Eardrum rupture is one of the most common injuries associated with explosive pressures. Estimates for pressures at rupture vary widely and are challenging to determine because of (I) a range of variables that can degrade the structural integrity of the auditory tissue, and (II) the difficulties of minimizing their impact. Improving predictions on the pressures at which eardrum tissue ruptures would provide useful measures in avoiding or reducing the chances of these injuries. Although a variety of animal models could provide useful data, ovine specimens are uniquely positioned to capture representative behavior for humans, given anatomical similarities, while ameliorating some of the pragmatic issues related to specimen preparation and analysis. The objective of this study is to refine estimates of explosive pressure that initiate rupture of the tympanic membrane in sheep. Fresh cadaveric sheep ears were directly exposed to outdoor blast pressures generated by either composition 1 (C-1) or trinitrotoluene (TNT) explosives. A variety of imaging methods were used to determine the range of pressures at which eardrum rupture occurs. The pressures were measured at a variety of scaled distances for three separate tests of C-1 (n=5), TNT (n=6), and C-1 (n=4). Direct imaging with a boroscope was used for the first two tests, and with more detailed photographic imaging for the third. There were three ranges of pressure that bounded eardrum rupture. For pressures under 30 kPa, no ruptures were observed. Pressures between 30 and 40 kPa resulted in a transition range where both ruptures and intact eardrums were observed. For pressures over 40 kPa, all eardrums ruptured. This included three ruptures that were on the opposite side of the blast direction, where the exposed ear canal entrance measured 75 kPa. Blast pressures that result in cadaveric ovine tissue rupture were narrowed from prior estimates to under 30 kPa (no rupture) to over 40 kPa (rupture) based on direct measurements (n=15). Ears on the opposite side of the blast direction were not spared from rupture.
Tendon injuries are common musculoskeletal conditions that affect both athletic and working populations. Although surgical intervention remains the mainstay of treatment for large tendon injuries, conventional approaches often result in suboptimal healing and functional outcomes. Recent evidence has shown that stem cell therapy may play a role in the management of these injuries. This review comprehensively examines the current literature on stem cell applications in tendon regeneration by analyzing both preclinical and clinical evidence. Specifically, we evaluated various stem cell populations, their characteristics, delivery mechanisms, and repair processes. Additionally, we addressed the limitations of stem cell-based therapies while highlighting emerging trends and future research directions in this rapidly evolving field. PubMed was searched for articles published in August 2025. Boolean operators "Tendon" OR "Tendon repair" OR "Tendon regeneration" OR "Tendon injury" AND "Scaffold" AND "Secretomes" OR "Exosomes" OR "Stem Cells" were used to search for articles. Inclusion criteria included studies within the last 10 years, performed on humans or animals, written in English, as well as articles considered clinical trials, meta-analyses, randomized controlled trials, reviews, or systematic reviews. We identified approximately 1,800 studies, which were screened for relevance to our topic. Additional reference screenings and targeted searches were performed to identify other relevant studies. With advancements in regenerative medicine and material science, new solutions, such as the integration of stem cells and growth factors with specialized scaffolds, offer innovative solutions for tendon regeneration. Various stem cell populations, including mesenchymal stem cells (MSCs), tendon-derived stem cells (TDSCs), and perinatal stem cells (PSCs), have demonstrated potential for assisting in tendon repair. However, significant challenges persist regarding ethical considerations, safety protocols, and treatment standardization. Stem cell therapy represents a promising frontier in tendon healing, with growing preclinical and clinical support for its regenerative efficacy.
