Search Results (7,049)

Background: Necrotizing fasciitis complicating diabetic foot infection requires rapid source control and is associated with substantial morbidity. A topical desiccating agent (TDA) may assist debridement by dehydrating necrotic tissue and potentially disrupting biofilm, but comparative clinical evidence is limited. Methods: We conducted a retrospective, single-center cohort study of 87 patients who underwent emergency surgery for diabetic foot-related necrotizing fasciitis between July 2023 and February 2026. Nineteen patients received a single application of TDA at the index operation in addition to standard care, and 68 received standard care without TDA. Treatment allocation was non-random and occurred in routine clinical practice. The primary outcome was the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score at Day 7. The primary analysis used linear regression adjusted for baseline LRINEC score and baseline septic status, with heteroskedasticity-consistent type 3 (HC3) standard errors. LRINEC was treated as a laboratory-based surrogate rather than as a validated treatment-response measure. C-reactive protein (CRP), white blood cell count, and glucose at Day 0 and Day 7 were summarized descriptively. Secondary clinical outcomes were 30-day major amputation and all-cause mortality. Results: The mean LRINEC score decreased from 8.58 to 2.95 in the TDA group and from 7.51 to 5.51 in the control group. The mean change was −5.63 in the TDA group and −2.00 in the control group, an unadjusted between-group difference of −3.63 points (95% confidence interval [CI], −4.83 to −2.43; p < 0.001). Baseline sepsis was more frequent in the TDA group than in the control group (89.5% vs. 51.5%). After adjustment for baseline LRINEC score and septic status, TDA exposure was associated with a 3.01-point lower Day-7 LRINEC score (95% CI, −4.00 to −2.02; p < 0.001). At Day 7, 18 of 19 TDA-treated patients (94.7%) and 34 of 68 controls (50.0%) had an LRINEC score below 6; this threshold analysis was exploratory. CRP, white blood cell count, and glucose decreased descriptively in both groups, with numerically larger reductions in the TDA group. No major amputations or deaths occurred within 30 days in either group. No TDA-related adverse event was documented in the retrospective clinical records. Conclusions: Adjunctive TDA use was associated with a lower Day-7 LRINEC score and a greater reduction from baseline. Because treatment was not randomized, baseline severity differed between groups, LRINEC is not a validated longitudinal treatment-response measure, and assessment of clinical outcomes was limited, the findings should be interpreted as exploratory associations and confirmed in prospective multicenter studies. Full article

Hemopericardium is a rare but serious complication of radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF). While prompt pericardial drainage is effective, the long-term clinical course and the role of adjunctive anti-inflammatory therapy remain unclear. In this prospective single-center cohort study, we included patients who developed hemopericardium requiring pericardiocentesis during RFCA for AF. All patients underwent immediate percutaneous drainage. Colchicine (0.6 mg twice daily for 14 days) was prescribed at the operator’s discretion. The primary outcome was freedom from AF or atrial tachycardia (AT) at 12 months after a 3-month blanking period. Among 2133 patients undergoing RFCA, 75 (3.5%) developed hemopericardium. Of these, 21 received colchicine and 54 received usual care. During a median follow-up of 367 days, freedom from AF/AT did not differ between groups (76.2% vs. 74.1%, log-rank p = 0.93). Residual pericardial effusion was infrequent and resolved in all patients by 3 months. Although colchicine was not associated with a reduction in atrial arrhythmia recurrence, patients receiving colchicine had lower CRP levels at 3 months than those receiving usual care (p = 0.021). However, treatment-limiting adverse events occurred in 6 of 21 patients (28.6%) receiving colchicine. No cases of constrictive pericarditis were observed. In patients with procedural hemopericardium during AF ablation, prompt pericardial drainage was associated with favorable clinical outcomes and absence of long-term pericardial sequelae. Adjunctive colchicine therapy was not associated with a significant reduction in arrhythmia recurrence; however, given the small sample size and limited number of events, a clinically meaningful treatment effect cannot be excluded. Full article

