cDDD) revealed a dose-response relationship, with lower stroke risk observed in higher quartiles of cDDD. Additionally, patients with a daily defined dose (DDD) > 1 had a reduced risk of stroke with an aHR of 0.49 (95 % CI: 0.31-0.63), while those with DDD ≤ 1 showed an aHR of 0.59 (95 % CI: 0.40-0.84). CONCLUSIONS: Our study provides evidence supporting the beneficial effects of statin use during the CCRT period in reducing radiation-induced stroke risk among patients with advanced NPC undergoing definitive CCRT. Notably, pravastatin and atorvastatin demonstrated significant reductions in stroke occurrence. Furthermore, the findings suggest a dose-response relationship, where higher cumulative doses and greater daily dose intensity of statin use were associated with a lower risk of stroke.

Antihistamines H1 use on survival outcomes in esophageal squamous cell carcinoma patients undergoing concurrent chemoradiotherapy.

Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related mortality in Taiwan, with poor survival rates despite standard treatment with concurrent chemoradiotherapy (CCRT). Antihistamines H1 (AH1) may have anticancer effects by reducing allergic reactions, activating mitogen-activated protein kinases, and regulating the immune system. However, the impact of AH1 use during CCRT on survival outcomes in patients with ESCC remains uncertain. A propensity score-matched cohort study was conducted using data from the Taiwan Cancer Registry Database and National Health Insurance Research Database. The primary outcome measures were overall survival and ESCC-specific survival. We analyzed the effects of AH1 use during CCRT on these outcomes using multivariable Cox proportional hazards regression models. The current study involved 981 individuals diagnosed with ESCC who underwent standard CCRT. Out of these, 309 were placed in the non-AH1 group and 672 in the AH1 group. AH1 use during CCRT was found to be associated with improved overall survival (adjusted hazard ratio [HR], 0.52; 95% CI, 0.44-0.60; P<0.0001) and ESCC-specific survival (adjusted HR, 0.47; 95% CI, 0.39-0.56; P<0.0001) compared with nonuse. A dose-response relationship was also observed, with higher cumulative defined daily doses of AH1 associated with lower mortality. The optimal daily intensity dose for AH1 use was found to be 0.84 defined daily doses with the lowest mortality. Our study demonstrates that AH1 use during CCRT for ESCC is associated with improved overall survival and ESCC-specific survival.

Drastic Synergy of Lovastatin and Antrodia camphorata Extract Combination against PC3 Androgen-Refractory Prostate Cancer Cells, Accompanied by AXL and Stemness Molecules Inhibition.

Prostate cancer (PC) is the second most frequently diagnosed cancer and the fifth leading cause of cancer-related death in males worldwide. Early-stage PC patients can benefit from surgical, radiation, and hormonal therapies; however, once the tumor transitions to an androgen-refractory state, the efficacy of treatments diminishes considerably. Recently, the exploration of natural products, particularly dietary phytochemicals, has intensified in response to addressing this prevailing medical challenge. In this study, we uncovered a synergistic effect from combinatorial treatment with lovastatin (an active component in red yeast rice) and Antrodia camphorata (AC, a folk mushroom) extract against PC3 human androgen-refractory PC cells. This combinatorial modality resulted in cell cycle arrest at the G0/G1 phase and induced apoptosis, accompanied by a marked reduction in molecules responsible for cellular proliferation (p-Rb/Rb, Cyclin A, Cyclin D1, and CDK1), aggressiveness (AXL, p-AKT, and survivin), and stemness (SIRT1, Notch1, and c-Myc). In contrast, treatment with either AC or lovastatin alone only exerted limited impacts on the cell cycle, apoptosis, and the aforementioned signaling molecules. Notably, significant reductions in canonical PC stemness markers (CD44 and CD133) were observed in lovastatin/AC-treated PC3 cells. Furthermore, lovastatin and AC have been individually examined for their anti-PC properties. Our findings elucidate a pioneering discovery in the synergistic combinatorial efficacy of AC and clinically viable concentrations of lovastatin on PC3 PC cells, offering novel insights into improving the therapeutic effects of dietary natural products for future strategic design of therapeutics against androgen-refractory prostate cancer.

Effectiveness of various treatment modalities in children with vesicoureteral reflux grades II-IV: a systematic review and network meta-analysis.

