Search Results (74)

Diabetes mellitus and obesity represent a growing global health burden with high morbidity and mortality. In the last several years, novel incretin-based therapies have been developed, and their use has risen dramatically. Beyond their proven metabolic, glycemic, cardiovascular, renal, and many other benefits, there are some observational data linking anemia development with their use. From the era of gliptins to retatrutide, in this review we tried to explore whether erythroid suppression is the hidden paradigm of advanced incretin-based therapies. Potential pathophysiological explanations include micronutrient vulnerabilities due to reduced food intake, lower dietary diversity, gastrointestinal intolerance, delayed gastric emptying, and weight loss. The most important concerns involve deficiencies in iron, vitamin B12, vitamin B2, vitamin D, calcium, magnesium, and zinc, along with others such as thiamine, folate, vitamin A, and potassium. The available evidence indicates a complex and heterogeneous relationship between incretin-based therapies and hematological parameters, with findings differing across therapies, study populations, and outcomes. Although observational studies suggest possible associations with anemia, iron deficiency, and nutritional deficiencies in selected populations, current evidence is insufficient to establish a direct causal relationship or a class-wide adverse effect. Further large-scale studies are needed, as well as increased clinician awareness of potential hematological and nutritional consequences that require laboratory follow-up before and during medication prescription. Full article

Diabetes constitutes one of the major prevailing diseases worldwide, with cardiovascular pathologies as the primary cause of the morbidity and mortality rates reported. Hyperglycemia, the principal hallmark of diabetes, results from accumulated glucose levels. Although molecular mechanisms induced by high glucose (HG) have been extensively investigated, their complex interconnections and immediately activated signaling pathways remain unresolved. Hence, in the present study, we tried to identify effectors directly responsive to HG, focusing on the early activated signal transduction routes in H9c2 cardiac cells. MTT analysis illustrated the apoptosis- and oxidative-stress-mediated detrimental effect of 25 mM glucose on H9c2 viability. Initiation of oxidative-stress-related mechanisms was corroborated via detection of POR and HOX-1 augmented expression levels. Additionally, western blot analysis demonstrated activation of p38-MAPK and ERK1/2, along with autophagy- and ER-stress-related markers. Of note, involvement of biomechanical signaling players was also revealed, with Piezo1, connexin 43 and GJA1-20k expression being gradually enhanced. Intriguingly, ERK1/2 and ER-stress-associated effectors were observed to mediate connexin 43 and GJA1-20k upregulation. With connexins playing a nodal biological role in diabetes-driven cardiovascular pathologies, exploring potential modulatory effectors may provide insight into development of promising therapeutic interventions, favoring preservation of cell function and systems homeostasis under hyperglycemic conditions. Full article

Background: Early cardiovascular complications after non-traumatic intracerebral hemorrhage (ICH) contribute to short-term morbidity and mortality, yet reliable prognostic markers remain limited. We examined the association between admission serum albumin and 30-day cardiovascular complications after ICH, including dose–response patterns and consistency across subgroups. Methods: In this retrospective cohort study using the TriNetX US Collaborative Network, adults hospitalized with ICH (ICD-10-CM I61) and serum albumin measured within 24 h of admission were stratified into reduced (≤3.4 g/dL) and normal (≥3.5 g/dL) groups and balanced by 1:1 propensity score matching on demographics, cardiovascular comorbidities, ICH severity, neurosurgical procedures, and medications. The primary outcome was a 30-day composite of all-cause death, acute myocardial infarction, heart failure, atrial fibrillation or flutter, ventricular arrhythmias, and Takotsubo cardiomyopathy. Sensitivity analyses addressed age, sex, comorbidity burden, and chronic hypoalbuminemia. Results: Of 241,228 patients, 94,925 (39%) had reduced albumin; 79,751 were retained per group after matching. The composite outcome occurred in 40.4% versus 33.3% (HR 1.28, 95% CI 1.26–1.30; p < 0.0001). Reduced albumin was associated with higher all-cause mortality (HR 1.50), myocardial infarction (HR 1.36), heart failure (HR 1.22), ventricular arrhythmias (HR 1.41), and Takotsubo cardiomyopathy (HR 1.41; all p < 0.005). Atrial fibrillation or flutter did not differ (HR 1.02; p = 0.779). A dose–response was observed, with severe hypoalbuminemia conferring greater composite risk (HR 1.49) than mild (HR 1.16). Findings were consistent across all sensitivity analyses. Conclusions: Reduced admission serum albumin is independently associated with higher short-term mortality and cardiovascular complications after ICH and may aid early risk stratification. Prospective studies are needed to clarify its utility. Full article

