Search Results (644)

Background/Objectives: Postoperative pulmonary complications (PPCs) remain frequent and increase morbidity, mortality, and resource use. Preoperative risk scores (ARISCAT, NSQIP-derived calculators) use mostly static variables and may miss the dynamic perioperative host response preceding respiratory deterioration or infection. We address the gap in clinically interpretable syntheses of perioperative blood biomarker trajectories that distinguish infectious from non-infectious PPCs and clarify bedside-ready versus exploratory markers. Methods: We conducted a narrative review with a structured Medline search (inception to 1 November 2025) plus reference screening. We included English-language adult surgical studies (observational or interventional) evaluating perioperative blood biomarkers in relation to PPCs or postoperative pulmonary infection; case reports, editorials, and reviews were excluded. No formal risk-of-bias assessment or quantitative meta-analysis was performed. Results: Across 298 cited publications, serial patterns of routinely available biomarkers (C-reactive protein, procalcitonin, lactate, albumin, and leukocyte-derived indices) were most consistently associated with PPC risk and helped separate expected postoperative inflammation from evolving infection when interpreted longitudinally rather than as single values. Mechanistic biomarkers (cytokines/immune-function assays, endothelial injury and coagulation/fibrinolysis markers, oxidative stress indicators) add biological insight but are limited by assay availability, heterogeneous sampling windows, and absent standardized cut-offs. Omics signatures and machine learning models combining biomarker kinetics with clinical variables are promising but require prospective, transportable validation. Conclusions: Key barriers to implementation include biological variability, non-specificity across postoperative syndromes, heterogeneous sampling windows, and lack of standardized cut-offs. Integrating multimarker panels into validated, dynamic predictive frameworks represents a promising direction for perioperative precision medicine. Full article

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are debilitating disorders with overlapping symptoms such as chronic pain and fatigue. Dysregulation of the endogenous opioid system, particularly µ-opioid receptor function, may contribute to their pathophysiology. This study examined whether epigenetic modifications, specifically µ-opioid receptor 1 gene (OPRM1) promoter methylation, play a role in this dysfunction. Using a repeated-measures design, 28 ME/CFS/FM patients and 26 matched healthy controls visited the hospital twice within four days. Assessments included blood sampling for epigenetic analysis, a clinical questionnaire battery, and quantitative sensory testing (QST). Global DNA (hydroxy)methylation was quantified via liquid chromatography–tandem mass spectrometry, and targeted pyrosequencing was performed on promoter regions of OPRM1, COMT, and BDNF. ME/CFS/FM patients reported significantly worse symptom outcomes. No differences in global (hydroxy)methylation were found. Patients showed significantly higher OPRM1 promoter methylation, which remained after adjusting for symptom severity and QST findings. Across timepoints, OPRM1 methylation consistently correlated with BDNF Promoter I and Exon III methylation. This is, to the best of our knowledge, the first study examining OPRM1 methylation in ME/CFS/FM. Increased OPRM1 methylation in patients, independent of symptoms or pain sensitivity measures, supports the hypothesis of dysregulated opioidergic signaling in these conditions. Full article

Background: Postoperative pain levels and opioid requirements vary considerably, even among patients undergoing similar surgical interventions. The pupillary pain index—a pupillometry-derived measure of nociception-antinociception balance—may help individualize postoperative analgesia. We therefore tested the hypothesis that a pupillary pain index-guided opioid titration at the end of surgery reduces postoperative pain and opioid consumption compared with standard care. Methods: At the end of surgery, a portable infrared pupilometer was used to measure pupillary dilation reflex during stepwise tetanic stimulation (10–60 mA), generating a pupillary pain index score. Adult patients undergoing elective ear-nose-throat surgery under general anesthesia were randomized to pupillary pain index-guided opioid therapy or standard care. Opioid administration in the pupillary pain index group followed predefined pupillary pain index cutoffs; in the control group, analgesia was managed per routine practice. Postoperative opioid consumption and pain—assessed using a numerical rating scale (NRS, 0–10)—were recorded every 30 min for 2 h in the post-anesthesia care unit. Linear models with covariates including remifentanil, weight, nose surgery, and sex were calculated to compare outcomes between groups. Results: Mean (±SD) opioid consumption during the first 2 postoperative hours was 4.9 ± 4.3 mg in the pupillary pain index-guided group and 6.5 ± 4.3 mg in the control group (adjusted p = 0.12). Mean pain scores were 2.0 ± 1.1 and 2.6 ± 1.4, respectively (adjusted p = 0.10). Conclusions: Pupillary pain index-guided analgesia resulted in a nearly 25% reduction in opioid consumption and lower pain scores, although not statistically significant. This suggests that PPI-guided analgesia is not inferior to standard care in terms of pain management. Full article