BACKGROUND: Vesicoureteral reflux (VUR) is one of the most common risk factors of urinary tract infection (UTI) among children. Various treatment modalities including antibiotic prophylaxis, surgical or endoscopic corrections and conservative treatment were used depending on the severity of VUR. The aim of this study is to compare the effectiveness of these treatment modalities in children with VUR grades II-IV by conducting a systematic review and network meta-analysis. METHODS: A systematic search from different databases was performed from their earliest records to December 2022 without any language restriction. Only randomised controlled trials were included in this study. Effectiveness of treatment modalities was mainly compared by UTI. Other outcomes for renal scarring and resolution by renal units were also measured between treatments. RESULTS: A total of 11 studies with 1447 children were included in this study. While comparing with antibiotic prophylaxis in network meta-analysis for UTI recurrence, surgical treatment probably lowers the rate of UTI recurrence (Log OR -0.26, 95% CI -0.54 to 0.02, high quality). However, endoscopic treatment (Log OR 0.2, 95% CI -1.41 to 1.81, high quality) and conservative treatment (Log OR 0.15, 95% CI -0.45 to 0.75, high quality) revealed probably inferior to antibiotic treatment. CONCLUSION: Both pairwise and network meta-analytic results probably showed no difference between the treatments in terms of their impact on UTI recurrence, progression of previous renal scars, or formation of new renal scars in children with VUR grades II-IV. These findings may offer a better understanding of each treatment and evidence-based suggestions for the choice of treatment, which should be individualised and based on the patient's risk factors.

Childhood body mass index trajectories and asthma and allergies: A systematic review.

BACKGROUND: Previous systematic reviews have focused on associations between single time point measures of Body Mass Index (BMI) and asthma and allergic diseases. As BMI changes dynamically during childhood, examination of associations between longitudinal trajectories in BMI and allergic diseases is needed to fully understand the nature of these relationships. OBJECTIVE: To systematically synthesise the association between BMI trajectories in childhood (0-18 years) and allergic diseases (asthma, eczema, allergic rhinitis, or food allergies outcomes). DESIGN: We conducted a systematic review following the PRISMA guidelines, and two independent reviewers assessed the study quality using the ROBINS-E and GRADE tools. A narrative synthesis was performed as the statistical heterogeneity did not allow a meta-analysis. DATA SOURCES: A search was performed on PubMed and EMBASE databases on 4th January 2023. ELIGIBILITY CRITERIA: Longitudinal cohort studies assessing the associations between childhood BMI trajectories and allergic diseases were included. RESULTS: Eleven studies met the inclusion criteria with a total of 37,690 participants between 0 and 53 years of age. Ten studies examined asthma outcomes, three assessed association with allergic rhinitis, two assessed eczema, and one assessed food allergy. High heterogeneity and high risk of bias were observed. Overall, the quality of evidence was very low. Nevertheless, two consistent findings were identified: (1) a persistently high BMI between 6 and 10 years of age may be associated with an increased risk of asthma at 18 years and (2) a rapid increase in BMI in the first 2 years of life may be associated with subsequent asthma. CONCLUSIONS: Maintaining a normal BMI trajectory during childhood may reduce the risk of asthma. Future research that adequately addresses confounding and includes longer-term follow-up is needed. Moreover, additional studies examining potential associations with eczema, food allergies, and allergic rhinitis outcomes are needed.

Understanding the medication experience of patients with advanced non-small cell lung cancer taking epidermal growth factor receptor-tyrosine kinase inhibitors: A phenomenological study.

BACKGROUND AND OBJECTIVE: Patients with cancer taking oral antineoplastic medications may encounter problems including suboptimal adherence as well as physical and psychological disease burden. Despite increase in the use of oncology pharmacy services, there are wide variations between healthcare professionals and patient perceptions of patients' medication experiences. The objective of the study was to explore the medication experience of taking oral targeted therapy in patients with advanced non-small cell lung cancer (NSCLC). METHOD: We purposively sampled advanced stage (stage III or IV) NSCLC patients taking epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in a medical center in Taiwan. Face-to-face interviews using semi-structured interview guides were conducted. Interviews were transcribed verbatim and thematic analysis was applied. A phenomenological methodology was adopted to explore the underlying meaning of patients' lived experience. RESULTS: A total of 19 participants with a mean age of 68.2 years were interviewed. The duration of EGFR-TKIs use ranged from 2 weeks to 5 years. When first learned about the unexpected yet 'treatable' cancer, participants expressed strong emotional responses based on their intrinsic beliefs of the terminal disease and therapy. They walked along an unfamiliar trail while confronting physical and psychological challenges and made compromises to treatment. Gaining experiences from cancer journey, patients with cancer continuously seek the ultimate goals-'return to normal'. CONCLUSIONS: This study also revealed medication experiences of participants' journey from seeking information in the initial phase and living with cancer, to taking back control of their own lives. Healthcare professionals could better empathize with patients' loss of control and understand their perspectives when making clinical decisions. These findings can guide interdisciplinary teams to integrate patients' beliefs and conduct pre-screening assessments of health literacy levels to tailor communication. Subsequent interventions should be developed to identify barriers to medication self-management and empower patients by building social networks.

