医学最新文献

Globally, there are over 3 million severe cases of influenza each year, leading to up to half a million deaths. This study provides a comprehensive analysis of the current status of children's influenza vaccine research over the past 20 years and explores potential future research trends, including improvements in vaccine coverage and strategies to address vaccine hesitancy. We extracted all research data on children's influenza vaccines from 2004 to 2024 using the Web of Science Core Collection (WOSCC). The contributions of various countries/regions, institutions, authors, and journals in this field were assessed, and research hotspots as well as promising future trends were predicted through keyword analysis using CiteSpace and VOSviewer. A total of 2,598 related publications from 2004 to 2024 were identified and collected for analysis. The United States (USA) and England emerged as the leading contributors with the highest number of published papers. AstraZeneca was identified as a key leader among research institutions, and Ambrose Christopher S was recognized as the most productive author in this field. The journals Vaccine and Human Vaccines & Immunotherapeutics stood out as the most prominent publications in this area. The keyword analysis highlighted that international research collaboration maybe a promising strategy for bridging global gaps; Addressing vaccine hesitancy could potentially increase vaccination coverage; Live attenuated vaccines, intranasal administration and universal vaccines are promising directions for future development. These insights highlight potential avenues for improving influenza vaccine coverage and inform strategies to mitigate vaccine hesitancy, crucial for protecting children and enhancing public health.

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.

Regulatory T cells (Tregs) contribute significantly to the immunosuppressive nature of the tumor microenvironment which is a main barrier for immunotherapies of solid cancers. Reducing Treg numbers enhances anti-tumor immune responses but current depletion strategies also impair effector T cells (Teffs), potentially leading to reduced anti-tumor immunity and/or autoimmune diseases. CD137 has been identified as the most differentially expressed gene between peripheral Tregs and intratumoral Tregs in virtually all solid cancers. Further, CD137 is expressed by malignant cells of certain cancers, making it a potential target for tumor immunotherapy. Here, we report the development of a fully human anti-human CD137 antibody of the IgG1 isotype, clone P1A1, that induces antibody-dependent cell-mediated cytotoxicity (ADCC) in CD137⁺ Tregs and cancer cells. P1A1 cross-reacts with murine CD137 which allowed testing murine chimeric P1A1 in syngeneic murine tumor models where P1A1 significantly reduced the number of CD137⁺ Tregs and inhibited tumor growth in a murine hepatocellular carcinoma (HCC) and a melanoma lung metastasis model. P1A1 can also be internalized thus enabling it as a carrier for drugs to target CD137⁺ Tregs and cancer cells. These anti-cancer properties suggest a translation of P1A1 to human immunotherapy.

Background: The body composition of National Collegiate Athletic Association (NCAA) athletes is well documented but no such data exist for university club sports athletes. Additionally, the majority of norms for NCAA athletes were created from individual methods requiring assumptions.

Objective: This study used a four-component (4C) model to measure the body composition of university club sports athletes.

Methods: Data were collected on club athletes participating in baseball, climbing, cycling, figure skating, gymnastics, ice hockey, lacrosse, pickleball, powerlifting, racquetball, rodeo, rugby, soccer, swimming, ultimate, and volleyball. The 4C model consisted of body volume, total body water, and bone mineral content measured by air displacement plethysmography, bioimpedance spectroscopy, and dual-energy x-ray absorptiometry, respectively. Percentile ranks were created for body fat percentage (%BF) and fat-free mass index (FFMI). Mean differences across teams were quantified with Cohen's d.

Results: In total, 225 athletes (137 men, 88 women) completed data collection. Athletes varied in competitive experience (1 to 22 y) and body mass index (16.9 to 36.4 kg·m^-2). The density of the FFM was significantly greater than the assumed value of 1.100 g·cm^-3 for both men (p = .043) and women (p = .011). The %BF ranged from 4.9% to 35.7% (14.3 ± 5.8% BF) for men and from 15.5% to 42.8% (25.2 ± 6.0% BF) for women. FFMI ranged from 15.6 kg·m^-2 to 26.8 kg·m^-2 (30.0 kg·m^-2 outlier removed) for men and from 14.1 kg·m^-2 to 22.6 kg·m^-2 for women. Differences across sports in %BF and FFMI were considered large-sized effects (d ≥ 0.80) for both men and women. Weight-sensitive sports (e.g. cycling and climbing) had the lightest athletes and were among the leanest, whereas power athletes (e.g. powerlifting and rugby) were among the heaviest athletes and had the highest FFMI.

Conclusions: Differences in %BF and FFMI are evident across sports. Due to the small sample size, use caution when interpreting the data as reference values for club sports athletes.

Background: In Egypt, there were 150,578 new cancer cases and 95,275 cancer deaths in 2022, indicating a substantial burden on patients and the healthcare system. The analysis aims to support decision-making related to investments in cancer prevention and new treatments, by highlighting the economic burden associated with five types of cancer.

