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Once-weekly IcoSema versus once-daily insulin glargine U100 in type 2 diabetes management (COMBINE 4): an open-label, multicentre, treat-to-target, randomised, phase 3b trial.
Lancet Diabetes Endocrinol
Linong Ji, Malik Benamar, Viswanathan Mohan +5 more
Stepwise treatment intensification is recommended for managing type 2 diabetes, including insulin initiation when non-insulin glucose-lowering medications are insufficient. Guidelines recommend combining a GLP-1 receptor agonist with basal insulin to improve glycaemic efficacy while reducing weight gain and hypoglycaemia risk. COMBINE 4 evaluated the efficacy and safety of IcoSema, a once-weekly combination therapy of basal insulin icodec and semaglutide (a GLP-1-receptor agonist) versus insulin glargine U100 (glargine U100) in people with type 2 diabetes on oral glucose-lowering medications.
[Gastrointestinal metabolic surgery improves salt-sensitive hypertension via GLP-1-mediated inhibition of the RAS/NHE3 axis].
Zhonghua Xin Xue Guan Bing Za Zhi
D Tong, Q L Peng, L J Wang +6 more
Objective: To investigate the effect of Roux-en-Y gastric bypass (RYGB) on salt-sensitive hypertension and its underlying molecular mechanism. Methods: (1) Clinical study: A total of 57 patients who underwent RYGB at Daping Hospital, Army Medical University between December 2010 and May 2025 were enrolled. According to the diagnostic criteria for hypertension, the patients were divided into normotensive group and hypertensive group. Baseline and postoperative clinical data were collected. Daily sodium intake was calculated based on 24-hour urinary sodium excretion, and the correlation between preoperative sodium intake and the reduction of postoperative systolic blood pressure was analyzed. (2) Animal experiment: Forty-eight 6-week-old male Dahl salt-sensitive hypertensive rats were fed an 8% high-salt diet for 8 weeks to establish the salt-sensitive hypertension models. Thirty modeled rats were randomly divided into the RYGB group (n=15) and the sham operation group (n=15). The remaining 18 rats were randomly divided into control group (n=6), liraglutide group (n=6) and liraglutide+EX9-39 group (n=6), which were treated with normal saline, liraglutide (0.2 mg·kg-1·d-1), and liraglutide combined with EX9-39 (75 μg·kg-1·d-1), respectively. Rat blood pressure was measured via non-invasive tail-cuff method and invasive radiotelemetry method, and isolated vascular function was detected. HE, PAS and Masson staining were used to evaluate mesenteric vascular remodeling, glomerular matrix distribution and renal fibrosis degree, respectively. Enzyme-linked immunosorbent assay was adopted to detect serum levels of glucagon-like peptide-1 (GLP-1) and angiotensin Ⅱ (AngⅡ). Western blot was performed to determine the protein expression of tumor necrosis factor-α, interleukin-6, GLP-1 receptor (GLP-1R), angiotensin-converting enzyme (ACE) 1, ACE2, angiotensin Ⅱ type 1 receptor (AGTR1), phosphorylated Na⁺/H⁺ exchanger 3 (NHE3) and total NHE3 in renal cortex. (3) Cell experiments: Rat renal epithelial NRK-52E cells were used. Four experimental groups were set up: high-salt group (treated with 160 mmol/L NaCl for 24 h), high-salt+liraglutide group (100 nmol/L liraglutide), high-salt+liraglutide+EX9-39 group(100 nmol/L liraglutide+150 nmol/L EX9-39), and control group (equal volume of drug vehicle). Western blotting was performed to detect the expression of ACE1, AGTR1, phosphorylated NHE3 and total NHE3. Results: (1) Clinical study: The enrolled patients had an age of (43.91±10.19) years, including 33 males (58%). There were 24 patients in the normotensive group and 33 in the hypertensive group. Compared with the baseline levels, both systolic blood pressure ((133.26±16.48) mmHg vs. (118.23±15.40) mmHg, 1 mmHg=0.133 kPa) and diastolic blood pressure ((83.16±12.44) mmHg vs. (74.54±8.80) mmHg) were decreased after RYGB (both P<0.05). The median daily preoperative sodium intake of all participants was 10.45 (8.19, 15.58) g/d. A positive correlation was observed between preoperative sodium intake and the reduction in postoperative systolic blood pressure (R=0.326, P=0.013). (2) Animal experiment: At the 8th week after surgery, the tail-cuff systolic blood pressure ((125.33±12.16) mmHg