Background: Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) usually coexist and are related to increased morbidity and mortality. Cardiovascular benefits have been demonstrated by drugs such as sodium-glucose cotransporter-2 inhibitors (SGLT2i) and GLP-1 receptor agonists including the dual GIP/GLP-1 receptor agonist tirzepatide (collectively, incretin-based therapies); however, their relative effectiveness in patients with concomitant AF and HFpEF remains undefined. Methods: We conducted a retrospective, propensity score-matched cohort study utilizing the TriNetX Global Collaborative Network. Adults with AF or atrial flutter with a diagnosis of HFpEF who initiated incretin-based therapies (GLP-1 receptor agonists or dual GLP-1/GIP receptor agonists) or SGLT2i were included; index medication was required to be initiated within 30 days of a qualifying AF/HFpEF diagnosis. 1:1 matching was performed based on baseline medications, demographics, and comorbidities. Co-primary outcomes were all-cause mortality, inpatient visits, and emergency department (ED) visits at 1 year. Secondary outcomes included myocardial infarction, ischemic stroke, acute kidney injury, transient ischemic attack, major adverse cardiovascular events (MACE; all-cause mortality/MI/stroke composite), and AF-related procedures. Agent-specific subgroup analyses were performed for semaglutide and tirzepatide separately. Sensitivity analyses were conducted at 6 months and 2 years. Results: 7624 patients were included in each cohort after matching (mean age: 70.8 years; 52% women). At 1 year, incretin-based therapy was associated with lower all-cause mortality (5.3% vs. 7.3%, HR 0.721, 95% CI 0.634–0.820; p < 0.001), fewer inpatient visits (30.0% vs. 37.4%, HR 0.743, 95% CI 0.702–0.787; p < 0.001), and no statistically significant difference in ED visits (27.0% vs. 28.0%; HR 0.946, 95% CI 0.888–1.007; p = 0.081) compared with SGLT2i. Incretin-based therapy was also associated with lower risk of MACE (HR 0.709), acute kidney injury (HR 0.751), myocardial infarction (HR 0.583), catheter ablation (HR 0.685), and electrical cardioversion (HR 0.472). No significant differences were observed in ischemic stroke or transient ischemic attack. These findings were broadly consistent at 6-month and 2-year follow-up, and directionally consistent in agent-specific subgroup analyses of semaglutide and tirzepatide. Conclusions: In this large propensity-matched cohort of patients with AF and HFpEF, initiation of incretin-based therapy (GLP-1 receptor agonists or dual GLP-1/GIP receptor agonists) was associated with lower all-cause mortality, fewer inpatient visits, and reduced cardiovascular events compared with SGLT2i. These findings, while subject to observational limitations, suggest potential benefits of incretin-based therapy in this high-risk population and support the need for prospective comparative trials. Full article

Background/Objectives: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with psychiatric burden, but longitudinal data on incident psychiatric outcomes remain limited. This study aimed to evaluate incident psychiatric disorders in adults with HS compared with matched non-HS controls and to assess sex-specific risk. Methods: We conducted a retrospective propensity score–matched cohort study using the TriNetX Global Collaborative Network. Adults with at least two HS diagnoses and no prior psychiatric diagnosis were compared with non-HS controls with repeated general health examination encounters and no psychiatric history. Time-to-event analyses estimated hazard ratios (HRs) with 95% confidence intervals (CIs). Sensitivity analyses used a 30-day lag and restriction to the most recent 5-year period. Results: After matching, 37,964 pairs were retained for the primary individual-outcome analysis. Median follow-up was shorter in the HS cohort than in matched controls (844 vs. 1505 days). HS was associated with increased risk of any psychiatric disorder (12.3% vs. 5.8%; HR 3.17, 95% CI 3.01–3.34) and severe psychiatric illness (0.6% vs. 0.1%; HR 6.70, 95% CI 4.77–9.41). Elevated risks were observed for bipolar/manic disorders, personality disorders, substance use disorders, psychotic disorders, suicidal ideation, depression, eating disorders, anxiety, and insomnia/parasomnia. Women had higher hazards of depression and anxiety, whereas men had higher hazards of substance use disorders; insomnia/parasomnia showed a nominal association with higher hazard in men. Conclusions: In this observational EHR-based study, HS was associated with broad incident psychiatric morbidity. These findings support consideration of proactive mental health assessment and integrated dermatologic–psychiatric care in patients with HS. Full article

