Search Results (3,428)

Serratia marcescens has emerged as an important opportunistic pathogen in intensive care units (ICUs), where critically ill patients, invasive devices, antimicrobial exposure, and complex environmental reservoirs create favorable conditions for colonization, infection, and recurrent outbreaks. This narrative review synthesizes evidence from the past decade regarding the clinical and molecular epidemiology, environmental persistence, device-associated transmission, biofilm-mediated resistance, and infection-control strategies of S. marcescens in ICU settings. The literature was reviewed using an integrative approach informed by Ferrari’s narrative review framework, with thematic synthesis across clinical, microbiological, environmental, and genomic domains. Recent evidence indicates that ICU-associated S. marcescens infections frequently involve respiratory tract colonization, ventilator-associated pneumonia, bloodstream infection, urinary tract infection, and device-related transmission. Hospital water systems, sink drains, wet surfaces, ventilator circuits, reusable equipment, and contaminated antiseptic or liquid products may serve as persistent reservoirs, particularly when biofilm formation supports long-term survival and recurrent dissemination. At the molecular level, S. marcescens demonstrates substantial genomic diversity, intrinsic and acquired antimicrobial resistance, inducible AmpC β-lactamase activity, efflux-mediated tolerance, and plasmid-associated resistance gene transfer. This review particularly emphasizes the molecular determinants that enable S. marcescens to persist in ICU ecosystems, including AmpC-mediated β-lactam resistance, efflux-associated tolerance, quorum-sensing-regulated biofilm formation, plasmid-mediated horizontal gene transfer, and WGS-defined clonal transmission. Whole-genome sequencing, rapid molecular diagnostics, active surveillance, environmental sampling, and integrated infection-control bundles have become increasingly important for distinguishing clonal outbreaks from endemic transmission and guiding timely interventions. Emerging perspectives emphasize the need to combine antimicrobial stewardship, environmental engineering, respiratory-care auditing, anti-biofilm strategies, and AI-assisted real-time surveillance into adaptive ICU infection-control frameworks. Overall, S. marcescens should be regarded not merely as an episodic outbreak organism, but as a highly adaptable ICU-associated pathogen requiring multidisciplinary prevention strategies. Full article

Apnea of prematurity (AOP) remains a critical challenge in neonatal care, with caffeine citrate serving as the cornerstone of pharmacological intervention. However, the current standardized dosing schedule fails to account for significant inter-individual variability in caffeine pharmacokinetics and clinical response. This narrative review explores the transformative potential of integrating wearable sensor technologies and multi-modal data analytics into a closed-loop framework for personalized caffeine therapy. Based on a synthesis of current monitoring literature, we propose a theoretical, comprehensive monitoring system utilizing the area under the respiratory curve (rAUC) as a continuous proxy metric, alongside waveform amplitude analysis aligned with pediatric polysomnography standards. By incorporating emerging metrics such as respiratory rate variability (RRV) and hypoxic burden, the framework enables the objective quantification of respiratory stability. Furthermore, the integration of established neonatal intensive care unit (NICU) parameters for bradycardia and oxygen saturation detection provides a critical cross-validation layer to minimize artifact-induced false alarms. This conceptual model bridges the gap between advanced signal processing and clinical oversight, offering a scalable pathway toward precision dosing. By shifting from reactive to predictive neonatology, sensor-driven optimization can enhance therapeutic efficacy, reduce alarm fatigue, and ultimately improve developmental outcomes for preterm infants. Full article

Mucopolysaccharidosis (MPS) are a group of inherited lysosomal storage genetic disorders that affect the body’s ability to break down glycosaminoglycans (GAGs) due to the deficiency of required enzymes. This leads to depositions of these GAGs in various tissues and organs resulting in multi-systemic manifestations including pulmonary and sleep related issues. In recent years, there have been significant advancements in therapeutic options and supportive management which have led to the overall improvement in respiratory care, culminating in improved quality of life for MPS patients. Management of pulmonary and sleep disorders in mucopolysaccharidosis requires a multidisciplinary approach due to the multi-systemic affectation of the genetic disorders. Therapeutic options such as enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) have yielded varying success in mitigating respiratory complications. Emerging treatments such as gene therapies have shown exciting and promising results thus far. Supportive therapies such as airway clearance, regular vaccination and use of positive airway pressure devices are also essential. Pre-operative airway and anesthesia planning is critical to mitigate peri-operative and post-operative complications. Early diagnosis, close monitoring and a patient focused individualized approach are essential for respiratory optimization and overall improvement in clinical outcomes. This review article aims to discuss these advancements in a comprehensive format, making it accessible to medical providers who care for this subset of patients. Full article

