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Ileal ureter replacement is generally reserved for extensive ureteral defects not amenable to conventional reconstructive options. We report a challenging case of radiation-induced long-segment ureteral stricture in a 56-year-old woman with a history of carcinoma of the anal canal treated with abdominoperineal resection, sigmoid colostomy, chemotherapy, and radiotherapy. She subsequently developed bilateral ureteric obstruction with a small-capacity bladder. Right-sided stenting was feasible, but left-sided stenting failed, requiring percutaneous nephrostomy. She underwent an exploratory laparotomy with left ileal ureter replacement after endourological management of the right ureter. Intraoperatively, dense pelvic fibrosis, prior surgical scarring, bowel adhesions, intrarenal pelvis, and long-segment left ureteric obliteration made reconstruction technically demanding. Despite these challenges, the patient tolerated the procedure well, serum creatinine showed a declining postoperative trend, and recovery was uneventful. This case highlights the utility of ileal ureter replacement as a salvage option in selected patients with complex ureteral loss in hostile pelvic anatomy. RésuméLe remplacement urétéral par iléon est généralement réservé aux pertes urétérales étendues non accessibles aux options reconstructives conventionnelles. Nous rapportons un cas difficile de sténose urétérale longue d’origine radique chez une femme de 56 ans ayant des antécédents de carcinome du canal anal traité par résection abdominopérinéale, colostomie sigmoïdienne, chimiothérapie et radiothérapie. Elle a ensuite développé une obstruction urétérale bilatérale avec une vessie de petite capacité. La pose d’une endoprothèse du côté droit a été possible, mais celle du côté gauche a échoué, nécessitant une néphrostomie percutanée. Elle a bénéficié d’une laparotomie exploratrice avec remplacement de l’uretère gauche par un segment iléal, après prise en charge endo-urologique de l’uretère droit. En peropératoire, une fibrose pelvienne dense, des cicatrices chirurgicales antérieures, des adhérences intestinales, un bassinet intrarénal et une oblitération longue de l’uretère gauche ont rendu la reconstruction techniquement exigeante. Malgré ces difficultés, la patiente a bien toléré l’intervention, la créatininémie a montré une tendance à la baisse en postopératoire, et les suites ont été simples. Ce cas souligne l’utilité du remplacement urétéral par iléon comme option de sauvetage chez des patients sélectionnés présentant une perte urétérale complexe dans une anatomie pelvienne hostile.

This study investigated the relationships between ambivalent sexism, social roles, and body compassion in Albanian and Italian women. The participants were 251 Albanian and 280 Italian women who completed validated measures assessing hostile and benevolent sexism, social role transcendence, link to social roles, and three subdimensions of body compassion (defusion, common humanity, and acceptance). Path analyses indicated excellent model fit across samples. In Albanian women, hostile sexism negatively predicted social role transcendence and positively predicted a link to social roles, both of which were associated with lower body compassion. Benevolent sexism was positively associated with social role transcendence, which in turn was related to higher body compassion. In contrast, Italian women showed a different pattern: benevolent sexism positively predicted a link to social roles, while social role transcendence and link to social roles were both negatively related to defusion. Age positively predicted defusion and acceptance, highlighting a possible protective effect. Explained variance was higher in the Italian sample, particularly for the link to social roles. Overall, the findings suggest that the pattern of associations between sexist attitudes, social role attitudes, and body compassion was not identical across the two samples. These findings should be interpreted as exploratory evidence from two distinct sociocultural contexts rather than as formal cross-cultural comparisons.

The General Medical Council states that doctors should 'understand and have experience of the principles and methods of improvement, including audit' [1]. Medical students can face barriers including lack of opportunity, hostile environments and inadequate training, resulting in lower participation in such projects [2,3]. At Northwick Park Hospital, London Northwest University Healthcare NHS Trust, we were able to support students to effectively contribute to audit and quality assurance, utilising experiential learning theory, with knowledge creation through the process of experience [4]. In this paper, we provide a narrative report of their perspectives on participating in the project and learning.

