Problemy sotsial'noi gigieny, zdravookhraneniia i istorii meditsinyG K Kanatbekova, O A Bolbachan, D D Ibraimova
The article presents results of analysis of medical demographic indicators of the Kyrgyz Republic in 2016-2024. The study was carried out concerning dynamics of population size, natality, mortality and migration processes based on statistical data from the National Statistical Committee and the Center of E-Health Care. The regional differences in demographic trends were revealed. The high natality is specific for Southern regions, while in Northern regions its steady decreasing was fixed. It is established that COVID-19 pandemic had short-term impact on mortality growth in 2020. Despite positive natural increase, its pace is decreasing that requires elaboration of state demographic policy and mechanisms stimulating natality, population health promotion and development of regional health care infrastructure. In 2022-2023 migration flows demonstrated positive balance that reflects changes in social economic priorities of population. The main motives for migration remain low wages, limited career opportunities and uncertainty about future. The obtained results confirm necessity of systematic approach to prognostication of demographic processes and development of measures stabilizing medical demographic situation in the Republic.
Cancer biology & therapyJolanta Kryczka, Jakub Mateusz Kryczka, Łukasz Janczewski, Sho Shimida, Andrzej Frączyk, Beata Kolesińska, Joanna Boncela, Ewa Brzeziańska-Lasota
BACKGROUND: Lung cancer presents complex etiopathology involving a mix of genetic predispositions and environmental factors. The best treatment modality is surgical resection. However, it becomes ineffective in the advanced metastatic stage. Thus, cisplatin-based chemotherapy, though restricted by an intrinsic and/or acquired chemo-resistant phenotype, remains the first-line therapy for advanced non-small-cell cancer (NSCLC). METHODS: Various tools were used to verify the mRNA expression and protein levels of ABC and ALDH proteins in patient-derived non-small-cell lung cancer (NSCLC) samples (GSE102287, GSE43580) and cell lines A549 and NCI-H158 (including their respective cisplatin-resistant variants) to verify the cisplatin-sensitizing abilities of newly synthesized bis-(di-4-phenyl-benzylaminethiocarbonyl)disulfide-non-toxic ALDH and ABCC2 inhibitors. RESULTS: We identified significant molecular differences in the expression levels of ABCC1, ABCC5, ABCC3, ALDH7A1, and ALDH3A1. Additionally, a fairly significant patient subgroup (Z-score > 1.5), characterized by ABCC2 and ALDH3A1 overexpression, was identified. Importantly, in vitro, ABCC2 and ALDH3A1 accompany the acquisition of cisplatin resistance in A549 cells. Bis-(di-4-phenyl-benzylaminethiocarbonyl)disulfide reverses cisplatin resistance in a cisplatin-resistant variant of A549 cells (via ALDH and ABCC2 inhibition) but not in NCI-H158 cells. CONCLUSIONS: Molecular categorization of NSCLC cancer is essential for predicting therapy outcomes, enabling the use of bis-(di-4-phenyl-benzylaminethiocarbonyl)disulfide as a cisplatin therapy enhancer for NSCLC patients' subpopulation with significant ABCC2 and ALDH3A1 overexpression.
BACKGROUND: Evidence for hypertonic saline (HS) in nontuberculous mycobacterial lung disease (NTM-LD) remains limited, particularly during watchful waiting when non-antibiotic strategies are needed. We evaluated inhaled 3% HS as a potential adjunct in antibiotic-naïve NTM-LD. METHODS: In this prospective cohort study, antibiotic-naïve NTM-LD patients were enrolled between September 2024 and December 2025. Patients receiving daily inhaled 3% HS were compared with contemporaneous controls. Symptom burden (visual analog scale, 0-60) and sputum smear status at month 3 were analysed using generalised estimating equations. In vitro experiments assessed HS effects on Mycobacterium abscessus growth and macrophage function, including intracellular bacterial burden, viability, phagocytosis, and pro-inflammatory gene expression. RESULTS: Among 45 patients (HS: n = 22; control: n = 23), 3% HS was associated with a significant reduction in symptom burden from baseline (coefficient -4.40, 95% CI -6.43 to -2.37; p < 0.001) and a lower odds of sputum smear positivity at month 3 (odds ratio 0.15, 95% CI 0.03-0.64; p = 0.011) in adjusted analyses. In vitro, HS inhibited extracellular M. abscessus growth in a concentration-dependent manner. Pretreatment of macrophages with 3% HS reduced intracellular M. abscessus burden by 51% (p = 0.021) without impairing viability or phagocytosis, while upregulating pro-inflammatory gene expression, including TNF-α (p = 0.004), IL-6 (p = 0.030), and IL-1β (p = 0.058). CONCLUSIONS: In antibiotic-naïve NTM-LD, inhaled 3% HS was associated with improved symptom burden and reduced progression to sputum smear positivity. Complementary in vitro findings support both direct antimycobacterial effects and enhanced macrophage-mediated control, supporting HS as a biologically active adjunct during conservative management of NTM-LD.