Background: Stroke significantly increases morbidity and mortality in patients receiving extracorporeal membrane oxygenation (ECMO). This study evaluates the prognostic impact of stroke subtypes, acute ischemic stroke (AIS) and hemorrhagic stroke (HS), and neurologic injury severity in a contemporary adult population. Methods: We conducted a retrospective cohort study using the TriNetX federated electronic health record network, including adult patients who underwent ECMO between 1 October 2015 and 31 December 2025. Stroke was defined as a first-instance diagnosis of AIS, HS, or unspecified cerebrovascular event occurring within 24 h of ECMO cannulation during the index hospitalization. Propensity score matching (1:1 nearest neighbor) was performed to balance baseline demographics, comorbidities, anticoagulant use, and ECMO modality between the stroke and non-stroke cohorts. Primary outcomes included all-cause mortality at 30 days, 90 days, and 1 year. Secondary outcomes included cardiac arrest, seizures, palliative care utilization, and hospital readmission. Kaplan–Meier survival analysis and multivariable Cox proportional hazards modeling were performed. Results: Among 18,981 ECMO patients, 1481 (7.8%) developed a stroke within 24 h of ECMO cannulation, including 814 AIS (54.9%), 454 HS (30.6%), and 213 unspecified cerebrovascular events (14.4%). After propensity score matching, stroke was associated with significantly higher all-cause mortality at 30 days (RR 1.16), 90 days (RR 1.18), and 1 year (RR 1.18), all p < 0.05. Stroke was also associated with higher rates of cardiac arrest, seizures, hospital readmission, and palliative care utilization (all p < 0.001). AIS was associated with significantly lower mortality than HS at 30 days, 90 days, and 1 year (all p < 0.0001). In multivariable Cox regression, only HS was independently associated with increased 30-day mortality compared with no stroke. Markers of neurologic injury severity, including cerebral edema, brain compression, and coma, were among the strongest independent predictors of mortality. Conclusions: Stroke occurring early after ECMO cannulation is associated with substantially worse short- and long-term survival, with hemorrhagic subtype and markers of neurologic injury severity driving the strongest prognostic signals. These findings support early stroke recognition and subtype-informed prognostic discussions in ECMO patients. Full article

Background: Body contouring surgery is a critical aspect of reconstructive and esthetic care, addressing both functional and psychosocial needs. As the global prevalence of obesity and related metabolic disorders is constantly on the rise, it is inevitable that patients presenting for body contouring procedures would display comorbid cardiometabolic conditions that can negatively impact surgical outcomes. Clustered cardiometabolic abnormalities have been linked to increased rates of surgical complications, medical adverse events, prolonged hospitalization, and need for revision procedures. However, its impact on body contouring surgery outcomes remains insufficiently characterized. Materials and Methods: TriNetX Global Collaborative Network, comprising deidentified electronic medical records from over 170 healthcare organizations was utilized for this study. Adults undergoing body contouring surgery were stratified by the presence of a composite cardiometabolic burden, defined as the combination of obesity, diabetes mellitus and hypertension, in the year preceding surgery. Cohorts were matched 1:1 using propensity score matching based on baseline demographics, comorbidities, and substance use. Risk ratios with 95% confidence intervals were calculated, with statistical significance set at p < 0.05. Outcomes were assessed at 30, 60, and 90 days postoperatively. Results: Among 188,164 body contouring patients, 6892 with composite cardiometabolic burden were propensity score–matched to controls. The study group was associated with significantly higher wound complications, surgical site infections, antibiotic use, and emergency department visits at 30, 60, and 90 days postoperatively, with no difference in hypertrophic scarring. Conclusions: Composite cardiometabolic burden, as defined in the study, demonstrated a significantly increased risk of adverse events following body contouring surgery, including wound-related morbidity, surgical site infection and increased healthcare utilization. These risks are evident from the early postoperative period and persist through at least the first 90 days after the procedure. Full article

