Defect width and operative time are the most significant predictors of venous thromboembolism in ventral hernia repair.

BACKGROUND: Venous thromboembolism is a significant cause of morbidity and mortality among patients undergoing ventral hernia repair. Several risk-assessment models have been developed to predict venous thromboembolism risk for various surgical procedures. However, these models do not include hernia-specific risk factors. Therefore, we sought to evaluate the predictors of venous thromboembolism in patients with a ventral hernia repair in a national hernia-specific database. METHODS: The Abdominal Core Health Quality Collaborative database was retrospectively queried for ventral hernia repair data. The ventral hernia repair procedures were divided into 2 groups on the basis of whether the patients developed perioperative venous thromboembolism. Baseline and operative characteristics and perioperative outcomes were compared between the 2 groups. The logistic regression was used to assess the association between different risk factors and venous thromboembolism. RESULTS: A total of 43,558 patients were included in the study. The 30-day venous thromboembolism rate among these patients was 0.62% (n = 269). Venous thromboembolism was associated with greater 30-day readmission (odds ratio, 4.29; 95% confidence interval, 3.20-5.76), reoperation (odds ratio, 3.97, 95% confidence interval, 2.63-6.00), and mortality rates (odds ratio, 5.95, 95% confidence interval, 2.62-13.48), all P < .001. Bivariate analysis identified a statistically significant association between several patient characteristics, operation, and hernia- related details; however, multivariate analysis revealed that that only hernia width (each increasing centimeter: odds ratio, 1.07, 95% CI, 1.05-1.09) and operative time compared with 0-59 minutes (60-119 minutes: odds ratio, 4.23; 95% confidence interval, 1.86-9.62; 120-179 minutes: odds ratio, 5.78; 95% confidence interval, 2.57-13.0; 180-239 minutes: odds ratio, 8.01; 95% confidence interval, 3.54-18.10; and 240+ minutes: odds ratio, 17.4; 95% confidence interval, 7.88-38.37) were significantly associated with venous thromboembolism risk. CONCLUSIONS: Venous thromboembolism is an uncommon complication of ventral hernia repair. It is associated with increased readmission, reoperation, and mortality rates. Larger defect width and operative time are most predictive of perioperative venous thromboembolism risk for patients undergoing ventral hernia repair.

Central pathology review and its prognostic value in upper tract urothelial carcinoma patients: a nationwide multi-institutional study.

The prognostic value of central pathology review in upper urinary tract cancer (UTUC) remains inadequately addressed in existing literature. In this study, we conducted an extensive central pathology review and presented its influence on multi-center UTUC studies. We conducted a retrospective review of patients who underwent radical nephroureterectomy or segmental resection for UTUC to determine eligibility for central pathology review. In the Taiwan UTUC Collaboration cohort, 377 cases met the criteria for pathology review. We assessed agreement between pathologists using both the total percentage of agreement and simple kappa statistics. The prognostic implications of original and review pathology for various parameters were examined using the Cox regression model. This study included 209 female and 168 male participants. Pathology review revealed substantial interobserver variability in pT staging, with a particularly high rate of pT2 cases being upgraded to pT3 upon central review (17/70 pT2 stage made by local pathologists were finally confirmed as pT3 disease by the review pathologist). The local pathologist cohort identified fewer significant histological predictors in survival models compared to the review pathology cohort. Advanced pT stage, perineural invasion (PNI), and positive surgical margin were independent predictors of poorer overall survival and cancer-specific survival. PNI, lymphatic vascular invasion, and positive surgical margin were independent predictors of disease recurrence. Substantial interobserver variability in histological assessment underscores the importance of centralized pathology review for both multi-center studies and accurate post-operative management of UTUC patients. Advanced stage, perineural invasion, and margin status were significant histological predictors of oncological outcomes.

Roles of transcriptional factor PsrA in the regulation of quorum sensing in Pseudomonas aeruginosa PAO1.

