Modern predictors and management of incidental prostate cancer at holmium enucleation of prostate.

BACKGROUND: To evaluate contemporary preoperative risk factors and subsequent postoperative management of incidental prostate cancer (iPCa) and incidental clinically significant prostate cancer (icsPCa, Grade Group [GG] ≥ 2 PCa). METHODS: A retrospective cohort of 811 men undergoing Holmium enucleation of the prostate (HoLEP) (January 2021-July 2022) were identified. Advanced preoperative testing was defined as prostate health index (PHI), prostate MRI, and/or negative preoperative biopsy. Descriptive statistics (Whitney-Mann U test, Chi-squared test) and multivariable logistic regression were performed. RESULTS: iPCa and icsPCa detection rates were 12.8% (104/811) and 4.4% (36/811), respectively. Advanced preoperative testing (406/811, 50%) was associated with younger age and higher (prostate specific antigen) PSA, prostate volume, and PSA density. On multivariable analysis, PHI ≥ 55 was associated with iPCa (OR 6.91, 95% CI 1.85-26.3, p = 0.004), and % free PSA (%fPSA) was associated with icsPCa (OR 0.83, 95% CI 0.67, 0.94, p = 0.01). GG1 disease comprised the majority of iPCa (65%, 68/104) with median 1% involvement. iPCa patients were followed with active surveillance (median follow up 9.3 months), with higher risk patients receiving prostate MRI and confirmatory biopsy. Three patients proceeded to radical prostatectomy or radiation. CONCLUSIONS: In the era of MRI and advanced biomarkers, the majority of iPCa following HoLEP is low volume GG1 suitable for active surveillance. A tentative follow-up strategy is proposed. Patients with PHI ≥ 55 or low %fPSA, even with negative prostate MRI, can consider preoperative prostate biopsy before HoLEP.

A Genomics-Driven Artificial Intelligence-Based Model Classifies Breast Invasive Lobular Carcinoma and Discovers CDH1 Inactivating Mechanisms.

Artificial intelligence (AI)-systems can improve cancer diagnosis, yet their development often relies on subjective histological features as ground truth for training. Here, we developed an AI-model applied to histological whole-slide images (WSIs) using CDH1 bi-allelic mutations, pathognomonic for invasive lobular carcinoma (ILC) in breast neoplasms, as ground truth. The model accurately predicted CDH1 bi-allelic mutations (accuracy=0.95) and diagnosed ILC (accuracy=0.96). A total of 74% of samples classified by the AI-model as having CDH1 bi-allelic mutations but lacking these alterations displayed alternative CDH1 inactivating mechanisms, including a deleterious CDH1 fusion gene and non-coding CDH1 genetic alterations. Analysis of internal and external validation cohorts demonstrated 0.95 and 0.89 accuracy for ILC diagnosis, respectively. The latent features of the AI-model correlated with human-explainable histopathologic features. Taken together, this study reports the construction of an AI-algorithm trained using a genetic rather than histologic ground truth that can robustly classify ILCs and uncover CDH1 inactivating mechanisms, providing the basis for orthogonal ground truth utilization for development of diagnostic AI-models applied to WSI.

Enhancing Health Literacy: Evaluating the Readability of Patient Handouts Revised by ChatGPT's Large Language Model.