Cancer-Associated Thrombosis: A Taiwanese Perspective on Therapeutic Options with Focus on Non-Vitamin K Antagonist Oral Anticoagulants.

Cancer-associated thrombosis (CAT) is a common complication of malignancies. Patients with CAT are at risk of venous thromboembolism recurrence, but also at risk of bleeding while anticoagulated. Taiwanese patients are perceived to have a lower incidence of CAT, likely leading to false reassurance for Taiwanese patients with cancer. Because of this, oncologists and cardiologists from multiple medical institutions in Taiwan have set forth to provide clinical consensus guidelines on the management of CAT, based on local clinical practices and guided by predominant international clinical practice guidelines. This paper aims to describe the current disease burden of cancer-associated venous thromboembolism in Taiwanese cancer patients, and discusses the unmet needs and gaps in the management of this medical complication. It also outlines diagnostic and management strategies relevant to the different treatment options available, such as non-vitamin K antagonist oral anticoagulants.

Is antenatal or early-life vitamin D associated with eczema or food allergy in childhood? A systematic review.

OBJECTIVE: To summarise the associations between antenatal or early-life blood vitamin D and the development of eczema/food allergy in childhood. DESIGN: A systematic review and meta-analyses were conducted to synthesize the published literature. Two reviewers independently performed the study selection and data extraction on Covidence. We assessed the risk of bias for observational studies by using the Newcastle-Ottawa Scale and the Cochrane Risk of Bias tool for clinical trials. The certainty of the evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). DATA SOURCES: We systematically searched PubMed and Embase from inception and April 2022. ELIGIBILITY CRITERIA: Human studies that investigated prospective associations between antenatal or early-life blood vitamin D levels, dietary intake or supplementation and childhood eczema/food allergy. RESULTS: Forty-three articles including six randomised controlled trials (RCTs) were included. Four RCTs of vitamin D supplementation during pregnancy showed no evidence of an effect on the incidence of eczema (pooled odds ratio [OR] = 0.85; 0.67-1.08, I2  = 6.7%, n = 2074). Three RCTs reported null associations between supplementation in pregnancy/infancy and food allergy. From six cohort studies, increasing cord blood vitamin D levels were associated with reduced prevalence of eczema at/close to age one (OR per 10 nmol/L increase = 0.89; 0.84-0.94, I2  = 0%, 2025 participants). We found no evidence of an association between maternal antenatal or infant vitamin D level or dietary intake and the development of food allergy or eczema in offspring. CONCLUSIONS: We found an association between higher vitamin D levels in cord blood and reduced risk of eczema in cohort studies. Further trials with maternal and infant supplementation are needed to confirm if vitamin D supplementation can effectively prevent eczema or food allergy in childhood. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, No. CRD42013005559.

σP-NagA-L1/L2 Regulatory Circuit Involved in ΔompA299-356-Mediated Increase in ß-Lactam Susceptibility in Stenotrophomonas maltophilia.