Background/Objectives: Early feeding intolerance (FI) affects 20–50% of critically ill patients receiving enteral nutrition, yet no validated predictive tool exists and diagnosis remains retrospective. Plasma citrulline, mainly synthesized by enterocytes, is considered as the “factor V of the intestine”. The citrulline generation test (CGT) evaluates small bowel mucosal function by measuring the increase in plasma citrulline after glutamine administration. We hypothesized that patients with a lower CGT would be more prone to FI. We aimed to compare CGT results according to the presence or absence of FI and to identify factors associated with CGT. Methods: This prospective study was conducted in the medical intensive care unit (ICU) of Besancon Hospital. Plasma citrulline and glutamine concentrations were measured at admission and after an alanine–glutamine dipeptide bolus. CGT was defined as the slope between basal and 90 min peak plasma citrulline concentrations. Signs of FI were collected during follow-up. Results: Among the sixty-six included patients, nine (14%) developed FI by day three, only characterized by vomiting and gastric residual volumes above 500 mL; abdominal pain or diarrhea were not observed. CGT values did not differ between patients with and without FI. CGT correlated positively with baseline citrulline and peak glutamine concentrations. Conclusions: FI was not associated with CGT, possibly because FI was predominantly gastric rather than intestinal. Low CGT values were associated with low plasma citrulline concentrations, suggesting reduced functional enterocyte mass. The positive correlation between CGT and peak plasma glutamine suggests that CGT not only reflects enterocyte function but also glutamine bioavailability. Full article

Background/Objectives: Prehospital identification of non-ST-elevation acute coronary syndrome remains unresolved, and available risk scores incorporate troponin categorically. We compared the discriminative performance of cardiac troponin I measured in a blood sample obtained at first prehospital medical contact, analysed as a continuous variable, against the HEART, GRACE, and TIMI scores for predicting 30-day major adverse cardiac events. Methods: We conducted a prospective cohort study in 333 adults with non-traumatic chest pain suggestive of non-ST-elevation acute coronary syndrome, which was attended by two physician-staffed advanced life support units. Venous blood was drawn at first medical contact and analysed later in the laboratory; the results were not available during patient care. All three scores used this same determination as their troponin component. The primary outcome was a composite of all-cause mortality, type 1 myocardial infarction, and unplanned coronary revascularisation at 30 days. Results: The primary outcome occurred in 82 patients (24.6%). Prehospital troponin discriminated better (area under the curve 0.916, 95% CI 0.875–0.952) than TIMI (0.817), GRACE (0.767), and HEART (0.721); all comparisons were p < 0.001. An exploratory rule-out threshold of 80 ng/L identified 61 patients (18.3%) with no events (sensitivity and negative predictive value 100%, exact 95% CI 95.6–100 and 94.1–100), whereas the ≥780 ng/L stratum showed an event rate of 69.4%. Conclusions: A blood sample obtained at first prehospital medical contact carries substantial prognostic information that clinical scores discard by categorising it. Because it was analysed subsequently in the laboratory, these findings do not evaluate a real-time strategy; they support development and validation of point-of-care devices. Full article

Background: Candidozyma auris (C. auris) is an emerging multidrug-resistant yeast that has become an important cause of healthcare-associated outbreaks, particularly in intensive care units (ICUs). Colonization frequently precedes invasive infection, yet the epidemiology, progression to candidemia, and mortality among critically ill patients remain incompletely characterized. Methods: We conducted a narrative review of published studies evaluating C. auris colonization and infection in ICU populations. Studies reporting colonization rates, progression to invasive infection, and mortality were synthesized. Descriptive pooled proportions were calculated from aggregated data across eligible observational studies. Results: Colonization rates varied widely according to local epidemiology, ranging from 0.2 to 0.4% in routine surveillance studies to over 50% during outbreaks. Across 17 observational studies including 1879 colonized ICU patients, 616 developed invasive infection, yielding a descriptive pooled incidence of 32.8% (95% CI, 30.7–34.9%), predominantly candidemia. The median interval from ICU admission to candidemia was 25.8 days. Among 13 studies including 1354 colonized and/or infected ICU patients, the descriptive pooled 30-day in-hospital mortality was 36.4% (95% CI, 33.8–39.0%). In 12 studies comprising 396 patients with C. auris candidemia, the descriptive pooled 30-day mortality was 45.9% (95% CI, 41.0–50.8%), significantly higher than that observed in mixed colonized/infected ICU populations. Conclusions: C. auris represents a major threat in ICUs because of its ability to establish persistent colonization, progress to invasive candidemia, and cause high mortality among critically ill patients. Early identification of colonized patients, rigorous infection prevention measures, and prompt antifungal management are essential to reduce transmission and improve clinical outcomes. Full article

