Search Results (305)

Background/Objectives: Postoperative recurrence is a critical issue in the treatment of resectable pancreatic ductal adenocarcinoma (rPDAC). Moreover, the prognosis after early recurrence is extremely poor. This study aimed to develop a recurrence prediction model and to define early recurrence after upfront surgery (UFS) for rPDAC. Methods: This multicenter retrospective study included patients who underwent UFS for anatomically rPDAC between January 2013 and December 2017. Multivariate analyses were conducted to identify the risk factors for recurrence-free survival and to construct a recurrence prediction model. Subsequently, a minimum p value approach was used to determine the optimal cutoff values for early and late recurrence. Results: The cohort included 603 patients (325 men and 278 women). During the median follow-up period of 25 months (interquartile range, 15–38 months), 381 patients (63.2%) experienced a recurrence. Multivariate analyses revealed carbohydrate antigen 19-9 ≥37 U/mL (hazard ratio [HR], 1.58; p < 0.001), tumor size ≥ 2.2 cm (HR, 1.59; p < 0.001), lymph node metastasis (HR, 1.86; p < 0.001), R1 resection (HR, 1.56; p = 0.002), and no adjuvant chemotherapy (HR, 1.54; p < 0.001) as independent predictors. The recurrence prediction model demonstrated an area under the curve of 0.72–0.75. The optimal threshold for early and late recurrences was a recurrence-free interval of five months. Carbohydrate antigen 19-9 ≥ 156 U/mL was a significant predictor of early recurrence (OR, 3.28; p < 0.001). Conclusions: This study identified the prognostic risk factors for recurrence and developed a recurrence prediction model for patients undergoing UFS for rPDAC. Moreover, a recurrence-free interval of five months was identified as the optimal threshold for distinguishing between early and late recurrences. Full article

Background/Objectives: Healthcare-associated ventriculitis and meningitis (HAVM) is a life-threatening complication of neurosurgical procedures. Conventional cerebrospinal fluid (CSF) indices cannot reliably distinguish bacterial infection from sterile postoperative inflammation, and cultures are frequently delayed or negative. We conducted the first systematic review and meta-analysis to determine the pooled diagnostic accuracy of CSF heparin-binding protein (HBP) for HAVM and to establish clinically actionable decision thresholds. Methods: PubMed, Embase, the Cochrane Library, and China National Knowledge Infrastructure were searched from inception to 15 February 2026. Risk of bias was assessed using QUADAS-3. Sensitivity and specificity were pooled with a bivariate random-effects model, and heterogeneity was explored through subgroup analyses and metaregression. Thresholds were derived using likelihood ratio (LR)-based and diagmeta cutoff modeling. Results: Twelve studies (n = 1761) were included. Pooled sensitivity was 0.861 (95% confidence interval [CI]: 0.777–0.917) and specificity was 0.848 (95% CI: 0.781–0.897), with a positive LR (LR+) of 5.65 and a negative LR (LR−) of 0.164. At a 50% pretest probability, post-test probability was increased to 85% by a positive result and reduced to 14% by a negative result. Intracerebral hemorrhage cohorts showed lower accuracy (sensitivity: 0.675, specificity: 0.755), whereas brain tumor-predominant cohorts demonstrated the highest performance (sensitivity: 0.935, specificity: 0.922; p = 0.017). Thresholds of ≥41.3 (rule-in; LR+ ≥10) and ≤30.1 ng/mL (rule-out; LR− ≤0.1) defined clinically actionable decision zones. Conclusions: CSF HBP provides quantitatively defined rule-in and rule-out thresholds that meaningfully shift the post-test probability and may support antimicrobial decision-making in suspected HAVM. Prospective multicenter validation is warranted. Full article