The transcription factor PsrA regulates fatty acid metabolism, the type III secretion system, and quinolone signaling quorum sensing system in Pseudomonas aeruginosa. To explore additional roles of PsrA in P. aeruginosa, this study engineered a P. aeruginosa PAO1 strain to carry a recombinant plasmid with the psrA gene (pMMBpsrA) and examined the impact of elevated psrA expression to the bacterium. Transcriptomic analysis revealed that PsrA significantly downregulated genes encoding the master quorum-sensing regulators, RhlR and LasR, and influenced many quorum-sensing-associated genes. The role of PsrA in quorum sensing was further corroborated by testing autoinducer synthesis in PAO1 [pMMBpsrA] using two reporter bacteria strains Chromobacterium violaceum CV026 and Escherichia coli [pSB1075], which respond to short- and long-chain acyl homoserine lactones, respectively. Phenotypic comparisons of isogenic ΔpsrA, ΔlasR, and ΔpsrAΔlasR mutants revealed that the reduced elastase, caseinase, and swarming activity in PAO1 [pMMBpsrA] were likely mediated through LasR. Additionally, electrophoretic mobility shift assays demonstrated that recombinant PsrA could bind to the lasR promoter at a 5'-AAACGTTTGCTT-3' sequence, which displays moderate similarity to the previously reported consensus PsrA binding motif. Furthermore, the PsrA effector molecule oleic acid inhibited PsrA binding to the lasR promoter and restored several quorum sensing-related phenotypes to wild-type levels. These findings suggest that PsrA regulates certain quorum-sensing phenotypes by negatively regulating lasR expression, with oleic acid acting as a crucial signaling molecule.

Dienogest treatment in women with endometriosis: A retrospective cohort study in Taiwan.

OBJECTIVE: To assess the treatment efficacy of dienogest specifically in the Taiwanese population with endometriosis. MATERIALS AND METHODS: Eighty-eight patients diagnosed with endometriosis receiving at least 3 months of dienogest 2 mg once daily, from January 2018 to June 2022, were enrolled. They were divided into two groups: surgery group and non-surgery group. The assessment of pain improvement was based on visual analog scale (VAS) scores (0-100 mm) recorded at 0, 3, 6, and 12 months following the initiation of dienogest. Serum CA-125 value and ovarian endometrioma size were analyzed at 0 and 6 months. RESULTS: A total of 65 patients with endometriosis presented painful symptoms. In the surgery group (N = 28), the initial VAS score was 47.5 mm, which significantly declined to 9.6 mm at 3 months (p < 0.01), then to 7.5 mm, 2.9 mm, and 2.1 mm at 6, 9, and 12 months, respectively. In the non-surgery group (N = 37), the initial VAS score was 65.7 mm, which significantly declined to 13.2 mm at 3 months (p < 0.01) and 4.9 mm at 6 months (p < 0.05), remained low at 0.3 mm at both 9 and 12 months. Endometrioma size (N = 33) exhibited a significant 35% decrease from 38.2 mm to 24.8 mm after 6 months treatment (p < 0.01). Serum CA-125 levels showed significant improvement from 86.5 to 30.2 U/ml (p < 0.01) at 6 months. CONCLUSION: This retrospective cohort study proved that dienogest is effective in reducing endometriosis-associated pain and endometrioma size in Taiwanese population.

Probiotic Lactobacillus fermentum TSF331, Lactobacillus reuteri TSR332, and Lactobacillus plantarum TSP05 improved liver function and uric acid management-A pilot study.

