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Publication Metadata only Ethics of deep brain stimulation for neuropsychiatric disorders(Springer, 2024) Darko, K.; Detchou, D.; Barrie, U.; Aydın, Serhat; School of MedicineDeep Brain Stimulation (DBS) has emerged as a revolutionary neurosurgical technique with significant implications for the treatment of various neuropsychiatric disorders. Initially developed for movement disorders like Parkinson’s disease, DBS has expanded to psychiatric conditions such as obsessive-compulsive disorder, depression, anorexia nervosa, dystonia, essential tremor, and Tourette’s syndrome. This paper explores the clinical efficacy and ethical considerations of DBS in treating these disorders. While DBS has shown substantial promise in alleviating symptoms and improving quality of life, it raises ethical challenges, including issues of informed consent, patient selection, long-term management, and equitable access to treatment. The irreversible nature of DBS, potential adverse effects, and the high cost of the procedure necessitate a rigorous ethical framework to guide its application. The ongoing evolution of neuromodulation requires continuous ethical analysis and the development of guidelines to ensure that DBS is used responsibly and equitably across different patient populations. This paper underscores the need for a balanced approach that integrates clinical efficacy with ethical considerations to optimize patient outcomes and ensure sustainable practice.Publication Metadata only Endometriosis, staging, infertility and assisted reproductive technology: time for a rethink(Elsevier Inc., 2024) Somigliana, Edgardo; Ata, Mustafa Barış; School of MedicineHow endometriosis causes infertility, with the exception of tubal dysfunction caused by adhesions, is unclear. The inflammatory milieu in the pelvis and impaired receptivity of the eutopic endometrium are considered to be possible factors. Anatomical staging systems fail to predict the fertility status of endometriosis patients. Data from assisted reproductive technology cycles consistently suggest that oocytes from patients with endometriosis have a normal potential to develop into euploid blastocysts. Moreover, oocyte or embryo recipients with endometriosis seem to have similar or slightly lower pregnancy and live birth rates compared with recipients without endometriosis, suggesting that eutopic endometrium is not or is only minimally affected, which may be caused by undiagnosed adenomyosis. In-vivo observations from women with endometriomas provide evidence against a detrimental effect of endometriomas on oocytes. Combined with the absence of an obvious improvement in fertility following the surgical destruction or excision of peritoneal endometriosis or from temporary medical suppression of the disease and the associated inflammation, the available evidence makes endometriosis-associated infertility questionable in the absence of tubal dysfunction caused by adhesions. It is likely that no anatomical staging will correlate with fertility beyond assessing tubal function. In patients with endometriosis assisted reproductive technology is as effective as for other indications.Publication Metadata only The effect of adrenalectomy on overall survival in metastatic adrenocortical carcinoma(Endocrine Society, 2024) Assad, A.; Incesu, R.B.; Morra, S.; Scheipner, L.; Baudo, A.; Siech, C.; De Angelis, M.; Tian, Z.; Ahyai, S.; Longo, N.; Chun, F.K.H.; Shariat, S.F.; Briganti, A.; Saad, F.; Karakiewicz, P.I.; Tilki, Derya; Koç University HospitalContext: Although complete surgical resection provides the only means of cure in adrenocortical carcinoma (ACC), the magnitude of the survival benefit of adrenalectomy in metastatic ACC (mACC) is unknown. Objective: This work aimed to assess the effect of adrenalectomy on survival outcomes in patients with mACC in a real-world setting. Methods: Patients with mACC aged 18 years or older with metastatic ACC at initial presentation who were treated between 2004 and 2020 were identified within the Surveillance, Epidemiology, and End Results database (SEER 2004-2020), and we tested for differences according to adrenalectomy status. Intervention included primary tumor resection status (adrenalectomy vs no adrenalectomy). Kaplan-Meier plots, multivariable Cox regression models, and landmark analyses were used. Sensitivity analyses focused on use of systemic therapy, contemporary (2012-2020) vs historical (2004-2011), single vs multiple metastatic sites, and assessable specific solitary metastatic sites (lung only and liver only). Results: Of 543 patients with mACC, 194 (36%) underwent adrenalectomy. In multivariable analyses, adrenalectomy was associated with lower overall mortality without (hazard ratio [HR]: 0.39; P < .001), as well as with 3 