Search Results (34,034)

Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), is strongly associated with metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD). IH exacerbates MASLD progression through oxidative stress, inflammation, and lipid accumulation. This study aims to investigate the impact of oxygen normalization on metabolic dysfunction in OSA patients using continuous positive airway pressure (CPAP) therapy, and in mice exposed to IH followed by a reoxygenation period. In the clinical study, 76 participants (44 OSA patients and 32 controls) were analyzed. OSA patients had higher insulin resistance, triglycerides, very low density lipoprotein (VLDL) content, and liver enzyme levels, along with a higher prevalence of liver steatosis. After 18 months of CPAP therapy, OSA patients showed significant improvements in insulin resistance, lipid profiles (total cholesterol and VLDL), liver function markers (AST and albumin), and steatosis risk scores (Fatty Liver Index and OWLiver test). In the experimental study, IH induced hepatic lipid accumulation, oxidative stress, and inflammation, and reoxygenation reversed these deleterious effects in mice. At the molecular level, IH downregulated fatty acid oxidation (FAO)-related genes, thus impairing the FAO process. Reoxygenation maintained elevated levels of lipogenic genes but restored FAO gene expression and activity, suggesting enhanced lipid clearance despite ongoing lipogenesis. Indeed, serum β hydroxybutyrate, a key marker of hepatic FAO in patients, was impaired in OSA patients but normalized after CPAP therapy, supporting improved FAO function. CPAP therapy improves lipid profiles, liver function, and MASLD progression in OSA patients. Experimental findings highlight the therapeutic potential of oxygen normalization in reversing IH-induced liver damage by FAO pathway restoration, indicating a metabolic reprogramming in the liver. Full article

Obstructive sleep apnea syndrome (OSAS) is a prevalent disorder with significant systemic and oral health consequences. This narrative review synthesizes the current knowledge on the interplay between dental health and sleep apnea, highlighting the expanding role of dentists in the screening, early detection, and management of OSAS. Validated questionnaires, anatomical assessments, and anthropometric measurements have enhanced dentists’ capacity for early screening. However, knowledge and training gaps remain, particularly in low- and middle-income countries. Dentists are uniquely positioned to identify anatomical and oral risk factors, facilitate referrals for diagnosis, and provide therapeutic interventions such as oral appliance therapy. Interdisciplinary collaboration between dental and medical professionals is essential to improve early detection, treatment outcomes, and patient quality of life. Enhancing education, standardizing protocols, and integrating dentists into multidisciplinary care pathways are critical steps for advancing the management of sleep apnea. Full article

Pain management in multiple trauma patients presents a complex clinical challenge due to competing priorities such as hemodynamic instability, polypharmacy, coagulopathy, and the urgency of life-saving interventions. In this context, peripheral nerve blocks (PNBs) are increasingly recognized as a valuable asset for their role in managing pain in patients with multiple traumatic injuries. By reducing reliance on systemic opioids, PNBs support effective pain control and facilitate early mobilization, aligning with enhanced recovery principles. This narrative review summarizes current evidence on the use of PNBs in the context of polytrauma, focusing on their analgesic efficacy, integration within multimodal analgesia protocols, and contribution to improved functional outcomes. Despite these advantages, clinical application is limited by specific concerns, including the potential to mask compartment syndrome, the risk of nerve injury or local anesthetic systemic toxicity (LAST), and logistical barriers in acute trauma settings. Emerging directions in the field include the refinement of ultrasound-guided PNB techniques, the expanded use of continuous catheter systems, and the incorporation of fascial plane blocks for anatomically complex or multisite trauma. Parallel efforts are focusing on the development of decision-making algorithms, improved risk stratification tools, and integration into multimodal analgesic pathways. There is also growing emphasis on standardized clinical protocols, simulation-based training, and patient education to enhance safety and consistency in practice. As evidence continues to evolve, the long-term impact of PNBs on functional recovery, quality of life, and healthcare utilization must be further explored. With thoughtful implementation, structured training, and institutional support, PNBs may evolve into a cornerstone of modern trauma analgesia. Full article

