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Current American Heart Association (AHA) guidelines recommend moving patients to a hard surface, when possible, to improve cardiopulmonary resuscitation (CPR) quality. However, the time to move a patient detracts from the time actively performing CPR. Studies show mixed results on the effect of a soft surface on CPR quality. The primary objective of this study was to compare the fatiguability of performing CPR on the floor versus a standard mattress. This pilot randomized trial enrolled currently employed emergency medical services (EMS) clinicians from two EMS agencies in North Carolina from 10/2022 to 12/2022. Participants performed continuous compressions on a CPR manikin with integrated electronic feedback, randomized 1:1 to a floor or a mattress. The primary outcome was time to failure, defined as voluntary cessation of compressions by the participant or 30 seconds of inadequate compressions. Adequate compressions were defined using the current AHA recommendations for high-quality CPR, including a compression rate of 100-120/min and depth of at least 2 in. We describe time to failure and compression rate with median and interquartile range (IQR), and compare them between surfaces with the Wilcoxon Rank-Sum test. We constructed a survival curve of the time to failure by surface and compared them with a log-rank test. Among 40 participants, 47.5% (19/40) were female and 90.0% (36/40) were White with an average age of 28 (IQR 24-33) years. The time to failure for floor CPR was 145 seconds (IQR 65-240) vs. 140 seconds (IQR 100-420) for mattress CPR (p = 0.64). Floor participants performed compressions at a median rate of 112 (IQR 104-118) compressions per minute vs. 105 (IQR 101-113) compressions per minute for mattress participants (p = 0.12). Using a survival analysis, the time to failure was not statistically different between surfaces (p = 0.4). This prospective pilot study suggests no difference in fatigability of a person performing CPR on a mattress versus a floor. Further study is necessary to validate our findings.

Non-healing perineal wounds (NHPWs), including persistent presacral sinuses, remain a common and morbid complication after elective intersphincteric proctectomy (ISP) for fistulizing perianal Crohn's disease (pCD), with reported healing rates of approximately 70% at 1 year. These complications significantly impair quality of life and increase healthcare utilization, highlighting the importance of prevention. This narrative review summarizes contemporary evidence and expert practice to present ten pragmatic strategies to reduce perineal wound dehiscence after ISP for pCD. Prevention begins with comprehensive preoperative optimization, including correction of malnutrition and anemia, minimization of corticosteroid exposure, smoking and nicotine cessation, and optimization of relevant medical comorbidities. Careful assessment and control of Crohn's disease activity are emphasized through current disease staging, proactive therapeutic drug monitoring, and aggressive surgical control of perianal sepsis. These measures often involve repeated examinations under anesthesia, drainage of abscesses and fistula tracts, fecal diversion when indicated, and selective use of hyperbaric oxygen therapy to improve local conditions before definitive surgery. Operative strategies focus on technical decisions that minimize perineal wound burden and promote healing. Key elements include performing proctectomy in the intersphincteric plane with total mesorectal excision when feasible, meticulous debridement and management of fistula tracts, and robust multilayered perineal closure. Adjunctive techniques such as horizontal mattress suturing of the levators to enhance tissue apposition, use of pedicled omental flaps with fluorescence angiography to confirm perfusion, and prophylactic incisional negative pressure wound therapy are highlighted. Collectively, these strategies provide a practical framework to reduce perineal wound complications after ISP for pCD.