Bisphosphonates (BPs) and Denosumab (DMB) are antiresorptive agents (AA) commonly used in treatment of osteoporosis, multiple myeloma (8.0%), breast cancer (3.3%), prostate cancer (2.9%) and other malignancies (0.7%), bone metastases, and cancer-induced hypercalcemia. However, this therapy is associated with a significant risk of medication-related osteonecrosis of the jaw (MRONJ), particularly after tooth extraction. The aim of this narrative review was to summarize current evidence on measures aimed to reduce the risk of MRONJ after tooth extraction, and to critically discuss the strength of evidence supporting each of these measures. Articles published in the years 2013–2025 were reviewed using PubMed, Scopus, Web of Science databases. Available studies were categorized and compared with the use of selected prevention methods. The duration of the treatment, route of administration, dosage and type of AA have a significant impact on the risk of developing MRONJ. Antibiotic prophylaxis is considered in most published preventive protocols. However, the evidence supporting a single optimal regimen is limited. Patients from a high-risk group of MRONJ, demonstrating cancer, who were administered intravenous antiresorptive agents for longer than three years or zoledronic acid, or those with a history of jawbone necrosis or inflammation require prolonged antibiotic therapy (started before the procedure and continued up to 14 days after the procedure). Moreover, studies on the use of platelet-rich fibrin (PRF) and Concentrated Growth Factors (CGF) as a preventive measure have shown promising results in observational studies, along with antibiotic prophylaxis and optimal oral hygiene. Pentoxifylline with tocopherol and low-level laser therapy (LLLT) are recognized as potentially useful non-invasive preventions. However, evidence is limited due to the small sample sizes and heterogenous protocols. Vitamin D levels should be monitored, and oral supplementation should be considered if needed. AA therapy suspension prior to the surgical procedure must always be consulted with the attending physician. A multidisciplinary approach along with well-planned pre- and postoperative care is essential for safe tooth extraction in patients receiving AA therapy. Full article

Background/Objectives: Food allergy prevention is no longer understood as the simple avoidance of allergenic foods. The first 1000 days (from conception to, approximately, 24 months of age) include prenatal, perinatal and postnatal windows in which diet, epithelial barrier integrity, microbial ecology, immune maturation and family-level implementation interact. This narrative review was developed as a Commission-proposed SIAIP-oriented clinical framework, rather than a formal guideline or consensus statement. Evidence from guidelines, systematic reviews, randomised trials, birth cohorts and mechanistic studies was organised by developmental window and interpreted according to endpoint validity, confounding, feasibility and clinical readiness. Prenatal factors include maternal allergen non-avoidance, whole-diet quality, micronutrient and fatty acid status, antibiotic exposure, environmental context and maternal microbiome. Perinatal factors include mode of delivery, intrapartum and neonatal antibiotics, gestational maturity, early colonisation, breastfeeding initiation and routine vaccination. Postnatal factors include eczema, skin barrier inflammation, the timing and regularity of allergen introduction, breastfeeding management, infant diet diversity, siblings, daycare, pets, smoke and pollution, physical activity and equitable implementation. The strongest actionable evidence remains eczema-linked risk recognition and timely, sustained oral exposure to peanut and well-cooked egg. Maternal and environmental factors are clinically important, but many are contextual rather than prescriptive; they should guide non-restrictive, non-blaming counselling rather than deterministic risk labelling. Full article

Waterbirth has become a widely adopted alternative to a conventional delivery, with well-documented maternal benefits, but there is an ongoing debate regarding neonatal safety. We would like to report a case of a 10-day-old male neonate who developed acute otitis externa (AOE) following waterbirth. Despite the rare occurrence of this disease in children under 2 years of age, prompt diagnosis and timely initiation of appropriate therapy led to a full recovery. This case represents a previously undocumented, yet plausible, complication of waterbirth and underscores the importance of careful neonatal ear assessment and preventive measures in aquatic deliveries. Full article