OmpA, the most abundant porin in Stenotrophomonas maltophilia KJ, exists as a two-domain structure with an N-terminal domain of ß-barrel structure embedded in the outer membrane and a C-terminal domain collocated in the periplasm. KJΔOmpA299-356, an ompA mutant of S. maltophilia KJ with a truncated OmpA devoid of 299 to 356 amino acids (aa), was able to stably embed in the outer membrane. KJΔOmpA299-356 was more susceptible to ß-lactams than wild-type KJ. We aimed to elucidate the mechanism underlying the ΔompA299-356-mediated increase in ß-lactam susceptibility (abbreviated as "ΔOmpA299-356 phenotype"). KJΔOmpA299-356 displayed a lower ceftazidime (CAZ)-induced ß-lactamase activity than KJ. Furthermore, KJ2, a L1/L2 ß-lactamases-null mutant, and KJ2ΔOmpA299-356, a KJ2 mutant with truncated OmpA devoid of299 to 356 aa, had comparable ß-lactam susceptibility. Both lines of evidence indicate that decreased ß-lactamase activity contributes to the ΔOmpA299-356 phenotype. We analyzed the transcriptome results of KJ and KJΔOmpA299-356, focusing on PG homeostasis-associated genes. Among the 36 genes analyzed, the nagA gene was upregulated 4.65-fold in KJΔOmpA299-356. Deletion of the nagA gene from the chromosome of KJΔOmpA299-356 restored ß-lactam susceptibility and CAZ-induced ß-lactamase activity to wild-type levels, verifying that nagA-upregulation in KJΔOmpA299-356 contributes to the ΔOmpA299-356 phenotype. Furthermore, transcriptome analysis revealed that rpoE (Smlt3555) and rpoP (Smlt3514) were significantly upregulated in KJΔOmpA299-356. The deletion mutant construction, ß-lactam susceptibility, and ß-lactamase activity analysis demonstrated that σP, but not σE, was involved in the ΔOmpA299-356 phenotype. A real-time quantitative (qRT-PCR) assay confirmed that nagA is a member of the σP regulon. The involvement of the σP-NagA-L1/L2 regulatory circuit in the ΔOmpA299-356 phenotype was manifested. IMPORTANCE Porins of Gram-negative bacteria generally act as channels that allow the entry or extrusion of molecules. Moreover, the structural role of porins in stabilizing the outer membrane by interacting with peptidoglycan (PG) and the outer membrane has been proposed. The linkage between porin deficiency and antibiotic resistance increase has been reported widely, with a rationale for blocking antibiotic influx. In this study, a link between porin defects and ß-lactam susceptibility increase was demonstrated. The underlying mechanism revealed that a novel σP-NagA-L1/L2 regulatory circuit is triggered due to the loss of the OmpA-PG interaction. This study extends the understanding on the porin defect and antibiotic susceptibility. Porin defects may cause opposite impacts on antibiotic susceptibility, which is dependent on the involvement of the defect. Blocking the porin channel role can increase antibiotic resistance; in contrast, the loss of porin structure role may increase antibiotic susceptibility.

Genetic and Cross Neutralization Analyses of Coxsackievirus A16 Circulating in Taiwan from 1998 to 2021 Suggest Dominant Genotype B1 can Serve as Vaccine Candidate.

Coxsackievirus A16 (CVA16) is well known for causing hand-foot-and-mouth disease (HFMD) and outbreaks were frequently reported in Taiwan in the past twenty years. The epidemiology and genetic variations of CVA16 in Taiwan from 1998 to 2021 were analyzed in this study. CVA16 infections usually occurred in early summer and early winter, and showed increased incidence in 1998, 2000-2003, 2005, 2007-2008, and 2010 in Taiwan. Little or no CVA16 was detected from 2017 to 2021. CVA16 infection was prevalent in patients between 1 to 3 years old. A total of 69 isolates were sequenced. Phylogenetic analysis based on the VP1 region showed that CVA16 subgenotype B1 was dominantly isolated in Taiwan from 1998 to 2019, and B2 was identified only from isolates collected in 1999 and 2000. There was a high frequency of synonymous mutations in the amino acid sequences of the VP1 region among CVA16 isolates, with the exception of position 145 which showed positive selection. The recombination analysis of the whole genome of CVA16 isolates indicated that the 5'-untranslated region and the non-structural protein region of CVA16 subgenotype B1 were recombined with Coxsackievirus A4 (CVA4) and enterovirus A71 (EVA71) genotype A, respectively. The recombination pattern of subgenotype B2 was similar to B1, however, the 3D region was similar to EVA71 genotype B. Cross-neutralization among CVA16 showed that mouse antisera from various subgenotypes viruses can cross-neutralize different genotype with high neutralizing antibody titers. These results suggest that the dominant CVA16 genotype B1 can serve as a vaccine candidate for CVA16.

Facilitators and barriers to participation in health mothers' groups in improving maternal and child health and nutrition in Nepal : A mixed-methods study.