OBJECTIVE: To use an artificial intelligence (AI)-powered large language model (LLM) to improve readability of patient handouts. STUDY DESIGN: Review of online material modified by AI. SETTING: Academic center. METHODS: Five handout materials obtained from the American Rhinologic Society (ARS) and the American Academy of Facial Plastic and Reconstructive Surgery websites were assessed using validated readability metrics. The handouts were inputted into OpenAI's ChatGPT-4 after prompting: "Rewrite the following at a 6th-grade reading level." The understandability and actionability of both native and LLM-revised versions were evaluated using the Patient Education Materials Assessment Tool (PEMAT). Results were compared using Wilcoxon rank-sum tests. RESULTS: The mean readability scores of the standard (ARS, American Academy of Facial Plastic and Reconstructive Surgery) materials corresponded to "difficult," with reading categories ranging between high school and university grade levels. Conversely, the LLM-revised handouts had an average seventh-grade reading level. LLM-revised handouts had better readability in nearly all metrics tested: Flesch-Kincaid Reading Ease (70.8 vs 43.9; P < .05), Gunning Fog Score (10.2 vs 14.42; P < .05), Simple Measure of Gobbledygook (9.9 vs 13.1; P < .05), Coleman-Liau (8.8 vs 12.6; P < .05), and Automated Readability Index (8.2 vs 10.7; P = .06). PEMAT scores were significantly higher in the LLM-revised handouts for understandability (91 vs 74%; P < .05) with similar actionability (42 vs 34%; P = .15) when compared to the standard materials. CONCLUSION: Patient-facing handouts can be augmented by ChatGPT with simple prompting to tailor information with improved readability. This study demonstrates the utility of LLMs to aid in rewriting patient handouts and may serve as a tool to help optimize education materials. LEVEL OF EVIDENCE: Level VI.

Temporal trends of adolescents and young adults (AYA) with gynecologic malignancy in the United States.

In this retrospective cohort study examining 13,763,447 patients with 16 different malignancies, including 1,232,841 patients with five gynecologic malignancies (uterus [n = 690,590], ovary [n = 276,812], cervix [n = 166,779], vulva [n = 81,575], and vagina [n = 17,085]), identified in the Commission-on-Cancer's National Cancer Database from 2004 to 2020, cervical cancer (25.3 %) had the highest rate of adolescent and young adult (AYA) patients among 27 gender-stratified cancer groups (25.3%). There were 8 groups that the annual rates of AYA patients statistically increased during the study period at a P < .05 level, of which 7 (87.5 %) groups were for female malignancies. Among these 7 female malignancies, the annual percentage rate increase in AYA patients was largest for colorectal cancer (4.1 %, 95 % confidence interval 3.6-4.6), followed by malignancies in the ovary (3.1 %, 95 % confidence interval 1.6-4.5 in 2014-2020), pancreas (2.1 %, 95 % confidence interval 1.0-3.2), uterus (1.2 %, 95 % confidence interval 0.3-2.0 in 2013-2020), breast (0.8 %, 95 % confidence interval 0.2-1.4 in 2012-2020), cervix (0.8 %, 95 % confidence interval 0.2-1.5 in 2011-2020), and kidney (0.4 %, 95 % confidence interval 0.1-0.9). In conclusion, these data suggested that proportion of cancers attributable to AYA patients is increasing in several obesity-related female malignancies and in the three most common gynecologic malignancies.

Stage IC grade 1 endometrioid adenocarcinoma of the ovary: assessment of post-operative chemotherapy de-escalation.

OBJECTIVE: Given limited real-world practice data evaluating the National Comprehensive Cancer Network clinical practice guidelines for possible post-operative chemotherapy omission as a treatment option for patients with stage IC grade 1 endometrioid ovarian carcinoma, this population-based study examined the association between post-operative chemotherapy and overall survival in this tumor group. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results program was retrospectively queried. The study population was 1207 patients with stage IC grade 1-3 endometrioid ovarian carcinoma who received primary cancer-directed surgery from 2007 to 2020. Overall survival was assessed with multivariable Cox proportional hazard regression model. RESULTS: The median age was 52, 54, and 55 years for grade 1, 2, and 3 groups, respectively (p=0.02). Grade 1 and 2 tumors were more common than grade 3 tumors (n=508 (42.1%), n=493 (40.8%), and n=206 (17.1%), respectively). Chemotherapy use rate for grade 1 tumors was lower compared with grade 2-3 tumors (67.9%, 76.5%, and 78.6%, respectively, p<0.001). When nodal evaluation was performed for grade 1 tumors, among patients who did not receive post-operative chemotherapy and among those who did, 5-year overall survival rate exceeded 90% (93.3% and 96.0%, respectively), with statistically non-significant hazard estimates (adjusted hazard ratio (aHR) 1.54, 95% CI 0.63 to 3.73). In contrast, post-operative chemotherapy omission for patients who did not undergo nodal evaluation was associated with decreased overall survival (5-year rates 82.3% vs 96.0%, aHR 5.41, 95% CI 1.95 to 15.06). Results were similar for node-evaluated grade 2 tumors (5-year overall survival rates, 94.6% and 94.4% for node-evaluated post-operative chemotherapy omission and administration, respectively), but not in grade 3 tumors. CONCLUSION: The results of this population-based study may partially support the current clinical practice guidelines for post-operative chemotherapy omission as a possible option for patients with stage IC grade 1 endometrioid adenocarcinoma of the ovary for those who had lymph node evaluation. Observed data were also supportive for node-evaluated grade 2 tumors, warranting further evaluation.