Background/Objectives: Achieving optimal metabolic control in phenylketonuria (PKU) remains challenging, particularly in adolescents and adults. Conventional free amino acid–based protein substitutes are absorbed rapidly, whereas prolonged-release formulations are designed to provide a more gradual amino acid release profile. Whether this translates into more favorable 24 h Phe and Tyr profiles and improved short-term biochemical parameters of metabolic control remains uncertain. This study evaluated whether a prolonged-release amino acid–based protein substitute (PR-AA) could improve 24 h metabolic control compared with standard protein substitutes. Methods: This randomized, controlled, open-label crossover study included adolescents and adults with PKU aged ≥16 years. Participants received either conventional protein substitutes (standard of care; SC) or PR-AA three times daily for two consecutive days, followed by crossover to the alternate treatment. Blood spot samples were collected at five time points over 24 h on the second day of each treatment period. The primary outcome was the 24 h blood Phe profile. Secondary outcomes included blood Tyr, Phe/Tyr ratio, and exploratory assessment of branched-chain amino acids (BCAAs). Results: Twenty-one patients were enrolled, of whom 16 were included in the intention-to-treat analysis and 12 in the per-protocol analysis. PR-AA treatment resulted in significantly lower mean blood Phe levels over 24 h compared with SC (522 ± 194 vs. 561 ± 165 µmol/L; p = 0.0009), corresponding to a reduction of approximately 6–7%. The effect was consistently observed throughout the 24-h assessment period, particularly during the early morning, and became detectable after only two days of treatment. PR-AA was also associated with significantly higher blood Tyr levels (approximately +18–20%; p < 0.05) and a lower Phe/Tyr ratio (approximately −20%; p < 0.001) compared with SC. Exploratory analyses demonstrated modestly lower and more stable BCAA profiles with PR-AA. No significant carryover effects or treatment-related safety concerns were observed. Conclusions: Short-term treatment with a prolonged-release protein substitute was associated with modest but consistent improvements in short-term biochemical parameters of metabolic control in adolescents and adults with PKU, including lower blood Phe and higher Tyr levels, resulting in a reduced Phe/Tyr ratio. These findings suggest that optimizing amino acid delivery kinetics may represent a promising strategy to improve short-term metabolic control in PKU. Given the preliminary nature of these findings and the limited number of participants who completed the study protocol, larger studies with longer follow-up, including direct clinical and neurocognitive outcomes and formal variability metrics, are needed to determine the clinical relevance of these biochemical effects. Full article

Background/Objectives: Mechanical power (MP) quantifies the energy delivered to the respiratory system during ventilation and serves as a promising marker for ventilator-induced lung injury (VILI). According to its original definition by Gattinoni, MP reflects the energy transferred from the ventilator to the respiratory system under conditions of deep sedation, passive breathing, neuromuscular blockade, and volume-controlled ventilation. Its role in coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome (ARDS) remains under investigation. This systematic review aimed to synthesize the available evidence on the association between MP and VILI, complications related to mechanical ventilation (MV), and mortality in adult patients with COVID-19 undergoing invasive mechanical ventilation (IMV). Methods: A systematic review was conducted using PubMed-MEDLINE (Medical Literature Analysis and Retrieval System Online) for studies published in recent years, focusing on adult COVID-19 patients undergoing IMV. Inclusion criteria centered on studies reporting MP and its association with VILI, complications, or mortality. Ten studies met eligibility criteria after screening 356 retrieved articles. Results: Most included studies were retrospective and observational, encompassing critically ill COVID-19 patients. Elevated MP was correlated with more severe outcomes, including increased 28-day mortality, prolonged MV, and weaning failure. Franck et al. demonstrated strong correlations between MP and driving pressure, elastance, and positive end-expiratory pressure, emphasizing the importance of calculation methods. González-Castro et al. identified a threshold of 17 J/min, above which mortality risk increased. Stalla et al. highlighted that dynamic MP reductions during prone positioning were associated with survival. Registry-based analyses confirmed that both magnitude and cumulative exposure above 18 J/min increased intensive care unit mortality. Novel indices combining MP with oxygenation parameters improved prognostic accuracy. While absolute MP at initiation provided limited predictive value, temporal trends and individual components were strongly linked to VILI. Conclusions: Higher MP has been associated with adverse clinical outcomes in patients with COVID-19 receiving invasive mechanical ventilation, supporting its potential role as a prognostic indicator. Its dynamic assessment, thresholds, and integration with ventilatory strategies such as prone positioning enhance risk stratification and may guide individualized, lung-protective ventilation. Continuous monitoring and standardized calculation are recommended to optimize clinical decision-making. Full article