PulmonologyMarcela Bhering, Carla Conceição, Martha Oliveira, Ana Paula Razal Dalvi, Marcelo Cordeiro-Santos, Adriana Rezende Moreira, Anna Cristina Calçado Carvalho, Ali…
BACKGROUND: Tuberculosis infection (TBI) diagnosis in BCG-vaccinated, high-burden settings remains challenging. RESEARCH QUESTION: We aimed to assess the sensitivity, specificity, and safety of the C-tuberculin skin test (C-TST), compared with PPD RT-23, for tuberculosis infection in BCG-vaccinated adults. STUDY DESIGN AND METHODS: Randomised, double-blind clinical trial in Brazil. Adults with pulmonary tuberculosis (PTB) and asymptomatic controls without known TB exposure or prior TB/TPT underwent C-TST, PPD RT-23, and QuantiFERON-TB Gold Plus (QFT-Plus). Skin tests were read by two strategies: (a) induration only or (b) induration or erythema, at a ≥5-mm cut-off. Sensitivity was assessed in PTB; specificity for C-TST and PPD RT-23 was estimated against QFT-Plus. Adverse events were monitored. RESULTS: Among 446 participants (141 PTB; 305 controls), at the 5-mm cut-off, C-TST showed lower sensitivity but higher specificity than PPD RT-23. With strategy (a) and (b), C-TST sensitivity was 0.67 and 0.68, specificity was 0.92 and 0.9, compared to 0.74 sensitivity and 0.78 specificity for PPD RT-23. Adverse events were more frequent in PTB: 12.1% (C-TST) and 6.4% (PPD RT-23); none were serious. CONCLUSION: In BCG‑vaccinated adults, C-TST showed a trade-off of higher specificity and lower sensitivity than PPD RT-23 at the 5-mm cut-off; and a favourable safety profile. Adding erythema to readings did not improve accuracy, suggesting that C-TST may be a useful alternative for programmatic TBI screening in high-burden settings. TRIAL REGISTRATION: Trial registry number RBR-7tn2ysw (https://ensaiosclinicos.gov.br/ registered on 25 January 2021).
This work reports the development and systematic evaluation of a carboxymethyl cellulose (CMC)-based nanocarrier system co-loaded with cerium oxide (CeO2) and carbon quantum dots (CQDs) for pH-responsive delivery of quercetin (QC) and in vitro evaluation in lung cancer cells. The nanocarriers were prepared using a water-in-oil-in-water (W/O/W) double emulsion approach, yielding spherical particles with an average size of approximately 134 nm and a high positive surface charge (+66 mV), indicative of favourable colloidal stability. FESEM analysis confirmed a uniform morphology and compact internal structure. The incorporation of CeO2 appears to reinforce the polymer matrix, contributing to improved drug encapsulation. The optimized formulation exhibited high encapsulation efficiency (88%) and drug loading capacity (47%), outperforming CeO2-free systems. In vitro release studies demonstrated a clear pH-dependent biphasic behaviour, with significantly faster release under pH 5.4 compared to physiological pH (7.4), reaching 98% and 58% after 96 h, respectively. Drug release followed the Higuchi model, suggesting diffusion-controlled kinetics, while the Korsmeyer-Peppas model indicated a non-Fickian mechanism. An AI-guided nonlinear modelling workflow was used to extract interpretable kinetic descriptors directly from experimental release data. Biological evaluation revealed enhanced anticancer activity against A549 cells, with viability reduced to 49.1%, while maintaining high biocompatibility towards L929 cells.