Surgical site infection is a common complication after abdominal surgery and is associated with delayed wound healing, prolonged hospitalization, and increased healthcare costs. Secondary closure of infected abdominal incisions after debridement and negative pressure wound therapy remains challenging because tissue edema, inflammation, and skin retraction often lead to excessive wound tension. Super-tension-reduction suture has been proposed to redistribute wound tension and improve tissue perfusion, but its effectiveness in abdominal wound salvage remains unclear. We performed a retrospective cohort study of patients undergoing abdominal wound salvage for superficial/incisional surgical site infection between January 2020 and May 2024. Patients were categorized according to the final closure technique: standard interrupted suture or super-tension-reduction suture using a modified buried vertical mattress technique. Patient demographics, operative characteristics, and postoperative outcomes were collected. Primary outcomes included recurrent surgical site infection, wound breakdown, hematoma, seroma, fat necrosis, and reoperation. Secondary outcomes included operative duration, time to drain removal, time to suture removal, and length of hospitalization. Propensity score matching was used to mitigate the selection bias. Multivariable binary logistic regression identified significant predictors of complications. We included 89 patients (standard interrupted suture group: 39; super-tension-reduction suture group: 50). In the unmatched cohort, super-tension-reduction suture was associated with lower rates of recurrent surgical site infection (6.0% vs. 23.1%, P&#x2009;=&#x2009;0.028) and reoperation (4.0% vs. 17.9%, P&#x2009;=&#x2009;0.039), alongside shorter hospitalization (17.5 vs. 21 days, P&#x2009;<&#x2009;0.001), despite a modestly longer operative time (24 vs. 20&#x2005;min, P&#x2009;<&#x2009;0.001). After 1:1 propensity score matching (n&#x2009;=&#x2009;58), super-tension-reduction suture group maintained a significantly lower overall complication rate (17.2% vs. 41.4%, P&#x2009;=&#x2009;0.043). Crucially, multivariable logistic regression identified the super-tension-reduction suture as an independent protective factor against overall complications (aOR: 0.22, 95% CI: 0.08-0.59, P&#x2009;=&#x2009;0.003) and recurrent surgical site infection (aOR: 0.21, 95% CI: 0.05-0.85, P&#x2009;=&#x2009;0.028). The super-tension-reduction suture was associated with favorable clinical outcomes in abdominal wound salvage. Compared with conventional closure, it was associated with lower overall complication rates despite a modest increase in operative time. While clinically promising, these observational associations warrant further validation in prospective, randomized trials.

Allergic rhinitis is often underdiagnosed despite its high prevalence and considerable impact on academic achievement and quality of daily living. The study aims to describe the epidemiological patterns of allergic rhinitis among adolescents aged 13-14 years in Anuradhapura, Sri Lanka. An analytical cross-sectional study was conducted in 2023 among adolescents from 32 grade 8 classes in 6 government secondary schools located in the Anuradhapura municipal council area and randomly selected via multistage sampling. The prevalence and associated factors were assessed using the validated and translated International Study of Asthma and Allergy in Childhood questionnaire. The study sample included 1,029 participants, of whom 528 (51.3%) were males. The prevalence of lifetime and current allergic rhinitis and eye symptoms was 37.6% (n = 387; 95% confidence interval [CI], 34.6-40.6), 25.9% (n = 266; 95% CI, 23.2-28.6), and 13.8% (n = 142; 95% CI, 11.8-16.0), respectively. Nasal symptoms negatively affected the activities of daily living in 195(18.9%; 95% CI, 16.6-21.5) adolescents, with moderate-to-severe disruption reported by 54 of them (20.3%; 95% CI, 15.6-25.6). Nasal symptoms were more common from October to February, with monthly precipitation significantly affecting the temporal variation (P = 0.003). Severe asthma (P < 0.01, adjusted odds ration [OR] 5.75; 95% CI, 3.79-8.72) was independently associated with allergic rhinitis, while sleeping on a rubber-mixed-coir mattress (adjusted OR 1.61; 95% CI, 0.95-2.74), and playing 4-6 times per week (adjusted OR 1.50; 95% CI 0.98-2.29) had higher odds for allergic rhinitis. Over a quarter of adolescents had current allergic rhinitis, and their symptom exacerbation followed a temporal pattern predicted by monthly precipitation. Severe asthma was an independent determinant of allergic rhinitis.

This study explores the efficacy of localized heat treatment as a method for controlling bed bug (Cimex lectularius L.) infestations. Experiments were carried out to determine the lethal temperature and time necessary to achieve mortality in bed bugs and their eggs. Various combinations of lethal temperatures and exposure times were applied. A temperature of 45&#xb0;C resulted in the highest mortality rates, establishing it as a promising pest control approach. The lethal temperatures (36&#xb0;C-49&#xb0;C) and times (20-100&#x2009;min) were optimized using response surface methodology with a central composite design. The study showed that maximum mortality of bed bugs and their eggs was achieved at 45&#xb0;C with a 60-min exposure time (100&#x2009;&#xb1;&#x2009;0%). Additionally, lethal temperature and time were evaluated for infested cracked wood and mattress surfaces. For these surfaces, a lethal temperature of 75&#xb0;C and an exposure time of 30&#x2009;min were identified. These findings highlight the potential of heat treatment as an effective pest management strategy, accelerating the elimination of this persistent pest from infested homes.