Classification of lung adenocarcinoma into subtypes is relatively recent and not universally practiced. Consequently, large representative studies describing clinical outcomes are rare, failing to pervasively present the advantages of subtyping, which might potentially improve treatment and survival. Although many related studies have been published, few of them include large patient numbers of unselected adenocarcinoma subtypes, which has probably resulted in discrepant results. We describe the situation in Sweden with the largest study on a European population with a focus on survival. Patient data were obtained from the Swedish Cancer Registry from 2005 to 2021, accounting for 1,418 patients, less than 5% of the reference group 'adenocarcinoma not otherwise specified (NOS)'. All reported adenocarcinoma patients were included from the cancer registry, with complete national coverage of patients and pathological verification of diagnoses. Non-parametric survival estimates were calculated using the Kaplan-Meier method and testing for linear consistency using Weibull modelling. Survival was generally better for women compared to men and this was most prominent for early-stage cancers. Female 5-year survival decreased in order, lepidic [59%, 95% confidence interval (CI): 55-65%], papillary (51%, 95% CI: 40-64%), invasive mucinous (46%, 95% CI: 32-66%), colloid (36%, 95% CI: 30-43%) and adenocarcinoma NOS (24%, 95% CI: 24-25%). Male 5-year survival for lepidic (46%, 95% CI: 40-53%) and colloid subtypes (22%, 95% CI: 16-29%) was significantly lower than female survival. Survival slopes for T1, T2, N0, M0 cases of lepidic, papillary and adenocarcinoma NOS were almost linear, suggesting homogeneous diagnostics. Survival kinetics were in agreement with Weibull modelling k-values of 1.00 or slightly higher, implying that mortality increased slowly with time, only moderately faster than for the background population of similar age. The present study is among the largest ones so far published on unselected stages of adenocarcinoma subtypes. Our findings demonstrate a significant female survival advantage across most adenocarcinoma subtypes. Survival in T1 and T2 classes with N0 and M0 for lepidic, papillary and adenocarcinoma NOS was close to linear, suggesting that patients are homogeneously diagnosed and treated. Survival benefits of lepidic and papillary subtypes over adenocarcinoma NOS give justification for adenocarcinoma subclassification, and independently validate the prognostic advantage of lepidic and papillary subtypes proposed in the World Health Organization (WHO) 2021 adenocarcinoma grading classification.
Tobacco plays a complex role in patients with inflammatory bowel disease (IBD). Its impact on inpatient outcomes of IBD needs additional study. We aimed to assess the impact of smoking on clinical outcomes in hospitalized patients with IBD. We conducted a retrospective cohort study using data from the National Inpatient Sample (NIS) spanning from 2016 to 2019. Patients with UC and CD were identified utilizing ICD-10 codes. Patients were stratified according to the smoking status in two groups. A propensity score matching was utilized to balance comorbidities between study groups. Study outcomes included rates of steroid use, surgeries, gastrointestinal (GI) bleeding, perianal abscess, and overall mortality. All outcomes were assessed during the index hospitalization. Statistical analysis was performed using Stata 17 software. Results were reported as adjusted odds ratios (aORs) with 95% confidence intervals (CIs). A total of 413,208 patients were included in our study, 180,558 patients had UC, and 232,650 patients had CD. After propensity score matching, we had a total of 151,106 patients: 39,616 patients had UC, with a total of 19,808 in each group. The CD patients were 111,490, with a total of 55,745 patients in each group. For UC patients, smokers had lower odds of steroid use (aOR =0.69, 95% CI: 0.61-0.79, P=0.001), and all-cause mortality (aOR =0.54, 95% CI: 0.32-0.96, P=0.03). For CD patients, smokers had higher odds of steroid use (aOR =1.13, 95% CI: 1.03-1.25, P=0.009), perianal abscess (aOR =1.12, 95% CI: 1.10-1.36, P=0.02), and all-cause mortality (aOR =1.51, 95% CI: 1.27-1.84, P=0.04). All other outcomes were not significant between the study cohorts. Tobacco use in hospitalized patients with UC was associated with lower steroid use, while in patients with CD, it correlated with higher steroid use and increased odds of perianal abscesses. These findings highlight the complex impact of tobacco use on IBD outcomes.