PulmonologyCláudia Chaves Loureiro, Filipa Carriço, Ulisses Brito, Inês Belchior, Rosa-Anita Fernandes, Nuno Sousa, Ana Mendes, Carlos Loureiro, Cecília Pardal, Anna Soko…
BACKGROUND AND OBJECTIVES: Severe eosinophilic asthma (SEA) is often inadequately controlled. The BETREAT study evaluated the real-world effectiveness of benralizumab, an anti-IL-5 receptor monoclonal antibody, in Portugal, focusing on treatment persistence, asthma control, exacerbation rates, and quality of life (QoL). STUDY DESIGN AND METHODS: Retrospective, observational study including SEA adults who received benralizumab between July 2019 and October 2020 across 16 sites in Portugal. Data from electronic medical records were analysed over 24 months, with evaluations at 3, 6, 12, and 24 months after treatment initiation. Key outcomes included exacerbation rates, oral corticosteroid use, asthma and lung function, and QoL. RESULTS: Of the 74 patients (mean ± SD age 56 ± 11 years and 73.0% female), 66.2% were biologic-naïve. After initiating benralizumab, median eosinophil counts decreased to 0 cells/µL after 3 months. Exacerbation rates decreased from a mean annual rate of 3.12 at baseline to 0.48 by 24 months. Patient-reported asthma control and QoL improved, with ACT and CARAT scores reaching well-controlled levels in most patients by 24 months. Notably, 20.0% of patients achieved clinical remission by the end of the study. CONCLUSIONS: Benralizumab significantly improved SEA outcomes and contributed to clinical remission over a 24-month period, demonstrating potential for long-term disease control and QoL improvement.
BACKGROUND: Cognitive impairment is a relatively prevalent comorbidity in chronic obstructive pulmonary disease (COPD), yet its neuropathological mechanism remains poorly understood. METHODS: We enrolled 48 stable COPD patients, categorized into cognitively normal (CogN, n = 22) and impaired (Cog, n = 26) groups based on Montreal Cognitive Assessment (MoCA) scores, along with 34 matched healthy controls. All participants underwent 3T MRI with quantitative susceptibility mapping (QSM) to quantify regional brain iron content. Group comparisons of whole-brain and region-of-interest susceptibility were performed. Mediation analysis was then used to test whether specific brain iron deposition mediates the relationship of both COPD status and peripheral inflammatory markers with cognitive performance. RESULTS: Cog patients showed increased total iron in the right cerebellum crus I, while CogN patients exhibited higher paramagnetic susceptibility (χpara) in the left orbitofrontal cortex (OFC), right precentral gyrus, and right brainstem. χpara in the left OFC and right brainstem were positively correlated with total MoCA, abstraction, and orientation scores. Mediation analysis demonstrated that χpara of the left OFC mediated the effects of both COPD status and systemic neutrophil counts on impaired abstraction. Additionally, right brainstem χpara mediated the relationship between COPD and deficits in orientation. CONCLUSIONS: COPD patients with cognitive impairment exhibited distinct patterns of brain iron deposition. Importantly, deposition in several key regions served as a potential mediator, linking both COPD and systemic inflammation to specific cognitive deficits. These preliminary findings suggest a possible association between brain iron accumulation and cognitive impairment in COPD, offering candidate neuroimaging markers for early identification. .
This study examines mass testing in three Chinese cities since 2020 as a 'stress test' for local governance. It analyses the governance performance of Shenzhen, Nanjing and Wuxi in terms of efficiency, equity and community resilience. Using Melbourne's pandemic lockdown as a reference case, it discusses the underlying mechanisms linking different governance approaches to health equity outcomes. The study adopts a nested governance framework to examine how governance capacities and policy logics operate across different local contexts. The results indicate that Chinese cities can efficiently complete mass testing within a few days, but face pressures related to health equity and community resilience. Melbourne's lockdown governance emphasised participation and institutional transparency, but advanced policies at a relatively slower pace. This study recommends building a dynamic governance mechanism that better balances efficiency and equity.