Sepsis is a complex and life-threatening syndrome arising from a dysregulated immune response to infection that can lead to severe organ dysfunction and increased mortality. This multifactorial condition is marked by intricate interactions between immune, inflammatory, and coagulation pathways, which together contribute to systemic effects and multiorgan damage. The aberrant immune activation seen in sepsis includes profound leukocyte activation, endothelial dysfunction, imbalanced coagulation leading to disseminated intravascular coagulation (DIC), and the production of both pro-inflammatory and anti-inflammatory mediators. These events culminate in pathological alterations that extend beyond the initial site of infection, adversely impacting distant tissues and organs. Early recognition and timely intervention are crucial to mitigate the progression of sepsis and its associated complications. This review aims to explore the underlying biological mechanisms, including host–pathogen interactions, immune dysregulation, and the cascade of systemic and organ-specific effects that define sepsis. By delving into the pathophysiological processes, we intend to provide insights into the determinants of multiorgan failure and inform strategies for therapeutic intervention. Understanding these mechanisms is pivotal for advancing clinical outcomes and reducing mortality rates associated with this critical condition. Full article

Background/Objectives: This is a retrospective review of 36 patients with electrodiagnostic (EDX) confirmation of carpal tunnel syndrome (CTS) and ultrasound (US) detection of marked median nerve enlargement (defined as a cross-sectional area [CSA] of 40 mm² or greater) at the wrist. Methods: We describe the clinical, electrodiagnostic (EDX), and US findings in these patients and discuss the pathophysiologic basis of a markedly enlarged median nerve. Results: The markedly enlarged median nerve was detected by US in a total of 39 hands (36 patients, with 3 bilateral). Of the 39 hands, thenar atrophy was observed in 15 (38.5%) hands, and pinprick loss in the median nerve distribution was noted in all hands. Moderately severe or severe median nerve entrapment at the carpal tunnel (CT) was confirmed by EDX studies in 21 (53.8%) and 16 (41.0%) hands, respectively. A total of 12 (30.8%) hands had no compound muscle action potentials (CMAPs) over the abductor pollicis brevis muscle, and sensory nerve action potentials (SNAPs) were not detected in 31 (79.5%) hands. The wrist CSA was between 40 and 44 mm² in 20 (51.3%) hands, between 45 and 49 mm² in 13 (33.3%) hands, and 50 mm² or greater in 6 (15.4%) hands. Conclusions: The implications of the markedly enlarged median nerve for surgical management of CTS are unknown, and future prospective studies are needed. Full article

Aseptic abscess syndrome is a clinical entity that is being increasingly documented. Unfortunately, apart from the French registry, there are no other studies presenting collective data. In this review, we sought to analyze clinical and laboratory data from case reports published from the rest of the world. A total of 107 articles were found through our literature search in PubMed, Scopus, and Google, which contained 108 patients who met our eligibility criteria, including pediatric cases. The mean age at diagnosis was 39.1 years, and 54.6% of the patients were female. Cases were found affecting almost every organ, but the most common abscess locations were the spleen (51.9%), liver (35.2%), and lung (23.1%); 34.3% of the patients had multiorgan disease at diagnosis. An inflammatory syndrome was evident, with fever (79.6%), pain (66.7%), median white blood cell count of 16,200/μL, median C-reactive protein level of 15.5 mg/dL, and mean erythrocyte sedimentation rate of 79 mm/h. In total, 88.9% had an associated disease, with the most frequent being neutrophilic dermatosis (43.5%) and inflammatory bowel disease (31.5%); associated disease was inactive during abscess diagnosis in approximately one-quarter of patients. Moreover, 93.5% received corticosteroids with or without other agents, while 21.3% underwent excision surgery, which led to relapse if immunosuppressants were not concomitantly administered. No deaths were reported due to the syndrome, but 42.4% of cases that provided relevant data relapsed despite the relatively short follow-up period (median 1 year), either in the same or different organs. Combined immunomodulatory treatment, based on subgroup analysis, appeared protective against relapse in females and patients with splenic abscess or C-reactive protein >12 mg/dL (odds ratio 0.16 [95% CI 0.04–0.59]/p = 0.004, 0.09 [95% CI 0.01–0.62]/p = 0.008 and 0.23 [95% CI 0.06–0.92]/p = 0.03, respectively). Infection should always be the working diagnosis in patients with abscesses. However, if the infectious workup is negative, antimicrobials have failed, and no sepsis is present, then aseptic abscess syndrome should be considered; response to high-dose corticosteroids is a therapeutic criterion in almost all cases. Full article