Preeclampsia (PE), a multisystem and complex disorder diagnosed when maternal hypertension manifests after 20 weeks of gestation with proteinuria, is one of the direct causes of maternal morbidity and mortality, in addition to bleeding and infection. Despite its critical impact, effective preventive dietary interventions are scarce. Oxidative stress and microvascular damage are central to PE pathophysiology. Extra virgin olive oil (EVOO), particularly early harvested EVOO (EVOOEH), is rich in antioxidant compounds and may mitigate these issues. This randomized, single-masked (investigator and data analysis) interventional pilot study protocol will enroll 156 high-risk pregnant women (8 to 16 weeks of gestation) at Barzilai University Medical Center. Participants will be allocated to two parallel arms: the EVOOEH arm (n=78), receiving 42 mL/day (three tablespoons) of EVOOEH in addition to general Ministry of Health (MOH) dietary recommendations for 4 weeks; and the Control arm (n=78), receiving MOH dietary recommendations only. Low-dose aspirin prophylaxis will be co-administered, if indicated. Adherence will be monitored via phone calls and assessment of maternal whole blood and plasma hydroxytyrosol (HT) at recruitment and approximately four weeks post-intervention initiation. Primary outcomes are incidence of gestational diabetes mellitus (GDM), PE, Cesarean section, preterm birth, and small for gestational age (SGA) newborns. Secondary outcomes include post-intervention maternal 1-hour glucose challenge test (GCT) and serum ratio of soluble fms-like tyrosine kinase 1 to placental growth factor (sFlt-1/PlGF), as well as maternal blood pressure, gestational age at delivery, and newborn percentile. Blood samples will be analyzed for serum 25-hydroxyvitamin D [25(OH)D], sFlt-1/PlGF ratio and HT. Statistical analysis will include use of JMP Pro software, with compared by chi-squared or Fisher's exact tests for categorical variables and Student's t-tests or Wilcoxon rank-sum tests for continuous variables when appropriate. Multivariate analyses will be performed for significant variables. This pilot study will provide crucial insights into the potential of EVOOEH as a dietary intervention for reducing PE risk in high-risk pregnancies, addressing a significant gap in current preventive strategies. This protocol study findings can inform larger-scale trials and contribute to evidence-based nutritional recommendations for PE prevention. This study was registered on ClinicalTrials.gov (NCT06759545).
Breast cancer is the most frequently diagnosed malignancy among women of reproductive age, and advances in cancer survival have increased the relevance of fertility preservation (FP) as a component of comprehensive oncologic care. Concerns regarding treatment-related gonadotoxicity, potential delays in chemotherapy initiation, and long-term oncologic safety continue to influence clinical decision-making. This narrative review of systematic reviews aimed to synthesize contemporary evidence on FP methods in young women with breast cancer, focusing on effectiveness, timing, and oncologic safety. A structured narrative review of systematic reviews and meta-analyses was conducted using PubMed/MEDLINE and Web of Science from database inception through December 2025. Eligible articles were English-language systematic reviews evaluating FP strategies in premenopausal or perimenopausal women with breast cancer and reporting reproductive and/or oncologic outcomes. Data were extracted using a predefined framework, and findings were integrated through qualitative synthesis. Sixteen systematic reviews were included. FP strategies evaluated included temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy, controlled ovarian stimulation (COS) with oocyte or embryo cryopreservation, and alternative approaches such as ovarian tissue cryopreservation (OTC) and in vitro maturation (IVM). COS followed by embryo cryopreservation demonstrated the highest rates of clinical pregnancy and live birth. GnRHa use was consistently associated with improved ovarian function recovery, reduced premature ovarian insufficiency, and increased post-treatment pregnancy rates. Across studies, FP interventions were not associated with increased risks of disease recurrence or compromised survival outcomes. Current evidence supports the effectiveness and oncologic safety of established FP preservation strategies in young women with breast cancer. Importantly, the integration of structured oncofertility pathways into routine oncology practice requires early referral systems, multidisciplinary coordination, and individualized risk assessment. Translating these findings into practice is essential to ensure equitable access to FP within comprehensive cancer care.
