Understanding how subtle structural changes control electronic communication is central to mimicking the function of natural photosynthetic special pairs. Here, we present a combined experimental and DFT study of ethane- and ethene-bridged cofacial heterobimetallic Ag(II)Cu(II)-octaethylporphyrin dimers as synthetic analogues of chlorophyll special pairs. X-ray crystallography reveals clear geometric differences: the ethane-bridged dimer adopts a more slipped arrangement with greater lateral displacement and longer Cu···Ag distance, whereas the ethene-bridged analogue is more cofacial. These variations strongly influence electronic structure and redox properties. The ethane-bridged system shows a lower-energy HOMO and reduced oxidation potentials. Upon one-electron oxidation, both dimers undergo Ag-centered oxidation to form Ag(III), accompanied by significant HOMO-LUMO gap reduction and enhanced cofaciality. Differences become pronounced during the second oxidation step. The ethane-bridged dimer undergoes Cu(II)-porphyrin-centered oxidation to yield Ag(III)-Cu(II)(por•+), producing a triplet state with coupling between Cu(II) and a π-cation radical. In contrast, the ethene-bridged analogue oxidizes exclusively at the Ag(III)-porphyrin, maintaining a closed-shell Cu(II) center. These distinct pathways are reflected in their NIR absorptions (1006 vs. 876 nm) and calculated SOMO-LUMO gaps (0.49 vs. 0.28 eV). Overall, minor bridge modifications significantly tune coupling, redox localization, and spin states in these systems.
Oropharyngeal dysphagia is prevalent in hospitalized geriatric and neurological populations and constitutes a major driver of disease-related malnutrition. Conventional texture-modified diets frequently rely on diluting solid foods with liquid agents to achieve safe swallowing consistency, a process that reduces caloric and protein density per gram and creates a so-called volume paradox, whereby large meal volumes deliver inadequate nutrients. This retrospective observational study, conducted at the Fondazione Policlinico Gemelli IRCCS in Rome, compared nutritional intake in 208 hospitalized dysphagic adults receiving either a traditional homogenized standard diet (THSD; n = 58) or a density-enriched dysphagia-prepared diet (DPD; n = 150). Following propensity-score matching, total daily energy intake was significantly higher with the DPD compared to the THSD (1024 ± 307 kcal vs. 523 ± 161 kcal; p < 0.0001), as was total protein intake (37.3 ± 12.9 g vs. 26.2 ± 12.7 g; p < 0.0001). Clinically meaningful differences were observed across all meal components, including a more than twofold advantage in breakfast protein content (6.6 ± 1.7 g vs. 3.0 ± 1.5 g). Despite these improvements, total energy and protein intake remained below estimated daily requirements in both groups, highlighting the need for systematic nutritional monitoring alongside catering optimization. These findings support density-enrichment as a practical and safe strategy for improving nutritional adequacy in dysphagic inpatients, with implications for reducing reliance on oral nutritional supplements and mitigating disease-related malnutrition in clinical settings.
Background: Gastric cancer (GC) is characterized by late-stage diagnosis and a lack of reliable non-invasive biomarkers. This study aims to investigate the plasma bile acid (BA) profile to enhance the understanding of GC metabolism and identify potential diagnostic and prognostic tools. Methods: In a case-control design, 62 GC patients (stages I III) and 70 matched controls were recruited. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), the concentrations of 48 metabolites in plasma were measured. Statistical analysis included univariate tests, principal component analysis, and linear discriminant analysis (LDA). Results: GC patients showed a significantly lower CA/CDCA ratio and alterations in secondary and conjugated bile acids, including TLCA, GLCA, TDCA, GDCA, and GUDCA, suggesting involvement of the gut liver microbiome axis. The ability to distinguish between groups was moderate (AUC = 0.731). Furthermore, BA levels were negatively correlated with tumor stage, tumor size, and systemic inflammatory markers (CRP, mGPS), while they were positively correlated with nutritional and hematological markers such as albumin and hemoglobin. Conclusions: Gastric cancer is associated with a distinct circulating BA profile that reflects not only tumor-related metabolic remodeling, but also systemic inflammation, nutritional status, and disease burden. The reduced CA/CDCA ratio and alterations in secondary and conjugated bile acids support the involvement of the gut-liver-microbiome axis in GC biology. Although BA profiling alone showed moderate diagnostic performance, its integration with conventional tumor markers, inflammatory indices, and clinico-pathological parameters may improve multimodal biomarker panels for noninvasive patient stratification, disease assessment, and future prognostic evaluation.