BACKGROUND: In Nepal, Health Mother's Groups (HMG) are women's group-based programmes for improving maternal and child health. However, they remain underutilised with only 27% of reproductive-aged women participating in an HMG meeting in 2016. This study aimed to understand the facilitators and barriers to HMG meeting participation. METHODS: We conducted a convergent mixed-methods study using cross-sectional quantitative data from the 2016 Nepal Demographic and Health Survey and primary data collected via 35 in-depth interviews and eight focus group discussions with 1000-day women and their family members, female community health volunteers (FCHVs) and health facility staff in two geographies of Nepal, Kaligandaki and Chapakot. Quantitative data were analysed using logistic regression and qualitative data using deductive coding. The results were triangulated and thematically organised according to the socio-ecological model (SEM). RESULTS: Facilitators and barriers emerged across individual, interpersonal and community levels of the SEM. In the survey, women with more children under five years of age, living in a male-headed household, or in rural areas had increased odds of HMG participation (p < 0.05) while belonging to the Janajati caste was associated with lower odds of participation (p < 0.05). Qualitative data helped to explain the findings. For instance, the quantitative analysis found women's education level associated with HMG participation (p < 0.05) while the qualitative analysis showed different ways women's education level could facilitate or hinder participation. Qualitative interviews further revealed that participation was facilitated by women's interest in acquiring new knowledge, having advanced awareness of the meeting schedule and venue, and engagement with health workers or non-government organisation staff. Participation was hindered by the lack of meeting structure and work obligations during the agricultural season. CONCLUSIONS: To improve women's participation in HMGs in Nepal, it is necessary to address factors at the SEM's individual, interpersonal, and community levels, such as enhancing FCHV literacy, providing advance notice of the meeting schedule, upgrading the meeting venues and reducing women's workload through family support, particularly during agricultural season. These improvements are essential for strengthening effective implementation of HMG meetings and similar women's group-based platforms, and for ultimately improving maternal and child health in Nepal.

Selenium Yeast and Fish Oil Combination Diminishes Cancer Stem Cell Traits and Reverses Cisplatin Resistance in A549 Sphere Cells.

Cisplatin is a prevalent chemotherapeutic agent used for non-small cell lung cancer (NSCLC) that is difficult to treat by targeted therapy, but the emergence of resistance severely limits its efficacy. Thus, an effective strategy to combat cisplatin resistance is required. This study demonstrated that, at clinically achievable concentrations, the combination of selenium yeast (Se-Y) and fish oil (FO) could synergistically induce the apoptosis of cancer stem cell (CSC)-like A549 NSCLC sphere cells, accompanied by a reversal of their resistance to cisplatin. Compared to parental A549 cells, sphere cells have higher cisplatin resistance and possess elevated CSC markers (CD133 and ABCG2), epithelial-mesenchymal transition markers (anexelekto (AXL), vimentin, and N-cadherin), and cytoprotective endoplasmic reticulum (ER) stress marker (glucose-regulated protein 78) and increased oncogenic drivers, such as yes-associated protein, transcriptional coactivator with PDZ-binding motif, ß-catenin, and cyclooxygenase-2. In contrast, the proapoptotic ER stress marker CCAAT/enhancer-binding protein homologous protein and AMP-activated protein kinase (AMPK) activity were reduced in sphere cells. The Se-Y and FO combination synergistically counteracted the above molecular features of A549 sphere cells and diminished their elevated CSC-like side population. AMPK inhibition by compound C restored the side population proportion diminished by this nutrient combination. The results suggest that the Se-Y and FO combination can potentially improve the outcome of cisplatin-treated NSCLC with phenotypes such as A549 cells.

Association between long-term opioid use and cancer risk in patients with chronic pain: a propensity score-matched cohort study.