As the population ages, the need for palliative care among patients with non-cancer conditions has increased. Although the benefits of palliative care for non-cancer conditions are well established, integration of such care remains limited across many health systems. Taiwan's universal health system offers a unique opportunity to examine how hospital characteristics influence the delivery of non-cancer palliative care. We conducted a retrospective nationwide analysis of all hospitals providing palliative care through either dedicated palliative care units (PCUs) or palliative shared care (PSC) under Taiwan's National Health Insurance (2016-2020). Non-cancer patients were identified based on the absence of cancer-related diagnostic codes within the National Health Insurance (NHI) claims data. The proportion of these patients receiving palliative care per hospital year was calculated. Generalized Estimating Equations (GEE) were used to stratify the data by admission year and hospital characteristics, and to assess the associations between these hospital characteristics and the delivery of non-cancer palliative care. Values represent adjusted estimates from GEE models. Among 355 hospital-years of PCU care, the mean proportion of non-cancer patients was 18.8% and was significantly higher at the secondary-level (7.3%, p&#x2009;=&#x2009;0.019), community (13.5%, p&#x2009;=&#x2009;0.003), and rural (20.1%, p&#x2009;<&#x2009;0.001) hospitals, as well as those with more palliative care beds. In 699 hospital-years of PSC, the mean proportion of non-cancer patients was 39.7%, and it was significantly higher in hospitals without radiation oncology departments (18.1%, p&#x2009;<&#x2009;0.001) and with fewer acute care beds (p&#x2009;<&#x2009;0.05). In both models, the proportion of non-cancer patients steadily increased over time (p&#x2009;<&#x2009;0.05). Metropolitan tertiary medical centers with advanced cancer-care infrastructure have not yet accommodated a sufficient number of non-cancer patients relative to their capacity for providing palliative care. Meanwhile, rural areas as well as secondary-level and community hospitals have shown potential to deliver such care to a larger number of patients. These findings suggest that institutional size, function, and geographic location all influence access to non-cancer palliative care. They also indicate a policy implication: strengthening capacity in smaller and rural hospitals may help expand system-wide service coverage for non-cancer patients at a reasonable cost.

To provide national data on intensivist coverage and interprofessional team staffing in Canadian ICUs. Cross-sectional survey. All Canadian hospitals identified as potentially having an adult ICU. ICU nurse/physician leaders. None. We contacted ICU nurse/physician leadership by email. The questionnaire included questions about interprofessional ICU staffing, availability and roles. Questionnaires were administered from September 2024 to February 2025; data were cleaned and analyzed February to May 2025. We included responses from 137 unique adult ICUs in 123 hospitals (40.9% of 301 hospitals queried), representing all Canadian provinces and territories with ICUs. ICU size varied (median [interquartile range]: 14 beds [8, 20]); most were for mixed patient populations (123 [89.8%]) and had intensivist coverage (119 [86.9%]). Among units with intensivists, they were onsite 24&#x2009;hr/d in 28/119 (23.5%), and intensivists had simultaneous responsibilities outside the ICU in 47/119 (39.5%). Physicians-in-training were present on weekdays in 112/137 units (81.8%) and advanced practice providers (APPs) in 32/136 (23.5%). For mechanically ventilated patients, the nurse:patient ratio was most commonly 1:1 (66.7%). Respiratory therapists were available on weekdays in 133/137 (97.1%), clinical pharmacists in 123/136 (90.4%) and physical therapists in 126/134 (94.0%). Most Canadian adult ICUs were staffed by intensivists with less than 25% having onsite intensivist coverage 24&#x2009;hr/d. Physicians-in-training were present in the majority of ICUs, whereas APPs were uncommon. Nurses most commonly provided care for one mechanically ventilated patient each shift. These data establish contemporary staffing benchmarks to inform assessment of baseline ICU workforce needs and guide surge planning at local, provincial, and national levels. They also enable international comparisons and provide essential context for interpreting Canadian critical care research.