Injury to the recurrent laryngeal nerve (RLN) remains a significant concern in thyroid surgery. The inferior thyroid artery (ITA) is frequently used as a landmark. Yet, the RLN-ITA relationship shows substantial anatomical variability, and the non-recurrent laryngeal nerve (NRLN) represents a rare but high-risk variant. This systematic review and meta-analysis quantified the prevalence of RLN-ITA topographic patterns and NRLN occurrence. A PRISMA-compliant search was performed across major databases up to May 1, 2025. Eligible studies included intraoperative, cadaveric, or mixed anatomical series reporting extractable numerical data on RLN-ITA relationships (anterior, posterior, interposed) and/or NRLN prevalence, using the hemisoma as the unit of analysis. Study quality was assessed with the AQUA tool. Proportions were pooled using Freeman-Tukey double arcsine transformation under a random-effects model with REML estimation. Heterogeneity was quantified with I², τ², and Cochran's Q, and prespecified subgroup analyses were conducted by study setting. Sixty studies (1973-2025) comprising 9,032 patients and 14,820 hemisomas were included. Fifty-seven studies contributed 14,169 hemisomas to the RLN-ITA synthesis. Crude proportions were posterior 54.43% (7,712/14,169), anterior 27.11% (3,841/14,169), and interposed 18.46% (2,616/14,169). Random-effects pooling confirmed a posterior course as the most frequent configuration (~ 52%, 95% CI ~ 46-58%), followed by anterior (~ 30%, 95% CI ~ 24-36%) and interposed (~ 18%, 95% CI ~ 15-21%), with very high heterogeneity (I² > 97%). Subgroup analyses of intraoperative (30 studies; 10,376 hemisomas) and cadaveric (25 studies; 3,589 hemisomas) series yielded similar distributions, with persistently high heterogeneity (I² > 94%). Across all studies, 39 NRLNs were identified, all on the right side, corresponding to a prevalence of 0.78% among right hemisomas (n = 4,974); no left-sided NRLNs were reported. The RLN most commonly courses posterior to the ITA, but anterior and interposed variants are sufficiently frequent to mandate systematic intraoperative verification before vessel ligation. The NRLN is rare and exclusively right-sided in available data, yet clinically significant due to its high injury risk. Marked between-study heterogeneity highlights the need for standardized definitions and side-specific reporting in future anatomical research.
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Minimally invasive liver resection (MILR), encompassing laparoscopic and robotic techniques, has transformed hepatobiliary surgery. Despite its advantages, intraoperative conversion to open surgery remains a critical event, often associated with increased blood loss, morbidity, and longer hospital stay. Timing of conversion - whether early or delayed - emerges as a key determinant of patient outcomes yet remains poorly defined in the literature. Aim: This review synthesizes current evidence on the indications, timing, and outcomes of conversion in MILR, with a focus on identifying risk factors, perioperative consequences, and existing knowledge gaps. A systematic search of PubMed, MEDLINE, and Embase was performed (2010-2025). We included studies comparing converted vs. non-converted MILR. A quantitative synthesis was performed for key outcomes. Fifteen studies (15,834 patients) were included. A quantitative analysis revealed that conversion was associated with significantly increased blood loss (mean difference: 450 mL), higher overall morbidity (OR: 2.5), and longer hospital stays (mean difference: 4.2 days). We propose an operational definition: Early Conversion ( 60 mins or pre-parenchymal transection), **Late Conversion** ( 60 mins or post-parenchymal transection), and Emergency Conversion (life-threatening event). We propose operational definitions for conversion timing (Early, Late, Emergency) and developed a decision-making algorithm. Conversion during MILR is a pivotal safety measure, but its timing substantially influences outcomes. There is a pressing need for a national, prospective, multicentre UK-based audit to define optimal conversion timing, identify modifiable risk factors, and inform standardised intraoperative decision-making frameworks.