Background: Coronary artery disease (CAD) and heart failure with preserved ejection fraction (HFpEF) are major causes of morbidity and mortality. Systemic inflammation contributes to both, suggesting potential benefit from colchicine, though data in CAD-HFpEF are limited. Methods: We conducted a real-world study using the TriNetX Research Network, identifying 480,434 adults with CAD and HFpEF. Patients were categorized as colchicine users (n = 30,254) or non-users (n = 450,180). One-to-one propensity score matching yielded 28,941 patients per group. The primary outcome was a composite of acute myocardial infarction, stroke, all-cause mortality, and acute heart failure. Secondary outcomes included individual components, hospitalizations, atrial fibrillation, and gastrointestinal events, assessed at 1- and 3-year follow-up. Results: At 1 year, the primary outcome occurred in 16.9% of the colchicine group versus 19.8% of non-users (HR: 0.86, 95% CI: 0.81–0.91; p < 0.001). All-cause mortality was 11.4% versus 14.5% (HR: 0.77, 95% CI: 0.73–0.80; p < 0.001). At 3 years, the primary outcome occurred in 34.2% versus 39.7% (HR: 0.88, 95% CI: 0.85–0.92; p < 0.001), with acute heart failure slightly higher in the colchicine group (27.5% vs. 26.5%; HR: 1.04, 95% CI: 1.01–1.08; p = 0.009). Stroke was modestly reduced (HR: 0.93, 95% CI: 0.88–0.99; p = 0.014). No significant differences were seen in all-cause hospitalization, atrial fibrillation, or gastrointestinal events. Conclusions: In patients with CAD and HFpEF, colchicine was associated with lower short- and medium-term risk of composite cardiovascular events and mortality, with modest attenuation over time, suggesting early time-dependent association rather than sustained structural effects. Prospective randomized trials are warranted. Full article

Background: Subarachnoid hemorrhage (SAH) is associated with high morbidity and mortality despite advances in neurocritical care. Vitamin D plays a role in immune modulation, endothelial function, and neuroprotection; however, its impact on outcomes following SAH remains poorly defined. We evaluated the association between low vitamin D status and clinical outcomes in patients with nontraumatic SAH. Methods: We conducted a retrospective propensity score-matched cohort study using the TriNetX Research Network database. Adult patients with nontraumatic SAH and at least one recorded serum 25-hydroxyvitamin D level obtained within 3 months on or before diagnosis were included. The low vitamin D cohort was defined as 0–20 ng/mL, and the comparator cohort as 20–40 ng/mL. Cohorts were matched 1:1 using propensity scores adjusted for demographic and clinical covariates, including chronic kidney disease, liver disease, osteoporosis, and intestinal malabsorption. The primary outcome was 30-day all-cause mortality. Secondary outcomes included seizures, hydrocephalus, cerebral edema, and external ventricular drain placement. Results: After matching, 2314 patients were included in each cohort. Thirty-day mortality occurred in 9.3% of patients in the low vitamin D cohort and 7.6% of patients in the comparator cohort (hazard ratio [HR] 1.229; 95% CI, 1.006–1.503; p = 0.043). Seizures were more frequent in the low vitamin D cohort (8.6% vs. 6.9%; odds ratio [OR] 1.274; 95% CI, 1.026–1.581; p = 0.028). Hydrocephalus was also more common among patients with low vitamin D (5.1% vs. 3.9%; OR 1.328; 95% CI, 1.003–1.758; p = 0.047). No significant differences were observed in cerebral edema or external ventricular drain placement. Conclusions: Low vitamin D status was associated with increased short-term mortality, seizure incidence, and hydrocephalus following nontraumatic SAH. These findings suggest that vitamin D status may represent a potential prognostic biomarker warranting prospective investigation. Full article