Biotransformation of 6:2/4:2 fluorotelomer alcohols by Dietzia aurantiaca J3: Enzymes and proteomics.

Per- and polyfluoroalkyl substances (PFAS) are recalcitrant synthetic organohalides known to negatively impact human health. Short-chain fluorotelomer alcohols are considered the precursor of various perfluorocarboxylic acids (PFCAs) in the environment. Their ongoing production and widespread detection motivate investigations of their biological transformation. Dietzia aurantiaca strain J3 was isolated from PFAS-contaminated landfill leachate using 6:2 fluorotelomer sulphonate (6:2 FTS) as a sulphur source. Resting cell experiments were used to test if strain J3 could transform fluorotelomer alcohols (6:2 and 4:2 FTOH). Strain J3 transformed fluorotelomer alcohols into PFCAs, polyfluorocarboxylic acids and transient intermediates. Over 6 days, 80 % and 58 % of 6:2 FTOH (0.1 mM) and 4:2 FTOH (0.12 mM) were degraded with 6.4 % and 14 % fluoride recovery respectively. Fluorotelomer unsaturated carboxylic acid (6:2 FTUCA) was the most abundant metabolite, accounting for 21 to 30 mol% of 6:2 FTOH (0.015 mM) applied on day zero. Glutathione (GSH) conjugates of 6:2/4:2 FTOH and 5:3 FTCA adducts were also structurally identified. Proteomics studies conducted to identify enzymes in the biotransformation pathway have revealed the role of various enzymes involved in ß oxidation. This is the first report of 6:2/4:2 FTOH glutathione conjugates and 5:3 FTCA adducts in prokaryotes, and the first study to explore the biotransformation of 4:2 FTOH by pure bacterial strain.

Glioblastoma vulnerability to neddylation inhibition is dependent on PTEN status, and dysregulation of the cell cycle and DNA replication.

Background: Neddylation (NAE) inhibition, affecting posttranslational protein function and turnover, is a promising therapeutic approach to cancer. We report the cytotoxic vulnerability to NAE inhibitors in a subset of glioblastoma (GBM) preclinical models and identify genetic alterations and biological processes underlying differential response. Methods: GBM DNA sequencing and transcriptomic data were queried for genes associated with response to NAE inhibition; candidates were validated by molecular techniques. Multi-omics and functional assays revealed processes implicated in NAE inhibition response. Results: Transcriptomics and shotgun proteomics depict PTEN signaling, DNA replication, and DNA repair pathways as significant differentiators between sensitive and resistant models. Vulnerability to MLN4924, a NAE inhibitor, is associated with elevated S-phase populations, DNA re-replication, and DNA damage. In a panel of GBM models, loss of WT PTEN is associated with resistance to different NAE inhibitors. A NAE inhibition response gene set could segregate the GBM cell lines that are most resistant to MLN4924. Conclusions: Loss of WT PTEN is associated with non-sensitivity to 3 different compounds that inhibit NAE in GBM. A NAE inhibition response gene set largely consisting of DNA replication genes could segregate GBM cell lines most resistant to NAEi and may be the basis for future development of NAE inhibition signatures of vulnerability and clinical trial enrollment within a precision medicine paradigm.

Dietaryindex: A User-Friendly and Versatile R Package for Standardizing Dietary Pattern Analysis in Epidemiological and Clinical Studies.