Background: Obstructive sleep apnea (OSA) is increasingly recognized as a systemic disorder associated with insulin resistance and elevated risk of type 2 diabetes. While continuous positive airway pressure (CPAP) is the standard therapy, its long-term metabolic benefits remain inconsistent. The metabolic impact of upper airway surgery is less well defined. Methods: In this retrospective study, 49 patients with polysomnography-confirmed OSA who underwent upper airway surgery were evaluated. Respiratory and metabolic parameters—including apnea–hypopnea index (AHI), fasting plasma glucose, fasting insulin, glycated hemoglobin (HbA1c), and homeostatic model assessment for insulin resistance (HOMA-IR)—were assessed preoperatively and at 6 months postoperatively. Associations between changes in AHI (ΔAHI) and insulin resistance (ΔHOMA-IR) were analyzed using correlation and receiver operating characteristic (ROC) analyses. Results: Significant improvements were observed in both respiratory and metabolic parameters. AHI decreased from 46.6 ± 25.8 to 20.7 ± 14.1 events/h (p < 0.001). Fasting plasma glucose, insulin levels, and HOMA-IR were significantly reduced postoperatively (all p < 0.05), while HbA1c showed a downward trend. Reduction in AHI was moderately correlated with improvement in insulin resistance (r = 0.527, p < 0.001). ROC analysis demonstrated modest discriminative ability of ΔAHI for identifying normalization of insulin resistance (AUC = 0.62). Conclusions: Upper airway surgery was associated with significant improvements in insulin resistance and glycemic parameters in patients with OSA. The correlation between airway improvement and metabolic change supports a physiological link between upper airway obstruction and insulin sensitivity. These findings suggest that upper airway surgery may represent a clinically relevant adjunct within multimodal strategies for metabolic risk reduction, particularly in patients unable to tolerate CPAP therapy. Full article

Preterm infants, especially extremely preterm infants under 28 weeks of gestation, face high mortality rates due to respiratory distress resulting from pulmonary immaturity. Conventional mechanical ventilation and extracorporeal membrane oxygenation (ECMO) therapy inevitably cause irreversible lung injury or severe complications, respectively. Here, we developed a microfluidic oxygenator (MO) mimicking the human alveolar-capillary barrier to provide respiratory support for preterm infants. These structures promoted uniform flow distribution, reduced high-shear stress and flow stagnation, and improved gas exchange efficiency. In vitro experiments demonstrated that a single-layer MO raised blood oxygen saturation from 64.7% to 96.5% at 8 mL/min, with a corrected vol% oxygen transfer of 5.24% (52.4 mL O₂/L blood). Hemolysis and coagulation measurements after a 6 h circulation confirmed good hemocompatibility, with most blood damage attributable to the pump. An eight-layer stacked MO was configured with a total priming volume of approximately 5.6 mL and a pressure drop of 25–35 mmHg at 24–40 mL/min, indicating its potential in pumpless extracorporeal circulation for preterm neonates. This MO holds promise for providing minimally invasive and customizable respiratory support in an artificial uterus system. Full article