Background and Objectives: Breast cancer surgery is increasingly performed in older patients with multimorbidity, in whom cardiovascular disease and frailty may substantially modify perioperative risk, including vulnerability to heart failure decompensation and other major medical complications. However, most available studies report global perioperative complication rates and composite medical endpoints, with heart failure events only rarely captured as dedicated outcomes, and operative technique, cardiovascular comorbidity, and frailty are often treated as separate domains rather than components of an integrated risk framework. Materials and Methods: We conducted a systematized narrative review with a structured literature search in PubMed/MEDLINE, Scopus, and Web of Science from inception to 31 January 2026, including original studies of adult patients undergoing breast-conserving surgery, mastectomy, and/or reconstruction that reported early postoperative outcomes in relation to comorbidities, cardiovascular risk, or frailty. Eligibility assessment, data extraction, and qualitative synthesis followed key PRISMA 2020 principles, and findings were organized into three prespecified domains: surgical complexity, cardiovascular vulnerability (including patients with heart failure where reported), and frailty. Results: Nineteen studies (retrospective cohorts, registry-based analyses, and large database studies, primarily ACS NSQIP) met inclusion criteria, encompassing diverse breast surgery populations, including elderly, metastatic, and reconstructive cohorts. Across datasets, escalation from breast-conserving surgery to mastectomy and then to increasingly complex reconstruction was associated with a stepwise increase in perioperative complications, reoperations, bleeding, and, in selected series, catastrophic events. Preexisting cardiovascular disease and systemic vascular pathology significantly amplified postoperative morbidity even in procedures considered low or intermediate cardiac risk, with signals that patients with underlying heart failure carry particularly heightened vulnerability, although HF-specific events were infrequently reported as separate endpoints. Frailty, mainly assessed using modified frailty indices, consistently emerged as a strong, age-independent predictor of 30-day complications, mortality, and readmissions across surgical types, including both breast-conserving and reconstructive procedures. Conclusions: Early postoperative outcomes after breast cancer surgery are associated with the interaction between surgical complexity, cardiovascular comorbidity (with limited HF-specific reporting), and frailty rather than by operative technique alone. In this context, our synthesis primarily reflects overall cardiovascular vulnerability in comorbid and frail patients, with heart failure risk inferred indirectly from the available data. These findings support a patient-centered, risk-adapted surgical strategy in which the extent and timing of surgery and reconstruction are tailored to each patient’s cardiovascular profile and frailty status, with preferential use of breast-conserving or less complex procedures in vulnerable individuals. Integrating standardized frailty assessment and cardio-oncologic evaluation into preoperative workflows, and prospectively validating this tri-axial framework in dedicated cohorts, may improve perioperative risk stratification and reduce the burden of postoperative medical complications in an aging breast cancer population. Full article

Cytomegalovirus (CMV) establishes lifelong latency following primary infection and can reactivate to cause severe illness in immunocompromised hosts. CMV DNAemia in non-HIV-infected, non-solid organ/bone marrow transplant (NHNT) hosts is poorly characterized, with limited clinical insights. We aim to describe the clinical presentation, prognostic indicators, and outcomes of CMV DNAemia among NHNT patients. We used the TriNetX international patient database to identify adult patients diagnosed with CMV DNAemia from 2016 until March 2023. We evaluated hospitalization, intensive care unit (ICU) level care, and all-cause mortality at 30 days and 1 year. We also completed a post-propensity score analysis comparing clinical characteristics of survivors versus non-survivors at 90 days. We identified 1123 NHNT patients with CMV DNAemia, most of whom had neoplasms (63%). Venous thromboembolism occurred in 31% of the population. The 30-day hospitalization and all-cause mortality rates were 35% and 14%, respectively. After propensity score matching and Bonferroni correction, weakness, purpura, acute respiratory failure, malnutrition, encephalopathy, and hypotension were associated with increased 90-day all-cause mortality. NHNT patients with CMV DNAemia carry a substantial morbidity and all-cause mortality. Further studies are warranted to clarify whether CMV DNAemia is a causative factor or an incidental finding in this population. Full article

