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Treatment of Pulmonary Arterial Hypertension in Lithuania: Current Situation and Analysis of Survival of Patients Treated with Different Treatment Regimens.
J Clin Med
Skaidrius Miliauskas, Deimante Hoppenot, Ieva Dimiene +5 more
Background/Objectives: Since 2015, pulmonary arterial hypertension (PAH)-specific medications have been fully reimbursed in Lithuania. To describe the current situation of PAH treatment in the country and to determine survival during different PAH treatment regimens. Methods: The data from the Institute of Hygiene and the State Data Agency of Lithuania cases with administrative codes I27.0 and I27.8 have been evaluated. Results: In 2025, 225 confirmed cases of PAH were treated with PAH-specific medications in two PH centers. At least one PAH-specific medication was prescribed to 163 (72.4%) female and 62 (27.6%) male patients. Among these, 96 (42.7%) received sildenafil monotherapy, 82 (36.4%) received a combination of sildenafil and an ERA, 36 (16.0%) were on triple PAH-specific therapy (including selexipag or treprostinil), and 11 (4.9%) received other regimens due to specific medical considerations. The age of adults treated with sildenafil monotherapy vs. other therapies was 63.9 ± 14.8 (n = 117) and 51.5 ± 17.3 (n = 116) years, respectively (p < 0.05). A total of 191 PAH patients who received targeted therapy died during the observational period 2017-2025. Of these, 105 received monotherapy, 57 sildenafil and endothelin receptor antagonist and 29 triple therapies (treprostinil [n = 19], selexipag [n = 6], or inhaled iloprost [n = 4] were prescribed as the third drug). Patients who died and received triple therapy were younger than those on mono- and dual therapy (age at diagnosis 45.0 ± 21.6, 67.2 ± 14.7 and 61.6 ± 16.3 years, respectively, p < 0.01). Survival was longer in patients on dual therapy compared with monotherapy (43.1 ± 28.1 vs. 31.7 ± 25.0 months, p = 0.04), and the longest was in those receiving triple therapy (59.9 ± 29.4 months; p < 0.05). Conclusions: The availability of reimbursed medications dramatically increased the number of treated PAH cases in Lithuania. In 2025, most of the PAH patients received sildenafil monotherapy. Patients treated with sildenafil only were significantly older than the rest of cohort. In the survival analysis, combination PAH therapies were more often prescribed to younger patients and were associated with longer duration of life than monotherapy.
Ceftazidime-avibactam-based regimens for the treatment of central nervous system infections caused by carbapenem-resistant Klebsiella pneumoniae in a pediatric patient.
J Glob Antimicrob Resist
Liming He, Wanzhen Li, Weiming Chen +8 more
Carbapenem-resistant Klebsiella pneumoniae (CRKP) central nervous system (CNS) infections are difficult to treat in children because effective and safe therapeutic options are limited. We report a pediatric case of CRKP meningitis successfully treated with ceftazidime-avibactam (CZA) combination with intraventricular polymyxin B (PMB).
High Expression of PAPP-A Predicts Poor Outcomes in Oestrogen Receptor-Positive Breast Cancer Patients.
Cancer Med
Zeanap Mabruk, Esme Bullock, Xue Xiao +10 more
Insulin-like growth factor 1 (IGF-1)/IGF-1 receptor (IGF-1R) signalling is activated in breast cancer and associated with disease progression. Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase that can cleave IGF binding proteins leading to the release of bioactive IGF-1 and the subsequent activation of IGF-1 signalling. Here, we aimed to assess the prognostic significance of PAPP-A in breast cancer.
Molecular and Cellular Effects of Therapies for Thyroid Eye Disease on Ocular Surface and Adnexal Homeostasis.