Background/Objectives: To evaluate the incidence of rapid recurrence within 6 months of curative resection for hepatocellular carcinoma (HCC) and to identify preoperative gadoxetic-acid-enhanced MRI features associated with rapid recurrence (<6 months) in the entire cohort. Methods: This retrospective study included 200 patients who underwent curative resection for HCC and had preoperative gadoxetic-acid-enhanced MRI between January 2016 and December 2023. Patients were categorized into a rapid recurrence group (n = 21) and a non-rapid recurrence group (n = 179). Preoperative MRI features, including tumor size, multiplicity, tumor margin, arterial peritumoral enhancement, peritumoral hepatobiliary phase (HBP) hypointensity, diffusion restriction, apparent diffusion coefficient (ADC) values, and presence of non-hypervascular hepatobiliary phase hypointense nodule (NHHN), were evaluated. Univariate and multivariate Firth penalized logistic regression analyses were performed. Results: Rapid recurrence occurred in 10.5% (21/200) of patients (median, 4.0 months). Multivariate analysis revealed that larger tumor size (odds ratio [OR], 1.25 per 1-cm increase; p = 0.012) and the presence of NHHN (OR, 11.30; p < 0.001) were independent predictors of rapid recurrence. A nomogram incorporating these features demonstrated excellent discriminative performance, with a bootstrap-corrected area under the curve (AUC) of 0.864 (95% CI, 0.791–0.922). Conclusions: The presence of NHHN and larger tumor size on preoperative MRI were associated with rapid recurrence (<6 months) after curative resection for HCC. These findings may provide additional support for preoperative risk stratification and the planning of postoperative surveillance strategies. Full article

Background: As life expectancy increases, a growing number of elderly patients are considered for curative hepatectomy for hepatocellular carcinoma (HCC). However, perioperative outcomes in elderly patients in the contemporary era of minimally invasive liver surgery remain incompletely defined. Methods: We retrospectively reviewed 277 consecutive patients who underwent elective curative hepatectomy for HCC between 2019 and 2023. Outcomes were compared using age thresholds of ≥75 and ≥80 years. The primary endpoints were 90-day mortality and major postoperative complications (Clavien–Dindo grade ≥ III). Multivariable logistic regression identified predictors of major complications. Results: Elderly patients had more comorbidities, whereas liver function, tumor characteristics, and extent of resection were comparable across age groups. Laparoscopic hepatectomy was performed more frequently in patients aged ≥80 years. Major complication rates and 90-day mortality were similar regardless of age, with no deaths among patients aged ≥75 or ≥80 years. Age ≥75 years, higher ALBI score, major comorbidities, and longer Pringle maneuver time were independently associated with major postoperative complications. Conclusions: Hepatectomy for hepatocellular carcinoma may be performed with acceptable short-term outcomes in carefully selected elderly patients, including octogenarians. Chronological age alone should not be considered an absolute contraindication to surgery, although findings should be interpreted with caution. Full article

Background: Advanced liver fibrosis (LF) is a major determinant of prognosis across chronic liver diseases. Current biomarkers are often etiology-specific and lack cross-cohort robustness. Shared molecular drivers across etiologies remain incompletely defined, and effective anti-fibrotic therapies are limited. Methods: We developed a multi-algorithm consensus machine-learning framework to derive a robust LF progression signature. In the training non-alcoholic fatty liver disease (NAFLD) cohort GSE213621 (n = 368), samples were formulated as a binary classification task (mild fibrosis, F0–F2; advanced fibrosis, F3–F4). Candidate genes were screened in parallel using Boruta, Least Absolute Shrinkage and Selection Operator (LASSO), random forest, and eXtreme Gradient Boosting (XGBoost). Genes selected by at least two algorithms were defined as a high-consensus pool, and genes consistently selected by all four algorithms were prioritized to construct a core signature. Model performance was evaluated by stratified cross-validation in the training cohort and externally validated in four independent cohorts of different etiologies (GSE49541, GSE84044, GSE130970, and GSE276114). Cellular sources of signature genes were characterized using single-cell RNA sequencing (scRNA-seq) datasets GSE136103 (human) and GSE172492 (mouse). For therapeutic discovery, the high-consensus expression profile was queried against the Connectivity Map (CMap) to prioritize compounds predicted to reverse the fibrotic transcriptional program. Withaferin A (WFA) was selected for experimental validation in a carbon tetrachloride (CCl₄)-induced mouse LF model and in the transforming growth factor-β1 (TGF-β1)-stimulated human hepatic stellate cell line LX-2. Bulk liver RNA-seq profiling was performed to interrogate WFA-associated molecular changes in vivo. Results: We identified a six-gene signature (CLEC4M, COL25A1, ITGBL1, NALCN, PAPPA, and PEG3) that discriminated advanced from mild fibrosis, achieving a mean AUC of 0.890 in internal cross-validation and an average AUC of 0.864 across external validation cohorts. scRNA-seq analysis revealed cell-type-specific expression with prominent enrichment in fibroblast populations. In vivo, WFA markedly attenuated CCl₄-induced fibrosis (p < 0.05) and reversed 1314 fibrosis-associated differentially expressed genes (adjusted p < 0.05), which were enriched in fatty acid metabolism and PPAR signaling, as well as extracellular matrix (ECM)–receptor interaction and focal adhesion (adjusted p < 0.05). In vitro, WFA suppressed TGF-β1-induced LX-2 activation, reducing α-SMA and Fibronectin expression (p < 0.05). Conclusions: We report a six-gene signature that robustly predicts advanced LF across etiologies, define its cellular context using single-cell atlases, and validate the anti-fibrotic activity of WFA in both in vivo and in vitro models. Bulk liver RNA-seq and cellular evidence further suggest that WFA-associated effects are linked to lipid metabolic programs, ECM remodeling, and attenuation of hepatic stellate cell activation. Full article