vs. (182.00±11.61) mmHg), 24-hour mean systolic blood pressure ((125.81±12.89) mmHg vs. (182.11±10.21) mmHg) and 24-hour mean diastolic blood pressure ((97.36±6.59) mmHg vs. (144.85±16.58) mmHg) in the RYGB group were lower than those in the sham group (all P<0.05). Compared with the sham group, the RYGB group presented a lower ratio of vascular wall thickness to outer vessel diameter, higher vasodilation of mesenteric arteries, and less glomerular collagen deposition. Meanwhile, the levels of serum creatinine, blood urea nitrogen and urinary protein, as well as the expression of tumor necrosis factor-α and interleukin-6 in renal cortex were also lower in RYGB group than sham group (all P<0.05). In addition, compared with sham group, the serum GLP-1 level, renal cortical GLP-1 receptor expression and NHE3 phosphorylation level were higher in the RYGB group, while serum AngⅡ and the expression of ACE1 and AGTR1 in renal cortex were lower (all P<0.05). Drug intervention results showed that tail-cuff systolic blood pressure was lower in the liraglutide group than in the control group ((167.00±9.98) mmHg vs. (182.00±6.26) mmHg, P<0.05). No significant difference in tail-cuff systolic blood pressure was found between the liraglutide+EX9-39 group and the control group (P>0.05). (3) Cell experiments: High-salt treatment upregulated the expression of ACE1 and AGTR1 and inhibited NHE3 phosphorylation in NRK-52E cells. Liraglutide reversed the above abnormalities, whereas EX9-39 antagonized the regulatory effects of liraglutide. Statistically significant differences were observed in the expression levels of the above proteins among all groups (all P<0.05). Conclusion: RYGB can effectively ameliorate salt-sensitive hypertension. The underlying mechanism is associated with GLP-1-mediated inhibition of renin-angiotensin system activity and promotion of NHE3 phosphorylation.
Liraglutide and Βeta-Cell Function in Young Adults With Long-Standing Type 1 Diabetes and Residual C-Peptide: A Blinded, Randomized Controlled Trial.
Diabetes Obes Metab
José Caballero-Corbalán, Per Lundkvist, Daniel Espes +1 more
To evaluate the effect of liraglutide on residual beta-cell function in adults with long-standing type 1 diabetes (T1D) and detectable C-peptide.
FECH, a novel metabolic target influencing CAR T-cell phenotype and function.
Biomark Res
Marsha Pellegrino, Simone Vespa, Illari Salvatori +21 more
Recent phase I/II clinical trials have demonstrated that chimeric antigen receptor (CAR) T cells targeting the disialogangliosade GD2 represent a promising therapeutic option for pediatric patients with relapsed or refractory high-risk neuroblastoma (NB). However, incomplete and heterogeneous clinical responses highlight the need to improve CAR T-cell efficacy and persistence. We previously demonstrated the therapeutic benefit of combining the dual insulin-like growth factor 1 receptor/insulin receptor (IGF1R/IR) inhibitor linsitinib (LIN) with third-generation GD2.CAR T cells in diffuse intrinsic pontine glioma, where LIN induced tumor cell death and modulated the CAR T-cell phenotype. Here, we extended these findings to NB and explored the mechanisms of LIN-mediated CAR T-cell modulation. LIN, in combination with CAR T cells, significantly enhanced antitumor activity in LIN-sensitive NB cell lines. Mechanistically, we investigated ferrochelatase (FECH), a mitochondrial enzyme involved in heme biosynthesis, and a known off-target of LIN. LIN treatment or selective FECH inhibition with N-methyl protoporphyrin IX reduced intracellular heme, attenuated activation and exhaustion marker expression and promoted central memory characteristics associated with improved in vivo CAR T-cell persistence and functionality. Both treatments similarly decreased ATP production by reducing glycolysis and mitochondrial respiration in chronical antigen-activated CAR T cells. Collectively, these data reveal a dual mechanism of action for LIN, combining direct tumor cell cytotoxicity with metabolic reprogramming of CAR T cells linked to heme biosynthesis. These findings identify heme metabolism as regulator of CAR T-cell phenotype and function and support further investigation of FECH to enhance therapeutic efficacy in NB and beyond.
Recent advances in the medical management of thyroid eye disease.