Metabolic syndrome comprises a constellation of comorbidities, including obesity, hypertension, and disorders in carbohydrate and lipid metabolism, associated with an elevated risk of cardiovascular mortality. Obesity is regarded as the principal cause of metabolic syndrome (both collectively and in relation to its components), frequently linked in previous scientific studies with a deficiency of magnesium, one of the most important cations found in the human body. Objectives: The objective of this study was to assess the prevalence of hypomagnesemia in patients with metabolic syndrome and to determine the most significant risk factor among its components for this nutritional deficiency. Methods: Retrospective medical data from 403 patients admitted to the hospital for conditions unrelated to magnesium levels from 2015 to 2019 were evaluated, encompassing serum magnesemia and specific data about components of metabolic syndrome. Data underwent statistical analysis, including linear and logistic regression, to assess the principal risk variables of hypomagnesemia. Results: Hypomagnesemia was observed in 14.89% of the patients with metabolic syndrome, exhibiting a 2.42-fold greater risk of this deficiency (95%CI: 1.40–3.40). Among the components of metabolic syndrome, hyperglycemia emerged as the most significant determinant affecting both the incidence and severity of hypomagnesemia, elevating the risk by a ratio of 2.72 (95%CI: 1.52–4.87). In the multivariate regression model, hyperglycemia was the sole factor independently influencing magnesium concentration (β = −0.145; p < 0.001). Conclusions: Patients presenting signs of metabolic syndrome are at heightened risk for hypomagnesemia. Hyperglycemia appears to be the most important variable affecting the risk of magnesium insufficiency; however, additional research is needed in this area. Full article

Background: Fibromyalgia syndrome (FMS) is a complex condition with poorly understood pathophysiology, characterized by widespread pain and an increasing recognition of its associations with genitourinary symptoms. The objective of this study was to characterize the prevalence, phenotype, and common comorbidities of lower urinary tract symptoms (LUTS) in women with FMS. Methods: A retrospective observational study was conducted using electronic medical records of 440 women diagnosed with FMS at a single institution between 1 January 2018, and 1 January 2024. Study subjects were evaluated for diagnoses associated with LUTS, including interstitial cystitis (IC), overactive bladder (OAB), and stress urinary incontinence (SUI), alongside comorbidities such as irritable bowel syndrome (IBS), generalized anxiety disorder (GAD), and major depressive disorder (MDD). Multivariate analyses were performed to assess predictors of conditions associated with LUTS. Results: LUTS were identified in 37.0% of FM patients. GAD and IBS were significantly associated with conditions associated with LUTS (OR = 4.62; OR = 8.53, p < 0.001). SUI was present in 17.05% of patients, falling between survey-based and confirmed prevalence rates in the general population. IC was diagnosed in 2.95% of FMS patients. OAB was observed in 6.8% of patients and associated with GAD (OR = 5.98, p < 0.001). Conclusions: This study highlights a substantial burden of diagnoses associated with LUTS in patients with FMS. There is relatively high prevalence of SUI and IC in this dataset. IBS and GAD were commonly found to co-occur with one or more LUTS-associated condition. Future prospective studies are needed to investigate a multimodal approach to the treatment of LUTS in these patients. Full article

Background: Sodium–glucose cotransporter-2 inhibitors (SGLT2is), initially developed as antihyperglycemic agents, have emerged as multifunctional therapeutics with profound cardiorenal and metabolic benefits. Their unique insulin-independent mechanism, targeting renal glucose reabsorption, distinguishes them from conventional antidiabetic drugs. Mechanisms and Clinical Evidence: SGLT2is induce glycosuria, reduce hyperglycemia, and promote weight loss through increased caloric excretion. Beyond glycemic control, they modulate tubuloglomerular feedback, attenuate glomerular hyperfiltration, and exert systemic effects via natriuresis, ketone utilization, and anti-inflammatory pathways. Landmark trials (DAPA-HF, EMPEROR-Reduced, CREDENCE, DAPA-CKD) demonstrate robust reductions in heart failure (HF) hospitalizations, cardiovascular mortality, and chronic kidney disease (CKD) progression, irrespective of diabetes status. Adipose Tissue and Metabolic Effects: SGLT2is mitigate obesity-associated adiposopathy by shifting macrophage polarization (M1 to M2), reducing proinflammatory cytokines (TNF-α, IL-6), and enhancing adipose tissue browning (UCP1 upregulation) and mitochondrial biogenesis (via PGC-1α/PPARα). Modest weight loss (~2–4 kg) occurs, though compensatory hyperphagia may limit long-term effects. Emerging Applications: Potential roles in non-alcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), and neurodegenerative disorders are under investigation, driven by pleiotropic effects on metabolism and inflammation. Conclusions: SGLT2is represent a paradigm shift in managing T2DM, HF, and CKD, with expanding implications for metabolic syndrome. Future research should address interindividual variability, combination therapies, and non-glycemic indications to optimize their therapeutic potential. Full article