Severe emphysema in chronic obstructive pulmonary disease causes lung hyperinflation, increased intrathoracic pressure and loss of pulmonary vasculature, which together contribute to pulmonary hypertension (PH) and right heart dysfunction. Historically, PH was considered an absolute contraindication to lung volume reduction surgery (LVRS) because clinicians feared that removing lung tissue and pulmonary vessels would raise pulmonary artery pressures and provoke right-heart failure. The objective of this narrative review is to synthesize recent evidence on the safety, feasibility and haemodynamic impact of LVRS and bronchoscopic lung volume reduction (BLVR) in patients with emphysema-associated PH and to propose practical recommendations for future research and clinical practice. We searched PubMed, MEDLINE and Web of Science from January 1990 to January 2026 using combinations of related to lung volume reduction (LVR) and PH. Reference lists of key articles were manually screened. Both surgical and bronchoscopic interventions were considered, and study designs ranging from randomized trials to observational cohorts and case series were eligible due to limited randomized data. Hemodynamic and clinical endpoints were extracted and narratively synthesized. Lung hyperinflation compresses the heart and pulmonary vessels, raising pulmonary artery pressures and reducing venous return and cardiac output. LVR decreases intrathoracic pressure and improves ventilation-perfusion matching; endobronchial valves improve lung function, exercise capacity and survival. A total of 21 studies were included, comprising one randomised control trial [the National Emphysema Treatment Trial (NETT) cardiovascular substudy], 15 observational cohort studies, and 5 case series. Overall, the literature consistently indicates that the benefits of LVR on respiratory mechanics may offset the theoretical risk of losing pulmonary vasculature, provided PH is mild to moderate and patients are carefully assessed. Current evidence challenges the dogma that PH is an absolute contraindication to LVR. In selected emphysema patients with heterogeneous disease and mild-to-moderate PH, LVRS and BLVR can be performed safely and may reduce pulmonary artery pressures and improve right-ventricular function. Right heart catheterisation should be strongly considered for haemodynamic phenotyping before intervention and multidisciplinary selection protocols are recommended. Severe PH or decompensated right-heart failure remains a relative contraindication, and bronchoscopic procedures should be reserved for carefully selected cases.
Although the global incidence of hematologic malignancies is decreasing, the risk of developing these cancers is increasing due to increased lifespan and modern treatments including targeted therapy, chemotherapy, and radiation. Intrathoracic manifestations of hematologic malignancies may be the presenting sign leading to diagnosis or result from various treatment toxicity. The most common respiratory manifestation of hematologic malignancies is infectious, but up to half of pulmonary findings are from non-infectious etiologies. We aim to summarize the current literature on non-infectious intrathoracic manifestations of hematologic malignancies and their treatment. We performed a literature review using PubMed Central and Google Scholar for articles published between January 1st, 2014, and January 1st, 2024. We used medical subject heading terms to search titles, abstracts, and diagnoses. We reviewed textbook chapters, literature reviews, practice guidelines, randomized controlled trials, and retrospective articles. There are many pulmonary manifestations of hematologic malignancies. Lymphadenopathy and disease of serosal membranes are common. Pleural effusions can be malignant or related to treatment, and interventions include serial thoracentesis or indwelling pleural catheters (IPCs). Parenchymal diseases consist of primary pulmonary lymphoma, leukemic pulmonary infiltration, myeloid sarcoma, pulmonary alveolar proteinosis, and leukemic cell lysis pneumopathy. Endobronchial disease is rare. Pulmonary vascular disorders involve leukostasis, thromboembolic disease, pulmonary hypertension (PH), superior vena cava (SVC) syndrome, and pseudohypoxemia. Therapy-related sequelae may also occur. Intrathoracic manifestations of hematologic malignancies should be considered in the differential diagnosis at the time of presentation since their management differs substantively.
Light therapy encompasses a broad spectrum of interventions, ranging from established clinical applications to emerging and experimental indications. This review evaluates the current state of light therapy across medical disciplines, emphasizing the need to distinguish validated clinical uses, exploratory findings, and preclinical research. The biological effects of light therapy are diverse, with mechanisms depending on wavelength, route of delivery, and biological target. Ocular exposure to bright light primarily acts through the circadian system to influence mood and sleep, whereas peripheral photobiomodulation (PBM) and ultraviolet (UV) phototherapy act directly on local tissues to promote healing. Mitochondrial activation is a proposed general mechanism, but its centrality is likely modality- and context-dependent. Robust clinical evidence supports bright light therapy for seasonal affective disorder (SAD) and UV-B for psoriasis, while moderate evidence exists for dermatological and sleep applications. For delirium, bright light therapy has shown promise in small-scale studies, but large-scale confirmatory clinical trials are still lacking. Other reported uses, including pain management, ischemia-reperfusion (IR) injury, clotting disorders, and infectious lung injury, are largely supported by preclinical and mechanistic studies, particularly those involving intense light that elicits the circadian core protein Period 2 (PER2). The clinical relevance of these mechanisms remains under investigation. Overall, light therapy remains safe when used according to established protocols. This review aims to provide a nuanced synthesis of the field, highlighting both the promise and the limitations of light therapy and emphasizing the importance of the evidence hierarchy in guiding clinical translation and research priorities.