Background: Several genes and genomic regions have been implicated in COVID-19 susceptibility and severity, but their clinical relevance remains uncertain. We comprehensively assessed both copy number variants (CNVs) and single-nucleotide variants (SNVs) disrupting genes implicated in COVID-19 in a Swedish cohort of ICU-treated COVID-19 patients with detailed phenotype data. Methods: Patients (n = 301) with severe COVID-19 treated in intensive care units (ICU) between March 2020 and January 2021 at two large Swedish university hospitals were included. Whole exome sequencing (WES) was performed to identify both large copy number variations (CNVs) and single-nucleotide variants (SNVs), including small indels, using the Genome Analysis Toolkit (GATK) pipelines. We focused our analyses on variants disrupting coding genes implicated in severe COVID-19, but also assessed variants known to cause human disease. Results: We identified 11 rare CNVs and several SNVs potentially linked to severe COVID-19. Patients carrying a CNV spanning a COVID-19-implicated gene had higher levels of the heart failure marker NT-proBNP (median 4440 [1558–8160] vs. 1170 [329–3152], p = 0.017), worse renal function at ICU admission (p = 0.0026), and a higher need for continuous renal replacement therapy (CRRT) (28% vs. 10%, p = 0.045) compared to patients without a potentially damaging CNV. Conclusions: Although patients with a potentially damaging CNV or SNV exhibited some differences in cardiac and renal markers, our findings do not support broad genetic screening as a predictive tool for COVID-19 severity. Full article

Psychotropic medicinal plants are commonly used among oncology patients, yet their relevance in the perioperative setting remains insufficiently characterized. We conducted a literature-based identification of 18 neuroactive plants and surveyed 123 cancer patients and 109 healthcare professionals at a tertiary hospital in Northern Thuringia, Germany. Seventy-five percent of patients reported using at least one psychotropic plant. Knowledge levels were high and similar across groups (median 11 plants), while professionals reported a broader usage spectrum (p = 0.042). Frequently known and applied species included Valeriana officinalis, Lavandula angustifolia, Hypericum perforatum, and Urtica. Women used more plants than men (p = 0.024), and higher usage rates were observed in breast cancer and head and neck cancer patients. Heat-map analyses showed substantial overlap in knowledge but differences for species such as Atropa, Cannabis, and Papaver somniferum. Given the potential interactions with anesthetic and analgesic medications, structured preoperative assessment of herbal use is warranted to enhance perioperative safety. Full article

Type 2 diabetes mellitus (T2D) affects hundreds of millions worldwide, with recent estimates indicating approximately 589 million adults living with diabetes, most with type 2 disease. Beyond classical insulin signaling pathways, increasing evidence implicates altered protein glycosylation in metabolic dysfunction. The solute carrier 35 (SLC35) family of nucleotide sugar transporters mediates the import of activated sugars into the endoplasmic reticulum and Golgi lumen, thereby influencing global glycosylation patterns. Dysregulation of these transporters can perturb glucose homeostasis, insulin responsiveness, and nutrient-sensing pathways through changes in glycosylation flux. In this review, we dissect the molecular mechanisms by which these transporters modulate glucose homeostasis, insulin signaling pathways, protein O-GlcN acylation, and broader glycosylation processes. We integrate findings from human genetic studies, rodent models, and in vitro functional analyses to characterize how altered SLC35 activity is associated with T2D and metabolic syndrome. Four members demonstrate particularly compelling evidence: SLC35B4 modulates hepatic glucose metabolism, SLC35D3 mutations impair dopaminergic signaling and energy balance, and SLC35F3 variants interact with high-carbohydrate intake to increase metabolic-syndrome risk. SLC35A3, though less studied, may influence glycosylation-dependent insulin signaling through its role in N-glycan biosynthesis. Beyond these characterized transporters, this review identifies potential metabolic roles for understudied family members, suggesting broader implications across the entire SLC35 family. We also discuss how such alterations can lead to disrupted hexosamine flux, impaired glycoprotein processing, aberrant cellular signaling, and micronutrient imbalances. Finally, we evaluate the therapeutic potential of targeting SLC35 transporters, outlining both opportunities and challenges in translating these insights into novel T2D treatments. Full article