Cells
Monika Sarnat-Kucharczyk, Wojciech Luboń, Dorota Wyględowska-Promieńska +1 more
Thyroid eye disease (TED) is an autoimmune inflammatory disorder primarily affecting orbital tissues, but ocular surface and adnexal involvement represent a frequent and clinically significant component of disease burden. Beyond mechanical exposure resulting from eyelid retraction and proptosis, TED-associated ocular surface disease arises from complex interactions between immune activation, epithelial stress, glandular dysfunction, and altered neuro-epithelial signaling. Increasing use of systemic immunomodulatory therapies, biologics, and orbital radiotherapy has improved control of orbital inflammation; however, their molecular and cellular effects on ocular surface homeostasis remain incompletely defined. This review summarizes current evidence on the cellular and molecular mechanisms underlying ocular surface dysfunction in TED and examines how disease-modifying therapies influence epithelial integrity, tear film stability, meibomian and lacrimal gland function, and local immune signaling. Key pathways discussed include cytokine-mediated inflammation, thyroid-stimulating hormone receptor and insulin-like growth factor-1 receptor crosstalk, pro-fibrotic signaling, neuro-inflammatory mechanisms, and epithelial stress responses involving mitogen-activated protein kinase and nuclear factor kappa B pathways. We further highlight the challenge of disentangling therapy-induced molecular effects from persistent exposure-related mechanical stress. Understanding how TED therapies modulate ocular surface and adnexal homeostasis is essential for optimizing integrated management strategies that address both orbital inflammation and long-term ocular surface stability.
Effects of Glial Cell Line-Derived Neurotrophic Factor and Ciliary Neurotrophic Factor on Extraocular and Limb Muscle Precursor Cells.
J Histochem Cytochem
Austin J Winker, Laura L Johnson, Linda K McLoon
SummaryMyogenic precursor cells within skeletal muscles are responsible for the maintenance of skeletal muscle over a lifetime. Neurotrophic and growth factors play critical roles in this maintenance and in responses of myogenic precursor cells. Both glial cell line-derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) play roles in the maintenance and/or development of strabismus, yet few studies have examined their roles in the control of myogenic precursor cell proliferation and differentiation. Two populations of myogenic precursor cells were isolated from extraocular and leg muscle by fluorescence-activated cell sorting: EECD34 cells, largely PITX2-positive, and PAX7-positive cells. Cultures were treated with GDNF or CNTF and processed immunohistochemically to determine proliferation and differentiation rates. Neither GDNF nor CNTF affected cell proliferation rates for either muscle. Both treatments impacted cell differentiation by increasing multinucleated cell number, with TA-derived precursor cells producing cells containing large numbers of nuclei and EOM-derived precursor cells producing shorter multinucleated fibers with fewer nuclei. These differences may explain the presence of extremely short myofibers within normal adult EOM compared with limb muscle. As GDNF and CNTF are downregulated in strabismic muscles, data suggest that myofiber length homeostasis may be disrupted in strabismic EOM and suggest possible approaches for strabismus treatment.
Differential Impact of Metabolic Bariatric Surgery Versus Semaglutide on Adverse Hepatic and Extrahepatic Outcomes in Individuals With Metabolic Dysfunction-Associated Steatotic Liver Disease and Type 2 Diabetes.
Diabetes Obes Metab
Weronika Stupalkowska, Alex E Henney, David R Riley +3 more
We compared the impact of metabolic bariatric surgery (MBS) versus semaglutide on clinical outcomes in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2D).
Association of Semaglutide Treatment With Liver Cirrhosis and Hepatocellular Carcinoma in Type 2 Diabetes: A Population-Based Cohort Study.
Diabetes Obes Metab
Assaf Issachar, Talish Razi, Ilya Borochov +2 more
Metabolic dysfunction-associated steatotic liver disease is common among individuals with type 2 diabetes mellitus and substantially increases the risk of liver cirrhosis and hepatocellular carcinoma. Effective therapies that improve metabolic control while preventing advanced liver outcomes are limited.
SemaGBA: A System Dynamics Model of the Semaglutide-Responsive Gut-Brain Axis A Model of How the Brain and Semaglutide Regulate Appetite and Weight.
Diabetes Obes Metab
Vivan C W Kennis, Natal A W van Riel
Semaglutide is a GLP-1 receptor agonist for the treatment of type 2 diabetes and obesity. Its clinical effects are well established, but the underlying mechanisms remain unclear. This study aims to use computational modelling to generate hypotheses about semaglutide's long-term metabolic (body weight, net energy intake, blood glucose, insulin, insulin sensitivity, glucotoxicity, leptin, leptin sensitivity, lipotoxicity, GLP-1 and βcell function) and neural (AgRP, POMC, and dopamine neural activity) effects.