The global crisis concerning multidrug-resistant microorganisms necessitates the development of innovative antimicrobial strategies that avoid conventional antibiotics and overcome the toxicity and environmental persistence associated with traditional metal-based biocides. This work aims to develop safe and sustainable antibacterial filtration materials by integrating cationic hyperbranched polymer dendrimers (HBP) into electrospun nanofibers. Cationic HBPs were successfully embedded into recycled polyamide 6 nanofibers using industrial needleless electrospinning. Filtration efficiency, assessed against a 0.3 µm paraffin oil aerosol according to EN 149:2001, consistently exceeded 99.8%, meeting and surpassing the FFP3 classification threshold while maintaining low air resistance. The HBP-functionalized nanofibers exhibited pronounced contact-active antibacterial activity against Staphylococcus aureus and Escherichia coli. Quantitative plate count assays confirmed viability reductions of up to 74.1% after 2 h of co-incubation. Crucially, the absence of inhibition zones in agar diffusion tests confirmed that the active polymer was stably embedded within the nanofiber matrix and did not leach. Comprehensive toxicological tests, including cell line and 3D human skin and airway tissue models, confirmed the material’s safety for both dermal and respiratory contact. This study presents a scalable, metal-free, and environmentally responsible next-generation filtration system that combines high mechanical efficiency with active antimicrobial functionality. Full article

Background: Epstein–Barr virus (EBV)-related primary splenic tumors are exceptionally rare and encompass a heterogeneous group of entities, including inflammatory pseudotumor (IPT), IPT-like follicular dendritic cell (FDC) tumors or sarcomas, and EBV-positive diffuse large B-cell lymphoma (DLBCL). Because clinical presentation and imaging findings are often nonspecific, establishing a definitive diagnosis remains challenging and frequently necessitates splenectomy for histopathologic confirmation. Methods: We retrospectively reviewed patients who underwent laparoscopic splenectomy for suspected primary splenic lesions at a single tertiary institution between June 2014 and August 2025. Among 67 patients, five consecutive patients were pathologically confirmed as EBV-related primary splenic tumors. Clinical characteristics, imaging features, histopathologic and immunophenotypic findings, EBV in situ hybridization results, treatment, and follow-up outcomes were analyzed. Results: This case series comprised four spindle cell–predominant EBV-related tumors (IPT or IPT-like FDC tumors/sarcomas) and one EBV-positive DLBCL. All patients presented with splenic masses that could not be definitively characterized by preoperative imaging alone and therefore required splenectomy. EBV in situ hybridization was positive in tumor cells in all cases. Patients with non-lymphomatous tumors achieved durable disease control following splenectomy alone, with disease-free survival of up to five years. In contrast, the patient with EBV-positive DLBCL required postoperative systemic immunochemotherapy. Conclusions: EBV-related primary splenic tumors represent a diagnostically challenging and clinically diverse disease spectrum. This case series highlights the pivotal role of splenectomy in establishing definitive diagnosis and guiding subsequent management, particularly for isolated splenic lesions with indeterminate imaging findings. Full article