Spinal cord injury (SCI) precipitates a multiphasic secondary injury cascade that establishes a hostile, inhibitory microenvironment, rendering the condition refractory to conventional surgical stabilization and rehabilitation. While cell-based therapies offer promise for neural reconstruction, their clinical translation is impeded by protocol heterogeneity and fragmented safety data. To address this, we mapped clinical trials for SCI to quantify patient demographic parameters, identify lineage-specific adverse-event patterns, evaluate objective motor and sensory efficacy outcomes, and analyze methodological trial designs to formulate concrete structural recommendations for future advanced-phase trials. We analyzed clinical trials from the Web of Science Core Collection (SCIE and ESCI) published since 2005. The dataset comprised 116 eligible studies involving patients with SCI receiving cellular therapies with reported safety outcomes. We employed a dual-method approach combining manual extraction of clinical characteristics (demographics, interventions, adverse events, efficacy outcomes) with quantitative data analysis. Statistical associations between therapeutic variables (cell type, route, dosage) and safety profiles were evaluated using Fisher's exact test. The clinical landscape is predominantly defined by early-phase (Phase 1: 59.5%), single-arm investigations (63.8%) utilizing autologous bone marrow-derived cells. Reflecting a cautious paradigm to minimize severe complications, patient selection frequently targeted the hemodynamically stable chronic phase (58.3%) and thoracic SCI (21.6%). Safety analyses revealed lineage-specific profiles: mesenchymal stromal cells were significantly associated with transient fever (P &#x2009;=&#x2009;0.038), whereas intrathecal administration correlated with procedural symptoms such as headache (P <&#x2009;0.001). The observation of higher systemic adverse event rates in low-dose cohorts was likely confounded by the mandatory concurrent immunosuppressive regimens required for specific allogeneic lineages, rather than the absolute cell dose. Regarding therapeutic efficacy, outcomes were critically influenced by the chronological phase of injury. Patients treated in the acute or subacute phases exhibited higher rates of neurological improvement, though distinguishing this from spontaneous recovery remains challenging, whereas chronic phase interventions demonstrated more limited primary sensorimotor gains. Additionally, intrathecal administration showed an advantage in preserving sensory pathways due to minimized structural disruption, while dose requirements could not be generalized and varied fundamentally based on specific cellular mechanisms of action. While the baseline safety of cellular transplantation for spinal cord injury is established, clinical translation remains hindered by methodological heterogeneity, imprecise patient stratification, and a reliance on single-arm trial designs. To navigate this translational bottleneck, future investigations should adopt multi-tiered methodological frameworks. First, study designs should transition toward controlled protocols, utilizing crossover designs for chronic cohorts and matched historical or synthetic controls for acute and subacute phases. Concurrently, patient selection must evolve from broad clinical grading to advanced stratification. Integrating biomarkers, electrophysiology, and imaging to objectively quantify tissue sparing can better identify responsive subgroups, thereby improving trial efficiency and accelerating clinical translation. Beyond cohort refinement, intervention parameters, specifically dosage and delivery routes, should be individualized according to cell lineage, as adverse events associate more with intrinsic cellular biology and procedural invasiveness. Furthermore, isolating the true therapeutic effect requires the standardization and reporting of confounding variables, such as immunosuppressive regimens and physical rehabilitation. Finally, by separating shorter-term efficacy measurements from long-term safety registries, the field can facilitate a more reliable and objective clinical translation.

Radiation-induced cardiovascular disease may appear decades after cancer therapy and can involve multiple vascular, valvular, myocardial, and conduction structures of the heart. Management is particularly challenging when prior irradiation results in a hostile chest environment and impaired wound healing. A 31-year-old woman with a history of childhood right forearm rhabdomyosarcoma treated with resection, chemotherapy, and radiotherapy presented with recurrent syncope. Computed tomography angiography revealed asymmetric growth of the right-sided arteries, leading to a transient ischaemic attack. Further cardiovascular evaluation revealed multiple concomitant cardiovascular disorders, including valvular heart disease, high-grade atrioventricular block, bradycardia, and heart failure. Permanent pacemaker implantation and right-to-left axillary artery bypass prevented further syncopal episodes; however, heart failure continued to worsen. Two years later, she was hospitalized with severe heart failure and dyspnoea, and echocardiography revealed aortomitral continuity calcification and elevated filling pressure. She subsequently underwent the Bentall procedure, tricuspid valve replacement, and coronary artery bypass grafting for advanced coronary stenosis. However, her postoperative course was complicated by pleural effusion and haemoptysis, and she eventually died of multiorgan dysfunction. This case illustrates the late cardiovascular effects of radiation therapy. Radiation-induced endothelial injury, fibrosis, and maladaptive wound-healing responses may contribute to delayed cardiovascular damage and poor postoperative recovery. In such patients, surgical decision-making should be multidisciplinary, and long-term follow-up is essential.