Aging is associated with organ and tissue function deterioration and consequent increased risk of disease occurrence and mortality. Recent scientific advancements have succeeded in increasing the human life span and attempts are being made to enhance the longevity further. This stretched longevity exposes the organism to increased cellular stress and accumulation of DNA damage. Mutations in leukemia-associated driver oncogenes like DNMT3A, TET2, ASXL1, TP53, PPM1D, SF3B1, SRSF2, and IDH1/2, provide selective growth advantage to the mutated clones over normal hematopoietic stem cells (HSCs). Altered bone marrow (BM) microenvironment and increased pro-inflammatory milieu further accelerates the clonal expansion and eventually reduces the hematopoietic heterogeneity. Significant increase in clonal hematopoiesis with more than two percent of peripheral blood cells arising from single hematopoietic clone is termed as clonal hematopoiesis of indeterminate potential (CHIP). CHIP is increasingly recognized as an age-associated risk factor linked to cardiovascular and neurological disorders. While epidemiological and experimental studies suggest mechanistic involvement of inflammation, current human evidence primarily supports risk association rather than definitive causality, which may vary across mutation types. Here, we have discussed the intrinsic and extrinsic changes occurring in the hematopoietic system and its role in enhancing the clonal expansion during aging. We have further discussed the role of CHIP in various diseases and diagnostic tools being currently used for CHIP diagnosis. Finally, we also discuss the current CHIP management strategies and global status of CHIP related research. Thus, the emerging CHIP-cantered research and new strategies to impede CHIP progression can play a critical role in the development of effective therapeutic strategies for managing age-related obnoxious disorders.
Magnetic resonance imaging (MRI)-based ex vivo thrombus imaging is an emerging modality for evaluating clot composition and guiding therapy. However, when it comes to sample handling, the effect of formalin fixation on MRI relaxation times (T1, T2, and T2*) of thrombus tissue remains poorly characterized. Formalin fixation is widely used in studies investigating the MRI properties of thrombus tissue; however, fixation alters tissue biochemistry and water dynamics. Understanding these effects is essential for accurately interpreting existing literature and for developing reliable ex vivo imaging biomarkers. This study aims to assess the impact of formalin fixation on human thrombus MRI properties using an ultra-high-resolution ex vivo 9.4 T MRI scanner. A total of 19 clot samples from 13 patients undergoing mechanical thrombectomy were evaluated. The samples were imaged fresh, after <6 hours of formalin fixation, and after >24 hours of formalin fixation. T1, T2, and T2* relaxation time maps were created and evaluated over the fixation stages. Linear mixed-effects models were used to assess the effect of fixation stage and biological covariates, including clot age, patient age, and body mass index (BMI). Formalin fixation induced significant reductions in T1 and T2 relaxation times. T1 decreased from 1,801.6±236.3 ms (fresh) to 1,205.0±491.6 ms (>24 h formalin, P<0.001). T2 declined from 77.6±16.5 ms (fresh) to 44.3±13.8 ms (>24 h formalin). Most T2 reduction occurred within the first 6 hours of fixation. T2* values showed minimal changes across fixation stages. Higher BMI and older clot age were significantly associated with shorter T1 values, while no covariates influenced T2 or T2*. Formalin fixation substantially alters T1 and T2 relaxation times in thrombus tissue, while T2* remains relatively stable. These findings highlight the necessity of accounting for fixation effects and patient-specific biological factors when designing and interpreting ex vivo thrombus MRI data and developing imaging biomarkers.
Decitabine, including its new oral formulation (decitabine-cedazuridine, DEC-C), is commonly used in AML and MDS, particularly in older or unfit patients. While its clinical efficacy and tolerability are well documented, evidence regarding patient-reported outcomes (PROs) and health-related quality of life (HRQoL) remains limited. We conducted a review of the available literature on PROs in patients with AML and MDS treated with decitabine, with the aim of evaluating its impact on HRQoL, symptom burden, and patient preferences. A systematic literature search of PubMed up to October 2024 identified studies evaluating HRQoL or PROs in adult AML and/or MDS patients receiving decitabine, regardless of study design. Ten studies met the inclusion critera. Decitabine-based regimens were associated with preservation of HRQoL compared with intensive chemotherapy and improvements in fatigue and physical functioning versus best supportive care. In patients with AML, baseline HRQoL scores were found to be predictive of survival outcomes. Surveys consistently indicated strong patient preference for oral DEC-C due to reduced treatment burden and greater convenience, though longitudinal data remain limited. In conclusion, currently available HRQoL evidence for decitabine provides meaningful insight to guide further research. Findings from patient surveys and the availability of decitabine in both intravenous and oral formulations emphasize new treatment aspects that can be effectively captured through PROs. Their systematic integration may help uncover critical issues such as symptom burden, adherence, and patient priorities, ultimately fostering more patient-centered care.