Variants in COL4A3 and COL4A4 cause autosomal dominant and recessive Alport syndrome, yet data on their distribution and clinical expression in different populations remain limited. This study investigated genotype–phenotype correlations and the distribution of COL4A3/COL4A4 variants in a Lithuanian Alport syndrome cohort. A total of 221 individuals from Lithuania were analyzed for COL4A3 and COL4A4 variants using either next-generation sequencing or Sanger sequencing in order to assess variant distribution and associated clinical features. Only individuals with pathogenic, likely pathogenic, or uncertain significance variants were included. Fifty-two individuals (38 index cases) with pathogenic, likely pathogenic, or variants of uncertain significance were identified, as follows: forty-eight were heterozygous, four had autosomal recessive, and four had digenic Alport syndrome. COL4A3 variants were found in 9.5% (21/221) and COL4A4 in 17.6% (39/221). Among the 28 identified variants, 18 were novel. Glycine substitutions (n = 8) were the most frequent and associated with worse kidney outcomes and increased hearing abnormalities. Hematuria was diagnosed significantly earlier than proteinuria (p = 0.05). Most individuals with autosomal dominant Alport syndrome had normal kidney function (eGFR > 90 mL/min/1.73 m²), while those with autosomal recessive Alport syndrome had more severe disease. Kidney failure occurred in 2/4 (50%) autosomal recessive Alport syndrome and 2/48 (4%) autosomal dominant Alport syndrome cases. A significant inverse correlation was found between eGFR and age in proteinuric individuals (r = –0.737; p = 0.013). This study expands knowledge of Alport syndrome in the Lithuanian population and contributes novel variant data to the global Alport syndrome genetic database. Full article

Obstructive sleep apnea (OSA) syndrome is a severe, debilitating, and pervasive sleep disorder. OSA mainly affects people with obesity, type 2 diabetes mellitus (T2DM), hypertension, and dyslipidemia and is strongly associated with cardiovascular complications. Based on the bidirectional relationship between T2DM and OSA, the latter represents a risk factor for the former, and, vice versa, people with T2DM have a high risk of OSA. Mechanical and hormonal factors, inflammatory mediators, and a dysregulated autonomic nervous system contribute to the mechanisms underlying the disease. Treatment of OSA is necessary even if the available remedies are not always effective. In addition to traditional treatments, including lifestyle adaptations and bariatric surgery, CPAP equipment, i.e., a breathing device ensuring continuous positive pressure to keep the airways open during sleep, represents the most common treatment tool. More recently, pharmacological research has paved the way to newer seemingly effective therapeutic strategies involving, in particular, two hypoglycemic agent classes, i.e., sodium–glucose co-transporter 2 inhibitors (SGLT2-is) and glucagon-like peptide-1 (GLP-1) receptor agonists (GLP1-ras). This narrative review provides an update on all of the above. Full article

Obesity, a multifactorial metabolic syndrome driven by genetic–epigenetic crosstalk and environmental determinants, manifests through pathological adipocyte hyperplasia and ectopic lipid deposition. With the limitations of conventional anti-obesity therapies, which are characterized by transient efficacy and adverse pharmacological profiles, the scientific community has intensified efforts to develop plant and fungal polysaccharide therapeutic alternatives. These polysaccharide macromolecules have emerged as promising candidates because of their diverse biological activities and often act as natural prebiotics, exerting beneficial effects through multiple pathways. Plant and fungal polysaccharides can reduce blood glucose levels, alleviate inflammation and oxidative stress, modulate metabolic signaling pathways, inhibit nutrient absorption, and reshape gut microbial composition. These effects have been shown in cellular and animal models and are associated with mechanisms underlying obesity and related metabolic disorders. This review discusses the complexity of obesity and multifaceted role of plant and fungal polysaccharides in alleviating its symptoms and complications. Current knowledge on the anti-obesity properties of plant and fungal polysaccharides is also summarized. We highlight their regulatory effects, potential intervention pathways, and structure–function relationships, thereby providing novel insights into polysaccharide-based strategies for obesity management. Full article