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Bowel urgency (BU) is a highly prevalent and distressing symptom in inflammatory bowel disease (IBD), yet its assessment remains inconsistent and insufficiently standardized. Although recent clinical trials and emerging guidelines increasingly recognize its clinical relevance, no standardized, multidimensional instrument specifically designed to assess BU has been established. This narrative review synthesizes current evidence on the prevalence, clinical and psychosocial burden, prognostic role, and measurement of BU. It outlines key priorities for developing a BU-specific patient-reported outcome (PRO). BU is reported by 30-98% of patients and frequently persists despite clinical or endoscopic remission. BU is independently associated with higher risks of hospitalization, corticosteroid use, colectomy, and disease relapse. Reported psychosocial effects included anxiety, avoidance behaviours, reduced physical activity, decreased work productivity, and impaired health-related quality of life. Existing assessment tools do not fully capture the complexity of BU: traditional disease activity indices overlook urgency, numeric rating scales assess severity alone, and behavioral measures focus on secondary coping strategies. Evidence from trials of JAK inhibitors, S1P modulators, and IL-23 inhibitors supports BU as a sensitive and early marker of treatment response. In conclusion, BU is a prevalent, burdensome, and prognostically relevant symptom in IBD. Current assessment instruments are limited and fail to encompass the emotional, behavioral, and functional dimensions of BU. A multidimensional BU-specific PRO is needed to enhance clinical evaluation, support patient-centered care, and refine outcome assessment in therapeutic trials.
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Despite improved treatments and survival, breast cancer (bc) remains a leading cause of cancer mortality in women. Thyroid dysfunction has been linked to bc risk, but its impact on bc survival is less clear. We investigated associations between pre-diagnosis thyroid-related biomarkers and all-cause and bc-specific survival. A prospective cohort study including 1,513 women with invasive bc from 7 European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) was conducted. We measured thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), and anti-thyroid peroxidase antibodies (Anti-TPO) in samples collected ∼8 years pre-diagnosis. We evaluated associations between these markers and all-cause and bc-specific mortality using Cox proportional hazards models adjusted for relevant covariates. After mean follow-up postdiagnosis of 7 years, 223 deaths occurred, including 161 from bc. We observed no overall associations between circulating levels of TSH, thyroid hormones, thyroid autoimmunity, and mortality. However, in stratified analyses, TSH was inversely associated with all-cause (HR1-standard deviation (SD)=0.70; 95%CI = 0.52-0.94) and bc-specific-mortality (HR1-SD=0.61(0.44-0.84) in premenopausal women, while fT4 was associated with all-cause mortality in metastatic bc (HR1-SD=1.67(1.20 to 2.32), and with bc-specific mortality among users of menopausal/contraceptive hormones (HR1-SD=2.76(1.47-5.19). Anti-TPO-positivity was inversely associated with all-cause mortality in women with body mass index <25kg/m2 and in women with oestrogen receptor-negative tumours, separately. Thyroid function before diagnosis does not appear to play a major role in bc survival. Although subgroup-specific associations were identified, these findings should be interpreted with caution due to limited statistical power and warrant confirmation in independent populations.