Metabolic-associated fatty liver disease (MAFLD) is predominantly associated with metabolic disturbances representing aberrant liver function and increased uric acid (UA) levels. Growing evidences have suggested a close relationship between metabolic disturbances and the gut microbiota. A placebo-controlled, double-blinded, randomized clinical trial was therefore conducted to explore the impacts of daily supplements with various combinations of the probiotics, Lactobacillus fermentum TSF331, Lactobacillus reuteri TSR332, and Lactobacillus plantarum TSP05 with a focus on liver function and serum UA levels. Test subjects with abnormal levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and UA were recruited and randomly allocated into six groups. Eighty-two participants successfully completed the 60-day intervention without any dropouts or occurrence of adverse events. The serum AST, ALT, and UA levels were significantly reduced in all treatment groups (P < 0.05). The fecal microbiota analysis revealed the intervention led to an increase in the population of commensal bacteria and a decrease in pathobiont bacteria, especially Bilophila wadsworthia. The in vitro study indicated the probiotic treatments reduced lipid accumulation and inflammatory factor expressions in HepG2 cells, and also promoted UA excretion in Caco-2 cells. The supplementation of multi-strain probiotics (TSF331, TSR332, and TSP05) together can improve liver function and UA management and may have good potential in treating asymptomatic MAFLD. Trial registration. The trial was registered in the US Library of Medicine (clinicaltrials.gov) with the number NCT06183801 on December 28, 2023.

Multisystem disorder associated with a pathogenic variant in CLCN7 in the absence of osteopetrosis.

BACKGROUND: We clinically and genetically evaluated a Taiwanese boy presenting with developmental delay, organomegaly, hypogammaglobulinemia and hypopigmentation without osteopetrosis. Whole-exome sequencing revealed a de novo gain-of-function variant, p.Tyr715Cys, in the C-terminal domain of ClC-7 encoded by CLCN7. METHODS: Nicoli et al. (2019) assessed the functional impact of p.Tyr715Cys by heterologous expression in Xenopus oocytes and evaluating resulting currents. RESULTS: The variant led to increased outward currents, indicating it underlies the patient's phenotype of lysosomal hyperacidity, storage defects and vacuolization. This demonstrates the crucial physiological role of ClC-7 antiporter activity in maintaining appropriate lysosomal pH. CONCLUSION: Elucidating mechanisms by which CLCN7 variants lead to lysosomal dysfunction will advance understanding of genotype-phenotype correlations. Identifying modifier genes and compensatory pathways may reveal therapeutic targets. Ongoing functional characterization of variants along with longitudinal clinical evaluations will continue advancing knowledge of ClC-7's critical roles and disease mechanisms resulting from its dysfunction. Expanded cohort studies are warranted to delineate the full spectrum of associated phenotypes.

Reference Values for Habitual and Fast Gait Speed in Singapore Adults Aged 21 to 80.

Objectives: Gait speed indicates the individual's functional status and predicts overall health. This study aims to determine (1) the intra- and inter-rater and test-retest reliability of the dynamic 4 m gait speed test protocol; (2) establish the normative reference values of habitual and fast gait speeds in community-dwelling healthy Singaporean adults aged 21 to 80; and (3) explore the association of age, gender, height, weight, and body mass index (BMI) on gait speed. Methods: This prospective cross-sectional study recruited healthy ambulatory community-dwelling Singaporeans aged 21 to 80 who could ambulate independently without aid. Participants were excluded if they required walking aids; were pregnant; or had physical, medical, or cognitive conditions that may affect gait. Each participant completed at least two habitual and fast gait speed test trials via a 4 m walkway with a dynamic start. The data were analysed by descriptive statistics, the Mann-Whitney test, the Spearman coefficient, and the interclass correlation coefficient (ICC). Results: In total, 178 males and 201 females were included in the data analysis. The median age was 45.0 years [interquartile range (IQR) 26.2-59.0], and the median height was 1.64 metres (m) (IQR 1.58-1.70). The median habitual gait speed was 1.08 metre/second (m/s) (IQR 0.97-1.22), and the fast gait speed was 1.55 m/s (IQR 1.40-1.70). The ICC for reliability ranged from 0.84 to 0.99, indicating that the 4 m gait speed test had good-to-excellent reliability. Conclusions: Gait speeds were not influenced by gender but declined with age advancement. Age and height and age and BMI were weakly correlated to habitual and fast gait speed, respectively. We established the norm values for the 4 m gait speeds in Singapore and proved it to be a reliable gait speed assessment ready for immediate community applications.