Annals of medicineYaqi Sun, Kaixin Zhou, Wenhui Wang, Qian Gao, Yan Lin
BACKGROUND: Tuberculosis (TB) remains the leading cause of death from infectious diseases worldwide, and its control is increasingly complicated by chronic comorbidities. Diabetes mellitus (DM), human immunodeficiency virus (HIV) infection, chronic obstructive pulmonary disease (COPD), and lung cancer (LC) substantially affect TB susceptibility, diagnosis, treatment, and prognosis. METHODS: This narrative review summarizes evidence on the interactions between TB and DM, HIV infection, COPD, and LC. Relevant literature was identified through PubMed, Web of Science, and World Health Organization publications, focusing on studies published between 2001 and 2025. Priority was given to peer-reviewed original studies and reviews addressing immune mechanisms, diagnosis, and treatment. RESULTS: DM increases TB risk by impairing innate and adaptive immunity and complicates prevention, diagnosis, and treatment. HIV-1 weakens antimycobacterial defense through lymphocyte depletion, macrophage dysfunction, granuloma instability, and immune exhaustion, markedly increasing susceptibility to active TB. TB and COPD mutually aggravate pulmonary inflammation, oxidative stress, and structural lung damage, contributing to poor respiratory outcomes. Mycobacterium tuberculosis(M.tb) infection may also be associated with LC development through chronic inflammation, oxidative stress-related genomic instability, and oncogenic signaling. Overall, these comorbidities increase diagnostic difficulty, therapeutic complexity, and the risk of adverse outcomes. CONCLUSIONS: TB associated comorbidities remain a major challenge to global TB control. Understanding these interactions may support bidirectional screening, risk stratification, and integrated management. Although these conditions share immune dysregulation, chronic inflammation, and oxidative stress, they differ in dominant mechanisms, diagnostic challenges, and treatment priorities. Future research should prioritize biomarker discovery, mechanistic clarification, and multilevel prevention and control strategies.
While interferon regulatory factor 1 (IRF1) has been implicated in reactive oxygen species (ROS)-dependent neutrophil extracellular trap (NET) release during acute lung injury, its regulatory role in mitochondrial dysfunction-driven NETosis specific to pediatric pneumonia remains unexplored. Neutrophils were isolated from the bronchoalveolar lavage fluid (BALF) of pediatric pneumonia patients and the bone marrow of mice. IRF1 expression was quantified via qRT-PCR and Western blotting. Mitochondrial ROS (mtROS) and total ROS were measured by flow cytometry. Mitochondrial dysfunction was assessed by ATP quantification. NETosis was evaluated through immunofluorescence staining and ELISA quantification of neutrophil elastase (NE), myeloperoxidase-DNA (MPO-DNA), and citrullinated histone H3 (Cit-H3) levels. For in vivo studies, pneumonia-related lung injury was induced by intratracheal LPS instillation in mice, with pathological severity graded by H&E staining, pulmonary edema quantified via the wet/dry weight ratio, and inflammation assessed by the BALF protein concentration. Mechanistically, the IRF1/MMP9 interaction was predicted by bioinformatics (STRING database) and validated by co-immunoprecipitation (Co-IP) and immunofluorescence staining, while MMP9 overexpression was achieved via lentivirus transduction to delineate pathway regulation. IRF1 was significantly upregulated in BALF neutrophils from patients and correlated with elevated ROS production and mitochondrial dysfunction, as well as NETs release. IRF1 knockdown attenuated ROS-driven NETosis in vitro. Matrix metalloproteinase 9 (MMP9) was predicted to interact with IRF1, and MMP9 overexpression effectively reversed the beneficial effects of IRF1 deficiency on ROS release, mitochondrial dysfunction, neutrophil apoptosis, and NETosis. Consistently, in mouse models, MMP9 overexpression abolished the protective effects of IRF1 deficiency, exacerbating acute lung injury and restoring NETs levels in BALF.