Controlled donation after circulatory determination of death (cDCDD) is increasingly vital to expanding deceased organ donation globally, yet variability exists in clinical, legal, and ethical practices. This study utilized a Delphi consensus process involving 37 international experts to develop recommendations to guide the development and operation of adult cDCDD programs. Two survey rounds evaluated agreement on system requirements, donor identification, medical suitability, communication, end-of-life care, and ante-mortem interventions. Consensus was achieved on numerous recommendations emphasizing the need for robust legal frameworks distinct from end-of-life care decisions, multidisciplinary approaches for donor suitability assessment, and clear, sensitive communication led by trained donation professionals. Ensuring patient comfort and dignity during withdrawal of life-sustaining measures, alongside optimizing donation outcomes, was prioritized. Use of ante-mortem interventions was deemed to require careful balancing of benefits and burdens in line with patient and family preferences. The findings highlight international variability and underscore the importance of tailored protocols, education, and further research to establish an evidence base for ante-mortem interventions and improve clinical prediction of donation feasibility. These consensus recommendations aim to advance ethical, effective, and sustainable adult cDCDD programs worldwide.
Trichobezoars are hair concretions in the stomach associated with trichophagia and trichotillomania. In most cases, they occur among young women with concomitant mental disorders. The treatment for this category of patients involves surgical removal of trichobezoars. We present a case of a 24-year-old female patient who complained of morning nausea, a sensation of a foreign body, and periodic pulling pain in the epigastric region. Palpation revealed a foreign mass that occupied the epigastric area. The patient underwent computed tomography (CT) and esophagogastroduodenoscopy (EGD) for differential diagnosis. Based on the instrumental studies, the diagnosis of a gastric trichobezoar was established. Laparoscopic gastrotomy was performed along the anterior wall of the stomach with removal of the trichobezoar through a Pfannenstiel-type mini-laparotomy site. The postoperative period was uneventful, and the patient was discharged on the second postoperative day. To prevent recurrence, psychiatric consultation and long-term outpatient follow-up were recommended as part of treatment. The uniqueness of this case lies in the presence of a trichobezoar that caused minimal discomfort for a long period of time. Laparoscopic removal of gastric trichobezoars represents an effective treatment option due to its minimally invasive nature and rapid postoperative recovery.
Pain is highly prevalent among hospitalised adults, and in Italy Law 38/2010 mandates its assessment and relief. We aimed to estimate pain prevalence and severity among adult inpatients and identify factors associated with moderate-to-severe pain and satisfaction with pain management in a university hospital. We conducted a cross-sectional survey in May 2023 at IRCCS Policlinico San Donato using a structured questionnaire in adult inpatients hospitalised for at least 24 hours. Multivariable logistic regression explored factors associated with pain severity and satisfaction. Among the 229 patients interviewed, 84% reported pain at the time of the interview, with 52.4% experiencing moderate pain and 9.6% severe pain. Pain in the previous 24 hours was associated with moderate-to-severe pain at the time of the interview and lower satisfaction with care. Thirty-two percent were aware of Law 38/2010, and awareness was associated with lower pain severity and higher satisfaction. Pain remains highly prevalent among adult inpatients. Experiencing pain in the previous 24 hours was associated with greater severity and lower satisfaction, suggesting the importance of timely and consistent pain assessment and relief throughout hospitalisation.
The updated European Society of Gynaecological Oncology guidelines recommend routine molecular classification to refine risk assessment and guide adjuvant treatment. However, the prognostic impact of sentinel lymph node involvement and molecular classification in apparent early-stage endometrial cancer remains incompletely defined. PROMISE-EC is a multi-center retrospective study including patients with apparently uterine-confined endometrial cancer who underwent surgical staging with sentinel lymph node biopsy at 16 European institutions (January 2014-February 2024). Clinicopathologic characteristics, sentinel lymph node status, and Cancer Genome Atlas-based molecular classification were collected and analyzed. The primary endpoint was progression-free survival. Among 2732 records, 2003 patients met inclusion criteria. International Federation of Gynecology and Obstetrics 2009 stage I was observed in 1585 patients (79.4%). Sentinel lymph node involvement was present in 282 patients (14.1%). p53-abnormal tumors were associated with poorer progression-free survival (p <.0001), whereas patients with POLE-mutated tumors showed excellent outcomes, with no significant difference compared with non-specific molecular profile (p =.103). Patients with deficient mismatch repair tumors showed intermediate outcomes (p =.484). In unadjusted Kaplan-Meier analysis, progression-free survival worsened with increasing sentinel lymph node tumor burden (p =.047). In multi-variable analysis, high-grade disease (p =.003) and p53 abnormal status (p <.001) remained independent predictors of recurrence. The association between sentinel lymph node tumor burden and recurrence was attenuated, with only macrometastatic involvement retaining independent prognostic significance. In multi-variable logistic regression, lymphovascular space invasion was the strongest predictor of sentinel lymph node metastases (p <.00001), while patients with POLE-mutated tumors were less likely to harbor clinically relevant nodal involvement (p =.032). Our study supports the prognostic relevance of both sentinel lymph node assessment and molecular classification in early-stage endometrial cancer, with potential implications for post-operative risk stratification and management.