Methods: The human capital approach was used to estimate productivity losses from premature mortality due to liver, lung, breast, bladder, and cervical cancer in Egypt in 2019 by calculating years of life lost (YLL), years of productive life lost (YPLL), and present value of future lost productivity (PVFLP). Mortality data were sourced from the World Health Organization (WHO), while life expectancy, retirement age, gross domestic product (GDP) per capita, and labor force participation rates were obtained from the World Bank. Income data, such as annual earnings and minimum wage were sourced from the Wage Indicator database. Deterministic sensitivity analysis (DSA) assessed the sensitivity of results to input variations.

Results: In 2019, Egypt had a total of 45,114 deaths, from liver, lung, breast, cervical, and bladder cancers, resulting in a productivity loss of $430,086,636. Liver cancer led to the most male deaths (17,745) and breast cancer to the most female deaths (6,754), with PVFLP of $232,663,468 and $130,745,592, respectively. The five cancers resulted in 551,336 YLL and 235,415 YPLL in Egypt. The total PVFLP was estimated at $217,224,178 for females and $212,862,458 for males, with a total PVFLP/death of $9,533. The DSA showed that the PVFLP was most sensitive to changes in the retirement age.

Conclusion: In conclusion, there is a substantial economic burden relating to premature cancer mortality in Egypt, highlighting that policies and treatment advances to decrease cancer are working, however, there is need for continuous prioritization of awareness programs, cancer screening and treatment advancements.

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.

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.

Purpose: Rugby sevens is a high-intensity contact sport often played in two-day tournaments. Caffeine is widely used by rugby players for its performance-enhancing effects. This study aimed to investigate the impact of caffeine supplementation on various performance metrics, including distance covered at different speeds, acceleration, deceleration, collisions, and repeated high-intensity efforts across four matches over two consecutive days in collegiate male rugby sevens players. Reactive agility, a key performance attribute in rugby sevens, was also assessed before each match.

Methods: A position-matched, double-blind, randomized crossover design was employed, with six male collegiate rugby players (mean height: 1.78 ± 0.09 m, mean weight: 81.3 ± 9.2 kg, mean age: 21.5 ± 0.8 years) participating in two trials. Each trial consisted of a two-day tournament, with two matches per day. Performance was monitored using global positioning system units to track distance covered in various speed zones, as well as total distance, frequency of acceleration, deceleration, collisions, and repeated high-intensity efforts.

Results: The results indicated that in the placebo trial, participants covered significantly more distance at a walking pace (0-6 km/h) in match 4 compared to match 3 (match 3: 480.3 ± 32.7 m; match 4: 629.4 ± 21.3 m, p < 0.001, d = 0.117). In the caffeine trial, players covered significantly more distance at a jogging pace (6-12 km/h) in match 4 compared to the placebo trial (caffeine: 405.9 ± 9.8 m; placebo: 303.6 ± 20.2 m, p = 0.015, d = 1.693). Reactive agility was significantly better in the caffeine trial before match 3 (caffeine trial: 1.80 ± 0.17 s; placebo trial: 2.07 ± 0.18 s, p = 0.038, d = 0.858).

Conclusions: Caffeine supplementation at 3 mg/kg may increase jogging and reduce walking and standing in the final match of a two-day rugby sevens tournament, while also improving reactive agility on the second day. This suggests that by mitigating fatigue in the later stages of the tournament, caffeine allowed players to shift from low-intensity activities to higher-intensity efforts. These adjustments may improve both offensive and defensive performance during rugby sevens matches. Therefore, rugby sevens players could benefit from taking caffeine supplements in the later stages of 2-day tournaments to optimize their performance.

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.

Background: Chronic kidney disease (CKD) is a prevalent chronic, non-communicable disease. The long-term health effects of dietary live microbes, primarily probiotics, on CKD patients remain insufficiently understood. This study aims to investigate the association between dietary intake of live microbes and long-term health outcomes among individuals with CKD.

Methods: Utilizing the National Health and Nutrition Examination Survey (NHANES) database, Cox regression analysis assessed the association between medium and high categories dietary live microbe intake and health outcomes (all-cause, cardiovascular disease [CVD], and cancer-related mortality) in CKD patients.

Results: A total of 3,646 CKD patients were enrolled. During the follow-up period, 1,593 all-cause mortality events were recorded, including 478 CVD deaths and 268 cancer deaths. In the fully adjusted model, compared to CKD patients in the lowest quartile (quartile 1) of live microbes intake, those in quartiles 3 and 4 exhibited a 20% and 26% reduced risk of all-cause mortality, with hazard ratios (HR) of 0.80 (95% confidence interval, CI: 0.69, 0.94) and 0.74 (95% CI: 0.62, 0.90), respectively. Additionally, compared to those with low live microbe intake (quartile 1), higher live microbe intake in quartile 4 was associated with a 37% reduction in the risk of CVD mortality for CKD patients, with an HR of 0.63 (95% CI: 0.45, 0.88). Consistent results were observed in subgroup and sensitivity analyses. A significant negative association was observed between live microbe intake and the risk of all-cause mortality as well as CVD mortality in the CKD population, with a p-value for trend < 0.05.

Conclusion: Our study indicated that high dietary live microbe intake could mitigate the risk of all-cause and CVD mortality in CKD patients. These findings support the inclusion of live microbes in dietary recommendations, highlighting their significant roles in CKD.