Curr Opin Endocrinol Diabetes Obes
Khushboo Agarwal, Vamshi Rao-Waronski, Nihal Thomas +1 more
Thyroid eye disease (TED) is a debilitating autoimmune disorder that can cause facial disfigurement, impair vision and reduce the quality of life. Novel insights into the pathogenesis of TED in the recent years have stimulated efforts to develop newer targeted medical therapies. This review summarizes latest advances in the medical management of TED, with a particular focus on novel targeted therapies.
Can Carica papaya Serve as an Adjunct to Semaglutide in Mitigating Diabetes-Induced Testicular Injury Through Modulation of Oxidative Stress, Inflammation, Apoptosis, and the miR-34c/miR-155-SIRT1/FOXO1 Axis? An Experimental and Chem-Bio-Informatics Study.
Int J Mol Sci
Mohamed M Zeweil, Asmaa F Khafaga, Marium M Shamaa +7 more
Diabetes mellitus (DM) induces significant endocrine disruption and oxidative stress (OS) within the testes, resulting in impaired spermatogenesis, increased sperm abnormalities, and compromised reproductive function. This study aimed to evaluate the combined protective effects of Semaglutide (SEM) combined with Carica papaya (papaya) juice against type 2 diabetes-induced testicular damage in rats. Forty adult male albino rats were divided into four experimental groups: a control group, a Streptozotocin (STZ)-induced diabetic group, a diabetic group treated with SEM (0.3 mg/kg), and a diabetic group treated with SEM (0.3 mg/kg) in combination with 10% papaya juice, administered for eight weeks. Statistically significant superiority over SEM alone was observed for selected endpoints; the findings primarily support the potential of papaya as a dose-sparing adjunct rather than demonstrating uniformly enhanced efficacy. They significantly improved systemic metabolic parameters, as evidenced by reduced fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) levels and restoration of the lipid profile. Importantly, it also attenuated diabetes-induced testicular injury, as demonstrated by improved reproductive hormone levels, enhanced sperm parameters, restoration of antioxidant defenses, modulation of inflammatory and apoptotic signaling, and marked histopathological recovery of seminiferous tubular architecture. Antioxidant markers revealed a notable reduction in malondialdehyde (MDA) and cytochrome P450 2E1 (CYP2E1), along with significant increases in reduced glutathione, catalase (CAT), and superoxide dismutase (SOD). Furthermore, a marked modulation of key pro-inflammatory and pro-apoptotic mediators was observed, including forkhead box protein O1 (FOXO1), microRNA-155 (miR-155), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B cell subunit 1 (NF-κB1), interleukin-6 (IL-6), caspase-3 (CASP3), and BCL2-Associated X Apoptosis Regulator (Bax), while a significant upregulation of sirtuin-1 (SIRT1), microRNA-34c (miR-34c), and B-cell lymphoma-2 (Bcl-2) was also detected. Histopathological assessments confirmed the restoration of normal testicular architecture in the treated groups. These findings indicate that the combination strategy may have the potential to achieve dose savings while maintaining efficacy comparable to the standard-dose SEM, through the enhancement of the antioxidant defenses, modulation of inflammation, and apoptosis, specifically via the modulation of the miR-34c/miR-155 and SIRT1/FOXO1 signaling.
Real-world use of oral semaglutide in adults with type 2 diabetes.
Dan Med J
Klaus Roslind, Ulrik Bodholdt, Tina Damgaard +1 more
PIONEER REAL Denmark assessed changes in HbA1c, body weight and treatment satisfaction with once-daily oral semaglutide in adults with type 2 diabetes.
Achieving the triple endpoint of body weight reduction thresholds, systolic blood pressure reduction ≥5 mmHg and non-HDL cholesterol <130 mg/dL with tirzepatide in people with obesity: A post hoc analysis from the SURMOUNT trials.
PLoS One
Naveed Sattar, Reshmi Srinath, Luis-Emilio García-Pérez +4 more
Modest body weight reduction can greatly improve many health-related outcomes. In the SURMOUNT clinical trial program, once-weekly tirzepatide resulted in substantial body weight reductions in people with obesity, without and with type 2 diabetes.
Semaglutide and Liraglutide Modulate Oxidative Stress and Wound Repair in Normal Human Skin Cells Exposed to an In Vitro Diabetic-like Environment.