EphA2 is highly expressed in colorectal cancer (CRC), and high EphA2 expression indicates a worse prognosis. We investigated EphA2 dynamics in a clinically relevant model: CRC patient-derived organoids (PDOs) treated with chemotherapy. We evaluated the number of EphA2-expressing cells and the Aldehyde dehydrogenase activity by flow cytometry, and analyzed EphA2 protein levels and phosphorylation status using Zn-Phos-tag gels and indirect ELISA. We employed siRNA to deplete the PDO cells of EphA2. EphA2-positive cells form a stable subpopulation in organoid cultures that persists after oxaliplatin treatment. Phosphorylation of EphA2 at Ser897 increases with treatment and correlates with higher EphA2 levels. Silencing EphA2 or reducing Ser897 phosphorylation decreases organoid formation, suggesting chemosensitization. Some EphA2-positive cells show increased ALDH activity after chemotherapy, and EphA2-ALDH1A3 interaction has prognostic value in CRC. Here, we discovered that EphA2-positive cells constitute a persistent, ALDH-positive cell subpopulation in CRC-PDOs that withstood exposure to oxaliplatin (OXA) and 5-fluorouracil (5-FU). The enforced suppression of EphA2 or diminished Ser897 stress results in a chemosensitization effect. This sheds further light on the role of EphA2 in the adaptive stress response of CRC.
Anterior shoulder instability is a common injury among professional athletes. Both soft-tissue and bone-block procedures are widely used for surgical stabilization, but it remains unclear whether one approach offers superior outcomes in terms of return to play (RTP) and recurrence. The purpose of this systematic review and meta-analysis was to compare RTP rates, time to RTP and recurrence of instability between professional athletes treated with coracoid bone-block procedures and those undergoing soft-tissue stabilization. A systematic search of PubMed, Embase and the Cochrane Library was conducted from database inception through August 2025 according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies including professional athletes treated surgically for anterior shoulder instability were analysed. Pooled effect estimates were calculated using random-effects models. Subgroup analyses compared bone-block versus soft-tissue stabilization for RTP, time to RTP and recurrence. Thirteen studies were included in the systematic review and meta-analysis and of these, eight analysed soft-tissue surgery and five coracoid bone block. The overall pooled RTP rate was 95.6% (95% confidence interval [CI], 88.2-99.8) in the coracoid bone-block group and 95.9% (95% CI, 91.6-98.9) in the soft-tissue group (p = 0.781). No significant differences were found in the level of RTP between the two treatment groups (p = 0.266). A shorter time to RTP was observed in the coracoid bone-block group (166.24 days [95% CI, 116.05-238.13]) compared with soft-tissue stabilization (271.09 [95% CI, 195.03-376.80]; however, this finding should be interpreted with caution due to overlapping CIs, borderline statistical significance and substantial heterogeneity. The overall recurrence rate was 4.8% (95% CI, 1.5-9.3) with no difference between coracoid bone-block procedure (2.6% [95% CI, 0.0-8.7]) and soft-tissue (6.9% [95% CI, 2.0-13.8]) (p = 0.302). Both coracoid bone-block and soft-tissue procedures allow professional athletes to achieve high RTP rates with low recurrence. No definitive differences between techniques can be established, particularly considering the low quality of evidence and the substantial heterogeneity across studies. Level III, systematic review and meta-analysis.