Background: Minimally invasive pancreatoduodenectomy (MIPD) has evolved from an experimental technique to a feasible surgical option for pancreatic cancer in selected settings. However, its oncologic adequacy, safety, and generalizability remain debated, particularly given the biological aggressiveness of pancreatic ductal adenocarcinoma (PDAC) and the technical complexity of the procedure. Methods: This narrative review critically summarizes contemporary evidence regarding MIPD for pancreatic cancer, with particular attention to randomized controlled trials (RCTs), meta-analyses, and large observational studies. We distinguish findings derived from mixed periampullary tumor cohorts from those specific to PDAC and evaluate methodological limitations, learning-curve effects, and sources of heterogeneity across studies. Results: Recent RCTs and meta-analyses demonstrate that, when performed by experienced surgeons in high-volume centers, MIPD achieves perioperative outcomes comparable to open pancreatoduodenectomy, with advantages including reduced blood loss, shorter hospital stay, and faster functional recovery. Importantly, oncologic parameters such as R0 resection rates and lymph node yield appear equivalent between approaches, although robust long-term survival data from PDAC-specific RCTs remain lacking. Emerging evidence supports the feasibility of MIPD in complex clinical scenarios, including after neoadjuvant therapy, in frail or elderly patients, and in selected cases requiring vascular resection. Nonetheless, outcomes are strongly influenced by surgeon experience, institutional volume, and patient selection. Cost-effectiveness analyses and data from lower-volume centers remain limited. Conclusions: Current evidence supports MIPD as a viable alternative to open surgery for pancreatic cancer in carefully selected patients treated at specialized centers. However, claims of oncologic superiority are premature. Future research should focus on PDAC-specific randomized trials, standardized quality metrics, and strategies to mitigate learning-curve and resource-related barriers to broader implementation. Full article

Introduction: Parents of children presenting global developmental delay (GDD) need to be involved in their therapy to intensify treatment. Vojta therapy (VT) is an intensive physiotherapeutic treatment that can be administered at home. Whilst parental experience of Home-Based Program (HBP) for preterm or cerebral palsy is well documented, there is a lack of understanding about parents of GDD children on HBP with VT. Objectives: The aim of this work was to describe parents’ perspectives concerning their participation in, concerns with, and perception of the results of an HBP with VT. Methods: A qualitative case design based on an interpretative approach was presented. A purposeful sampling was used. Data was collected in two stages: firstly, semi-structured interviews, and secondly, photo-elicitation. An inductive thematic analysis was used. Results: Seventeen parents were included. Three themes emerged from parents’ perspectives. Firstly, parents’ active participation in VT, which includes their desire to become an active agent to contribute to their child’s improvement, their implication of compromise, learning process, time required, effort, and factors that influence their adherence and continuity. Secondly, parents’ perception of the results achieved: motor improvement and better resting, feeding, and breathing; and time and commitment required to achieve them. Thirdly, parents’ initial concerns about suitability, daily implementation, therapy functioning, or evidence, as well as concerns about emotional bonds. Conclusions: Parents universally perceive that their commitment and efforts were rewarded. They recognized that the emotional bond with their child was strengthened by the therapy. The results regarding the beneficial effects perceived by the parents should be treated with caution, as no instruments for assessing the effect or efficacy were used in this study. Full article

Background: Pancreatic hamartoma (PH) is an exceptionally rare, benign, mass-forming lesion accounting for less than 1% of all pancreatic tumors. Its rarity and non-neoplastic nature contribute to significant diagnostic challenges, often leading to misclassification as malignant disease. This study presents a case of PH and a systematic review of all reported cases, with emphasis on histopathological and imaging characteristics. Methods: A comprehensive electronic search of PubMed, Scopus, and Web of Science was conducted up to 1 April 2025, to identify eligible case reports and series. Results: We describe a 37-year-old woman with a cystic lesion of the pancreatic tail, ultimately confirmed histologically as a cystic pancreatic hamartoma following distal pancreatectomy with splenectomy, with an uneventful postoperative course. Of 687 screened studies, 51 met the inclusion criteria, comprising 77 cases (68 adults, 9 pediatric). PHs occurred most frequently in males (52.9%), with a mean age of 59.5 ± 12.9 years, and were often asymptomatic (57.4%). The pancreatic head was the most common site (52.9%). On MRI, PHs typically exhibited low T1-weighted and high T2-weighted signal intensity, with no FDG uptake (82%) and moderate or no restriction on DWI, distinguishing them from neuroendocrine tumors (NETs). Histologically, most lesions were solid (64.7%) or solid–cystic (35.3%), with low spindle cell cellularity and absent Langerhans islets. Conclusions: Low T1WI signal and moderate DWI signal are the key features distinguishing PHs from NETs. Incorporating these findings with EUS-FNA and immunohistochemistry can support a provisional diagnosis and help avoid unnecessary radical surgery. Full article