To evaluate the association between clinical and MRI characteristics and histological outcomes of MRI-guided vacuum-assisted biopsies (MVAB) performed in the lumpectomy bed after malignant breast-conserving surgery (BCT). This retrospective study analyzed all MVABs performed in malignant lumpectomy beds between 2016 and 2022, evaluating the relationship between demographic and imaging characteristics and pathological outcomes (benign vs. malignant) using appropriate statistical methods. Malignancy was diagnosed in 14 of 72 biopsies (19%), most commonly invasive ductal carcinoma (50%). Fat necrosis was the predominant benign finding (38%). On univariate analysis, benign outcomes were more frequent in younger patients (median 60 vs. 69&#xa0;years), those with prior radiation therapy (90% vs. 69%, P&#xa0;=&#xa0;0.048), lesions adjacent to a postoperative cavity (28% vs. 7%, P&#xa0;=&#xa0;0.1), and when coarse calcifications were present on mammography (43% vs. 0%, P&#xa0;=&#xa0;0.011). Benign results were also more common for biopsies performed within one year or beyond six years after lumpectomy (97%, P&#xa0;=&#xa0;0.087). No MRI morphological or kinetic features reliably distinguished benign from malignant lesions. MVAB of lumpectomy bed lesions yielded a 19% malignancy rate, with benign outcomes often associated with specific clinical and imaging features. Larger studies are warranted to validate these findings and refine patient selection.

Medical resource distribution in China exhibits marked spatial disparities, with hospital bed allocation demonstrating particularly pronounced regional inequalities. These imbalances may significantly impact healthcare accessibility and population health outcomes across different provinces. This study employed a comprehensive analytical framework to examine hospital bed distribution across 31 provinces in China in 2022. We first conducted descriptive statistics and spatial autocorrelation analysis to identify distribution patterns. Subsequently, multiple linear regression (MLR) and spatial error model (SEM) were applied to evaluate the factors categorized into six dimensions: economic development, population structure, environmental conditions, education level, existing healthcare resources, and transportation infrastructure. Finally, the Geodetector method was systematically implemented to quantify individual factor contributions and their interaction effects based on spatial stratified heterogeneity principles. Our analysis revealed three key findings: (1) Significant regional disparities existed in hospital beds per 1,000 population, with global spatial autocorrelation confirming strong clustering patterns. Local indicators of spatial association (LISA) identified high-high clusters in southwestern regions and low-low clusters in southeastern provinces; (2) Both MLR and SEM analyses indicated a negative correlation between sex ratio and bed availability, with SEM demonstrating superior goodness-of-fit by effectively addressing spatial autocorrelation; (3) Geodetector results showed GDP per capita served as the primary driver of bed distribution, revealing a threshold effect where bed demand concentrated in low-GDP regions. Notably, significant interaction effects that substantially magnified individual factor impacts, with the synergistic effect between disposable income per capita and sex ratio emerging as the most pronounced. This study reveals substantial spatial disparities in hospital bed distribution across China, highlighting the necessity of integrated regional policymaking that explicitly addresses multifactorial synergies to optimize equitable healthcare resource allocation.

To examine the differential predictors of turnover intention among registered nurses (RNs) and nursing assistants (NAs). High turnover among RNs and NAs challenges healthcare systems worldwide. Although factors influencing RN turnover have been widely studied, those affecting NAs remain underexplored. A cross-sectional survey was conducted between July and August 2024 with 386 participants (193 RNs and 193 NAs) from various healthcare settings. Data were collected on demographics, work-related characteristics, and study variables, including burnout (exhaustion and cynicism), emotional labor, job stress, resilience, stress response, and turnover intention. Multiple regression analyses were performed separately for each group to identify significant predictors. For RNs, exhaustion (&#x3b2; = 0.368, p <&#xa0;.001) was the strongest predictor of turnover intention, followed by stress response (&#x3b2; = 0.322, p < &#xa0;.001) and cynicism (&#x3b2; = 0.196, p = &#xa0;.005). For NAs, cynicism (&#x3b2; = 0.277, p < &#xa0;.001) and stress response (&#x3b2; = 0.244, p = &#xa0;.002) were the most influential factors. Other predictors for NAs included working in hospitals with fewer than 100 beds compared to those with over 500 beds (&#x3b2; = 0.180, p = &#xa0;.015), having a diploma versus a bachelor's degree (&#x3b2; = 0.142, p = &#xa0;.009), and shorter working experience (&#x3b2; = -0.138, p = &#xa0;.036). Turnover among RNs mainly arises from exhaustion related to heavy responsibility, whereas among NAs it reflects cynicism stemming from limited recognition and hierarchical inequities. To reduce turnover, interventions should address exhaustion in RNs and cynicism and stress responses in both RNs and NAs. Tailored, role-specific interventions are needed to address these differing occupational stressors and enhance workforce retention. Policies should prioritize reducing exhaustion among RNs through workload adjustment, adequate staffing, and addressing cynicism and stress among NAs, particularly novices in smaller hospitals, through mentoring, supportive leadership, and stress management.