Real-world use of semaglutide in patients with type 2 diabetes and end-stage renal disease: a multicenter retrospective cohort study.
Front Endocrinol (Lausanne)
Omar Alkhezi, Lama Alfehaid, Amal Alanezi +2 more
Semaglutide and other Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated cardiovascular and renal benefits in patients with type 2 diabetes mellitus (T2DM); however, individuals with end-stage renal disease (ESRD) have been systematically excluded from landmark outcome trials. Consequently, real-world data evaluating the safety and effectiveness of GLP-1 RAs in this high-risk population remain limited.
Pharmacologic Treatment of Obesity in the Context of Type 2 Diabetes.
Curr Diab Rep
Caterina Conte, Anastassia Amaro
To examine the role of pharmacologic obesity treatment in people with type 2 diabetes (T2D), with a focus on efficacy, safety, and clinical positioning in the context of T2D-specific metabolic and therapeutic challenges.
Clinical Potential of GIP in Type 2 Diabetes and Obesity.
Diabetes Care
Michael Nauck, Fiona Gribble, Frank Reimann +2 more
Incretin-based pharmacology has revolutionized the medical treatment of type 2 diabetes and obesity. The most effective drug to date is tirzepatide, a dual incretin receptor agonist that engages both the glucagon-like peptide-1 receptor (GLP-1R) and the glucose-dependent insulinotropic polypeptide receptor (GIPR). While the relative contributions of GIPR and GLP-1R actions to the clinical effects of tirzepatide have not been established, the potency of this agent has reignited interest in the clinical potential of GIPR agonism. Here, we discuss incretin biology as it relates to metabolic pharmacology and contextualize the mechanisms by which GIPR activity could contribute to the development of new and effective drugs. We explore current and future applications of GIPR agonists and antagonists, to underscore the potential that this signaling system could add to treatment of type 2 diabetes and obesity.
Comparison of pharmacotherapies for obesity with sleeve gastrectomy: a network meta-analysis and systematic review.
Expert Rev Endocrinol Metab
Zachary Omeh, Tahira Khan, Olalekan Uthman +1 more
Tirzepatide, a glucagon-like peptide-1 receptor agonist (GLP1RA) and glucose-dependent insulinotropic-peptide (GIP), has shown efficacy regarding weight-loss.
The Roles of Macrophage Lineage Cells (MLCs) in Brain Aging.
CNS Neurosci Ther
Qin Qin, Liubin Zhang, Manning Guo +10 more
Brain aging poses a major public health challenge and is the primary risk factor for neurodegenerative diseases. Macrophage lineage cells (MLCs) have emerged as pivotal mediators of brain aging. While fundamental to central nervous system (CNS) homeostasis through their scavenging, detoxification, and neurotrophic functions, their transition to a senescent state is a primary driver of pathology. This shift is marked by a loss of clearance capacity and the adoption of a pro-inflammatory senescence-associated secretory phenotype (SASP).
A potential multimodal biomarker - cognitive signature associated with the conversion from subjective cognitive decline to mild cognitive impairment.
Alzheimers Dement (N Y)
Mohamed Haddad, Mohamed Raâfet Ben Khedher, Chadi Ouechtati +2 more
The disruption of key mechanisms involved in amyloid beta (Aβ) clearance during the early stages of dementia may contribute to the progression of cognitive decline toward irreversible brain damage. In this study, we investigated multiple immune-related pathways implicated in the management and clearance of Aβ within circulating extracellular vesicles (cEVs) and serum from individuals with subjective cognitive decline (SCD) who later progressed to mild cognitive impairment (MCI).
Oxidative Stress as a Mechanistic Link Between Severe Respiratory Viral Infection and Pulmonary Fibrosis.