Laryngeal adductor breathing dystonia (LABD) is a rare form of focal, task-specific respiratory dystonia affecting the laryngeal muscles of unknown aetiology. Unlike classical laryngeal dystonia (spasmodic dysphonia), LABD is not primarily characterised by impaired speech, but rather by dysfunction of respiratory laryngeal control. The hallmark pathophysiological alteration consists of involuntary, action-induced adductor spasms of the laryngeal muscles during respiration, particularly during inspiration. LABD must be distinguished from inducible laryngeal obstruction (ILO), a broader, heterogeneous condition encompassing episodic, stimulus-triggered supraglottic or glottic closure, associated with asthma, reflux, or psychological triggers, that is generally not task-specific and lacks the neurological substrate characteristic of dystonia. In contrast, LABD is a persistent, effort-dependent, neurologically driven dystonia, demonstrable by paradoxical adductor spasms on fibreoptic laryngoscopy during normal inspiration and confirmed electromyographically by paradoxical thyroarytenoid muscle activation instead of the expected inspiratory relaxation. Traditional treatments, including respiratory retraining, speech therapy, biofeedback, psychotherapy, benzodiazepines, dopamine-blocking agents, and anticholinergic drugs, have proved largely ineffective. Tracheostomy may be required in cases of severe respiratory compromise. Botulinum toxin type A (BoNT/A) injections have been reported to successfully reduce inspiratory stridor in selected patients. Here, we present three cases of LABD displaying distinct phenotypes, in which typical features were associated with involvement of extra-laryngeal cranial districts, further expanding the known phenotypic spectrum of this condition. Full article

Background: Obstructive sleep apnea syndrome (OSAS) is a prevalent sleep-related breathing disorder associated with significant systemic complications and reduced quality of life. Mandibular advancement devices (MADs) represent an established alternative therapy for patients who cannot tolerate continuous positive airway pressure (CPAP). However, concerns remain regarding their potential effects on temporomandibular disorders (TMD). Materials and Methods: This retrospective exploratory study analyzed clinical records of 26 patients (mean age 55.4 ± 5.8 years) with polysomnography-confirmed OSAS and baseline TMD-related symptoms treated with a custom-made monobloc MAD. Clinical parameters were evaluated at baseline (T0) and after approximately 6 months of therapy (T1). Outcomes included apnea–hypopnea index (AHI), Epworth Sleepiness Scale (ESS), Fonseca Anamnestic Index, and health-related quality of life assessed using the SF-36 questionnaire. Repeated measures ANOVA and linear regression analyses were performed. Results: After six months of MAD therapy, a significant reduction in AHI was observed (30 ± 13.76 vs. 10.87 ± 3.9; p < 0.00001). Daytime sleepiness significantly decreased (ESS: 9.31 ± 3.53 vs. 3.38 ± 1.77; p < 0.00001). TMD symptom severity also decreased significantly according to the Fonseca Index (33.85 ± 17.74 vs. 10.00 ± 8.94; p < 0.00001). Quality of life scores improved significantly (SF-36: 41.15 ± 9.52 vs. 65.38 ± 5.82; p < 0.00001). Linear regression analysis showed no significant association between changes in AHI and changes in TMD symptoms, ESS scores, or quality of life. Conclusions: Within the limitations of this retrospective study, MAD therapy was not associated with symptom aggravation of temporomandibular disorders in patients with pre-existing TMD symptoms. Significant improvements in respiratory parameters, daytime sleepiness, and quality of life were observed after six months of therapy. Full article

Background: Surface electromyography is emerging as a noninvasive tool to examine neurogenic dysphagia in Parkinson’s disease (PD). This pilot study evaluated the feasibility of surface electromyography (sEMG) (acceptability, resource use, and safety), and explored changes in swallowing-related sEMG parameters following rehabilitation. Methods: Ten patients with mild to moderate PD (Hoehn Yahr 1–3) underwent clinical, respiratory, and swallowing assessments, including sEMG recordings of perioral (orbicularis oris), masticatory (masseter) and cervical muscles (submental/mylohyoid and infrahyoid group). Feasibility outcomes included recruitment, protocol completion, and adverse events. Exploratory sEMG measures comprised amplitude indices (root-mean-square, RMS; peak-to-peak, P2P range; area under curve, AUC) and activation time during saliva swallowing and continuous drinking tasks. Results: Nine out of 10 participants completed the protocol, and no adverse events were reported, indicating good acceptability and safety. Exploratory pre–post analyses showed reduced sEMG amplitude during saliva swallowing of orbicularis oris [median ΔP2P Range = −0.273 (p = 0.020), median ΔAUC = −0.145 (p = 0.027); RMS (median Δ = −0.427) (p = 0.074)] and a generalized prolongation of activation time during continuous sipping across recorded muscles. Conclusions: Multichannel sEMG assessment of swallowing muscles during speech therapy is feasible and safe in patients with PD. Exploratory signal changes warrant cautious interpretation and should be validated in larger rehabilitation-oriented studies. Full article