Lipedema is a chronic adipose tissue disorder characterized by disproportionate fat deposition, pain, and progressive functional impairment. Although diagnosis remains primarily clinical, ultrasound has emerged as a valuable adjunctive tool for diagnosis, surgical planning, intraoperative guidance, and postoperative monitoring. The aim of this review was to provide a comprehensive overview of the current and potential applications of ultrasound throughout the entire surgical management pathway of patients with lipedema. A narrative review of the literature was conducted using PubMed/MEDLINE, Scopus, and Google Scholar databases. Articles published up to January 2026 were screened using the keywords "lipedema," "lipoedema," "ultrasound," "ultrasonography," "lipedema diagnosis," "lipedema imaging," "lipedema surgery," and "liposuction." Studies addressing ultrasound-based diagnosis, differential diagnosis, surgical planning, intraoperative guidance, and postoperative monitoring in lipedema patients were included. Both original investigations and review articles published in English were considered. Ultrasound demonstrated significant utility across all phases of lipedema management. In the preoperative setting, it improved diagnostic accuracy by identifying characteristic sonographic features, quantifying tissue thickness, differentiating lipedema from obesity and lymphedema, and enabling vascular mapping for surgical safety. Advanced techniques, including three-dimensional ultrasound, provided additional information regarding fascial alterations, fibrosis, and fluid accumulation. Intraoperatively, ultrasound off ered real-time visualization of anatomical structures, facilitated identification of fibrotic tissue, and supported more precise liposuction by improving cannula guidance andassessment of tissue homogeneity. Postoperatively, ultrasound enabled early detection of complications such asseromas and hematomas, assessment of fi brosis and tissue remodeling, and long-term monitoring of disease recurrence or progression. The available evidence suggests that ultrasound represents a versatile, accessible, and reproducible imaging modality capable of enhancing both diagnostic and surgical aspects of lipedema care. By integrating ultrasound intopreoperative evaluation, intraoperative decision-making, and postoperative follow-up, clinicians may improve surgical precision, patient safety, and treatment outcomes. Nevertheless, the current literature remains limited by heterogeneity, operator dependency, and the absence of standardized imaging protocols. Larger multicenter studiesare needed to validate diagnostic criteria and establish evidence-based guidelines for ultrasound utilization in lipedema management. Ultrasound has the potential to become an integral component of modern lipedema management. Its applications extend beyond diagnosis to encompass surgical planning, intraoperative guidance, and postoperative surveillance. The increasing availability of portable, high-resolution ultrasound devices may further facilitate its routine incorporation into clinical practice, ultimately contributing to safer procedures, more personalized treatment strategies, and improved long-term outcomes for patients with lipedema. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .
Sexual function during pregnancy is commonly described in terms of overall decline or sexual dysfunction prevalence, potentially overlooking heterogeneity across individual domains. We aimed to identify distinct sexual function phenotypes during pregnancy and to examine whether gestational diabetes mellitus (GDM) is associated with poorer sexual function or specific sexual profiles. In this cross-sectional observational study, 83 pregnant women undergoing routine GDM screening between weeks 24 and 28 of gestation completed the Female Sexual Function Index (FSFI). Clinical and obstetric data were collected. K-means cluster analysis on standardized FSFI domain scores identified multidomain phenotypes. Group comparisons and multivariable regression models were performed. Sexual dysfunction was present in 51 of 83 women (61.4%). Three sexual phenotypes were identified: preserved sexual function (n=49), global sexual impairment (n=25), and desire-satisfaction dissociation (n=9). Pre-pregnancy weight differed across phenotypes (p=0.026). Hypertensive disorders of pregnancy, twin pregnancy, and conception by assisted reproductive technology (ART) were more frequent in the desire-satisfaction dissociation phenotype (p=0.024, p=0.042, and p=0.048, respectively). Older age (OR 1.15, 95% CI 1.01-1.32; p=0.041) and lower pre-pregnancy weight (OR 0.95, 95% CI 0.92-0.99; p=0.019) were independently associated with global sexual impairment. GDM was not associated with total FSFI score, sexual dysfunction prevalence, or phenotype distribution. Female sexual function during pregnancy is heterogeneous and distributed across distinct multidomain phenotypes. Gestational diabetes mellitus did not explain this heterogeneity, whereas phenotype-based profiling identified distinctive sexual patterns. These findings support a more nuanced framework for studying sexuality in pregnancy beyond dichotomous definitions of dysfunction.