Int J Mol Sci
Ioanna A Anastasiou, Konstantinos Tentolouris, Athanasia Katsaouni +4 more
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) not only improve glycemic control but also possess anti-inflammatory and antioxidant properties. In this study, the effects of semaglutide and liraglutide on oxidative stress and wound healing were examined in human dermal fibroblasts (NHDFs) and keratinocytes (NHEKs) under diabetes-mimicking conditions. Cells were exposed to high glucose and hydrogen peroxide, followed by treatment with semaglutide or liraglutide at concentrations of 22.5 and 45 pg/mL for 48 h. We assessed cell viability, apoptosis, intracellular reactive oxygen species (ROS), Ki-67, and Pax-7. Advanced glycation end-products (AGEs) and their receptor (RAGE) were quantified via ELISA. Wound healing was evaluated by scratch assay, and the gene expression of antioxidants, cytokines, and matrix components was measured by real-time PCR. Semaglutide significantly improved NHDF viability and proliferation under diabetic conditions, reducing ROS production more effectively than liraglutide. Apoptosis decreased, evidenced by increased Bcl-2 alongside decreased Bax and cleaved caspase-3, particularly with semaglutide. Furthermore, semaglutide uniquely activated Pax-7 expression. While both agents upregulated antioxidants, semaglutide more effectively suppressed AGEs/RAGE and inflammatory cytokines. Both drugs enhanced collagen expression and accelerated wound closure; however, semaglutide achieved near-complete healing within 48 h. Neither drug induced observable changes in NHEKs. Semaglutide exhibits strong antioxidative, cytoprotective, and pro-regenerative effects in diabetic NHDFs, outperforming liraglutide across multiple parameters. These findings highlight semaglutide's therapeutic potential for diabetic wound healing, warranting further in vivo investigation.
Glucagon-like Peptide-1 Receptor Agonists and Chronic Pain: Preclinical Antinociceptive Mechanisms, Indirect Metabolic-Functional Effects, and Clinical Considerations-A Narrative Review.
J Clin Med
Sung-Woo Hyung, Ui Jin Park, Jeong Hwan Ryu +1 more
Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly encountered in pain practice, but reported pain improvement may reflect direct antinociception, weight loss, metabolic change, or disease-specific effects. This structured narrative review examined these possibilities and relevant safety issues. Methods: PubMed/MEDLINE, Embase, and Web of Science Core Collection were searched through 15 May 2026. Peer-reviewed human studies, key mechanistic preclinical studies, systematic reviews and meta-analyses, and professional guidance relevant to pain outcomes or procedural safety were considered. Metabolic-only and non-peer-reviewed reports were excluded, and human pain-primary evidence was prioritized. Results: Preclinical data support plausible mechanisms involving spinal microglia, interleukin-10, beta-endorphin, neuroinflammation, and sensory-neuron signaling, but direct analgesic efficacy at systemic clinical doses has not been demonstrated. In STEP 9 (n = 407), mean WOMAC pain scores at 68 weeks changed from baseline by -41.7 points with semaglutide 2.4 mg and -27.5 points with a placebo; body weight changed by -13.7% and -3.2%, respectively. Liraglutide produced additional weight loss without superior knee-pain reduction. Diabetic peripheral neuropathy evidence was mainly structural or neurophysiologic; idiopathic intracranial hypertension and ROSE-010-treated irritable bowel syndrome showed disease-specific signals, whereas fibromyalgia- and opioid-related findings remained observational or hypothesis-generating. Gastrointestinal dysmotility, reduced intake, and lean-mass loss may offset functional benefits. Conclusions: GLP-1RAs are not established analgesics. Current human signals are best interpreted as indirect metabolic-functional or disease-specific effects. Future trials should use validated pain-primary outcomes, control for weight loss, and monitor treatment-related harms.
Incretin-Based Therapies in Obesity-Related Obstructive Sleep Apnea: A Narrative Review of Evidence Tiers and Mechanistic Plausibility.