PulmonologyDavid Jimenez, Behnood Bikdeli, Victor Tapson, Cecilia Becattini, Lisa Moores, Geoffrey D Barnes, Manuel Monreal, Stavros Konstantinides, Gregory Piazza, Raque…
BACKGROUND: For patients with acute pulmonary embolism (PE), assessment of prognosis helps with risk stratification, triage for level of care, management strategy, and communication among healthcare workers and patients. We sought to identify prognostic models and individual factors associated with short-term outcomes after acute symptomatic PE. METHODS: We performed a systematic review of prognostic factors for PE, searching MEDLINE, Embase, and Web of Science for records up to 1 June 2024. Studies of any design evaluating potential prognostic models or individual variables (not contained in the models) associated with short-term mortality after acute PE were included. RESULTS: We identified 314 studies that included 2,495,115 patients. Of these, 225 studies included 2,267,952 patients and evaluated 24 prognostic models for patients with acute PE. The most frequently used validated models were the simplified Pulmonary Embolism Severity Index (sPESI) (127 studies), the original PESI (79 studies), and the European Society of Cardiology risk schema (34 studies). Each model-development study had a c-index ≥ 0.7. Individual factors associated with prognosis included older age, presence of coexisting conditions, abnormal clinical signs and symptoms, clot burden, markers of right‑ventricle dilatation/dysfunction and myocardial injury, altered laboratory results indicating impaired haemodynamics, and tests that assess for systemic inflammation. Pooled odds ratios for variables not contained in any eligible prognostic model ranged from 1.43 (for D-dimer) to 2.65 (for right heart thrombi). CONCLUSIONS: This systematic review identified 24 prognostic models and 18 individual variables distinct from the prognostic models associated with short-term mortality after acute PE.
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease, and currently, there are no effective means to reverse its progression. Cuproptosis is a newly discovered copper-dependent programmed cell death mechanism, but its role in IPF remains unknown. This study aimed to investigate whether Cuproptosis is involved in the pathogenesis of IPF and to evaluate its potential as a therapeutic target. METHODS: In vitro, a fibrosis model was induced in human lung epithelial cells by bleomycin treatment. In vivo, a C57BL/6J mouse IPF model was established by intratracheal instillation of bleomycin. The effects on fibrosis progression were observed using the Cuproptosis inhibitor ammonium tetrathiomolybdate and siRNA knockdown of the copper ion transporter Slc31a1. RESULTS: Significant Cuproptosis was observed in both BLM-induced lung epithelial cells and mouse lung tissue. Gene expression profiling identified key Cuproptosis-related genes, including Slc31a1. Pharmacological inhibition of Cuproptosis effectively reversed the Cuproptosis process in both in vitro and in vivo models and significantly reduced fibrotic pathological changes. At the cellular level, knockdown of Slc31a1 mimics the protective effect of TTM; however, its efficacy in whole animal models is limited. CONCLUSION: This study identifies cuproptosis as a significant contributor to the pathogenesis of pulmonary fibrosis. Pharmacological inhibition of this pathway alleviates disease phenotypes, supporting the feasibility of targeting copper metabolism.
The gut microbiome is increasingly recognized as a key modulator of cancer immunotherapy efficacy. Given that diet is one of the most important determinants of the gut microbiome composition and function, nutritional strategies have emerged as promising tools to modulate anti-tumor immune responses. Here, we demonstrate that dietary supplementation with inulin reduces tumor growth and enhances αPD-1 efficacy in mice. These effects were associated with increased frequencies of intra-tumoral CD8⁺ and CD4⁺ T cells, particularly CCR9⁺CXCR3⁺ subsets, and enrichment of beneficial taxa such as Akkermansia and Lachnospiraceae, alongside elevated short-chain fatty acids (SCFA) levels. Among the SCFA, butyrate alone recapitulated the anti-tumor effect of inulin and had an additive effect when combined with αPD-1 therapy in a CD8⁺ T cell-dependent manner. Butyrate exerted its anti-tumor effects by transcriptional changes in CD8⁺ T cells involving activation of proliferation, trafficking, and metabolic pathways. In a cohort of 117 non-small cell lung cancer (NSCLC) patients amenable to immunotherapy, the median dietary fiber intake was lower than previously published studies but correlated with enrichment of Faecalibacterium praunitzii and metabolic pathways related to sucrose degradation and tryptophan biosynthesis. Collectively, our findings highlight the therapeutic potential of targeting diet-microbiome-immune system interactions to improve cancer immunotherapy outcomes.