Percutaneous transaxillary access is an established alternative to transfemoral large-bore arterial access for transcatheter structural heart interventions and mechanical circulatory support (MCS). Although useful for overcoming hostile iliofemoral anatomy and providing prolonged support and patient mobilization in case of MCS, the axillary/subclavian territory poses distinct technical and anatomical challenges that demand meticulous pre-procedural imaging, patient selection, accurate puncture under ultrasound and angiographic guidance, preservation of bailout access, and familiarity with suture-based and balloon-assisted closure strategies. This review provides a contemporary practical framework for percutaneous transaxillary access, summarizing the available clinical evidence, technical aspects of puncture and closure, complication management, and procedural tips to improve safety and reproducibility.

This article offers a metatheoretical analysis of contemporary research on sexology from and beyond the late nineteenth century. We draw attention to the use of (pseudo)medical photography in this scholarship and the diverse methods developed by researchers to engage with this sensitive material-from the black bar, to description in lieu of reproduction, to affective speculation. Our article equips queer medical humanities researchers with a critical account of the modes of 'looking' we employ in our study of queer history. We demonstrate how&#xa0;the sexological visual archive has become increasingly central to queer medical humanities scholarship that interrogates the medical violences at the heart of queer histories. Our article dwells not on this photographic archive but, rather, on a meta-archive of contemporary critical methods of looking at, examining, and showing these photographs. Through this meta-archive, we ask: How is the fraught nature of sexological photographs registered, ignored, or challenged by researchers, be it in terms of their often disturbing content or the sometimes hostile conditions of their production? How do we 'look' at and 'show' these photographs ethically-or can we? What risks (to the historical patient, to the photograph, and to each other) are being negotiated in these encounters? Our article attempts to respond to these questions by recognizing the multitude of our visual research practices in sexology studies. It brings together methods both ubiquitous and exceptional to point to a research future being built in the present: one that seeks new and more ethical ways of looking at, for, and with the queer patient.

Chimeric antigen receptor (CAR)-based cell therapy holds great promise for the treatment of both hematological malignancies and solid tumors. However, primary and acquired resistance to CAR-based cell therapy remains a key obstacle to achieving effective and durable immunotherapy responses. Unlike small molecules or antibodies, CAR-engineered immune cells offer unique opportunities to design therapeutic agents, thereby enabling the improved products with potential to overcome multiple therapy resistance mechanisms. Therefore, elucidating the mechanisms of resistance to CAR-based cell therapy is crucial for the development of the next-generation CAR-based cell therapy. In this review, we outline the biological rationale of CAR-T, CAR-natural killer (NK), and CAR-macrophages, as well as other emerging CAR-based cell therapies. We focus on the mechanisms of resistance to CAR-based cell therapy, involving structural and functional defects of CAR products, tumor-intrinsic factors, and susceptibility of CAR-engineered cells to the hostile tumor microenvironment. We discuss key strategies to overcome multiple resistance mechanisms, such as targeting multiple antigens, optimizing CAR design and function, modifying the immunosuppressive tumor microenvironment, and developing combination treatment strategies. By systematically dissecting these multifaceted challenges, this review will provide insights for optimizing CAR-based cell therapy to overcome resistance and improve treatment efficacy.