Pulmonary fibrosis, particularly idiopathic pulmonary fibrosis (IPF), is a chronic and progressive interstitial lung disease characterized by alveolar epithelial injury, fibroblast activation, and excessive extracellular matrix deposition, which collectively lead to respiratory failure. Despite the availability of antifibrotic agents, disease-modifying therapies remain limited. Emerging evidence has identified dysregulated sphingolipid metabolism, especially ceramide accumulation, as a key driver of fibrotic pathogenesis. Ceramide is a central bioactive lipid in the sphingolipid pathway that regulates multiple cellular processes, including apoptosis, inflammation, endothelial barrier dysfunction, and fibroblast activation, all of which contribute to pulmonary fibrosis. This review is a narrative review that systematically summarizes the biosynthetic and metabolic pathways of ceramide, with an emphasis on chain length-specific functions and the ceramide to S1P rheostat. We further discuss the mechanistic roles of ceramide in alveolar epithelial cell apoptosis, inflammatory responses, and vascular barrier disruption in fibrotic lung disease. Finally, we highlight emerging therapeutic strategies that target ceramide metabolism, including inhibitors of acid sphingomyelinase (ASMase) and serine palmitoyltransferase (SPT), and propose future directions for clinical translation. Full article

Chronic obstructive pulmonary disease (COPD) extends beyond the respiratory system and is closely linked to an increased risk of cardiovascular complications. Exacerbations represent critical periods of cardiovascular vulnerability, with a marked rise in major adverse cardiovascular events observed in the early post-exacerbation phase. This narrative review synthesizes current evidence on the epidemiology, pathophysiological mechanisms, and therapeutic implications of cardiovascular risk following COPD exacerbations. A structured literature search was conducted to identify relevant studies in this setting. Cardiovascular risk is elevated following exacerbations, particularly within the first weeks, and remains increased for months thereafter. Multiple pathophysiological mechanisms contribute to this vulnerable window. Systemic inflammation, marked by elevated cytokines such as IL-6, IL-8, and CRP, promotes endothelial dysfunction, vascular oxidative stress, and impaired nitric oxide bioavailability. Despite the well-established link, cardiovascular disease remains overlooked and undertreated in patients with COPD, and the use of guideline-directed cardiovascular therapies is suboptimal. A more systematic, integrated approach to cardiovascular assessment and management in patients with COPD is warranted to improve outcomes. Full article

Umbilical cord mesenchymal stromal cells (UC-MSCs) are a key element of regenerative medicine due to their ability to secrete growth factors that stimulate proliferation and angiogenesis, and modulate the inflammatory response. Despite their widespread use, the influence of the perinatal microenvironment on their biological properties remains poorly understood. The aim of this study was to assess the influence of pH and blood gas parameters in umbilical cord blood on the global transcriptomic profile of UC-MSCs and to analyze the correlation between the metabolic status of the newborn and the expression of key trophic factors: EGF, FGF2, FGFR1, FGFR3, GDNF, HGF, IGF1, NES, NGF, and PGF. Methods: The study was conducted in two stages. In the first phase, transcriptomic screening was performed using Affymetrix HuGene 2.0 ST microarray on cells isolated from three environmental groups defined by cord blood pH: acidic (pH < 7.35), physiological (7.35–7.39), and alkaline (pH ≥ 7.4). In the second phase, the results were validated using qPCR on an expanded study group (N = 50). Gene expression levels (RQ) were related to blood gas parameters (pH, pCO₂, pO₂, cHCO₃) and the presence of clinical features of threatened neonatal asphyxia. Results: Microarray analysis revealed that environmental pH acts as a molecular phenotypic switch. Under low pH conditions (<7.35), a shift in cell profile from proliferative to structural–migratory was observed. Significant overexpression of genes responsible for extracellular matrix (ECM) organization and adhesion (e.g., COMP, DCN, LUM, FMOD) was observed, while pathways related to cell cycle and cell division (↓CDK1, AURKA, TOP2A) were downregulated. qPCR validation confirmed these observations, demonstrating a strong positive correlation between blood pH and the expression of regenerative mediators: FGFR1 (r = 0.28), EGF (r = 0.30), NGF (r = 0.39), and IGF1 (r = 0.30). A negative correlation was also found between carbon dioxide pressure (pCO₂) and the expression of NGF, FGFR1, and EGF. A significant clinical finding was that in newborns diagnosed with threatened asphyxia, EGF, FGFR1, and NGF gene expression was significantly reduced, indicating impaired trophic potential of the cells in response to metabolic stress. Conclusions: These results indicate that cord blood gas parameters are critical regulators of the genetic activity of UC-MSCs. Metabolic and respiratory acidosis not only inhibit the cells’ proliferative potential but also force them into a matrix remodeling mode, permanently modifying their transcriptomic profile. This suggests that the neonatal acid–base status may serve as an objective indicator of the “biological quality” of isolated stromal cells, which has significant implications for their future applications in cell therapies. Full article