Background/Objectives: Severe oral mucositis is widely viewed as a transient toxicity of antineoplastic therapy. Whether its long-term consequences differ between cancers that directly damage the upper aerodigestive tract (cancers of the lip, oral cavity, pharynx [CLOP]) and systemic hematologic malignancies is unknown. The aim of this study was to compare lifetime risks of mortality, dysphagia, malnutrition, respiratory disease, and cardiovascular disease in propensity-score-matched survivors of CLOP cancer versus leukemia with and without a history of ulcerative oral mucositis. Methods: Population-based retrospective cohort study using the TriNetX US Collaborative Network (90 healthcare organizations, >110 million patients). We identified 80,526 adults with a personal history of CLOP cancer (ICD-10-CM Z85.81) and 43,684 with leukemia (Z85.6) from 2005 to 2024. Cohorts were stratified by presence/absence of severe oral mucositis (K12.31 or K12.33 at any time). Separate 1:1 propensity-score matching was performed within each cancer type on age, sex, race/ethnicity, hypertension, diabetes, BMI, ECOG status, and external causes of morbidity. Exposures included documented severe (ulcerative) oral mucositis. Main outcomes and measures were all-cause mortality and incident dysphagia, malnutrition, respiratory disease (J00–J99), influenza/pneumonia (J09–J18), and circulatory disease (I00–I99) after the index date. Results: After 1:1 matching, 4181 CLOP patients with mucositis were compared with 4181 without, and 2508 leukemia patients with mucositis were compared with 2508 without. In CLOP survivors, mucositis was associated with markedly higher lifetime mortality (adjusted HR 1.94, 95% CI 1.87–2.01), dysphagia (HR 3.42, 95% CI 3.28–3.57), malnutrition (HR 2.81, 95% CI 2.66–2.97), any respiratory disease (HR 1.68, 95% CI 1.63–1.73), and influenza/pneumonia (HR 1.79, 95% CI 1.72–1.86). In leukemia survivors, mucositis conferred only modest or null excess risk (mortality HR 1.12, 95% CI 1.05–1.19; dysphagia HR 1.18, 95% CI 1.07–1.30; malnutrition HR 1.24, 95% CI 1.12–1.37; any respiratory disease HR 1.09, 95% CI 1.03–1.15). Conclusions and Relevance: Severe oral mucositis is a powerful, durable prognostic determinant in cancers of the upper aerodigestive tract, where it identifies patients associated with elevated lifelong risk of swallowing dysfunction, aspiration-related lung disease, malnutrition, and premature death. The markedly attenuated effect in leukemia survivors suggests that direct high-dose radiation-induced structural damage to the pharynx and oral cavity—rather than systemic immunosuppression or chemotherapy intensity alone—is the dominant mechanism. Full article

Articular cartilage, a highly specialised and avascular tissue, exhibits limited regenerative potential following trauma or degenerative conditions such as osteoarthritis (OA). Conventional surgical interventions, including microfracture and autologous chondrocyte implantation (ACI), have shown limited long-term efficacy due to donor site morbidity and restricted cell proliferation. In this context, mesenchymal stromal cells (MSCs) have emerged as a promising alternative owing to their multipotency, self-renewal capacity, and low immunogenicity. While bone marrow (BM) remains the traditional source of MSCs, recent studies have reported that peripheral blood-derived mesenchymal stromal cells (PB-MSCs) may possess chondrogenic, osteogenic, and adipogenic potential comparable to that of BM-derived MSCs. PB-MSCs can be harvested through minimally invasive methods, thereby avoiding the complications associated with BM aspiration. Experimental evidence indicates that PB-MSCs exhibit strong cell viability, proliferative potential, and the ability to synthesise cartilage-specific extracellular matrix proteins, such as type II collagen and sulphated glycosaminoglycans, within three-dimensional scaffolds. Immunophenotypically, PB-MSCs express mesenchymal markers including CD29, CD44, CD90, and CD105 while lacking hematopoietic markers CD34 and CD45. Flow cytometry analyses reveal that CD105⁺ populations increase following cryopreservation, highlighting their clinical utility. In contrast to these experimentally defined PB-MSCs, the term peripheral blood stem cells (PBSCs) is used in clinical studies to describe heterogeneous, non-cultured peripheral blood-derived cell preparations, typically enriched in hematopoietic stem and progenitor cells following granulocyte colony-stimulating factor (G-CSF) mobilisation, without full mesenchymal characterisation. In vitro studies confirm successful tri-lineage differentiation, whereas in vivo investigations have demonstrated effective cartilage regeneration using PB-based clinical approaches, including postoperative intra-articular administration of hyaluronic acid (HA) combined with PBSCs, as well as implantation of PBSCs covered with a collagen membrane. Furthermore, advancements in biomaterial engineering, such as poly(ethylene glycol)–cysteine–arginine–glycine–aspartic acid (PEG-CRGD) hydrogels, have enhanced PB-MSC adhesion, proliferation, and chondrogenic differentiation while promoting immunomodulation through M2 macrophage polarisation. Despite these promising outcomes, the available evidence remains limited and heterogeneous, with substantial variability in cell definitions, experimental models, and clinical study designs, which currently constrains definitive conclusions regarding clinical efficacy. Future research should focus on optimising isolation protocols, understanding molecular pathways governing PB-MSC chondrogenesis, and standardising clinical applications. Overall, PB-MSCs represent a viable, less invasive, and translationally relevant cell source for cartilage regeneration and regenerative orthopaedic therapies Full article