Mitochondria and endothelial cells engage in bidirectional crosstalk to maintain vascular tone, barrier integrity, and inflammatory quiescence. In cardiometabolic diseases (CMDs), metabolic overload and chronic inflammatory cues disrupt endothelial mitochondrial bioenergetics, dynamics, and quality-control mechanisms. As protective systems weaken, redox imbalance and impaired nitric oxide signaling-further exacerbated by barrier dysfunction-trigger endothelial activation and loss of homeostasis. Clinical translation has lagged largely because endothelial responses vary across vascular beds and microenvironments, and most clinical trials fail to align patient selection or endpoints with mitochondrial mechanisms. This review addresses a major translational gap: how mitochondrial stress programs map onto context-specific endothelial phenotypes in human CMDs, and how this mapping can inform the selection of actionable therapeutic strategies. Indeed, this review integrates single-cell and spatial multi-omics data to link mitochondrial stress and metabolic remodeling to specific anatomical niches, transforming the broad notion of "endothelial dysfunction" into defined biological programs for biomarker selection and target discovery. Moreover, this review categorizes translational opportunities by the strength of human evidence. Near-term priorities include repurposed cardiometabolic drugs (e.g., sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1(GLP-1) receptor agonists) and circulating biomarkers for patient stratification or pharmacodynamic monitoring (e.g., growth differentiation factor 15 (GDF15), cell-free mitochondrial DNA (cf-mtDNA), endothelium-derived extracellular vesicles). In contrast, gene and cell therapies, as well as advanced delivery and regenerative platforms, remain at the preclinical stage and require stronger mechanistic validation, improved safety profiles, and scalable delivery systems before clinical evaluation. Thus, a key unmet need is for multicenter, mechanism-informed trials that integrate endothelial functional endpoints (e.g., flow-mediated dilation (FMD)/peripheral arterial tonometry (PAT) with mitochondrial-associated molecular readouts under harmonized protocols and standardized reference criteria to enhance reproducibility and cross-study comparability. Collectively, these insights establish mitochondrial-endothelial biology as an evidence-based entry point for precision vascular medicine in CMDs.

In recent years, growing attention to the social integration of persons with psychosocial disabilities into their local communities has intensified calls to shift Korea's hospital-centered mental health system toward a community-based model. Historically, the Korean mental health system has often been framed through the narrative of a "delayed transition," which suggests that the country is belatedly undergoing the deinstitutionalization experienced in Western societies during the 1960s and 1970s. However, this linear account fails to explain a crucial divergence: during the very decades when deinstitutionalization was being debated and implemented in several Western countries, Korea was rapidly expanding its psychiatric institutions and hospital beds, entrenching a long-term institutional regime. This article reexamines the 1960s through the 1980s as a critical juncture in the formation of Korea's mental health system by tracing the debates and strategic interactions among the state, the psychiatric profession, and civil society surrounding the enactment of the Mental Health Act. During the 1960s and 1970s, authoritarian regimes adopted a social defense framework that cast people with mental illness as potential threats, thereby legitimizing a system of confinement. The 1983 "prayer house" (gidowon) scandal, however, publicly exposed the realities of institutionalization and briefly opened a window for communitybased alternatives within the psychiatric profession. The Korean Neuropsychiatric Association adopted community mental health as its official orientation, and in the mid-1980s a community mental health project was carried out on Ganghwa Island. Yet this opening was foreclosed by a convergence of countervailing forces: As the legislative process leading to the 1985 Mental Health Act became structured around a dichotomy between psychiatric nursing homes and hospitals, the psychiatric profession pursued a strategy of transition "from facilities to hospitals," thereby consolidating an admission-centered system. This strategy aligned with state interests in expanding hospital beds for purposes of social defense while simultaneously curtailing public welfare expenditure. At the same time, the expansion of health insurance and medical aid programs in the 1980s increased service utilization, creating economic incentives for further growth in psychiatric beds. Meanwhile, civil society's human rights discourse emerged as an extension of resistance to the authoritarian regime and focused on procedural safeguards against involuntary hospitalization; however, it did not lead to a fundamental reconfiguration of the confinement-centered system itself. Rather than reducing the formation of the Korean mental health system to a problem of developmental delay-often framed as a "fifty-year gap with the West"-this study highlights the multiple possibilities and alternative trajectories embedded in its history and invites a historically grounded rethinking of the current Korean mental health system.