Annals of medicineMeng Yuan, Si-Jin Lv, Meng-Ru Wu, Yu-Chen Lu, Min-Hao Zhang, Jian-Hua He
BACKGROUND: Postoperative pain after thoracic surgery remains common and challenging. Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive neuromodulation technique with potential analgesic effects. This study aimed to evaluate the efficacy and safety of taVNS for postoperative pain management in patients undergoing thoracoscopic partial lung resection. METHODS: Adults undergoing thoracoscopic partial lung resection were randomized to active or sham taVNS. The primary outcome was cough pain intensity at 48h post-surgery, assessed by Numeric Rating Scale (NRS). Secondary outcomes included cough pain at 24h and 72h, resting pain, moderate-to-severe pain incidence, opioid consumption, quality of recovery, postoperative pulmonary complications , chest tube duration, hospital stay, postoperative nausea/vomiting, and adverse events. RESULTS: Among 119 analyzed patients (active n = 60, sham n = 59), active taVNS reduced cough pain scores at 24h, 48h, and 72h postoperatively, as well as resting pain (p < 0.05). It also lowered the incidence of moderate-to-severe cough pain at 24h and 48h, reduced cumulative postoperative opioid use at 24h and 72h, and decreased rescue analgesia on postoperative day 3 (p < 0.05). Active taVNS was associated with a lower incidence of postoperative pneumothorax (p < 0.05). No serious adverse events occurred. CONCLUSION: Perioperative taVNS was associated with a modest analgesic benefit and reduced postoperative opioid requirements after thoracoscopic partial lung resection. The observed reduction in postoperative pneumothorax requires cautious interpretation, and further multicenter trials are needed to determine its clinical utility.
VirulenceYvette Kazungu, Shrilakshmi Hegde, Parul Sharma, Amy Marriott, Andrew Steven, Jesus Reine, Jessica Dagley, Matthias Mack, Anja Kipar, James P Stewart, Joseph D…
SARS-CoV2 can induce an acute respiratory distress syndrome (ARDS), provoked by a dysregulated hyper-inflammatory pulmonary immune response. Here, we used the keratinocyte-18 humanized angiotensin converting enzyme-2 (K18-hACE2) mouse model of SARS-CoV2, where expression of the CoV2 spike protein receptor, hACE-2, is restricted to epithelia, to characterize inflammatory pulmonary immune responses post-intranasal infections with the delta isolate SARS-CoV2(∆) B.1.617.2. Immune-profiling by focused transcript analysis, inflammatory protein array, and multi-color flow cytometry, confirmed that clinically relevant markers of COVID-19 (IL-6, GM-CSF, neutrophils, inflammatory monocytes) were significantly elevated in lungs of mice at day 5 post-infection and that remdesivir antiviral active metabolite (GS441524) treatment significantly modified SARS-CoV2∆ viral loads and pulmonary inflammation. Chemokine ligands of CCR2 (CCL2/7/8) were among the top 5% upregulated pulmonary transcripts in a focused human infection response array to SARS-CoV2∆. CCL2 was confirmed as elevated in protein assays in SARS-CoV2∆ infected lungs. To address the functional relevance of the CCR2 pathway of inflammatory cell recruitment to the lungs mediating disease, mice were administered with anti-CCR2 antibody daily at the point of infection for up to 6 d. Anti-CCR2 treated mice showed significant improved welfare scores, were protected from weight loss, modified myeloid pneumonitis, and displayed significantly blunted cytokine and chemokine response in the lungs, despite not affecting pulmonary viral loads. Our data supports therapeutic benefit of modifying CCR2-dependent cell recruitment in the treatment of viral-induced ARDS.