BACKGROUND: Few standardized and open-source tools exist for calculating multiple dietary pattern indexes from dietary intake data in epidemiological and clinical studies. OBJECTIVE: The primary aim is to develop and validate dietaryindex, a user-friendly and versatile R package that standardizes the calculation of dietary indexes. METHODS: Dietaryindex can calculate multiple dietary indexes of high interest in research, including Healthy Eating Index (HEI) - 2020, Alternative Healthy Eating Index 2010, Dietary Approaches to Stop Hypertension Index, Alternate Mediterranean Diet Score, Dietary Inflammatory Index, American Cancer Society 2020 dietary index, and Planetary Health Diet Index from the EAT-Lancet Commission. The package includes generic dietary index calculation functions that accept any dietary assessment with preprocessed serving sizes of food groups and nutrients, as defined by the research group that developed each index. For ease of use and to eliminate any need for data preprocessing, dietaryindex also offers one-step functions that directly reference common datasets and tools, including the National Health and Nutrition Examination Survey (NHANES), Automated Self-Administered 24-Hour Dietary Assessment Tool (ASA24), Diet History Questionnaire III (DHQ3), and Block Food Frequency Questionnaire. At least two independent researchers validated the serving size definitions and scoring algorithms of dietaryindex. RESULTS: In our validation process, dietaryindex demonstrated full accuracy (100%) in all generic functions with two-decimal rounding precision in comparison to hand-calculated results. Similarly, using NHANES 2017-2018 data and ASA24 and DHQ3 example data, the HEI2015 outputs from dietaryindex aligned (99.95% - 100%) with results using the SAS codes from the National Cancer Institute. CONCLUSIONS: Dietaryindex is a user-friendly, versatile, and validated informatics tool for standardized dietary index calculations. We have open-sourced all the validation files and codes with detailed tutorials on GitHub (https://github.com/jamesjiadazhan/dietaryindex).

The Development of a New Model of Educational Leadership: Leadership for Teacher Flourishing.

This paper contributes to a broader movement in which the telos of leadership is flourishing, and the primary role of a leader is to promote the flourishing of their team members through creating a loving environment. In support of this, we propose a new perspective on, and associated model, of educational leadership: 'leadership for teacher flourishing' (LFTF). This model was developed through a literature review and a mixed methods research project across 78 British schools with collaborative and participatory elements which asked how school leaders could improve the flourishing of teachers. The quantitative and qualitative findings suggested that key factors in enabling teachers to flourish, and therefore incorporated into the model 'LFTF', were positive relationships; opportunities for growth; positive impact on subjective wellbeing; and increasing teachers' sense of meaning at work. The ways leaders could impact these factors were reported as: being supportive and compassionate; being trustworthy; giving teachers autonomy; enabling teachers to grow; being appreciative and focusing on strengths; and enabling teachers to do meaningful work. It was also found that not only leaders could influence flourishing; teachers with no formal leadership role could also positively impact teacher flourishing. It is suggested that virtuous dispositions in leaders are required to ensure they are consistent in acting in ways that promote flourishing. We argue that this integration of virtue and a desire to promote flourishing is properly understood as love. The participatory and collaborative phase of the research showed that teachers wanted autonomy in deciding what would help them to flourish. The conclusion sets out the implications of this research for policy on the training and selection of school leaders, to improve not only the flourishing of teachers, but also pupils and communities.

Role of buccal mucosa graft ureteroplasty in the surgical management of pyeloplasty failure.

Objective: Secondary pyeloplasty for recurrent ureteropelvic junction obstructions may be a safe and feasible surgical option for patients. This study aimed to demonstrate outcomes of utilizing a non-transecting buccal mucosa graft ureteroplasty for management of recurrent ureteropelvic junction obstruction after prior failed pyeloplasty. Methods: We performed a retrospective review of our Collaborative of Reconstructive Robotic Ureteral Surgery database for all consecutive patients who underwent buccal mucosa graft ureteroplasty between April 2012 and June 2022 for management of recurrent ureteropelvic junction obstructions after prior failed pyeloplasty. The primary outcome included surgical success which was defined as the absence of flank pain and no obstruction on imaging. Results: Overall, ten patients were included in our analysis. The median stricture length was 2.5 (interquartile range [IQR] 1.8-4.0) cm. The median operative time was 230.5 (IQR 199.5-287.0) min and median estimated blood loss was 50.0 (IQR 28.8-102.5) mL. At a median follow-up of 10.3 (IQR 6.2-14.8) months, 80% of patients were surgically successful and there were no major (Clavien-Dindo Grade>2) complications. Conclusion: Buccal mucosa graft ureteroplasty is a valuable non-transecting surgical option for patients with recurrent ureteropelvic junction obstructions who failed prior pyeloplasty and has comparable outcomes to the literature regarding standard transecting techniques.