The rapidly changing landscape of abdominal transplantation including regional normothermic perfusion of abdominal organs during procurement, broadening indications for multi-visceral transplantation (MVT) in both benign and malignant pathology and the ever increasing gap between organ supply and demand have necessitated the normalisation of expanded criteria donors (ECD). Key to mitigating the increased risk of delayed or non-function of ECD organs is the development of suitable preclinical animal models that allow for the development of reliable viability assessment as well as reconditioning and repair protocols that can thereafter be translated to humans. Due to physiological and anatomical similarities to humans, pigs make ideal pre-clinical animal models. Our group has recently concluded a study assessing the feasibility of machine perfusion and reanimation in a porcine model. In this paper, the authors describe a reproducible en bloc surgical technique to retrieve a composite organ block containing the liver, pancreas, small bowel, and kidneys that can be used for preclinical translational studies on organ preservation, viability assessment and preconditioning with specific reference to pertinent porcine anatomy. Twenty-six adult female Large White pigs (Sus scrofa domestica) were procured to obtain a multi-visceral organ block to evaluate the functionality of a novel machine perfusion rig. The average weight of the pigs was 63.05 kg. Each organ block was excised consistently by the same surgical team. The block was re-animated using ex vivo normothermic perfusion to simulate transplant and confirm viability. We describe the stepwise surgical technique of multi-organ retrieval as a combined organ block. The average procedure time was 108.3 (range, 57-179) min. This surgical technique facilitated retrieval of all twenty-six organ blocks for experiments in MVT. The warm ischemia duration is minimal and closely replicates donation following brain death (DBD) in humans. With minor modifications, a donation following circulatory death (DCD) model would also be achievable. This technique is reproducible and safe and can be used to retrieve abdominal organs collectively for en bloc testing or to be divided subsequently on the back table, with each organ used for a distinct purpose or project.
Endobronchial one‑way valves (EBVs) were originally developed for lung volume reduction in severe emphysema. Because EBVs allow unidirectional airflow, they have been used off‑label to manage persistent air leaks (PALs)/bronchopleural fistulas (BPFs), haemoptysis, cavitary tuberculosis (TB), and other complex pulmonary conditions. This review summarises the evidence of endobronchial valve applications beyond emphysema. We conducted a narrative review of English‑language literature from January 1, 2000 to August 1, 2025, searching PubMed, Embase, Scopus, and Google Scholar for clinical trials, observational studies, case series, and case reports describing EBV use beyond emphysema. The selection of articles was based on relevance to the topic, with emphasis on clinical outcomes. No formal quantitative synthesis was performed given the narrative scope. Across case series, EBV placement achieves cessation or substantial reduction of air leaks in roughly half to 80% of patients with postoperative or spontaneous BPFs, often allowing chest tube removal within days and avoiding reoperation. Reported complications are uncommon and include valve migration, expectoration, transient hypoxaemia, and localized infection. Case reports indicate EBVs can serve as emergency bronchoscopic plugs to control massive haemoptysis when conventional therapy fails. Emerging evidence in multidrug‑resistant TB shows that collapse therapy using EBVs alongside appropriate chemotherapy accelerates sputum culture conversion and cavity closure; in a randomized trial, EBV treatment markedly improved culture conversion and long‑term cure rates compared with chemotherapy alone. EBVs have also been used in critical care settings to isolate injured lungs and facilitate weaning from mechanical ventilation or extracorporeal membrane oxygenation (ECMO). EBVs have evolved into a versatile tool in pulmonary medicine, extending well beyond emphysema treatment. The literature to date indicates that EBVs can effectively seal PALs, control focal pulmonary haemorrhage, and induce therapeutic lung collapse in cavitary disease-all with a minimally invasive approach. EBVs hold significant promise for improving patient care in challenging scenarios, and further research is warranted.