Nat Sci Sleep
Xize Zhang, Yuxin Jiang, Xiaotong Wei +4 more
Obesity-related obstructive sleep apnea (OSA) is common, clinically heterogeneous, and tightly linked to cardiometabolic dysfunction, impaired daytime function, and reduced quality of life. Positive airway pressure (PAP) remains the standard device-based treatment for moderate-to-severe disease because it immediately stabilizes the upper airway, but it does not directly reverse the obesity that drives disease in many patients and its long-term effectiveness is often constrained by adherence. This narrative, non-systematic review synthesizes direct OSA-specific randomized evidence, indirect obesity-trial evidence, and mechanistic literature to clarify what is established, what is inferred, and what remains hypothetical. The clinical evidence for incretin therapy in OSA is promising but uneven. Direct OSA-specific randomized evidence is concentrated in liraglutide and tirzepatide: SCALE Sleep Apnea established proof of concept that pharmacologic weight loss can improve the primary apnea-hypopnea index (AHI) outcome, whereas in SURMOUNT-OSA change in AHI was the primary endpoint. Reductions in body weight, sleep apnea-specific hypoxic burden, selected patient-reported sleep outcomes, hsCRP, and systolic blood pressure were reported as key secondary or additional secondary findings, supporting a broader disease-burden signal but not proving long-term cardiovascular event reduction. Discordant vascular-imaging evidence further cautions that GLP-1-mediated weight loss should not be assumed to reproduce all vascular effects of PAP or to prove cardiovascular event reduction. Semaglutide provides important indirect obesity and cardiometabolic evidence, but direct OSA-specific outcome data remain limited; evidence from other incretin agents also remains largely indirect because most trials were designed for obesity or cardiometabolic endpoints rather than sleep outcomes. The most parsimonious mechanistic interpretation is weight-loss-mediated anatomical unloading. This interpretation is supported by non-incretin weight-loss imaging studies and upper-airway physiology, but it has not yet been directly confirmed by serial upper-airway imaging, Pcrit measurement, or physiological endotyping within incretin-treated OSA cohorts. This narrative review organizes the field into three evidence tiers: direct OSA-specific randomized trials, indirect obesity-trial evidence relevant to OSA, and mechanistic extrapolation. We argue that the current evidence is strong enough to position incretin therapy as a disease-modifying adjunct for selected patients with obesity-driven, anatomically dominant OSA, but not yet strong enough to support class-wide claims, routine PAP replacement, or confident attribution of benefit to direct modulation of non-anatomical endotypes.
Gastroparesis induced by glucagon-like peptide-1 receptor agonists: A systematic review of clinical features, diagnosis, management, and outcomes.
PLoS One
Tope Olubodun, Morenike Adedoyin Osundina, David Olubukunmi Soyoye +3 more
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for the treatment of type 2 diabetes mellitus and obesity. Although gastrointestinal adverse effects are common, gastroparesis is an under-recognised but clinically important complication. This systematic review summarises published evidence on the presentation, diagnosis, management, and outcomes of gastroparesis associated with GLP-1RA therapy in real-world clinical practice.
Anti-Obesity Medications in Longevity and Aesthetic Medicine.
J Clin Med
Julia Bijoch
Anti-obesity medications (AOMs), led by the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) semaglutide and liraglutide and the dual GIP/GLP-1 receptor agonist tirzepatide, have produced substantial weight reduction and growing signals of benefit that extend well beyond adiposity. These agents are now discussed in relation to longevity and aesthetic medicine, raising the question of whether their effects reach ageing biology and appearance. This narrative review (PubMed, EMBASE, Scopus, Web of Science, Cochrane Library, and Clinical trial registries; January 2010-June 2026) integrates mechanistic studies, randomised cardiovascular and renal outcome trials, ageing-biomarker analyses, body-composition data, and patient-facing aesthetic phenomena. The evidence indicates that AOMs reduce major cardiovascular events, slow kidney and liver disease progression, and lower all-cause mortality in selected populations; exploratory proteomic and epigenetic analyses further suggest effects partly independent of weight loss, though these do not establish slowed ageing. Newer multi-receptor agents act with greater metabolic specificity: glucagon-containing agents such as survodutide and the triple agonist retatrutide preferentially reduce visceral and hepatic fat (liver-fat reductions of roughly 60-80% in places), a quality of weight loss arguably more relevant to healthspan than its quantity. Concurrently, rapid large-magnitude weight loss drives soft-tissue and appearance changes colloquially termed "Ozempic face" and "Ozempic body", alongside accelerated skin laxity and loss of lean mass, the latter tempered by data showing lean-loss proportions comparable to established agents.
Exercise as a Systemic Prevention and Management for Alzheimer's Disease: Restoring Brain-Body Homeostasis Through Metabolic, Neurovascular, Anti-Inflammatory, and Regenerative Mechanisms.