BACKGROUND: Whether long-term opioid use is an independent risk factor for cancer progression remains unclear. Therefore, we conducted a propensity score-matched population-based cohort study to compare cancer incidence between patients with chronic pain with and without opioid use. METHODS: Data from January 2008 to December 2019 were obtained from the Taiwan National Health Insurance Research Database. Patients were categorised into two groups according to the presence or absence of opioid use, and matched at a 4:1 ratio. The incidence rate ratios for specific cancers were determined. RESULTS: Propensity score-matching yielded 63 610 patients: 50 888 with opioid use (the opioid group) and 12 722 without (the non-opioid group). In a multivariate Cox regression analysis, the adjusted hazard ratio (95% confidence interval) for cancers in the opioid group compared with the non-opioid group was 2.66 (1.44-2.94; P<0.001). The incidence rate ratios (95% confidence interval) for lung, hepatocellular, colorectal, breast, prostate, head and neck, pancreatic, gastric, oesophageal, and ovarian cancers for the opioid group were 1.87 (1.41-2.43), 1.97 (1.56-2.50), 2.39 (1.87-3.03), 2.43 (1.75-3.33), 2.00 (1.35-3.03), 1.79 (1.14-2.86), 1.87 (1.13-2.12), 2.43 (1.52-3.85), 1.82 (0.92-3.70), and 2.33 (1.01-5.55), respectively. CONCLUSION: There was an association between long-term opioid use and development of cancer in patients with chronic pain, which should be confirmed in future studies.

Sarcopenia as an Independent Risk Factor for Specific Cancers: A Propensity Score-Matched Asian Population-Based Cohort Study.

Purpose: Whether preexisting sarcopenia is an independent risk factor for cancer incidence remains unclear. Therefore, we performed this propensity score (PS)-matched (PSM) population-based cohort study to compare the incidence rate ratios (IRRs) of specific cancers between patients with and without sarcopenia. Patients and Methods: The patients were categorized into two groups according to the presence or absence of sarcopenia, matched at a 4:1 ratio. Results: PS matching yielded a final cohort of 77,608 patients (15,527 in the sarcopenia and 62,081 nonsarcopenia groups) eligible for further analysis. In our multivariate Cox regression analysis, compared with the nonsarcopenia group, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) for cancer risk in the sarcopenia group was 1.277 (1.10 to 1.36; p < 0.001). Furthermore, the adjusted IRRs (95% CIs) for sarcopenia patients were pancreatic cancer 3.77 (1.79 to 4.01), esophageal cancer 3.38 (1.87 to 4.11), lung cancer 2.66 (1.15 to 2.90), gastric cancer 2.25 (1.54 to 3.23), head and neck cancer 2.15 (1.44 to 2.53), colorectal cancer 2.04 (1.77 to 2.30), hepatocellular carcinoma 1.84 (1.30 to 2.36), breast cancer 1.56 (1.12 to 1.95), and ovarian cancer 1.43 (1.10 to 2.29), respectively. Conclusions: Sarcopenia might be a significant cancer risk factor for lung, colorectal, breast, head and neck, pancreas, gastric, esophageal, and ovarian cancer, as well as hepatocellular carcinoma.

Anesthesia With Propofol Sedation Reduces Locoregional Recurrence in Patients With Breast Cancer Receiving Total Mastectomy Compared With Non-Propofol Anesthesia.

Purpose: We examined locoregional recurrence (LRR) in patients with breast invasive ductal carcinoma (IDC) receiving total mastectomy (TM) under propofol-based paravertebral block-regional anesthesia (PB-RA) versus sevoflurane-based inhalational general anesthesia (INHA-GA) without propofol. All-cause death and distant metastasis were secondary endpoints. Patients and Methods: Patients with breast IDC receiving TM were recruited through propensity score matching and categorized into INHA-GA with sevoflurane and PB-RA with propofol groups. Cox regression analysis was performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: In the multivariate Cox regression analysis, the adjusted HR (aHR; 95% CI) of LRR for the PB-RA with propofol group was 0.52 (0.28-0.96) compared with the INHA-GA with sevoflurane group. The aHRs of LRR for differentiation grade II, grade III, the American Joint Committee on Cancer clinical stage II, stage III, pathological tumor (pT) stage 2, pT stage 3-4, pathological nodal (pN) stage 1, and pN stage 2-3 were 1.16 (1.04-2.08), 1.28 (1.07-2.12), 3.71 (1.82-7.59), 4.67 (1.65-13.18), 1.09 (1.02-1.21), 1.17 (1.03-2.16), 1.10 (1.03-1.33), and 1.22 (1.06-2.41), respectively, compared with differentiation grade I, clinical stage I, pT1, and pN0. The aHR of LRR for adjuvant RT was 0.88 (0.64-0.94) compared with that for no adjuvant RT. Conclusion: PB-RA with propofol might be beneficial for reducing LRR in women with breast IDC receiving TM compared with INHA-GA without propofol.