Annals of human biologyQunyan Yao, Hui Zhang, Jinhua Jiang, Feng Yuan
BACKGROUND: Chronic inflammation is implicated in lung cancer pathogenesis. Inflammation-related haematologic indices are accessible biomarkers, but their associations with lung cancer risk and mortality in the general US population are not well-established. AIM: To investigate the associations of five inflammation-related haematologic indices (NLR, MLR, NMLR, ALI, PIV) with lung cancer risk and all-cause mortality among US adults. SUBJECTS AND METHODS: This population-based study analysed 47,862 adults from the 1999-2018 NHANES. Lung cancer was self-reported. Associations with lung cancer risk in the overall study population and with all-cause mortality among participants with lung cancer (followed through 2019) were assessed using weighted logistic and Cox regression models, respectively. Sensitivity analyses, including machine learning, were performed. RESULTS: Among participants, 114 had lung cancer. Higher NLR, MLR, NMLR, and PIV were significantly associated with increased lung cancer risk (e.g. per 1-SD increase: MLR OR = 1.50) and all-cause mortality (e.g. MLR HR = 1.40). Conversely, higher ALI was associated with decreased risk (OR = 0.58) and mortality (HR = 0.53). MLR showed the highest discriminative ability for risk (AUC = 0.715). Sensitivity analyses confirmed robustness. CONCLUSION: Inflammation-related haematologic indices are significantly associated with lung cancer risk and prognosis. These low-cost biomarkers show potential for risk stratification and prognostic assessment.
Seasonal influenza causes considerable morbidity and mortality, with influenza A and B viruses driving most influenza-associated hospitalizations and deaths. Vaccination remains a key influenza prevention strategy; however, current seasonal influenza vaccines based on traditional platforms provide inconsistent protection. Messenger RNA - based vaccines may offer several key advantages over other vaccines, including the flexibility to optimize antigen expression to enhance immunogenicity without the need for adjuvants. mRNA-1010 is an investigational seasonal influenza vaccine candidate that encodes hemagglutinins (HAs) from WHO-recommended influenza strains. In this randomized, phase 2 study, safety, reactogenicity, and immunogenicity of 3 mRNA-1010 vaccine candidate compositions were evaluated in healthy adults aged 18-49 y in the United States (NCT05868382). Eligible participants were randomly assigned to receive a single dose of one of the mRNA-1010 compositions at several dose levels. The primary objective was the safety and reactogenicity of mRNA-1010 vaccine candidate compositions against vaccine-matched strains; secondary and exploratory objectives included humoral and cellular immunogenicity at evaluable timepoints, respectively. Two hundred and seventy participants received study vaccination between May and December 2023. All mRNA-1010 vaccine compositions were well tolerated, with no safety concerns identified; all compositions induced HA-specific humoral and cellular immune responses against all influenza strains evaluated, with the optimized compositions exhibiting higher immune responses against influenza B strains compared with the original mRNA-1010 composition. These results, together with findings from other mRNA-1010 clinical studies, support continued evaluation of mRNA-1010 for enhanced protection against seasonal influenza.Clinical Trials Registration: Clinicaltrials.gov: NCT05868382.