Background and objective: Hypoxemia and respiratory failure (RF) in chronic obstructive pulmonary disease (COPD) are associated with exacerbations, comorbidities and increased mortality. However, the prevalence of hypoxemia and RF in stable COPD is unknown. We aimed at investigating the prevalence and determining predictive factors for chronic gas exchange abnormalities in COPD patients. Methods: A retrospective cohort study that enrolled clinically stable COPD patients referring to a pulmonary outpatient clinic. Anthropometrics, clinical characteristics, blood gas analysis and lung function were analyzed. Patients were grouped according to hypoxemia (PaO₂ <80 and ≥60 mmHg), type 1 (PaO₂ < 60 mmHg) or type II (PaO₂ < 60 and PaCO₂ > 45 mmHg) RF. A sensitivity analysis adopting an age-adjusted definition of hypoxemia was performed. Predictive factors for hypoxemia or RF were assessed with multifactorial analysis. Results: We analyzed data from 515 patients. Fixed-ratio hypoxemia, RF type 1 and type 2 were observed in 352 (68.3%), 27 (5.2%) and 43 (8.3%) patients, respectively. Risk of hypoxemia was associated with preserved alveolar volume, residual volume/total lung capacity, and lung diffusion capacity. Heart failure, ischemic heart disease, atrial fibrillation, and metabolic syndrome were predictive factors for RF. Patients with age-adjusted hypoxemia (n = 321 patients, 62.3%) showed no difference in terms of anthropometrics, lung function, and clinical characteristics as compared with fixed-threshold hypoxemia. Conclusions: Hypoxemia is frequent in stable COPD. Lung function parameters and comorbidities can support the identification of patients at risk of RF. Blood gas analysis should be always performed in patients with COPD to allow for personalized therapy and management. Full article

Pediatric respiratory infections remain among the leading causes of emergency department visits, hospitalization and pediatric intensive care unit (PICU) admission. Although most acute respiratory infections in children are viral, clinical manifestations overlap substantially among viral, bacterial and atypical pathogens, creating diagnostic uncertainty and promoting empirical antimicrobial use. Rapid antigen tests, nucleic acid amplification tests, multiplex respiratory panels and metagenomic sequencing have expanded the ability to detect pathogens within clinically actionable timeframes. However, evidence from pediatric emergency trials indicates that rapid pathogen detection alone does not necessarily reduce antibiotic prescribing or healthcare costs. These findings suggest that the value of rapid diagnostics depends less on analytical breadth than on whether testing is applied to the right child, in the right clinical scenario and within a predefined decision pathway. This narrative review reorganizes the evidence around a scenario-driven top-pathogen framework. Top pathogens are defined as organisms that, in a specific age group, syndrome, season or care setting, have high prevalence, severe disease potential, transmissibility, treatment implications, antimicrobial resistance relevance or infection-control value. We discuss how top-pathogen testing should differ across emergency triage, inpatient ward management, severe pneumonia, PICU care, hospital-acquired pneumonia, ventilator-associated pneumonia and outbreak settings. We further examine the economic mechanisms through which rapid testing may generate value, including reduced unnecessary antibiotics, timely antiviral therapy, optimized isolation, shorter length of stay, reduced repeated testing and prevention of healthcare-associated transmission. Finally, we propose implementation principles centered on diagnostic stewardship, antimicrobial stewardship, local epidemiology and real-world cost-effectiveness evaluation. A scenario-driven top-pathogen strategy may provide a practical bridge between broad syndromic testing and precision infectious disease management in children. Full article