Cardiovascular–Kidney–Metabolic (CKM) syndrome symbolizes a single pathophysiologic entity including obesity, type 2 diabetes, chronic kidney disease, and cardiovascular disease. These conditions altogether accelerate adverse outcomes when they coexist. Recent evidence has shown that the function of glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium–glucose cotransporter-2 inhibitors (SGLT2i) alleviate stress on multiple organs. SGLT2i has been demonstrated to benefit heart failure, hemodynamic regulation, and renal protection while GLP-1RA on the other hand has been shown to demonstrate a strong impact on glycemic management, weight loss, and atherosclerotic cardiovascular disease. This review will aim to understand and evaluate the mechanistic rationalization, clinical evidence, and the potential therapeutic treatment of SGLT2 inhibitors and GLP-1 receptor agonists to treat individuals who have CKM syndrome. This analysis also assesses whether combination therapy can be a synergistic approach that may benefit patients but is still underutilized because of the lack of clear guidelines, the associated costs, and disparities in accessibility. Therefore, in this review, we will be discussing the combination therapy’s additive and synergistic effects, current recommendations and clinical evidence, and mechanistic insights of these GLT2 inhibitors and GLP-1 receptor agonists in CKM syndrome patients. Overall, early and combination usage of GLP-1RA and SGLT2i may be essential to demonstrating a significant shift in modern cardiometabolic therapy toward patient-centered care. Full article

Background/Objectives: Adolescence is a critical period for the early detection of metabolic syndrome (MetS), a condition that increases the risk of cardiometabolic diseases in adulthood. Timely identification of at-risk adolescents enables targeted prevention strategies. This study aimed to analyze the discriminative capacity and accuracy of six biochemical and/or anthropometric indices related to lipid metabolism and adiposity for the early detection of MetS in a sample of Spanish adolescents. Methods: A cross-sectional study carried out according to the STROBE guidelines. A sample of 981 adolescents aged 11–16 years old were randomly recruited from schools in Southeastern Spain. The presence or absence of MetS was determined according to the International Diabetes Federation criteria. The following biochemical and/or anthropometric indices were evaluated: triglyceride glucose index, visceral adiposity index, logarithm children’s lipid accumulation product, triglyceride glucose-body mass index, triglyceride glucose-waist circumference, and triglyceride glucose-waist-to-hip ratio. Results: The triglyceride glucose-waist-to-hip ratio and triglyceride glucose-body mass index parameters were the strongest indicators associated with MetS in boys and girls, respectively, after adjusting for several factors. Moreover, all evaluated indices showed optimal AUC values, with the visceral adiposity index and triglyceride glucose-waist circumference index exhibiting the highest discriminative capacity in both genders. Conclusions: The evaluated biochemical and anthropometric indices—particularly visceral adiposity index and triglyceride-glucose-waist circumference—show promise as accessible biomarkers for identifying adolescents at metabolic risk. These indices may serve as practical tools in preventive health strategies aimed at improving metabolic health by screening adolescents at risk of MetS, thereby helping to reduce the future burden of non-communicable diseases. Full article

Acute Respiratory Distress Syndrome (ARDS) is a complex and devastating form of respiratory failure, with high mortality rates, for which there is no pharmacological treatment. The acute exudative phase of ARDS is characterized by severe damage to the alveolar–capillary barrier, infiltration of protein-rich fluid into the lungs, neutrophil recruitment, and high levels of inflammatory mediators. Rapid resolution of this reversible acute phase, with efficient restoration of alveolar functional integrity, is essential before the establishment of irreversible fibrosis and respiratory failure. Several lines of in vitro and in vivo evidence support the involvement of potassium (K⁺) channels—particularly KvLQT1, expressed in alveolar cells—in key cellular mechanisms for ARDS resolution, by promoting alveolar fluid clearance and epithelial repair processes. The aim of our study was to investigate whether pharmacological activation of KvLQT1 channels could elicit beneficial effects on ARDS parameters in an animal model of acute lung injury. We used the well-established bleomycin model, which mimics (at day 7) the key features of the exudative phase of ARDS. Our data demonstrate that treatments with the KvLQT1 activator R-L3, delivered to the lungs, failed to improve endothelial permeability and lung edema in bleomycin mice. However, KvLQT1 activation significantly reduced neutrophil recruitment and tended to decrease levels of pro-inflammatory cytokines/chemokines in bronchoalveolar lavages after bleomycin administration. Importantly, R-L3 treatment was associated with significantly lower injury scores, higher levels of alveolar type I (HTI-56, AQP5) and II (pro-SPC) cell markers, and improved alveolar epithelial repair capacity in the presence of bleomycin. Together, these results suggest that the KvLQT1 K⁺ channel may be a potential target for the resolution of the acute phase of ARDS. Full article