Cells
Li Xiao, Jeshka Meihua Green, Mai Mochizuki +1 more
Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide and remains a major unmet medical challenge in aging societies. Although amyloid-β (Aβ) plaques and tau pathology are hallmark features of AD, the limited efficacy of many Aβ- and tau-targeted therapies suggests that AD arises from systemic and cerebral dysfunction. Aging-associated homeostatic failure-including hepatic metabolic, vascular, neuroendocrine, inflammatory, oxidative, and mitochondrial dysfunctions-promotes the accumulation of neurotoxic Aβ and tau species, ultimately driving neurodegeneration and impairing endogenous neuroregeneration. Emerging evidence suggests that regular physical exercise induces metabolic, cardiovascular, and neuroendocrine adaptations, improving hepatic metabolic function, cerebral blood flow, oxygen delivery, mitochondrial activity, waste clearance pathways, and brain health. Exercise-induced musculoskeletal-brain crosstalk further contributes to these benefits through the release of myokines and extracellular vesicles, which facilitate systemic intercellular communication to regulate neurovascular function, neuroplasticity, and neuroregeneration. Collectively, these adaptations reduce chronic inflammation and oxidative stress while enhancing resilience across interconnected peripheral and cerebral systems. Therefore, physical exercise may represent a multifaceted preventive and therapeutic strategy capable of restoring brain-body homeostasis and mitigating AD progression. This comprehensive review discusses aging-associated systemic mechanisms underlying AD pathogenesis and summarizes recent advances in the understanding of exercise-mediated protection against AD progression.
Postoperative Complications Following Total Knee Arthroplasty in Patients with Chronic Lymphocytic Leukemia.
J Clin Med
Brandon Wood, Sri Tummala, Dharani Rohit Thota +1 more
Background/Objectives: Chronic lymphocytic leukemia (CLL), the most common leukemia in adults, predominantly affects the aging population. With improved survival from modern targeted therapies, a growing number of CLL patients are living long enough to become candidates for quality-of-life-improving procedures such as elective total knee arthroplasty (TKA). However, the impact of CLL on postoperative outcomes remains poorly understood. Methods: A retrospective cohort analysis was performed using the TriNetX Research Network. Adult patients who underwent primary TKA were identified and divided into two cohorts. CLL and non-CLL control, and 1:1 propensity score matching was performed on demographics and comorbidities. Medical complications were assessed at 30 and 90 days, and implant-related complications at 1 and 3 years postoperatively. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated. Within the CLL cohort, a Cox proportional hazards model was used to identify preoperative laboratory values, medications, and comorbid diagnoses associated with complication development. Results: After matching, 2054 patients, 1027 per cohort, were analyzed. Patients with CLL demonstrated significantly higher risks of postoperative pain at both 30 days (p < 0.001) and 90 days (p < 0.001), as well as transfusion (p = 0.035) and acute kidney injury (p = 0.036) at 90 days. At 1 year, the CLL cohort had elevated risks of periprosthetic joint infection (PJI; p = 0.015) and arthrofibrosis (p = 0.036), and these differences persisted at 3 years (PJI p = 0.033; arthrofibrosis p = 0.006). In the hazards model, preoperative hemoglobin < 8 g/dL (HR: 1.75, 95% CI: 1.27-2.41, p < 0.001), long-term anticoagulant or antiplatelet use (HR: 1.43, 95% CI: 1.13-1.80, p = 0.003), chronic kidney disease (CKD; HR: 1.28, 95% CI: 1.04-1.58, p = 0.021), and overweight/obesity (HR: 1.23, 95% CI: 1.00-1.50, p = 0.047) were independently associated with short-term complications. Chronic opioid use was found to be associated with an increased risk of long-term complications (HR: 2.80, 95% CI: 1.49-5.24, p = 0.001). Conclusions: Patients with CLL undergoing TKA had higher observed risks of both early medical and late implant-related complications. These findings may reflect the combined effects of CLL-related immune dysfunction, cytopenias, and chronic systemic inflammation, which may impair wound healing, reduce physiologic reserve, and blunt infection clearance. Identification of associated, modifiable preoperative risk factors-anemia, anticoagulant exposure, CKD, obesity, and chronic opioid use-may provide actionable targets for optimization and risk stratification.