Background: Performing and maintaining high-altitude cardiopulmonary resuscitation (CPR) could pose a significant physical challenge for rescuers. The objective of this study is to analyse the effects of reducing the oxygen fraction at altitudes of 3000 m and 5000 m above sea level (asl), with and without conditioning to hypoxia, on the quality of resuscitation performed in adults. Methods: An analytical before-after study in which 56 students with a Degree in Nursing between 18 and 30 years old perform 10 min of resuscitation on a mannequin at different altitudes (670, 3000 and 5000 m asl) will be carried out. Subsequently completing an intermittent hypoxia conditioning programme, the participants will perform the resuscitation manoeuvres at previously referenced altitudes. Sociodemographics, CPR quality, self-perception CPR, adequate anthropometric data, physical condition, blood tests, oxygenation in muscular tissue, biceps, brachii and erector spinae, subjective perception of effort, anxiety levels and quality of resuscitation will be measured in all participants at different altitudes. Discussion: Although CPR is a submaximal effort manoeuvre, it is subject to being performed by anyone without motor disabilities. Our study will also provide evidence as to whether this characteristic continues to hold true in a hostile environment such as medium and high altitudes. Our study aims to demonstrate that the improvement in physical performance and recovery capacity induced by intermittent hypoxia conditioning programmes increases the quality of CPR in prolonged cardiac arrests and in adverse conditions, such as at high altitudes. The proposed study will contribute as a novelty to the estimation of the influence of high altitudes and conditioning on performing basic CPR manoeuvres. If the hypothesis turns out to be true, recommendations about the practice of moderate-intensity physical exercise could be incorporated into the CPR guidelines as one of the important aspects in the training of rescuers to conduct CPR.

To quantify and characterize aggression and violence against nurses, identify associated clinical characteristics, evaluate measures in response, and explore predictors of recurrent incidents in the ICU. Retrospective single-center study. Incidence and characteristics of aggression and violence against ICU nurses were the primary outcomes. Aggression was defined as hostile behavior or resistance to care without intent to harm. Violence comprised verbal, physical, or sexual acts to threaten or inflict harm. Secondary outcomes included risk factors for recurrent incidents, defined as multiple episodes of aggression/violence separated by greater than or equal to 24 hours. Multivariable analyses were performed to identify potential independent associations. Data were collected from 2023 to 2024 at the tertiary medical-surgical ICU with up to 35 beds at the University Hospital Basel. Nursing operations followed a three-shift system: day (07:00-15:00), late (15:00-23:00), and night (23:30-07:00). Clinical reports from ICU nurses were screened. None. During 2190 shifts, 308 aggressive or violence incidents (14% of shifts) were reported. Most occurred during late (37%) or night (34%) shifts; 75% involved violence. Violent incidents were combined in nature (79% physical, 43% verbal, and 3% sexual). Patients were mainly involved (97%) and predominantly male (71%; median age 67; 90% emergency admissions). Psychiatric comorbidities, drug, and alcohol abuse were found in 20-33%. Recurrent aggression/violence occurred in 27%, predicted by longer ICU stay (adjusted odds ratio [OR] = 1.05/every additional hour), aggression as the first incident (adjusted OR = 6.9), and verbal violence as the first incident (adjusted OR = 4.3). Nurses (89%, two-thirds female, median 7 yr' experience) rarely documented harm (1.3%), but patients were reported to suffer complications in 60% of incidents, mainly from oversedation and physical harm from restraints. Violence in the ICU is frequent and almost always caused by patients. Recurring violence was independently associated with longer ICU stay, initial aggression, and verbal violence. Staff harm was rare, but incidents were frequently associated with complications in patients.

Natural killer (NK) cells represent a promising tool for cancer immunotherapy; however, their efficacy against solid tumors is severely limited by the hostile tumor microenvironment (TME). This review provides a comprehensive overview of the physical, molecular, and metabolic barriers that drive NK cell dysfunction and immune evasion, emphasizing the physical challenge posed by extracellular matrix (ECM) density, which restricts infiltration. Beyond structural barriers, we examine the role of immunosuppressive cytokines (e.g., TGF-&#x3b2;) and immune checkpoint upregulation, both of which directly inhibit NK cell activation. Furthermore, NK cell signaling and cytotoxicity are profoundly affected by metabolic stressors such as hypoxia and acidosis, which act synergistically with the accumulation of immunosuppressive metabolites, including adenosine. These factors impair antitumor activity through multiple mechanisms, particularly the shedding of activating ligands. To investigate these complex interactions, we evaluate the advantages and disadvantages of different three-dimensional (3D) preclinical platforms, including tumor spheroids and Organ-on-Chip technologies, highlighting their distinct characteristics. Rather than advocating for a single technology, we emphasize that each model offers unique advantages for studying specific physical, chemical, and cellular components of the TME. Ultimately, leveraging the capabilities of these advanced 3D platforms is essential for deciphering microenvironmental barriers and unlocking the full therapeutic potential of NK cells against solid tumors.