Efficacy of Lactococcus lactis subsp. lactis LY-66 and Lactobacillus plantarum PL-02 in Enhancing Explosive Strength and Endurance: A Randomized, Double-Blinded Clinical Trial.

Probiotics are posited to enhance exercise performance by influencing muscle protein synthesis, augmenting glycogen storage, and reducing inflammation. This double-blind study randomized 88 participants to receive a six-week intervention with either a placebo, Lactococcus lactis subsp. lactis LY-66, Lactobacillus plantarum PL-02, or a combination of both strains, combined with a structured exercise training program. We assessed changes in maximal oxygen consumption (VO2max), exercise performance, and gut microbiota composition before and after the intervention. Further analyses were conducted to evaluate the impact of probiotics on exercise-induced muscle damage (EIMD), muscle integrity, and inflammatory markers in the blood, 24 and 48 h post-intervention. The results demonstrated that all probiotic groups exhibited significant enhancements in exercise performance and attenuation of muscle strength decline post-exercise exhaustion (p < 0.05). Notably, PL-02 intake significantly increased muscle mass, whereas LY-66 and the combination therapy significantly reduced body fat percentage (p < 0.05). Analysis of intestinal microbiota revealed an increase in beneficial bacteria, especially a significant rise in Akkermansia muciniphila following supplementation with PL-02 and LY-66 (p < 0.05). Overall, the combination of exercise training and supplementation with PL-02, LY-66, and their combination improved muscle strength, explosiveness, and endurance performance, and had beneficial effects on body composition and gastrointestinal health, as evidenced by data obtained from non-athlete participants.

The Application of Rho Kinase Inhibitors in the Management of Glaucoma.

Glaucoma is a chronic neurodegenerative disease that poses a significant threat of irreversible blindness worldwide. Current treatments for glaucoma focus on reducing intraocular pressure (IOP), which is the only modifiable risk factor. Traditional anti-glaucomatous agents, including carbonic anhydrase inhibitors, beta-blockers, alpha-2 agonists, and prostaglandin analogs, work by either improving uveoscleral outflow or reducing aqueous humor production. Rho kinase (ROCK) inhibitors represent a novel class of anti-glaucomatous drugs that have emerged from bench to bedside in the past decade, offering multifunctional characteristics. Unlike conventional medications, ROCK inhibitors directly target the trabecular meshwork outflow pathway. This review aims to discuss the mechanism of ROCK inhibitors in reducing IOP, providing neuroprotection, and preventing fibrosis. We also highlight recent studies and clinical trials evaluating the efficacy and safety of ROCK inhibitors, compare them with other clinical anti-glaucomatous medications, and outline future prospects for ROCK inhibitors in glaucoma treatment.

Inequality in Older Volunteering: Association Between Volunteer Competency and Demographic Profiles.

The present survey research investigated older people's volunteering competency relating to social inequality by exploring the latent ability profile and demographic correlates of 1,000 older volunteers in 73 community care centersin southern Taiwan. Older volunteers were classified into advanced (n = 509), basic (n = 214), and novice (n = 277) groups. Demographics examined included: individualistic characteristics (religious beliefs), resources (education; number of chronic diseases), andsocial factors (serving area and spoken language, volunteering duration, marital status, and gender). Apparent inequality issues were revealed. The advanced group was better educated, Mandarin-speaking, and in urban areas. while the novice group featured the opposite (lower education Taiwanese-speaking suburban areas).

Exploring in vivo combinatorial chemo-immunotherapy: Addressing p97 suppression and immune reinvigoration in pancreatic cancer with tumor microenvironment-responsive nanoformulation.