Biology (Basel)
Shynggys Sergazy, Alexander Gulyaev, Zarina Shulgau
Post-viral pulmonary fibrosis represents a clinically significant and mechanistically complex consequence of severe respiratory infection. The COVID-19 pandemic has highlighted that a subset of survivors, particularly those with severe pneumonia or acute respiratory distress syndrome, develop persistent fibrosis-like lung abnormalities, including reticulation and traction bronchiectasis, often accompanied by impaired gas transfer. Although the clinical course is heterogeneous and many lesions regress over time, longitudinal studies indicate that structural and functional impairment may persist for years in susceptible individuals. Oxidative stress has emerged as a plausible convergent mechanism linking acute epithelial injury, dysregulated inflammatory resolution, and chronic fibrotic remodeling. Reactive oxygen and nitrogen species amplify inflammatory signaling, promote epithelial cell death and senescence, influence macrophage polarization, and activate canonical profibrotic pathways, notably the TGF-β axis. Redox imbalance is embedded within reinforcing circuits involving NOX4-dependent ROS amplification, mitochondrial dysfunction, endoplasmic reticulum stress, inflammasome activation, and senescence-associated secretory programs. Persistent immune activation and organelle stress may sustain redox dysregulation beyond viral clearance, thereby bridging acute lung injury to maladaptive remodeling. This review integrates epidemiological, clinical, and mechanistic evidence to position oxidative stress as a central mediator of post-viral lung fibrosis and discusses therapeutic and translational implications.
A Multicenter Randomized Clinical Trial of Dapagliflozin in Patients Receiving Chronic Dialysis (The DARE-ESKD-2 Trial).
Kidney Int Rep
Joaquim Barreto, Marilia Paiva Martins, Cleide Aparecida Moreira Silva +18 more
Dapagliflozin reduces heart failure (HF) incidence and hospitalizations in chronic kidney disease (CKD), but its efficacy and safety in patients on maintenance dialysis remain uncertain.
The attenuated incretin effect is associated with glucose intolerance in patients with hepatitis B-related acute-on-chronic liver failure.
Front Physiol
Meichuan Li, Han Hu, Yujuan Liu +6 more
The pathogenesis of glucose homeostasis disturbance in acute-on-chronic liver failure (ACLF) remains poorly defined. This study aimed to investigate the association between incretin effect (IE) and glucose intolerance in patients with hepatitis B virus-related ACLF (HBV-ACLF).
Subarachnoid Hemorrhage Induces mPFC CRF Neuronal Dysfunction Leading to Anxiety and Depression in Male Mice.
Stroke
Jin Yan, Fuming Liang, Na Wu +13 more
Anxiety and depression are common neuropsychiatric sequelae after subarachnoid hemorrhage (SAH), yet the underlying neural mechanisms remain poorly understood. The CRF (corticotropin-releasing factor) system in the medial prefrontal cortex (mPFC) is critical for emotional regulation and stress adaptation; however, its involvement in SAH-induced affective disorders has not been defined.
Challenging the known: unusual case report of acromegaly and subclinical Cushing's disease combination.
AME Case Rep
Xinlian He, Haiyan Li, Tingting Wu +3 more
Pituitary neuroendocrine tumors (PitNETs) are usually characterized by hormone secretion profiles that correspond to lineage-specific transcription factor expression. Growth hormone (GH) and prolactin (PRL) secretion is regulated by pituitary-specific transcription factor-1 (Pit-1), whereas adrenocorticotropic hormone (ACTH) production is classically dependent on T-box transcription factor 19 (T-pit). Accordingly, the concomitant secretion of GH and ACTH from a single pituitary adenoma is exceedingly rare.
Oral Health Considerations and Dental Management Guidelines for Semaglutide Medications.
Can J Diabetes
Karina Kofman, Aviv Ouanounou
Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated clinically meaningful weight loss effects in patients with Type 2 diabetes and high BMI, and dental practitioners and physicians are often encountering patients who take these medications. Semaglutide is known to be associated with several systemic side effects, including delayed gastric emptying, belching, reflux and nausea, nutritional changes, and gastrointestinal discomfort. Systemic effects secondarily manifest in the oral cavity, and as a result, patients taking semaglutide may present with xerostomia (dry mouth), halitosis (bad breath), enamel erosion tied to vomiting, altered taste, among other oral signs and symptoms. It is important for dental professionals and physicians to become informed of possible symptoms and corresponding management strategies, given the multiple potential indirect effects on the oral cavity and relevance to dental treatment planning. This article reviews the pharmacodynamics of semaglutide and dives into the current evidence on oral manifestations of the drug family and implications for dental and oral health. It outlines practical management recommendations for dentists and the broader interdisciplinary healthcare team.