Journal of medical economicsAlon Yehoshua, Rachel M Black, Manuela Di Fusco, Benjamin Carter, Danielle Sienko, Santiago Lopez, Maria D McColgan, Abby E Rudolph, Jingyan Yang
AIMS: This study assessed long-term healthcare resource utilization (HCRU) and direct medical costs associated with COVID-19 among adults and children in the United States. Using a large national claims database, we quantified the incremental healthcare burden during the year following a first COVID-19 diagnosis compared to matched controls without a COVID-19 diagnosis. MATERIALS AND METHODS: This retrospective cohort study used data from the IQVIA PharMetrics Plus database. Patients with a COVID-19 diagnosis (U07.1) between June 1 and November 30, 2022, were matched 1:1 to non-COVID-19 controls based on age, sex, region, insurance type, Charlson Comorbidity Index, and baseline HCRU. Outcomes were HCRU and all-cause healthcare costs accrued during the post-acute period (≥31 days after first COVID-19 diagnosis), measured cumulatively through 1, 3, 6, 9, and 11 months of follow-up. Generalized linear models estimated cost ratios. RESULTS: The study included 944,627 patients with a COVID-19 diagnosis (U07.1) and an equal number of matched controls. Compared with matched controls, mean total costs during 11 months of post-acute follow-up were 27% higher among adults ($11,508 vs $9,040; p < 0.001) and 42% higher among pediatric patients with COVID-19 ($3,997 vs $2,812; p < 0.001). Costs were higher for COVID-19 cases at all follow-up time points. Among adults at the 11-month follow-up time, costs increased with acute infection severity, with mean costs of $10,372 for outpatients, $36,848 for hospitalized patients, and $51,643 for ICU patients, compared with $8,617, $16,926, and $17,620, respectively, among matched controls (all p < 0.001). Among adults, cost ratios peaked at 1 month of follow-up (1.32; 95% CI: 1.31-1.33) and declined to 1.15 (95% CI: 1.14-1.15) at 11 months. CONCLUSIONS: There were significantly higher post-acute HCRU and costs among both adults and pediatrics with a COVID-19 diagnosis compared to matched controls without one, with elevated cost differences persisting up to 12 months post-infection.
Global public healthHang Duong, Nor Kamila Kamaruzaman, Katie Attwell
Conceptually, current definitions of vaccine mandates involve two key elements: the requirement to be vaccinated and sanctions for non-compliance. However, during COVID-19, governments frequently introduced vaccine mandates in contexts where people were already denied access to work, travel, and social activities due to lockdowns and restrictions. This important context disrupts the standard operation of vaccine mandates. Accordingly, this paper explores COVID-19 vaccine mandates in New South Wales (Australia), France, Israel, Malaysia, Singapore, and Vietnam, where mandates primarily served as incentives to restore basic rights to travel, work, and access public spaces, that were restricted during the pandemic. Through document analysis and key informant interviews, the paper examines how governments employed this "removal and restoration" model and explores how mandate policy instruments create incentive structures. In discussing the implications of mandates in relation to lockdowns and restrictions, and the perception of mandates as "coercive offers", the paper proposes a revised conception and a 7S vaccine mandate framework by adding synergy and sustainment to the existing 5S model. It concludes by outlining the significance of this revised conception and framework for vaccine mandate policy research, design, and communication.
Gut microbesJiang Yu, Jianbiao Meng, Zhongliang Shi, Jitao Zou, Zhizhen Lai
Cross-kingdom dysbiosis of the gut microbiome along the gut-lung axis has emerged as a key driver of chronic and acute respiratory diseases. Beyond bacteria, the intestinal mycobiome and virome, including bacteriophages, shape mucosal immunity and metabolism through partially overlapping but non-redundant pathways. In this Review, we synthesize rapidly expanding evidence that fungi, bacteria, and phages in the gut form an integrated network that may influence susceptibility, inflammatory tone, and therapeutic responsiveness across asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), and lung cancer via the gut-lung axis. We first summarize how cross-kingdom communities in the intestine are organized and interact, highlighting a tripartite framework centered on pathogen-associated molecular pattern-pattern recognition receptor (PAMP-PRR) circuits, the short-chain fatty acid (SCFA)-regulatory T-cell axis, and tryptophan-indole-aryl hydrocarbon receptor (AHR) signaling. We then compare how these shared axes are differentially perturbed across asthma, COPD, ARDS, and lung cancer, using these disorders as representative but non-sequential disease contexts along a conceptual gradient of immune-microecological disruption. Finally, we discuss how dietary modulation, pre-/pro-/postbiotics, mycobiome- and virome-targeted strategies, and phage-based approaches could be rationally combined to restore gut-derived immunometabolic circuits and improve respiratory outcomes. By integrating cross-kingdom ecology with mucosal immunology, this Review provides an integrative interpretive framework suggesting that gut microbiome-targeted strategies may help refine prevention, stratification, and adjunctive treatment approaches in selected respiratory disease contexts.