Outpatient care facilities combine high patient turnover, repeated short contacts, accompanying persons, clinically vulnerable subgroups, and healthcare-worker movement across functional zones. This study develops a synthetic dynamic contact-network simulation framework to evaluate how outpatient flow-control strategies affect simulated respiratory-infection risk and service efficiency. Public descriptions of the SocioPatterns hospital-ward study were used only to shape role composition and qualitative contact heterogeneity. A parameterized outpatient process model generated time-stamped locations for patients, accompanying persons, high-risk patients, and healthcare workers over a simulated clinic day. Zone- and role-dependent temporal contacts were then coupled to a stochastic SEIR process, with 500 replications per main scenario. In the baseline scenario, mean cumulative secondary infections were 0.502 per clinic day, the probability of at least one secondary infection was 0.354, and mean waiting time was 23.1 min. Time-spaced appointments reduced mean secondary infections by 45.4–52.2% while also reducing waiting time. Accompaniment restriction reduced risk by removing non-service nodes, whereas waiting-capacity control, protected scheduling, and healthcare-worker grouping were more context dependent. The strongest combined strategy reduced mean secondary infections by 52.6% and maintained a mean waiting time of 13.6 min. These results are comparative outputs under stated assumptions, not predictions for a specific clinic. The framework provides a reproducible computational basis for testing how operational policies reshape temporal contact opportunities before local implementation. Full article

Background/Objective: Ovarian hyperstimulation syndrome (OHSS) is a severe complication during controlled ovarian hyperstimulation. Ascites and consecutive hemoconcentration may lead to potentially life-threatening complications like thromboembolic events and the need for intensive care. The use of diuretics is widely used to treat ascites in non-OHSS patients. The aim of this study was to assess whether the use of furosemide in the treatment of OHSS was associated with a higher rate of complications compared to the literature. Methods: In this retrospective cohort study, 502 cases treated from January 2005 to June 2023 for OHSS at the Medical University of Vienna were evaluated regarding the distribution of OHSS severity, average duration of treatment, types and frequency of complications associated with antidiuretic treatment, and predictive factors for paracentesis. Results: The median AMH levels were 5.7 ng/mL. An antagonist protocol was used in 80% of stimulations. Human Chorionic Gonadotropin trigger was used in 80% of stimulations, with 71.7% of cases being early-onset. The incidence dropped from 8.4% (2006 to 2016) to 3.3% (from 2015 to 2023). The median duration of inpatient treatment was seven days, with about 75% of patients receiving furosemide as a diuretic treatment. Ascites drainage was necessary in 27.9%. None of our patients developed a thromboembolic complication following the furosemide treatment. Conclusions: During the study period, the incidence of OHSS declined, most probably as a result of advances in ovarian stimulation protocols and freezing strategies. In moderate to severe OHSS, standardized diuretic treatment with furosemide was not associated with additional thromboembolic complications as long as patients remain normovolemic. Full article