Background: The aim of the study is (1) to assess safety of opioids in nursing mothers after cesarean delivery and in breastfed infants and (2) to evaluate the role of CYP2D6 genetics in maternal and infant clinical outcomes after cesarean delivery. Methods: A total of 210 mother–infant dyads were enrolled after cesarean delivery. Oxycodone 5 mg orally was administered every 4–6 h as needed as part of a standardized opioid-sparing ERAS protocol. Primary outcomes were opioid-related adverse effects, including maternal respiratory depression (RD) and postoperative nausea and vomiting (PONV) and neonatal composite side effects (i.e., RD monitoring, sedation, and limpness). Results: In total, 77% of mothers received opioids during postpartum hospital stay, none experienced respiratory depression, 13% reported PONV, and composite opioid-related side effects were observed in 13% of neonates. Compared to mothers without opioid consumption, higher in-hospital opioid consumption was borderline significantly associated with a higher risk of neonatal composite side effects (adjusted relative risk, aRR = 3.79; 95%CI: 1.01–14.28; p = 0.07), with a similar trend toward higher risk in maternal PONV (aRR = 2.56; 95%CI: 0.70–9.29; p = 0.36). Mothers with a CYP2D6 ultra-rapid metabolizer phenotype also showed higher rates of PONV and neonatal composite side effects compared with normal or intermediate phenotypes, although these associations were not statistically significant. Conclusions: Higher maternal in-hospital opioid consumption is associated with a higher risk of neonatal composite side effects. Using the lowest effective doses of opioids as needed could reduce the risk of opioid-related side effects in neonates. Preoperative genotyping may help identify mothers and breastfed neonates at increased risk for opioid-related adverse outcomes. Additional studies are needed to evaluate preoperative genotyping and to evaluate the causality of increased neonatal adverse outcomes. Full article

Background/Objectives: Reducing the dietary intake of sugar and salt is considered a key strategy for preventing the onset and progression of lifestyle-related diseases. However, these dietary interventions often compromise the taste of foods, which can reduce patient satisfaction. To address this challenge, we focused on novel food-derived particles (NFPs; patent number P7383867) consisting of lipid, α-cyclodextrin, and xanthan gum formulated as an emulsion with excellent retention and diffusion properties. Methods: Here, we investigated the effects of NFPs on the taste responses of mice. Results: In two-bottle preference tests (n = 4–6), NFPs enhanced preferences for sweet and salty stimuli in behavioral tests (one-way ANOVA, p < 0.05) and increased the responses of the chorda tympani nerve (n = 6–8) to sweet and salty stimuli (two-way ANOVA, main treatment effect p < 0.05), but had no effect on the responses to sour, bitter, or umami stimuli. Conclusion: These findings suggest that NFPs may enhance peripheral taste responses to sweet and salty flavors, thereby helping maintain the palatability of foods with reduced sugar or salt content. Such modulation may have broad applications in improving the acceptability of therapeutic or restricted diets and supporting both disease management and prevention, including lifestyle-related diseases, kidney disease, and other conditions requiring dietary restriction and may offer translational relevance for human dietary interventions. Full article

Background and Aims: Gastric cancer (GC) remains a leading cause of cancer-related mortality, frequently diagnosed at advanced stages. High-risk features—tumor size ≥ 40 mm, cT3/cT4, nodal involvement, diffuse histology, and Borrmann type III/IV—are associated with peritoneal metastasis (PM). Staging laparoscopy with peritoneal washing (PW) is superior to conventional preoperative imaging modalities, including contrast-enhanced CT, MRI, PET/CT and endoscopic ultrasound, in detecting occult peritoneal disease. In this era of personalized medicine and expanding loco-regional strategies such as cytoreductive surgery (CRS)/Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) and Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC), accurate staging is crucial. This study assessed the impact of SL and PW in high-risk GC. Methods: We retrospectively analyzed 113 consecutive high-risk GC patients who underwent SL and PW between 2014 and 2024 at our institution. The primary endpoint was detection of PM or positive cytology (CY+). Secondary endpoints were treatment modification, eligibility for loco-regional therapy, and safety. Results: SL/PW identified PM or CY+ in 26 patients (23%), including 16 with CY+ only. None had radiologic signs of peritoneal disease. SL findings altered treatment in all cases: 21 patients (81%) with Peritoneal Cancer Index (PCI) < 6 underwent induction chemotherapy followed by CRS + HIPEC; 5 patients (PCI > 6) were spared non-therapeutic laparotomy and treated with bidirectional systemic chemotherapy and PIPAC. In 10 patients, systemic therapy was shifted from FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) to FOLFOX (fluorouracil, leucovorin, and oxaliplatin) ± nivolumab. No perioperative complications occurred; all patients were discharged within 24 h without delay in systemic treatment. Conclusions: SL with PW is safe and significantly improves staging accuracy in high-risk GC, enabling personalized therapeutic planning. Routine integration of SL should be considered essential in treatment algorithms to guide systemic and loco-regional strategies. Full article