Description of a novel robotic early post-prostatectomy anastomotic repair technique and institutional outcomes.

Objective: A vesicourethral anastomotic leak (VUAL) is a known complication following robotic-assisted radical prostatectomy. The natural history of a VUAL has been well described and is frequently managed with prolonged catheterization. With increasing emphasis on patient reported outcomes, catheter duration and VUAL are associated with significant short-term quality of life impairment. We aimed to present a case series of our robotic early post-prostatectomy anastomotic repair technique, defined as revision within 6 weeks from index surgery. Methods: A single institution prospective database identified eleven patients with a VUAL from July 2016 to October 2022 who underwent robotic early post-prostatectomy anastomotic repair by a single surgeon. Patients were diagnosed with a VUAL on pre-operative CT urogram or CT/fluoroscopic cystogram. The primary outcome was resolution of the anastomotic leak, defined as no contrast extravasation on post-operative cystography. Secondary outcomes included post-repair catheter duration and continence on the last follow-up defined as pad(s) per day. Results: The mean time to intervention after robotic-assisted radical prostatectomy was 21 days. Eight of the eleven (72.7%) patients had no evidence of extravasation on post-repair cystogram. The range from intervention to first cystogram was 7-20 days. The median catheter duration for those with successful intervention was 10 days. The median catheter duration for those with the leak on initial post-operative cystogram was 20 days. At a mean follow-up time of 25 months, eight (72.7%) patients reported using no pads per day, and three (27.3%) patients reported one pad per day. Conclusion: Management of a VUAL has traditionally relied on prolonged catheter drainage and the tincture of time. As the role of robotic reconstruction has been shown to be a viable modality for management of bladder neck contracture, it is important to reconsider prior dogmas of urologic care. Our case series suggests that an early repair is safe and has a high success rate. Early robotic intervention gives providers an additional tool in aiding patient recovery.

A review of complications after ureteral reconstruction.

Objective: This study aimed to provide a comprehensive overview of the complications unique to ureteral reconstruction in adults, emphasizing their presentation, diagnosis, and management in the treatment of ureteral structure disease. Methods: This review involves an in-depth analysis of existing literature and case studies pertaining to ureteral reconstruction, with a focus on examining the range of complications that can arise post-surgery. Special attention is given to the presentation of each complication, the diagnostic process involved, and the subsequent management strategies. Results: Ureteral reconstruction can treat ureteral stricture disease with low morbidity; however, complications, although uncommon, can have severe consequences. The most notable complications include urinary extravasation, stricture recurrence, urinary tract infections, compartment syndrome, symptomatic vesicoureteral reflux, and Boari flap necrosis. Each complication presents unique diagnostic challenges and requires specific management approaches. Conclusion: Ureteral reconstruction is a highly effective treatment for ureteral stricture disease. Having a strong understanding of the potential complications that patients may experience following ureteral reconstruction is not only critical to adequately counsel patients but also facilitate prompt diagnosis and management of complications when they arise.

Localization of protoporphyrin IX during glioma-resection surgery via paired stimulated Raman histology and fluorescence microscopy.