Pancreatic ductal adenocarcinoma (PDAC) has an extremely devastating nature with poor prognosis and increasing incidence, making it a formidable challenge in the global fight against cancer-related mortality. In this innovative preclinical investigation, the VCP/p97 inhibitor CB-5083 (CB), miR-142, a PD-L1 inhibitor, and immunoadjuvant resiquimod (R848; R) were synergistically encapsulated in solid lipid nanoparticles (SLNs). These SLNs demonstrated features of peptides targeting PD-L1, EGFR, and the endoplasmic reticulum, enclosed in a pH-responsive polyglutamic (PGA)-polyethylene glycol (PEG) shell. The homogeneous size and zeta potential of the nanoparticles were stable for 28 days at 4°C. The study substantiated the concurrent modulation of key pathways by the CB, miR, and R-loaded nanoformulation, prominently affecting VCP/Bip/ATF6, PD-L1/TGF-ß/IL-4, -8, -10, and TNF-α/IFN-γ/IL-1, -12/GM-CSF/CCL4 pathways. This adaptable nanoformulation induced durable antitumor immune responses and inhibited Panc-02 tumor growth by enhancing T cell infiltration, dendritic cell maturation, and suppressing Tregs and TAMs in mice bearing Panc-02 tumors. Furthermore, tissue distribution studies, biochemical assays, and histological examinations highlighted enhanced safety with PGA and peptide-modified nanoformulations for CB, miR, and/or R in Panc-02-bearing mice. This versatile nanoformulation allows tailored adjustment of the tumor microenvironment, thereby optimizing the localized delivery of combined therapy. These compelling findings advocate the potential development of a pH-sensitive, three-in-one PGA-PEG nanoformulation that combines a VCP inhibitor, a PD-L1 inhibitor, and an immunoadjuvant for cancer treatment via combinatorial chemo-immunotherapy.

Enhancing the Permeate Flux Improvement of Direct Contact Membrane Distillation Modules with Inserted S-Ribs Carbon-Fiber Filaments.

Three widths of manufacturing S-ribs carbon-fiber filaments acting as turbulence promoters were implemented into the flow channel of direct contact membrane distillation (DCMD) modules to augment the permeate flux improvement in the present study. Attempts to reduce the disadvantageous temperature polarization effect were made by inserting S-ribs turbulence promoters in improving pure water productivity, in which both heat- and mass-transfer boundary layers were diminished due to creating vortices in the flow pattern and increasing turbulence intensity. The temperature polarization coefficient ttemp was studied and found to enhance device performance (less thermal resistance) under inserting various S-ribs carbon-fiber thicknesses and operating both cocurrent- and countercurrent-flow patterns. The permeate fluxes in the DCMD modules with inserted S-ribs carbon-fiber turbulence promoters were investigated theoretically by developing the mathematical modeling equations and were conducted experimentally with various design and operating parameters. The theoretical predictions and experimental results exhibited a great potential to considerably achieve permeate flux enhancement in the new design of the DCMD system. The DCMD module with inserted S-ribs carbon-fiber turbulence promoters in the flow channel could provide a relative permeate flux enhancement up to 37.77% under countercurrent-flow operations in comparisons with the module of using the empty channel. An economic consideration on both permeate flux enhancement and power consumption increment for the module with inserted S-ribs carbon-fiber filaments was also delineated.

Nardilysin-regulated scission mechanism activates polo-like kinase 3 to suppress the development of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) develops through step-wise genetic and molecular alterations including Kras mutation and inactivation of various apoptotic pathways. Here, we find that development of apoptotic resistance and metastasis of KrasG12D-driven PDAC in mice is accelerated by deleting Plk3, explaining the often-reduced Plk3 expression in human PDAC. Importantly, a 41-kDa Plk3 (p41Plk3) that contains the entire kinase domain at the N-terminus (1-353 aa) is activated by scission of the precursor p72Plk3 at Arg354 by metalloendopeptidase nardilysin (NRDC), and the resulting p32Plk3 C-terminal Polo-box domain (PBD) is removed by proteasome degradation, preventing the inhibition of p41Plk3 by PBD. We find that p41Plk3 is the activated form of Plk3 that regulates a feed-forward mechanism to promote apoptosis and suppress PDAC and metastasis. p41Plk3 phosphorylates c-Fos on Thr164, which in turn induces expression of Plk3 and pro-apoptotic genes. These findings uncover an NRDC-regulated post-translational mechanism that activates Plk3, establishing a prototypic regulation by scission mechanism.