Background and Objectives: Type 2 diabetes mellitus (T2DM) affects over 537 million adults worldwide and disproportionately burdens low- and middle-income countries, where diagnostic resources are limited. Predictive models trained in one population often fail to generalize across regions due to shifts in feature distributions and measurement practices, hindering scalable screening efforts. Materials and Methods: We evaluated a few-shot domain adaptation framework using a simple multilayer perceptron with four shared clinical features (age, body mass index, mean arterial pressure, and plasma glucose) across three adult cohorts: Bangladesh (n = 5288), Iraq (n = 662), and the Pima Indian dataset (n = 768). For each of the six source-target pairs, we pre-trained on the source cohort and then fine-tuned on 1, 5, 10, and 20% of the labeled target examples, reserving the remaining for testing; a final 20% few-shot version was compared with threshold tuning. Discrimination and calibration performance metrics were used before and after adaptation. SHAP explainability analyses quantified shifts in feature importance and decision thresholds. Results: Several source → target transfers produced zero true positives under the strict source-only baseline at a fixed 0.5 decision threshold (e.g., Bangladesh → Pima F₁ = 0.00, 0/268 diabetics detected). Few-shot fine-tuning restored non-zero recall in all such cases, with F₁ improvements up to +0.63 and precision–recall gains in every zero-baseline transfer. In directions with moderate baseline performance (e.g., Bangladesh → Iraq, Iraq → Pima, Pima → Iraq), 20% few-shot adaptation with threshold tuning improved AUROC by +0.01 to +0.14 and accuracy by +4 to +17 percentage points while reducing Brier scores by up to 0.14 and ECE by approximately 30–80% (suggesting improved calibration). All but one transfer (Iraq → Bangladesh) demonstrated statistically significant improvement by McNemar’s test (p < 0.001). SHAP analyses revealed population-specific threshold shifts: glucose inflection points ranged from ~120 mg/dL in Pima to ~150 mg/dL in Iraq, and the importance of BMI rose in Pima-targeted adaptations. Conclusions: Leveraging as few as 5–20% of local labels, few-shot domain adaptation enhances cross-population T2DM risk prediction using only routinely available features. This scalable, interpretable approach can democratize preventive screening in diverse, resource-constrained settings. Full article

Precision perioperative medicine connects mechanisms across inflammation, metabolism, and neuroimmunomodulation to predict risk and individualize therapy. This review aims to incorporate landmark concepts and recent studies (2017–2025) as well as outlining how multi-omics and clinical analytics translate biology into actionable pathways. Key opportunities include cytokine-guided risk stratification, metabolic conditioning, and autonomic neuromodulation targeting the cholinergic anti-inflammatory reflex. Implementation requires robust phenotyping, interoperable data pipelines, and trials focused on functional recovery and cognition. Full article

The increasing complexity of airway management, particularly in high-stakes or emergency settings, demands a holistic approach that accounts not only for technical skill but also for the systems in which clinicians operate. Advances in airway devices such as videolaryngoscopes, videolaryngeal mask airways, flexible intubation scopes, combined techniques, and single-use technologies offer new opportunities for improving outcomes—but also introduce new challenges. This article explores the intersection of human factors and the implementation of new airway devices, using a systems-based lens informed by the SEIPS 3.0 framework. Drawing on recent guidelines, real-world case studies, and design principles, we examine how technological changes affect team dynamics, decision-making, equipment layout, and cognitive load. We also highlight the importance of standardized processes, training, and environmental design in mitigating risk and enhancing performance. Ultimately, we propose actionable strategies to integrate human factors into airway device adoption to improve both patient safety and clinician well-being. This review underscores the fact that embedding human factor principles into the adoption and use of airway technologies is essential to build safer, more resilient, and team-centered airway management systems. Full article