Mitral valve posteromedial papillary muscle head rupture presenting after liposomal doxorubicin chemotherapy for metastatic lung liposarcoma: a case report.
Eur Heart J Case Rep
Shivam U Desai, Narayana R Gandham
Doxorubicin-induced cardiotoxicity classically manifests as dose-dependent left ventricular systolic dysfunction. Herein, we describe an unusual case of acute mitral papillary muscle rupture following cumulative anthracycline therapy, presenting despite a preserved ejection fraction.
Development and External Validation of an AI-ECG Algorithm for Estimating Elevated Serum NT-proBNP Levels.
Eur Heart J Qual Care Clin Outcomes
Ciro Indolfi, Carmen Spaccarotella, Alberto Polimeni +10 more
N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a cornerstone biomarker for the diagnosis and management of heart failure, but its use may be limited by the need for blood testing and laboratory infrastructure. Artificial intelligence (AI) applied to electrocardiograms (ECGs) may offer a widely accessible, non-invasive approach to estimate NT-proBNP levels.
Serum Albumin Modifies the Prognostic Meaning of BNP in Acute Decompensated Heart Failure.
Clin Cardiol
Muneera O AlTaweel, Elbadri I Abdelgadir, Lulwah Al Turki +4 more
BNP is widely used for risk stratification in acute decompensated heart failure (ADHF), but its prognostic meaning may differ across clinical phenotypes, particularly cardiorenal syndrome type 1 (CRS1).
Structured Exercise During and After Incretin-Based Pharmacotherapy Discontinuation: A Narrative Review of Mechanisms, Evidence, and Prescription Guidance.
Healthcare (Basel)
Zachary Zeigler, Jacob Havenar, Eddie Smith +3 more
Background/Objectives: Incretin-based pharmacotherapies are the most effective non-surgical treatments for obesity to date, yet 85% of patients discontinue within the second year of real-world use. No established framework exists for managing this post-cessation transition. This narrative review evaluates the evidence for structured exercise to mitigate physiological rebound and support long-term weight management following discontinuation. Methods: A narrative review was conducted per Assessment of Narrative Review Articles (SANRA) guidelines using PubMed, Scopus, and Web of Science from January 2005 through to June 2026. Results: Post-cessation weight regain averages 5.6 kg within one year and is observationally associated with dose-dependent cardiometabolic worsening. Lean mass losses averaging 6-7 kg and reductions in bone mineral density are seen during active treatment, creating a metabolically unfavorable state at cessation compounded by fat-preferential regain. Exercise and pharmacotherapy generate fundamentally different body composition outcomes. Exercise preserves lean mass, bone density, cardiorespiratory fitness, and insulin sensitivity, while pharmacotherapy alone does not, with downstream implications for resting metabolic rate and post-cessation rebound. Controlled trial data show exercise initiated during incretin treatment is associated with significantly less weight regain, greater sustained weight loss, and maintained physical activity levels one year after medication and supervised program end. This evidence derives from a single liraglutide-based trial and may not generalize directly to semaglutide, tirzepatide, or next-generation agents. Real-world data associate exercise counseling with durable weight loss after discontinuation. Conclusions: No randomized controlled trial has directly evaluated exercise at pharmacotherapy cessation; conclusions are based on post-treatment extension, real-world observational, and mechanistic evidence. Combined aerobic and resistance training is a biologically plausible, low-risk adjunct to incretin-based pharmacotherapies. Resistance training, adequate dietary protein, and individualized clinical screening are likely important components pending direct evidence from post-cessation trials.
Effects of leuprorelin acetate microspheres on sex hormones, secondary sexual characteristics, and predicted adult height in early and fast puberty girls: a real-world, single-arm, retrospective cohort study.
Transl Pediatr
Hanze Du, Xu Huang, Dandan Feng +3 more
Gonadotropin releasing hormone analogs (GnRHa) are recommended for both central precocious puberty (CPP) and early and fast puberty, but their benefit on final adult height in later onset cases remains controversial. Boennuokang® leuprorelin acetate microspheres, the first domestic generic formulation, have been approved for CPP, but evidence in early and fast puberty girls is still limited. Considering the complexity of clinical management in early and fast puberty, more real-world studies are needed. Therefore, this study aimed to explore the effect of Boennuokang® leuprorelin acetate microspheres on hypothalamic-pituitary-gonadal (HPG) axis and predicted adult height (PAH) in early and fast puberty girls.