AI-assisted literature exploration of innovative Chinese medicine formulas.

Objective: Our study provides an innovative approach to exploring herbal formulas that contribute to the promotion of sustainability and biodiversity conservation. We employ data mining, integrating keyword extraction, association rules, and LSTM-based generative models to analyze classical Traditional Chinese Medicine (TCM) texts. We systematically decode classical Chinese medical literature, conduct statistical analyses, and link these historical texts with modern pharmacogenomic references to explore potential alternatives. Methods: We present a novel iterative keyword extraction approach for discerning diverse herbs in historical TCM texts from the Pu-Ji Fang copies. Utilizing association rules, we uncover previously unexplored herb pairs. To bridge classical TCM herbal pairs with modern genetic relationships, we conduct gene-herb searches in PubMed and statistically validate this genetic literature as supporting evidence. We have expanded on the present work by developing a generative language model for suggesting innovative TCM formulations based on textual herb combinations. Results: We collected associations with 7,664 PubMed cross-search entries for gene-herb and 934 for Shenqifuzheng Injection as a positive control. We analyzed 16,384 keyword combinations from Pu-Ji Fang's 426 volumes, employing statistical methods to probe gene-herb associations, focusing on examining differences among the target genes and Pu-Ji Fang herbs. Conclusion: Analyzing Pu-Ji Fang reveals a historical focus on flavor over medicinal aspects in TCM. We extend our work on developing a generative model from classical textual keywords to rapidly produces novel herbal compositions or TCM formulations. This integrated approach enhances our comprehension of TCM by merging ancient text analysis, modern genetic research, and generative modeling.

Drop the shortcuts: image augmentation improves fairness and decreases AI detection of race and other demographics from medical images.

BACKGROUND: It has been shown that AI models can learn race on medical images, leading to algorithmic bias. Our aim in this study was to enhance the fairness of medical image models by eliminating bias related to race, age, and sex. We hypothesise models may be learning demographics via shortcut learning and combat this using image augmentation. METHODS: This study included 44,953 patients who identified as Asian, Black, or White (mean age, 60.68 years ±18.21; 23,499 women) for a total of 194,359 chest X-rays (CXRs) from MIMIC-CXR database. The included CheXpert images comprised 45,095 patients (mean age 63.10 years ±18.14; 20,437 women) for a total of 134,300 CXRs were used for external validation. We also collected 1195 3D brain magnetic resonance imaging (MRI) data from the ADNI database, which included 273 participants with an average age of 76.97 years ±14.22, and 142 females. DL models were trained on either non-augmented or augmented images and assessed using disparity metrics. The features learned by the models were analysed using task transfer experiments and model visualisation techniques. FINDINGS: In the detection of radiological findings, training a model using augmented CXR images was shown to reduce disparities in error rate among racial groups (-5.45%), age groups (-13.94%), and sex (-22.22%). For AD detection, the model trained with augmented MRI images was shown 53.11% and 31.01% reduction of disparities in error rate among age and sex groups, respectively. Image augmentation led to a reduction in the model's ability to identify demographic attributes and resulted in the model trained for clinical purposes incorporating fewer demographic features. INTERPRETATION: The model trained using the augmented images was less likely to be influenced by demographic information in detecting image labels. These results demonstrate that the proposed augmentation scheme could enhance the fairness of interpretations by DL models when dealing with data from patients with different demographic backgrounds. FUNDING: National Science and Technology Council (Taiwan), National Institutes of Health.

The association of hernia-specific and procedural risk factors with early complications in ventral hernia repair: ACHQC analysis.