Seagrass beds are critical blue carbon ecosystems in the Yellow Sea and Bohai Sea currently facing severe degradation. Understanding the linkage between their distribution dynamics and carbon sink function is urgently needed. In this study, we developed an integrated assessment framework coupling ensemble species distribution models (eSDMs) with the InVEST model, using annual carbon accumulation rates for dynamic carbon accounting rather than instantaneous equilibrium to quantitatively evaluate seagrass habitats and carbon storage. Using carbon density data, we analyzed spatio-temporal patterns of suitable habitats and blue carbon stocks. Results indicate: (1) The ensemble model showed excellent predictive performance (TSS&#xa0;>&#xa0;0.90); (2) Human activity intensity was the dominant driver of seagrass distribution (24% contribution), challenging conventional temperature-salinity paradigms; (3) Suitable habitats concentrate along Liaoning, Hebei, and Shandong coasts; (4) Carbon density displays a latitudinal gradient at 50-100&#xa0;Mg C&#xb7;ha&#x207b;1 and&#xa0;>&#xa0;100&#xa0;Mg C&#xb7;ha&#x207b;1; (5) Baseline blue carbon storage reached 7.18&#xa0;&#xd7;&#xa0;10&#x2077; Mg C in high&#x2011;suitability and 9.36&#xa0;&#xd7;&#xa0;10&#x2077; Mg C in moderate&#x2011;suitability habitats, with future storage estimated using temporally explicit accumulation rates. Future projections show the high-emission pathway (SSP585) exacerbating habitat fragmentation and undermining carbon sink stability, while the low-emission pathway (SSP126) better maintains stability. Critically, carbon loss from degradation far exceeds gains from new habitats, emphasizing the priority of protecting existing carbon stocks. This study achieves raster-scale quantification of regional seagrass blue carbon sinks. Our eSDM-InVEST framework provides a scientific basis for temperate seagrass conservation and blue carbon management, supporting carbon neutrality and biodiversity conservation goals.

Endothelial cell functions are critical for cardiovascular health, and endothelial cell dysfunction underlies the pathology of many cardiovascular diseases. This review summarises the major aspects of endothelial physiology, which together contribute importantly to vascular homeostasis. These include regulation of haemostasis and thrombosis, vascular tone and permeability, lipid transport into the vessel wall, and leukocyte traffic from blood to tissue. Key examples are presented illustrating where endothelial cell dysfunction drives pathology and disease. Signalling pathways that are targets for current or future drug treatments for cardiovascular disease are highlighted. Control of endothelial cell phenotype is described in relation to vasculogenesis, angiogenesis, and other aspects of endothelial cell plasticity. This provides an overall framework linking endothelial physiology and pathology. By virtue of its pan-organ localisation endothelial phenotype is differentiated in multiple ways between different vascular beds due to its responses to organ-specific stimuli, which can change in disease. By virtue of its exposure to blood, endothelial phenotype is further maintained or modulated by prevailing and changing physical and chemical signals.

The glycocalyx is a carbohydrate-rich layer formed by glycoproteins, glycolipids, proteoglycans, and glycosaminoglycans at the outer cell surface. In cancer, this layer is not a passive coating. Its thickness, composition, charge, and nanoscale organization are altered by oncogenic signaling, dysregulated glycosyltransferases, protease-mediated shedding, and reciprocal interactions with stromal and immune cells. These changes affect how tumor cells sense force, bind the extracellular matrix, cluster receptors, evade immune surveillance, survive in circulation, and arrest at distant vascular beds. Studies in the past decade have linked a bulky glycocalyx to integrin activation and growth factor signaling, identified hyaluronan-CD44 and selectin-dependent steps in metastatic dissemination, and placed the sialoglycan-Siglec axis among the immune suppressive circuits operating in the tumor microenvironment. Meanwhile, pathology, imaging, glycoproteomics, and liquid-biopsy studies have started to define glycocalyx-derived biomarkers with diagnostic and prognostic value, especially in hepatocellular carcinoma, pancreatic cancer, breast cancer, and hematologic malignancies. This review summarizes the structure of the cancer glycocalyx, the molecular programs that remodel it, and the consequences of these changes for tumor progression. It also discusses analytical approaches, biomarker development, and therapeutic strategies aimed at mucins, proteoglycans, glycosyltransferases, hyaluronan signaling, heparanase, and tumor-associated sialoglycans. A central theme is that the glycocalyx should be viewed as an integrated biophysical and signaling interface, and its clinical value will depend on spatially resolved, context-specific analysis rather than single-marker measurements alone.