Background/Objectives: Prehospital management after traumatic brain injury (TBI) focuses on the avoidance of secondary injuries such as derangement of blood pressure. Recent guidelines specify an updated optimal systolic blood pressure (SBP) target of 110–149 mmHg. We aim to characterise the prehospital blood pressure profile of patients including the SBP range and variability after TBI, amongst other prehospital parameters, to determine associations with the outcome. Methods: We performed a retrospective cohort study of adult patients admitted to the intensive care unit at University Hospital Zurich. The first recorded SBP, SBP variability, and average range during two-thirds of the prehospital time were analysed along with other prehospital parameters for survival and GOSE at hospital discharge using univariate and multivariable logistic regression analyses. Results: In total, 680 patients were included, of whom 76% had moderate to severe head injury and 117 patients died. Among the sample, 51% of patients were in the target range of 110–149 on initial assessment and 50% remained in this range during 2/3 of the prehospital time. The initial SBP, SBP variability, and SBP range were significant for survival in the univariate analysis, but they lost statistical significance in the multivariable model. This may indicate a reduced effect of the analysed SBP parameters on the outcome once controlling for confounding factors. In the multivariable analysis, catecholamine administration reduced the odds of an unfavourable GOSE at hospital discharge (OR 1.84 [1.20–2.81], p = 0.005), which may point towards a benefit of early haemodynamic stabilisation after injury. A younger age (OR 0.95 [95% CI 0.93–0.97], p < 0.001), lower AIS Head/Neck (OR 0.45 [0.29–0.70], p < 0.001), higher initial GCS (OR 1.24 [1.15–1.35], p < 0.001), and higher first haemoglobin (OR 1.24 [1.04–1.46], p = 0.014) were independent predictors of survival. Conclusions: Haemodynamic instability in the prehospital phase is common after TBI and represents a potentially modifiable factor. Catecholamine administration was associated with improved functional recovery, suggesting a possible role of prehospital haemodynamic management, although causality cannot be inferred. Full article

Purpose: Lung resection surgery (LRS) induces a strong local and systemic inflammatory response that may extend to peripheral organs, including the liver. This study aimed to evaluate the potential effect of intravenous lidocaine on hepatic inflammatory and apoptotic responses during lung resection surgery with one-lung ventilation (OLV) in an experimental porcine model. Methods: Eighteen mini pigs were randomly assigned to three groups: lidocaine (LIDO), control (CON), and sham (SHAM). Animals underwent left caudal lobectomy. The LIDO group received a continuous intravenous infusion of lidocaine (1.5 mg/kg/h) during surgery. The CON group received the same volume of saline, and the SHAM group underwent thoracotomy without lobectomy or OLV. Different samples were collected at baseline, during surgery, and 24 h postoperatively to assess inflammatory cytokines and apoptosis-related proteins. Liver biopsy was taken 24 h after de surgery. Results: One-lung ventilation and lung resection surgery increased the expression of proinflammatory markers in the liver biopsy and enhanced apoptotic protein expression and iNOS production. Lidocaine administration attenuated these effects, showing lower levels of inflammatory mediators, a better balance between iNOS and eNOS, and reduced apoptotic activity compared with controls. Conclusions: Our findings suggest that intravenous lidocaine may serve as a personalized perioperative strategy to attenuate systemic inflammatory and apoptotic responses, contributing to improved hepatic protection during thoracic surgery. Full article

Artificial intelligence (AI) is rapidly transforming cardiovascular medicine, with profound implications for congenital heart disease (CHD). Tetralogy of Fallot (ToF), the most common cyanotic disease, requires lifelong surveillance and complex management because of late complications such as pulmonary regurgitation, arrhythmias, and right ventricular dysfunction. This review synthesizes current evidence on AI applications across the continuum of ToF care—from prenatal diagnosis to adulthood follow-up. We examine advances in imaging, perioperative planning, intraoperative monitoring, intensive care, and long-term surveillance, including wearable and implantable technologies. Machine learning (ML), deep learning (DL), and natural language processing (NLP) are revolutionizing diagnostic accuracy, risk stratification, surgical decision-making, and personalized long-term care. The future lies in the integration of multimodal data, including imaging, electronic health records (EHRs), genomic information, and continuous monitoring, to support precision medicine. Challenges remain regarding dataset limitations, interpretability, regulatory standards, and ethical concerns. Nevertheless, ongoing innovation and collaboration between clinicians, engineers, and regulators promise a new era in congenital cardiology. By embedding AI throughout the patient journey, healthcare systems may improve outcomes and quality of life for individuals with ToF. Full article