Background/Objectives: Introducing a demanding home-based program (HBP) of Vojta therapy (VT) into their daily activities is a life-altering event for parents of children with global developmental delay (GDD). This study aims to document the experiences of parents of children with GDD administering a HBP of VT. Methods: A multicentre study with a qualitative case design based on an interpretative approach is presented. Interviews were conducted with 10 parents using photo-elicitation (PE). Inductive and thematic analyses were used. Results: Four common experiential themes were identified. Firstly, crying was identified as the most significant barrier to administering therapy (despite parents accepting that crying was not pain-related). Secondly, parents described the intense and variable emotional impact of being responsible for the therapy and its effects on their child. Thirdly, parents unanimously felt that their involvement was worthwhile, with the developmental results they perceived outweighing the emotional, physical and time demands of administering the VT. Finally, parents developed a narrative of hope stemming from the therapy and its observed effects. Conclusions: The physical, emotional and time demands on parents when administering a HBP of VT are very significant. The main barriers to adherence to the program are identified as the child’s crying during therapy and time management. Intense emotional experiences, both positive and negative, arise while administering a HBP of VT. Parents are not only able to overcome all emotional and logistical challenges when they recognize improvements in their child, but they also begin to hope for further improvement. Implications for the professional design of HBPs of VT include the following: advanced warning that crying is normal, part of the therapy and not pain-related; training and ongoing support from a qualified therapist; training in recognising developmental improvement; and psychological support to deal with the emotional journey. Full article

Honeybee products (HBPs), including honey, bee pollen, bee bread, royal jelly, propolis, beeswax, and bee brood, are increasingly used in food, nutraceutical, and cosmetic contexts. Because of their natural origin, HBPs can provoke allergic reactions ranging from localised dermatitis to life-threatening, systemic anaphylaxis. As the use of bee products for health purposes grows in apitherapy (a branch of alternative medicine), raising public awareness of their potential risks is essential. This narrative review synthesises the clinical manifestations of HBP allergy, culprit allergens present in each product, immunological mechanisms, diagnostic approaches, at-risk populations, and knowledge gaps. The analysis of the available literature suggests that, although relatively rarely, HPB may trigger allergic reactions, including anaphylactic shock. The sensitisation mechanism may be associated with both primary sensitisation and cross-reactivity and can be classified into type I (IgE-mediated) and type IV (T-cell-mediated). However, bee bread appears less allergenic than other HBPs, potentially due to lactic fermentation that can degrade allergenic proteins. Severe reactions following intake of bee bread have not been reported to date. Management of HBP allergic reactions centres on avoiding the products, educating about the risks, and providing more precise product labelling, specifying the allergen content. Individuals with atopy and beekeepers are at heightened risk of developing anaphylaxis; therefore, they should be particularly aware of the potential dangerous consequences of HPB use. Further research is needed to clarify the mechanisms of HBP allergies and improve safety for all users. Full article