The most widely used fluorophore in glioma-resection surgery, 5-aminolevulinic acid (5-ALA), is thought to cause the selective accumulation of fluorescent protoporphyrin IX (PpIX) in tumour cells. Here we show that the clinical detection of PpIX can be improved via a microscope that performs paired stimulated Raman histology and two-photon excitation fluorescence microscopy (TPEF). We validated the technique in fresh tumour specimens from 115 patients with high-grade gliomas across four medical institutions. We found a weak negative correlation between tissue cellularity and the fluorescence intensity of PpIX across all imaged specimens. Semi-supervised clustering of the TPEF images revealed five distinct patterns of PpIX fluorescence, and spatial transcriptomic analyses of the imaged tissue showed that myeloid cells predominate in areas where PpIX accumulates in the intracellular space. Further analysis of external spatially resolved metabolomics, transcriptomics and RNA-sequencing datasets from glioblastoma specimens confirmed that myeloid cells preferentially accumulate and metabolize PpIX. Our findings question 5-ALA-induced fluorescence in glioma cells and show how 5-ALA and TPEF imaging can provide a window into the immune microenvironment of gliomas.

Dosing and Safety Profile of Aficamten in Symptomatic Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM.

BACKGROUND: Aficamten, a novel cardiac myosin inhibitor, reversibly reduces cardiac hypercontractility in obstructive hypertrophic cardiomyopathy. We present a prespecified analysis of the pharmacokinetics, pharmacodynamics, and safety of aficamten in SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM). METHODS AND RESULTS: A total of 282 patients with obstructive hypertrophic cardiomyopathy were randomized 1:1 to daily aficamten (5-20 mg) or placebo between February 1, 2022, and May 15, 2023. Aficamten dosing targeted the lowest effective dose for achieving site-interpreted Valsalva left ventricular outflow tract gradient <30 mm Hg with left ventricular ejection fraction (LVEF) ≥50%. End points were evaluated during titration (day 1 to week 8), maintenance (weeks 8-24), and washout (weeks 24-28), and included major adverse cardiac events, new-onset atrial fibrillation, implantable cardioverter-defibrillator discharges, LVEF <50%, and treatment-emergent adverse events. At week 8, 3.6%, 12.9%, 35%, and 48.6% of patients achieved 5-, 10-, 15-, and 20-mg doses, respectively. Baseline characteristics were similar across groups. Aficamten concentration increased by dose and remained stable during maintenance. During the treatment period, LVEF decreased by -0.9% (95% CI, -1.3 to -0.6) per 100 ng/mL aficamten exposure. Seven (4.9%) patients taking aficamten underwent per-protocol dose reduction for site-interpreted LVEF <50%. There were no treatment interruptions or heart failure worsening for LVEF <50%. No major adverse cardiovascular events were associated with aficamten, and treatment-emergent adverse events were similar between treatment groups, including atrial fibrillation. CONCLUSIONS: A site-based dosing algorithm targeting the lowest effective aficamten dose reduced left ventricular outflow tract gradient with a favorable safety profile throughout SEQUOIA-HCM. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05186818.

A foundation model for clinical-grade computational pathology and rare cancers detection.

The analysis of histopathology images with artificial intelligence aims to enable clinical decision support systems and precision medicine. The success of such applications depends on the ability to model the diverse patterns observed in pathology images. To this end, we present Virchow, the largest foundation model for computational pathology to date. In addition to the evaluation of biomarker prediction and cell identification, we demonstrate that a large foundation model enables pan-cancer detection, achieving 0.95 specimen-level area under the (receiver operating characteristic) curve across nine common and seven rare cancers. Furthermore, we show that with less training data, the pan-cancer detector built on Virchow can achieve similar performance to tissue-specific clinical-grade models in production and outperform them on some rare variants of cancer. Virchow's performance gains highlight the value of a foundation model and open possibilities for many high-impact applications with limited amounts of labeled training data.

Treatment options for patients with pilonidal sinus disease: PITSTOP, a mixed-methods evaluation.