Postoperative symptoms such as pain, burning, and itching are common following open excisional hemorrhoidectomy and are often associated with several factors, including wound healing. This study evaluated the efficacy of Propionibacterium extract gel (PeG) in promoting wound healing and reducing pain, burning, and itching compared to an ointment containing hyaluronic acid and silver sulfadiazine (HA-SSD). In this multicenter, phase IV randomized controlled trial, patients undergoing open excisional hemorrhoidectomy were randomly assigned in a 1:1 ratio to receive PeG or HA-SSD. The primary outcome (wound healing) was evaluated on the basis of grade of epithelialization. Secondary outcomes (pain, burning, and itching) were assessed using a 10-point visual analogue scale at baseline and 10, 20, and 40 days postoperatively. Of the 119 screened patients, 64 (53.78%) received PeG and 55 (46.22%) received HA-SSD. The baseline characteristics were comparable. After 20 days, 46 (75.4%) of the PeG group patients had an epithelialization grade > 50% (vs n = 37, 72.6% of the HA-SSD group; p = 0.02). By day 40, complete wound healing occurred in 52 (85.3%) of the PeG group patients (vs n = 25, 52.1% of the HA-SSD group; p = 0.003). Both treatments reduced postoperative pain over time, with no significant between-group difference (p = 0.24). PeG demonstrated a superior reduction in burning (p = 0.02) and itching (p = 0.001). Patient satisfaction was higher with PeG (n = 45, 75% vs n = 9, 18.8% of the HA-SSD group, p < 0.001), with no reported adverse reactions. PeG was more efficient than HA-SSD in promoting wound healing, alleviating burning and itching, and enhancing patient satisfaction following hemorrhoidectomy. This study supports the safety and effectiveness of PeG as a therapeutic option for postoperative management. NCT06872151, retrospectively registered on 6 March 2025.
For patients with hematologic malignancies, relapse is the leading cause of death after allogeneic hematopoietic cell transplantation (allo-HCT). Frequently, relapses are explained by immune evasion through alterations of human leukocyte antigens (HLAs), but determinants and clinical consequences remain poorly defined. We analyzed 533 relapses of hematologic cancers after allo-HCT from different donor types, conducted at 27 centers worldwide. Genomic loss of mismatched HLA (HLA loss) was assessed using a newly developed next-generation sequencing pipeline. Clinical and immunogenetic factors associated with HLA loss were evaluated. Using HLA data from approximately 5 million individuals, a web-based tool to infer HLA incompatibility phasing was developed. HLA loss occurred in 15.6% of relapses, with significant variation according to donor type (28.7% haploidentical family, 7.2% unrelated adult, 2.7% cord blood, P < .0001). The distribution of HLA mismatches across the patient's haplotypes, predicted through the phasing tool, was strongly associated with HLA loss, with an incidence of 27.6% when HLA mismatches were in the same haplotype, compared with 5.4% if present on different haplotypes (P < .0001). HLA loss affected postrelapse outcomes, abrogating the efficacy of original donor lymphocyte infusions, with significant survival advantage by second allo-HCT from a different donor. The likelihood of HLA loss varies significantly according to the number and positioning of HLA mismatches between patient and donor. A newly developed phasing tool enables reliable prediction of its risk, supporting informed donor selection. Routine assessment of HLA loss at relapse is warranted, as it critically affects the success of immunologic salvage therapies.