Background: Sjögren’s syndrome (SjS) is a chronic systemic autoimmune disease associated with substantial extraglandular morbidity, including osteoporosis, cardiovascular disease, and renal involvement. Vitamin D deficiency (VDD) is highly prevalent in patients with SjS and has been linked to immune dysregulation, systemic inflammation, and adverse cardiorenal outcomes in other clinical settings. However, the prognostic significance of VDD in patients with SjS and osteoporosis remains incompletely characterized. Methods: We conducted a retrospective cohort study using de-identified electronic health records from the TriNetX research network between 2010 and 2024. Adult patients with SjS and osteoporosis who had at least one serum 25-hydroxyvitamin D measurement within six months before or after cohort entry were included. VDD was defined as a serum 25-hydroxyvitamin D concentration below 20 ng/mL, and vitamin D adequacy (VDA) as a concentration of 30 ng/mL or higher. Propensity score matching was performed at a 1: 1 ratio using 95 baseline covariates. The primary outcome was all-cause mortality. Secondary outcomes included major adverse cardiovascular events (MACEs), major adverse kidney events (MAKEs), and fractures. Results: Among 19,177 eligible patients, 1218 with VDD and 7659 with VDA met the inclusion criteria. After propensity score matching, 1067 well-balanced pairs were analyzed. Over five years of follow-up, VDD was associated with higher risks of all-cause mortality, MACEs, and MAKEs compared with VDA. In contrast, fracture risk did not differ significantly between groups. Sensitivity analyses demonstrated consistent associations across analytic approaches. Conclusions: In patients with SjS and osteoporosis, VDD was associated with increased risks of mortality, MACEs, and MAKEs, but not fractures. These findings suggest that VDD may serve as a marker of a high-risk clinical phenotype and may be useful for long-term risk stratification in this vulnerable population. Full article

Background: Weight extremes are linked to morbidity, yet their impact on burn outcomes remains underinvestigated. Prior studies suggest an ‘obesity paradox’, showing survival benefits and better functional outcomes in obese patients. Methods: This study used the global real-world database TriNetX to assess the association between body mass index (BMI) and clinical outcomes in adult burn patients, categorized using WHO definitions. After 1:1 propensity score matching for demographics, burn severity, and smoke inhalation injury, clinical outcomes were analyzed over a six-month period following burn injury. Outcomes included mortality, sepsis, pneumonia, acute kidney injury (AKI), cardiovascular events, graft complications, skin infections, and psychological impairment. Results: After matching, 9736 patients were included in the underweight versus normal weight comparison, 72,274 in overweight versus normal weight, 71,195 in obesity versus normal weight, and 9732 in underweight versus obesity. Underweight patients were associated with higher mortality and increased risks of sepsis, pneumonia, cardiovascular events, and psychological impairment. Overweight and obese patients showed higher survival rates and overall better clinical outcome associations. Conclusions: These findings are consistent with the previously described ‘obesity paradox’ in burn care and identify underweight burn patients as a distinct high-risk subgroup. Full article