Panax notoginseng (P. notoginseng) has traditionally been used to support circulatory health. Its higher ginsenoside content and the presence of notoginsenoside R1 distinguish it from Panax ginseng and contribute to broader therapeutic potential. This review summarizes the anti-inflammatory mechanisms of P. notoginseng and their relevance to cardiovascular, hepatic, and metabolic disorders. A structured search of PubMed, Web of Science, Scopus, and Google Scholar was performed on December 20, 2024, covering January 2010 to July 2024. Studies published in English that provided mechanistic insights into anti-inflammatory activity in relation to P. notoginseng were included. Commentaries and studies without mechanistic detail were excluded. Screening was conducted independently by two authors. P. notoginseng modulates key inflammatory pathways-including nuclear factor-κB (NF-κB), modulating mitogen-activated protein kinase (MAPK), cytokine regulation, oxidative stress, and endothelial function-supporting its benefits in vascular injury, liver inflammation, metabolic dysfunction, and gut-liver axis imbalance. Its unique phytochemical profile explains its stronger cardiovascular and hepatoprotective actions compared to P. ginseng. The broad pharmacological activities of P. notoginseng are largely driven by its anti-inflammatory mechanisms. These findings provide a framework for its clinical relevance and highlight the need for further translational and integrative research.
Chronic eczematous skin disorders that first appear in later life are poorly characterized, partly because existing terminology is inconsistent and often conflates morphologic descriptors with specific diagnoses. This review introduces chronic eczematous eruptions of aging (CEEsA) as an umbrella term, summarizes current knowledge on its epidemiology, etiologies, and clinical presentation, outlines best practices in management, and highlights gaps requiring further investigation. CEEsA frequently present as ill defined, intensely pruritic eruptions on the trunk and extensor limbs, are often refractory to standard topical therapies, and may be precipitated by calcium channel blockers or thiazide diuretics. A structured diagnostic algorithm-incorporating exclusion of mimickers (e.g., tinea pedis-linked auto-eczematization, scabies, contact dermatitis, cutaneous T-cell lymphoma), lesional biopsy, patch testing, and strategic drug withdrawal-is essential before escalating to systemic therapy. This approach helps avoid unnecessary treatment or other etiologies with different management. Although traditional broad spectrum immunosuppressants carry age related safety concerns, emerging targeted agents that dampen type 2 cytokine signaling (dupilumab, tralokinumab) or Janus kinase pathways (upadacitinib) show promising efficacy and tolerability in small case series of CEEsA, including idiopathic forms. Recognizing CEEsA as a distinct clinical construct should streamline nomenclature, sensitize clinicians to reversible drug triggers, and catalyze research into pathophysiology-specific, age appropriate treatments for this under studied geriatric dermatology domain.
Sarcopenia is a multifactorial age-related muscle disorder of which its underlying pathophysiological mechanisms remain incompletely understood. To date, treatment strategies of sarcopenia have been largely confined to lifestyle interventions, underscoring an urgent need for pharmacological options that directly target the biological drivers of muscle deterioration. Despite increasing interest in drug development for sarcopenia, no specific pharmacological agent has yet received regulatory approval. This review provides a comprehensive synthesis of recent advances in investigational pharmacotherapeutic options for sarcopenia, with a focus on their mechanistic pathways and evidence from clinical trials. Key emerging classes include selective androgen receptor modulators (SARMs), myostatin antibodies, monoclonal antibodies targeting activin type 2 receptors, ghrelin receptor agonists, and growth differentiation factor-15 (GDF-15) monoclonal antibodies. In parallel, existing medications including testosterone, antidiabetic agents, classical renin-angiotensin system (RAS) inhibitors and anti-inflammatory drugs, have shown ancillary benefits in older populations but lack robust, indication-specific data. A critical contradiction persists: while several candidates increase muscle mass, few consistently improve muscle strength or physical function, reflecting a disconnect between surrogate endpoints and clinically meaningful outcomes. Moreover, some trials have been conducted in heterogeneous populations without clearly defined sarcopenia, limiting interpretability. As mechanistic insights evolve and regulatory frameworks advance, the field requires not only more targeted therapies but also clearer definitions of efficacy and patient classification.