Desquamating or blistering skin conditions may be referred to burns and plastic surgeons owing to the morphological similarity to burn injuries, given an increasing shortage of dermatology inpatient beds within the context of NHS care.&#xa0;Desquamating skin conditions, similar to burn injuries, carry the potential to be severe, debilitating and potentially fatal; however, they present more complexity owing to their underlying aetiologies. These conditions may present with similar physiological challenges, dressing requirements and need for extensive multidisciplinary input as burn injuries, and there is an increasing demand for burns and plastic surgery involvement in their management.&#xa0;In this review, the following blistering skin diseases (BSDs) are discussed: Bullous erythema multiforme, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TENS), pyoderma gangrenosum, impetigo, Staphylococcal scalded skin syndrome, erythroderma, pemphigus vulgaris (PV), bullous lupus, pemphigus paraneoplastica, acute generalised exanthematous pustulosis (AGEP), dermatitis artefacta, linear IgA bullous dermatosis and adverse drug reaction.&#xa0;All patients should undergo a thorough head to toe skin examination, including the mucous membranes, their current and recent medications should be reviewed, and considered for discontinuation if clinically safe. A full panel of blood investigations, including an auto-antibody screen, should be performed to identify the underlying cause and multiorgan disfunction. A single investigation of the greatest diagnostic value is an incision or punch biopsy, which should be sent for histology and immunofluorescence analyses. Antimicrobials and steroids should be initiated by dermatology after review. General care of these patients includes treatment of the underlying cause, management of acute deterioration and symptoms, and appropriate wound care.

Patients with acute-on-chronic liver failure (ACLF) are highly vulnerable to invasive fungal infections often requiring renal replacement therapy (RRT). The pharmacokinetics (PK) of isavuconazole, an antifungal against Aspergillus spp. and Mucorales, may be altered in ACLF due to effects of altered distribution and clearance. We investigated the impact of ACLF on isavuconazole PK in critically ill patients undergoing continuous RRT due to a paucity of data in this patient population and aimed to inform decisions about dosing. This prospective observational cohort study was conducted at the University Medical Center Hamburg-Eppendorf across twelve intensive care units with 140 beds. We included critically ill adults receiving isavuconazole and continuous RRT. Patients <18 years or with extracorporeal circuits other than RRT were excluded. Plasma, ultrafiltrate, and pre-/postfilter blood samples were analyzed using high-performance liquid chromatography. Key areas of interest were the effect of ACLF and continuous RRT on isavuconazole pharmacokinetics, particularly on clearance. Population PK modeling was performed using, inter alia, the integrated dialysis pharmacometric model in NONMEM&#xae;. Probability of target attainment (PTA) for established PK/PD thresholds developed in mice (50% or 90% survival) was assessed using Monte Carlo simulations. Thirteen patients were enrolled, including 4 with ACLF. A two-compartment model best described the data. Median clearance was similar between ACLF (4.2 L/h) and non-liver failure (4.8 L/h) groups (p = 0.92). Dialysis clearance was negligible (<1% of dose). The 50% efficacy target (AUC0-24h/MIC = 24.7) was achieved in 12/13 patients (92%), and the 90% target (AUC0-24h/MIC = 33.4) in 8/13 patients (62%). Simulations indicated suboptimal PTA at the Aspergillus fumigatus breakpoint of 1 mg/L. Considerable interindividual variability on clearance, particularly in ACLF, led to both sub- and supratherapeutic exposures. ACLF did not significantly alter isavuconazole clearance during RRT. However, high PK variability and frequent subtherapeutic exposures support routine therapeutic drug monitoring in critically ill patients.