The malignant progression of cancer depends not only on oncogenic driver mutations but also on the adaptive rewiring of organelle stress responses that sustain cell survival under hostile tumor microenvironment (TME) conditions. Among these, the hijacking of lysosomal homeostasis has emerged as a critical vulnerability and a driver of therapeutic resistance. Glycoprotein nonmetastatic B (GPNMB), a highly glycosylated type I transmembrane protein predominantly localized to lysosomes, is robustly upregulated across multiple cancer types as an adaptive responder to lysosomal stress. In tumors, GPNMB drives proliferation, metastasis, and immune evasion by engaging multiple oncogenic signaling cascades, while simultaneously shaping an immunosuppressive TME through CD8+ T cell exhaustion and cytokine networks. Clinically, high GPNMB expression correlates with poor prognosis in breast cancer, hepatocellular carcinoma (HCC), lung cancer, glioblastoma (GBM), gastric cancer (GC), and osteosarcoma (OS), positioning it as both a prognostic biomarker and a therapeutic target. The GPNMB-directed antibody-drug conjugate (ADC) glembatumumab vedotin (GV) has demonstrated clinical activity in triple-negative breast cancer (TNBC) and melanoma, yet its efficacy remains constrained by target expression heterogeneity, the reliance on lysosomal trafficking for payload release, and dose-limiting toxicities. Emerging strategies, including bispecific antibodies, immunotoxins, and senolytic elimination of GPNMB-high damaged cells, are expanding the therapeutic landscape. This review dissects the molecular mechanisms, pathological roles, and evolving clinical applications of GPNMB in cancer, highlighting current challenges and future directions for precision oncology.

Helicobacter pylori possesses an unusually high number of restriction-modification (R-M) systems relative to its small genome, contributing to a methylome increasingly implicated in bacterial gene regulation. In this study, we analyzed the methylomes of two mutant strains of H. pylori 26695: &#x2206;rdxA (control) and &#x2206;rdxA/&#x2206;arsS. Each mutant was cultivated under neutral (pH 7) and acidic (pH 5) growth conditions. We identified one conspicuous hypomethylated region of 21 kBp possessing 21 annotated genes across each methylome. Notably, over 600 protein coding regions and 10 different promoters displayed differential methylation between pH conditions, including several virulence factors. The vacA gene, encoding the Vacuolating Cytotoxin A, exhibited eight differentially methylated positions between pH 7 and pH 5 within the H. pylori 26695 control mutant methylome, potentially contributing to its previously documented 32-fold down regulation of mRNA in acidic environments. pH-dependent methylation changes were widespread within the cag pathogenicity island, genes encoding cell envelope proteins including adhesin-encoding sabA, babA, and hopQ, and numerous flagellar-associated genes. These results reveal the plasticity of the H. pylori methylome and suggest that DNA methylation is responsive to environmental pH in both ArsRS-dependent and independent manners. Methylome dynamics may serve as an important layer of gene regulation in acclimation to hostile gastric environments and promote persistent infection.

Endometriosis (EMs) is an estrogen-dependent chronic inflammatory gynecological disease characterized by ectopic growth of endometrial tissues, leading to dysmenorrhea, pelvic pain, and infertility. Although the retrograde menstruation theory clarifies the dissemination of endometrial fragments to ectopic sites, the mechanisms behind the survival of ectopic lesions and their immune evasion in hostile microenvironments remain unclear. Endometrial stromal cells (ESCs) are chronically exposed to a microenvironment of hypoxia, nutrient deprivation and oxidative stress, and this energy stress state drives the ESCs to develop adaptive metabolic reprogramming. Through remodeling glucose, lipid, and amino acid metabolic pathways, ESCs not only fulfill their own proliferative requirements but also utilize metabolites as signaling mediators to modulate immune cell functions. This review elaborates on the characteristics of energy stress-driven metabolic reprogramming in EMs, deciphers its mechanisms underlying immune evasion, and discusses the therapeutic potential of combined metabolic-immune intervention strategies.