Background: Emergency department (ED) use for cancer-related pain is common, particularly among patients with metastatic disease who frequently require opioid analgesia. In October 2014, the U.S. Drug Enforcement Administration rescheduled hydrocodone combination products from Schedule III to Schedule II, introducing stricter prescribing and dispensing requirements. We evaluated whether hydrocodone rescheduling was associated with pain-related ED visits and hospitalizations among older adults with metastatic lung cancer. Methods: We conducted a retrospective SEER–Medicare cohort study of beneficiaries aged 66 years or older diagnosed with metastatic lung cancer. Diagnoses from January 2011 through September 2014 were classified as pre-policy, October 2014 was excluded as a transition month, and November 2014 through December 2018 constituted the post-policy period. Monthly 365-day cumulative incidences were estimated using the Aalen–Johansen estimator with death treated as a competing event. Segmented interrupted time-series models estimated immediate level and slope changes. Adjusted cause-specific Cox models evaluated time to first event. Results: The cohort included 52,371 beneficiaries. For narrowly defined neoplasm-related pain ED visits, the policy was associated with an immediate increase of 0.834 percentage points (95% CI, 0.330–1.338) and a post-policy slope increase of 0.030 percentage points per month (95% CI, 0.011–0.049). Pain-related hospitalizations increased immediately by 0.946 percentage points (95% CI, 0.336–1.556), with a slope increase of 0.024 percentage points per month (95% CI, 0.005–0.042). At 12 months, fitted cumulative incidences exceeded no-policy projections by 1.193 percentage points for ED visits and 1.228 percentage points for hospitalizations. Adjusted cause-specific hazard ratios were 1.14 for pain-related ED visits (95% CI, 1.00–1.30; p = 0.054) and 1.14 for hospitalizations (95% CI, 1.00–1.29; p = 0.049). Conclusions: Hydrocodone rescheduling was temporally associated with modest increases in acute-care encounters explicitly coded for neoplasm-related pain. The findings underscore the importance of preserving timely analgesic access for patients with advanced cancer. Full article

Background: Given the rising global prevalence of dementia and its complex etiology, involving genetic and environmental risk factors, the aim of the present exploratory study was to investigate how offspring of individuals with dementia perceive genetic risk and the role of diet in dementia prevention. Methods: A mixed-methods study was conducted in Greece. Overall, 118 offspring completed an online questionnaire assessing demographics, risk perceptions, and dietary beliefs and practices in dementia risk reduction. Additionally, 22 semi-structured interviews explored dietary beliefs, practices, and influencing factors using framework analysis. Results: Most participants (76.3%) recognized diet’s role in dementia prevention, while 52.5% perceived offspring as having increased genetic risk; 40.7% reported making dietary changes to reduce disease risk. Healthcare professional consultation was the factor most strongly associated with dietary modification (OR = 26.61, 95% CI 7.47–94.76, p < 0.001). Qualitative findings showed that, while dementia was viewed as severe, personal susceptibility was often perceived as uncertain or distant. Key barriers, facilitators, and the role of self-efficacy in adopting healthier dietary practices were also explored. Conclusions: Our findings identify personalized dietary counselling and risk communication as priorities for evaluation in future intervention studies, aimed at supporting the implementation of dietary modifications and reducing the gap between knowledge and behavior in dementia risk reduction. Full article

Early-life calf mortality is a significant barrier to herd growth and overall productivity in yak husbandry. This retrospective study investigated the survival pattern and potential risk factors linked to yak calf mortality during the first 90 days of life. Analysis was performed on existing farm records from 428 yak calves born between 2013 and 2025 at a semi-intensive yak farm. The Kaplan–Meier method was used to estimate survival probability, and the log-rank test was used to compare survival probabilities; additionally, a multivariate Cox proportional hazards model was employed to identify independent risk factors. Overall, 70 (16.4%) calves died within the first 90 days after birth. The Kaplan–Meier analysis indicated significantly lower survival probability among low-birth-weight calves (≤12 kg; p = 0.0005) and calves born to primiparous dams (p = 0.0003). In contrast, survival did not differ according to calf sex (p = 0.620) and birth season (p = 0.658). In the multivariate Cox proportional hazards model, low birth weight (HR = 2.27, 95% CI: 1.24–4.16; p = 0.008) and primiparous dams (HR = 2.08, 95% CI: 1.28–3.38; p = 0.003) were independently associated with higher mortality risk. As a result, calf sex and birth season were not significant predictors. Diarrhea and respiratory disease were the predominant causes of calf deaths. The current study’s results indicate that maternal and neonatal factors are the major determinants of early-life calf survival. This highlights the need for special care with optimum nutrition and regular monitoring of primiparous dams and low-birth-weight calves in order to lower pre-weaning mortality and improve overall herd productivity. Full article