BACKGROUND: Many surgical risk assessment tools emphasize patient-specific risk factors. Our objective was to use a hernia-specific database to assess risk factors of complications in ventral hernia repair (VHR) focusing on hernia-specific and procedural factors. METHODS: The ACHQC database was queried for elective VHR in adults from 2012 to 2023. Primary outcome was overall 30-day complications. Multivariable logistic regression was used for analysis. RESULTS: 41,526 VHR were included. The rate of 30-day complications was 18%, surgical site infection 3%, surgical site occurrence requiring procedural intervention 4%, readmission 4%, reoperation 2%, and mortality 0.2%. Multivariable analysis demonstrated that BMI, ASA, frailty, COPD, anticoagulants, defect width, incisional and recurrent hernias, presence of stoma or prior mesh, prior abdominal wall infection, non-clean wound, operative time, open approach and myofascial release were associated with 30-day complications (OR â€‹= â€‹1.01-1.66). Preoperative chlorhexidine, bowel preparation and fascial closure were associated with lower complication risk (OR â€‹= â€‹0.70-0.89). CONCLUSION: Hernia and procedural risk factors are associated with early complications following elective VHR. These factors need to be included in surgical risk assessment tools, to supplement patient-specific factors.

Impact of Procedural Variation in Endoscopic Dilation for Idiopathic Subglottic Stenosis.

OBJECTIVES: A small number of Idiopathic subglottic stenosis (iSGS) patients are treated at institutions across the country. Divergence in operative techniques for endoscopic dilation (ED) of iSGS has been anecdotally recognized but not formally characterized. Additionally, the relationship between procedural variation and clinical outcome has not been studied. METHODS: Secondary analysis of the NoAAC iSGS1000 cohort investigated variation in procedural techniques and treatment outcomes in patients treated with ED across high-enrolling treatment centers (enrolled >10 patients in PR-02 trial). RESULTS: Thirteen NoAAC centers each enrolled >10 patients treated with ED for a total of 281 subjects. There was significant variation in procedural details and rate of recurrence among institutions. Hierarchal cluster analysis revealed significant heterogeneity among institutions and clusters in all procedural variables. However, analysis demonstrated a transient delay in disease recurrence in cluster 2 which disappeared with longer longitudinal follow-up. Patient-reported outcome and peak expiratory flow data supported the potential benefit of the technical variation in Cluster 2. Distinct to cluster 2, however, was routine use of adjuvant triple medical therapy (proton pump inhibitor (PPI), antibacterial agent, and steroid inhaler). CONCLUSIONS: Both outcome and procedural technique vary among centers employing ED to treat iSGS. A transient delay in recurrence was observed among centers that routinely prescribed adjuvant medical therapy (antibiotic, inhaled corticosteroid, and PPI) to iSGS patients after endoscopic dilation, which was further supported by patient-reported data and peak expiratory flow data. Prospective studies are needed to understand the effects of adjuvant medical therapy on recurrence after endoscopic dilation. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3260-3266, 2024.

The factors impacting on Gleason score upgrading in prostate cancer with initial low Gleason scores.

BACKGROUND: This study aims to investigate the factors contributing to the discrepancy in between biopsy Gleason score (GS) and radical prostatectomy GS in patients diagnosed with prostate cancer. METHODS: 341 patients who underwent radical prostatectomy from 2011/04 to 2020/12 were identified. 102 Patients with initial GS of six after biopsy were enrolled. Preoperative clinical variables and pathological variables were also obtained and assessed. The optimal cut-off points for significant continuous variables were identified by the area under the receiver operating characteristic curve. RESULTS: Upgrading was observed in 63 patients and non-upgrading in 39 patients. In the multiple variables assessed, smaller prostate volume (PV) (p value = 0.0007), prostate specific antigen density (PSAD) (p value = 0.0055), positive surgical margins (p value = 0.0062) and pathological perineural invasion (p value = 0.0038) were significant predictors of GS upgrading. To further explore preclinical variables, a cut-off value for PV (≤ 38 ml, p value = 0.0017) and PSAD (≥ 0.26 ng/ml2, p value = 0.0013) were identified to be associated with GS upgrading. CONCLUSIONS: Smaller PV and elevated PSAD are associated with increased risk of GS upgrading, whereas lead-time bias is not. A cut-off value of PV < 38 ml and PSAD > 0.26 ng/ml2 were further identified to be associated with pathological GS upgrading.