Chronic diabetic wounds, including diabetic foot ulcers, present significant clinical challenges due to persistent inflammation, oxidative stress, impaired angiogenesis, infection, and defective tissue regeneration. Central to these pathological features is macrophage dysfunction, wherein immune cells become locked in a pro-inflammatory state that impedes the transition to reparative phenotypes necessary for resolution of inflammation and tissue repair. Nanomedicine-based strategies have emerged as promising approaches to restore macrophage plasticity and promote regenerative healing. Multifunctional nanotherapeutic platforms including antioxidant nanozymes, extracellular vesicle- and exosome-based delivery systems, oxygen-generating and gasotransmitter-releasing materials, infection-controlling nanoparticles, plant-derived bioactive nanomedicines, and advanced hydrogel or scaffold-based carriers have demonstrated the ability to modulate oxidative stress, mitochondrial function, inflammasome activation, immunometabolism, efferocytosis, and intercellular communication. By reprogramming macrophages toward pro-regenerative states, these interventions facilitate angiogenesis, extracellular matrix remodeling, and epithelial restoration, effectively converting a hostile wound microenvironment into a tissue-repair permissive niche. This review highlights recent advances in nanoparticle-driven macrophage polarization for diabetic wound healing, detailing the molecular mechanisms, therapeutic platforms, and regenerative outcomes, while also discussing translational challenges including biological complexity, biosafety, manufacturing, and preclinical model limitations. Future perspectives emphasize precision immunomodulation, biomarker-guided patient stratification, and clinically translatable nanomedicine strategies to optimize chronic wound repair.

Infected wound healing is hindered by a hostile microenvironment and limited active treatment options. While current hydrogels offer partial benefits, they struggle to simultaneously modulate the wound environment and physically close wounds. We design a smart hydrogel by integrating two peptide coiled-coil motifs: an antimicrobial tetramer and a stimuli-responsive dimer. Covalent polymerization of the antimicrobial tetramers, unfolded monopeptides derived from the coiled-coil dimer, and star-shaped polyethylene glycol (PEG) yields an intrinsically antimicrobial hydrogel in situ at the wound site. When treated by Zn2+, the monopeptides fold and assemble into coiled-coil dimers within the matrix, triggering rapid, controllable hydrogel contraction that actively pulls wound edges together. Both coiled-coils also endow the hydrogel with intrinsic antioxidant activity. Furthermore, these coiled-coils function as reversible, sacrificial noncovalent crosslinks that effectively dissipate mechanical energy, synergistically enhancing the hydrogel's toughness and resistance to swelling. Collectively, this intrinsically multifunctional hydrogel accelerates infected wound healing without the need for dressing changes and through a coordinated cascade of actions: on-demand dynamic wound contraction, bacterial eradication, reactive oxygen species scavenging, inflammation suppression, and promotion of re-epithelialization. This integrated design represents a significant advance toward smart, bioactive dressings capable of actively orchestrating multiple phases of the wound healing process.

Diabetic bone defects are difficult to repair because chronic hyperglycemia creates a hostile inflammatory and oxidative microenvironment that impairs osteogenesis, enhances osteoclast activity and compromises vascular ingrowth. Plant-derived extracellular vesicle-like nanoparticles can transfer source-related biological signals to mammalian cells and are attractive for immune regulation, but native vesicles usually lack defined osteogenic instruction for diabetic bone regeneration. Here, we engineered Coptis chinensis-derived extracellular vesicle-like nanoparticles (Cc-EVs) with a BMP-2-derived osteogenic peptide (OP) through copper-free click chemistry, generating OP-Cc-EVs that combine the immunoregulatory potential of Cc-EVs with osteogenic peptide surface presentation. As a vesicle-only treatment in vitro, OP-Cc-EVs shifted inflammatory macrophages from a pro-inflammatory M1 phenotype toward a reparative M2 phenotype, with transcriptomic changes consistent with inflammatory resolution and repair-oriented tissue regulation. This macrophage response enhanced mesenchymal stromal cell osteogenesis, suppressed osteoclast formation and actin-ring maturation, and generated paracrine signals that promoted endothelial migration and tube formation. For in vivo application, GelMA hydrogel was used as a local carrier to retain OP-Cc-EVs within the diabetic bone-defect site. In a diabetic femoral condyle defect model, local delivery of OP-Cc-EVs promoted vascularized bone regeneration while reducing inflammatory and osteoclastic signals. These findings establish OP-Cc-EVs as a chemically engineered plant-derived vesicle platform with translational potential for immuno-osteogenic repair of diabetic bone defects.