β-hydroxy-β-methylbutyrate (HMB) is a metabolite of the essential amino acid leucine that promotes muscle protein synthesis and inhibits muscle cell degradation. This study aimed to clarify the effects of HMB on skeletal muscle mass loss using a mouse model of esophageal squamous cell carcinoma (ESCC). ESCC cells (TE-8) (5×106 cells/body) were subcutaneously transplanted into 10 nude mice to generate a mouse model of ESCC. Thirteen mice were divided into three groups: (I) non-tumor group (n=3), non-ESCC mice fed a normal diet; (II) ESCC + HMB group (n=5), ESCC-bearing mice fed HMB; (III) ESCC control group (n=5), ESCC-bearing mice fed a normal diet. A powdered Ca-HMB product was used as the HMB source. Body weight, grip strength, and gastrocnemius muscle weight of the three groups of mice were measured and compared. Body weight did not differ between the ESCC + HMB and ESCC control groups. Grip strength and gastrocnemius muscle weight were significantly higher in the ESCC + HMB group than those in the ESCC control group (grip strength, P=0.03; gastrocnemius muscle weight, P<0.01). No significant difference in grip strength or gastrocnemius muscle weight was observed between the ESCC + HMB and non-tumor groups (grip strength, P=0.94; gastrocnemius muscle weight, P=0.65). No difference in grip strength or gastrocnemius muscle weight was observed between non-tumor mice and ESCC mice (grip strength: P=0.35, gastrocnemius muscle weight: P=0.37). HMB administration to ESCC-bearing mice maintained grip strength and gastrocnemius muscle weight at levels comparable to those of non-transplanted (non-ESCC) mice. Future studies should elucidate the mechanisms by which HMB counteracts cachexia and confirm these physiological findings with molecular biological evidence.
Ischemic heart disease (IHD) remains a leading cause of death worldwide, with dietary risks being its most significant modifiable factor. Here, using the Global Burden of Diseases, Injuries and Risk Factors Study 2023, we estimated the mortality and disability-adjusted life years from diet-related IHD across 204 countries. In 2023, a suboptimal diet was responsible for 4.06 million (95% uncertainty interval (UI) 0.74-6.22) IHD deaths and 96.84 million (18.82-142.52) IHD disability-adjusted life years. The global age-standardized death rate of IHD attributable to suboptimal diet decreased by 43.92% (95% UI 34.44-53.23) per 100,000 population from 1990 to 2023. Among dietary factors, low intake of nuts and seeds (9.87, 95% UI 2.84-17.12 deaths per 100,000 population), low whole grains (9.22, 4.73-13.67), low fruits (7.25, 1.54-13.34) and high sodium (7.15, 0.92-17.97) were primary contributors to IHD deaths. The burden was particularly pronounced in low- and middle-sociodemographic index countries. By disentangling dietary risk factors, we identified the portion of IHD burden directly modifiable through food interventions.
Osteoarthritis (OA) is a degenerative joint disease involving cartilage loss and inflammation. Traditional histological evaluation is limited. Micro-computed tomography (micro-CT) offers non-invasive three-dimensional (3D) joint visualization but lacks detailed cartilage assessment. This study developed and evaluated a novel micro-CT-based scoring system for joint structure in a rat model of mono-iodoacetate (MIA)-induced OA. OA was induced in the right knees of 24 Wistar male rats using varying MIA concentrations (0.2, 0.5, 1, 3 mg). After 28 days, knee joints were scanned using micro-CT and segmented into 10 compartments. Degenerative changes in each compartment were scored (0-4), and a total joint score was calculated. Histological evaluation using a modified Mankin score was performed on sagittal sections of the patellar groove. Interobserver reliability and correlations between micro-CT joint scores and Mankin scores were analyzed statistically. The micro-CT 3D imaging scoring system demonstrated excellent interobserver reliability [interclass correlation coefficient (ICC) >0.75 for most compartments]. Micro-CT joint scores revealed statistically significant differences in joint degeneration between the highest MIA dose group (3 mg) and the lower dose groups (0.2 and 0.5 mg). Notably, micro-CT could differentiate between the 0.2 mg and 1mg groups, which was not fully reflected in histological scores. A strong correlation was found between the total micro-CT joint score and the modified Mankin score (ρ=0.8, P<0.001). The novel micro-CT-based 3D imaging scoring system provides a reliable method for quantifying gross degenerative changes in rat knee joints in the MIA-induced OA model. While it does not directly assess cartilage, its correlation with histological findings suggests its utility as a complementary tool for evaluating overall joint degeneration.