Background: Conduction system pacing (CSP) has emerged as an alternative to biventricular pacing (BiVp), but its implantation requires a specific learning curve. Early experience was dominated by His bundle pacing (HBP) with lumenless leads (LLL), whereas the subsequent adoption of left bundle branch area pacing (LBBAP) and the increasing procedural standardization led to a simplification of the technique and greater uniformity in its execution. This study evaluated the learning curve for CSP by analyzing the first consecutive implants of two electrophysiologists (operator 1: OP1 and operator 2: OP2). Methods: The first 55 CSP procedures performed by each operator (n = 110) were retrospectively analyzed. Implantation and fluoroscopy times were assessed in blocks of five cases. Univariate and multivariable linear regression were used to identify independent predictors of procedural complexity. Results: A total of 110 CSP implants (55 per electrophysiologist) were analyzed. Implantation time progressively decreased with experience, reaching a stable plateau after ~45 cases per operator, when inter-operator curves completely overlapped and differences were no longer significant. Fluoroscopy time stabilized earlier and showed no consistent differences between electrophysiologists. In the univariate analysis, longer procedural times were associated with larger left ventricular end-diastolic diameters (LVEDD: r: 0.43; p < 0.001), LLL (r: 0.25; p < 0.01) and earlier implant numbers (r: 0.36; p < 0.001). In the multivariable models, only LVEDD and implant number (IN) remained independent predictors of procedure duration (LVEDD: β: 2.04, p: 0.04; and IN: β: 3.26, p < 0.04). Conclusions: CSP implantation follows a distinct learning curve, with procedure duration stabilizing after approximately 45 cases per operator. Procedural complexity is mainly determined by patient factors (LVEDD) and operator-related factors, whereas differences between LLL and SL reflect historical experience rather than intrinsic technical characteristics. Full article

Sorghum, the fifth major global cereal, has potential as a source crop in temperate regions. To completely use sorghum bagasse, the ideal enzyme cocktail aims to identify and select the contributed enzymatic system. This study investigated the enzymatic system of Clostridium cellulovorans cellulosome and noncellulosomal enzymes using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and liquid chromatography–tandem mass spectrometry LC-MS/MS. Enzyme solutions from treated and untreated sorghum bagasse were prepared and compared based on carboxymethyl cellulase (CMCase) activity. As a result, the enzyme solution derived from untreated sorghum bagasse had the highest activity. Protein bands from each C. cellulovorans culture showed distinct patterns on SDS-PAGE examination: three enzyme fractions, including culture supernatants, crystalline cellulose (Avicel) bound, and unbound fractions. These results suggested that untreated sorghum bagasse induced a variety of cellulosomal and uncellulosomal proteins. On the other hand, 5% or 10% sorghum supernatants could not induce Avicel-bound proteins, including the cellulosome, although even 5% sorghum juice induced three major bands: 180 kilodalton (kDa), 100 kDa, and 70 kDa, respectively. In contrast, cellobiose induced three major bands, while the total number of all isolated proteins from the cellobiose medium was the most limited among all culture media. More intriguingly, our investigation detected one cellulosomal protein, hydrophobic protein A (HbpA) and three noncellulosomal enzymes, indicating that glycosyl hydrolase family 130 (GH130) was identified as a biomass-induced enzyme in good accord with previously published proteomic studies. Therefore, the proteomic dataset generated in this study provides us a foundation for future computational approaches, including machine learning-based prediction of optimal enzyme cocktails for target biomass degradation. Full article

Background/Objectives: Upfront surgery (UFS) remains the standard treatment for patients with resectable pancreatic ductal adenocarcinoma (PDAC). We aimed to investigate the prognostic factors for survival after UFS in patients with resectable PDAC and to develop a prognostic prediction model. Methods: This multicenter, retrospective study included 603 patients who underwent UFS for resectable PDAC between January 2013 and December 2017. Univariate and multivariate analyses were performed to identify prognostic factors for overall survival (OS). We constructed a prognostic prediction model for OS after UFS. An internal validation was performed to evaluate the discriminative performance of the model. Results: The 1-, 3-, and 5-year OS rates were 83.7%, 48.2%, and 37.5%, respectively. The Cox proportional hazards model showed that tumor size > 2 cm (hazard ratio [HR] 1.50, p = 0.001); tumor contact with the portal and superior mesenteric veins of ≤180° (HR 1.47, p = 0.003); carbohydrate antigen 19-9 levels of 40 to 500 U/mL (HR 1.59, p = 0.002) and ≥500 U/mL (HR 2.16, p < 0.001); and a modified Glasgow Prognostic Score of two (HR 1.56, p = 0.038) were predictors associated with OS. The prognostic prediction model for 5-year OS demonstrated an area under the curve of 0.68. The calibration plots indicate a concordance index of 0.63. Conclusions: We identified the preoperative prognostic factors for OS and developed a prognostic prediction model to estimate OS in patients undergoing UFS for resectable PDAC. Our model may be useful and internally validated for predicting OS. Full article