Background: There is no consensus on optimal management of pilonidal disease. Surgical practice is varied, and existing literature is mainly single-centre cohort studies of varied disease severity, interventions and outcome assessments. Objectives: A prospective cohort study to determine: • disease severity and intervention relationship • most valued outcomes and treatment preference by patients • recommendations for policy and future research. Design: Observational cohort study with nested mixed-methods case study. Discrete choice experiment. Clinician survey. Three-stage Delphi survey for patients and clinicians. Inter-rater reliability of classification system. Setting: Thirty-one National Health Service trusts. Participants: Patients aged > 16 years referred for elective surgical treatment of pilonidal disease. Interventions: Surgery. Main outcome measures: Pain postoperative days 1 and 7, time to healing and return to normal activities, complications, recurrence. Outcomes compared between major and minor procedures using regression modelling, propensity score-based approaches and augmented inverse probability weighting to account for measured potential confounding features. Results: Clinician survey: There was significant heterogeneity in surgeon practice preference. Limited training opportunities may impede efforts to improve practice. Cohort study: Over half of patients (60%; N = 667) had a major procedure. For these procedures, pain was greater on day 1 and day 7 (mean difference day 1 pain 1.58 points, 95% confidence interval 1.14 to 2.01 points, n = 536; mean difference day 7 pain 1.53 points, 95% confidence interval 1.12 to 1.95 points, n = 512). There were higher complication rates (adjusted risk difference 17.5%, 95% confidence interval 9.1 to 25.9%, n = 579), lower recurrence (adjusted risk difference -10.1%, 95% confidence interval -18.1 to -2.1%, n = 575), and longer time to healing (>34 days estimated difference) and time to return to normal activities (difference 25.9 days, 95% confidence interval 18.4 to 33.4 days). Mixed-methods analysis: Patient decision-making was influenced by prior experience of disease and anticipated recovery time. The burden involved in wound care and the gap between expected and actual time for recovery were the principal reasons given for decision regret. Discrete choice experiment: The strongest predictors of patient treatment choice were risk of infection/persistence (attribute importance 70%), and shorter recovery time (attribute importance 30%). Patients were willing to trade off these attributes. Those aged over 30 years had a higher risk tolerance (22.35-34.67%) for treatment failure if they could experience rapid recovery. There was no strong evidence that younger patients were willing to accept higher risk of treatment failure in exchange for a faster recovery. Patients were uniform in rejecting excision-and-leave-open because of the protracted nursing care it entailed. Wysocki classification analysis: There was acceptable inter-rater agreement (κ = 0.52, 95% confidence interval 0.42 to 0.61). Consensus exercise: Five research and practice priorities were identified. The top research priority was that a comparative trial should broadly group interventions. The top practice priority was that any interventions should be less disruptive than the disease itself. Limitations: Incomplete recruitment and follow-up data were an issue, particularly given the multiple interventions. Assumptions were made regarding risk adjustment. Conclusions and future work: Results suggest the burden of pilonidal surgery is greater than reported previously. This can be mitigated with better selection of intervention according to disease type and patient desired goals. Results indicate a framework for future higher-quality trials that stratify disease and utilise broad groupings of common interventions with development of a patient-centred core outcome set. Trial registration: This trial is registered as ISRCTN95551898. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/17/02) and is published in full in Health Technology Assessment; Vol. 28, No. 33. See the NIHR Funding and Awards website for further award information.

Pilonidal disease is caused by ingrowing hairs between the buttocks. It can cause pain and infection and may need surgery. We do not know which operation gives the best results, or who operations help. PITSTOP aimed to find out which operation is the best and what is important to patients when deciding on surgery, and to suggest ideas for better treatment and future research. We looked at what operations were done and their outcomes. We interviewed patients about their experiences. Some completed a survey to help us understand what operations they might prefer based on risks and outcomes. Surgeons completed a survey about their experiences, and we explored whether a new tool could help us tell the difference between 'mild' and 'bad' disease. We used findings from these studies to help patients and surgeons give priorities for future practice and research. Six hundred and sixty-seven patients joined PITSTOP. People who had a major operation had more pain and took longer to return to normal activities. Some were still affected 6 months after surgery. However, disease recurrence was lower than after a minor procedure. Patients based decisions about treatment on the likelihood of success and the time to recover. The study and the surgeons' survey both showed marked differences in practice. Surgeons tended to offer one or two operations learned during training. A classification tool put cases in similar groups, but this did not influence treatment choices. The consensus exercise identified five research priorities, the top one being to put types of surgery into two groups. Of the five practice priorities, the top one was that surgery should not make the patient worse than the disease. There is variation in the treatment of pilonidal disease. Wound issues and impact on daily living should be avoided. The highlighted research questions should be addressed to improve care.