Background: Acute intermittent porphyria (AIP) is the most common and severe form of acute hepatic porphyria, caused by heterozygous mutations in the HMBS gene. Due to its non-specific clinical manifestations and low clinical awareness among clinicians, AIP is frequently misdiagnosed, leading to significant diagnostic delays and potentially fatal complications. Case presentation: We report a 20-year-old female patient who presented with a 9-month history of recurrent abdominal pain, paralytic ileus, unexplained liver injury, and hyponatremia, followed by progressive limb weakness. She was initially misdiagnosed with Guillain–Barré syndrome (GBS) and received intravenous immunoglobulin and systemic glucocorticoids. However, her condition deteriorated, and she developed life-threatening respiratory muscle paralysis requiring invasive mechanical ventilation. The diagnosis of AIP was confirmed by positive urinary porphobilinogen (PBG) testing and identification of the heterozygous HMBS c.517C>T pathogenic variant. The patient was treated with high-dose carbohydrate loading therapy and comprehensive supportive care, resulting in gradual clinical improvement. Discussion and Conclusions: This case exemplifies the substantial diagnostic challenges associated with AIP, especially when it manifests with peripheral neuropathy that closely mimics GBS. The triad of absent albuminocytologic dissociation in cerebrospinal fluid, preceding visceral symptoms, and inadequate response to standard first-line GBS therapy should immediately raise clinical suspicion for AIP. Enhanced clinical awareness of this rare disorder and timely implementation of urinary PBG screening are of paramount importance to prevent irreversible neurological complications and optimize long-term patient outcomes. Full article

Background: Continuous Positive Airway Pressure (CPAP) therapy is the standard treatment for obstructive sleep apnea–hypopnea syndrome (OSAHS), and photoplethysmography (PPG) sensors are commonly used in wearable devices for home sleep apnea testing. The recorded airflow and PPG signals from both sensors capture rich physiological patterns. We hypothesize that by combining information from these signals, we can efficiently estimate sleep dynamics of patients receiving CPAP treatment. Methods: The airflow signals were obtained from CPAP titration devices, denoted as CPAP-airflow, while the PPG signals were collected using the PranaQ TipTraQ (TTQ001), a fingertip-worn wearable device. We separately trained one-dimensional convolutional neural networks for CPAP-airflow and PPG signals and fused their outputs through probabilistic ensembling to predict sleep stages. The ensemble method is a late-fusion soft-voting scheme that computes a linearly weighted combination of synchronized softmax probability vectors from the modality-specific models. Results: For three-stage classification (Wake, REM, NREM), the PPG-based and CPAP-airflow-based models achieved overall Cohen’s kappa scores of 0.511 and 0.452, respectively, while the ensembled model improved the overall kappa to 0.587. The F1-score for the REM stage improved to 0.706 using the ensemble method, compared to 0.685 and 0.532 achieved by the individual models, respectively. In the four-stage classification (Wake, REM, Light, Deep) task, a deep sleep sensitivity of 0.596 was attained through the application of probabilistic ensembling. Conclusions: A fusion scheme of complementary information from the CPAP and PPG enhances the accuracy of sleep stage detection and hence enables more precise sleep monitoring, especially with an improved REM identification. Clinical implications include applying the proposed algorithm to improve in-home auto-CPAP titration by capturing REM-related respiratory instability and avoiding under-titration in REM-dominant OSAHS, better reflecting the patient’s true nocturnal respiratory needs. Full article