months' landmark analyses (HR: 0.57; P = .002). The same association effect with 3 months' landmark analyses was recorded in patients exposed to systemic therapy (HR: 0.49; P < .001), contemporary patients (HR: 0.57; P = .004), historical patients (HR: 0.42; P < .001), and in those with lung-only solitary metastasis (HR: 0.50; P = .02). In contrast, no statistically significant association was recorded in patients naive to systemic therapy (HR: 0.68; P = .3), those with multiple metastatic sites (HR: 0.55; P = .07), and those with liver-only solitary metastasis (HR: 0.98; P = .9). Conclusion: The present results indicate a potential protective effect of adrenalectomy in mACC, particularly in patients exposed to systemic therapy and those with lung-only metastases.Publication Metadata only Does the holy grail of the evidence pyramid vindicate the controversial practice of endometrial scratching or is there room for healthy skepticism?(Oxford University Press, 2024) N/A; Ata, Mustafa Barış; Kalafat, Erkan; School of MedicineN/APublication Metadata only Deep learning-augmented T-junction droplet generation(Elsevier Inc., 2024) N/A; Department of Mechanical Engineering; Ahmadpour, Abdollah; Shojaeian, Mostafa; Taşoğlu, Savaş; Department of Mechanical Engineering; KU Arçelik Research Center for Creative Industries (KUAR) / KU Arçelik Yaratıcı Endüstriler Uygulama ve Araştırma Merkezi (KUAR); Koç Üniversitesi İş Bankası Yapay Zeka Uygulama ve Araştırma Merkezi (KUIS AI)/ Koç University İş Bank Artificial Intelligence Center (KUIS AI); Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); College of EngineeringDroplet generation technology has become increasingly important in a wide range of applications, including biotechnology and chemical synthesis. T-junction channels are commonly used for droplet generation due to their integration capability of a larger number of droplet generators in a compact space. In this study, a finite element analysis (FEA) approach is employed to simulate droplet production and its dynamic regimes in a T-junction configuration and collect data for post-processing analysis. Next, image analysis was performed to calculate the droplet length and determine the droplet generation regime. Furthermore, machine learning (ML) and deep learning (DL) algorithms were applied to estimate outputs through examination of input parameters within the simulation range. At the end, a graphical user interface (GUI) was developed for estimation of the droplet characteristics based on inputs, enabling the users to preselect their designs with comparable microfluidic configurations within the studied range.Publication Metadata only Perspective on smart materials for empowering small-scale manipulation(Elsevier B.V., 2024) Zhang, Mingchao; Department of Mechanical Engineering; Sitti, Metin; Department of Mechanical Engineering; College of EngineeringPublication Metadata only Feasibility of next-generation sequencing of liquid biopsy (circulating tumor DNA) samples and tumor tissue from patients with metastatic prostate cancer in a real-world clinical setting in germany(Elsevier B.V., 2024) Mandel, Philipp; Hoeh, Benedikt; Humke, Clara; Doering, Claudia; Wenzel, Mike; Cano Garcia, Cristina; Fuhr, Nina; Koll, Florestan; Fassl, Anne; Steuber, Thomas; Faull, Iris; Jeroch, Jan; Ebner, Silvana; Schmitt, Christina; Reis, Henning; Köllermann, Jens; Kokkaliaris, Konstantinos D.; Demes, Melanie C.; Chun, Felix K.H.; Wild, Peter J.; Tilki, Derya; School of MedicineBackground and objective: With European Medicines Agency approval of PARP inhibitors in metastatic castration-resistant prostate cancer and ongoing trials in metastatic hormone-sensitive prostate cancer, detection of genetic alterations in BRCA1/2 and other homologous recombination repair genes has gained an important role. Our aim was to investigate the feasibility and comparability of comprehensive next-generation sequencing (NGS) of liquid biopsy (LB; circulating tumor DNA) and tumor tissue (TT) samples in a real-world clinical setting. Methods: The study cohort consisted of 50 patients with metastatic prostate cancer (mPC) who had TT NGS performed for BRCA1/2 alterations and consent for additional LB NGS. The Oncomine Comprehensive Assay v3 (Thermo Fisher Scientific, Waltham, MA, USA) was used for TT NGS. The Guardant360 83-gene assay (Guardant Health, Palo Alto, CA, USA) was used for LB NGS, including all types of somatic alterations, microsatellite instability, and blood tumor mutational burden. We calculated BRCA1/2 alteration rates and the negative percentage agreement (NPA) and positive percentage agreement (PPA) between TT and LB results. Key findings and limitations: TT NGS was successful in 44/50 patients (88%), with pathogenic BRCA1/2 alterations detected in four (9%). LB NGS was successful in all 50 patients (100%), with BRCA1/2 alterations detected in ten (20%). In a subgroup analysis for the 44 patients with successful TT NGS, NPA was 85% and PPA was 50%. The median time between TT sample collection and blood sampling for NGS was 132 wk (IQR 94–186). The limited sample size and differences in the time of NGS assessment are limitations. Conclusions and clinical implications: LB NGS resulted in a higher detection rate for BRCA1/2 alterations in comparison to conventional TT NGS (20% vs 9%). Ideally, BRCA1/2 testing should be based on both approaches to identify all patients with mPC eligible for PARP inhibitor therapy. Patient summary: Our study shows that genetic tests for both tumor tissue and blood samples results in higher rates of detection of BRCA1/2 gene alterations in patients with metastatic prostate cancer.Publication Metadata only EAU-EANM-ESTRO-ESUR-ISUP-SIOG guidelines on prostate cancer—2024 update. Part i: screening, diagnosis, and local treatment with curative intent(Elsevier B.V., 2024) Cornford, Philip; van den Bergh, Roderick C.N.; Briers, Erik; Van den Broeck, Thomas; Brunckhorst, Oliver; Darraugh, Julie; Eberli, Daniel; De Meerleer, Gert; De Santis, Maria; Farolfi, Andrea; Gandaglia, Giorgio; Gillessen, Silke; Grivas, Nikolaos; Henry, Ann M.; Lardas, Michael; van Leenders, Geert J.L.H.; Liew, Matthew; Linares Espinos, Estefania; Oldenburg, Jan; van Oort, Inge M.; Oprea-Lager, Daniela E.; Ploussard, Guillaume; Roberts, Matthew J.; Rouvière, Olivier; Schoots, Ivo G.; Schouten, Natasha; Smith, Emma J.; Stranne, Johan; Wiegel, Thomas; Willemse, Peter-Paul M.; Tilki, Derya; School of MedicineBackground and objective: The European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Urological Pathology (ISUP)-International Society of Geriatric Oncology (SIOG) guidelines provide recommendations for the management of clinically localised prostate cancer (PCa). This paper aims to present a summary of the 2024 version of the EAU-EANM-ESTRO-ESUR-ISUP-SIOG guidelines on the screening, diagnosis, and treatment of clinically localised PCa. Methods: The panel performed a literature review of all new data published in English, covering the time frame between May 2020 and 2023. The guidelines were updated, and a strength rating for each recommendation was added based on a systematic review of the evidence. Key findings and limitations: A risk-adapted strategy for identifying men who may develop PCa is advised, generally commencing at 50 yr of age and based on individualised life expectancy. The use of multiparametric magnetic resonance imaging in order to avoid unnecessary biopsies is recommended. When a biopsy is considered, a combination of targeted and regional biopsies should be performed. Prostate-specific membrane antigen positron emission tomography imaging is the most sensitive technique for identifying metastatic spread. Active surveillance is the appropriate management for men with low-risk PCa, as well as for selected favourable intermediate-risk patients with International Society of Urological Pathology grade group 2 lesions. Local therapies are addressed, as well as the management of persistent prostate-specific antigen after surgery. A recommendation to consider hypofractionation in intermediate-risk patients is provided. Patients with cN1 PCa should be offered a local treatment combined with long-term intensified hormonal treatment. Conclusions and clinical implications: The evidence in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. These PCa guidelines reflect the multidisciplinary nature of PCa management. Patient summary: This article is the summary of the guidelines for “curable” prostate cancer. Prostate cancer is “found” through a multistep risk-based screening process. The objective is to find as many men as possible with a curable cancer. Prostate cancer is curable if it resides in the prostate; it is then classified into low-, intermediary-, and high-risk localised and locally advanced prostate cancer. These risk classes are the basis of the treatments. Low-risk prostate cancer is treated with “active surveillance”, a treatment with excellent prognosis. For low-intermediary-risk active surveillance should also be discussed as an option. In other cases, active treatments, surgery, or radiation treatment should be discussed along with the potential side effects to allow shared decision-making.Publication Metadata only CPAP may promote an endothelial inflammatory milieu in sleep apnoea after coronary revascularization(Elsevier B.V., 2024) Behboudi, Afrouz; Redline, Susan; Lyu, Jing; Wei, Ying; Gottlieb, Daniel J.; Jelic, Sanja; Peker, Yüksel; Çelik, Yeliz; School of MedicineBackground: Continuous positive airway pressure (CPAP) has failed to reduce cardiovascular risk in obstructive sleep apnoea (OSA) in randomized trials. CPAP increases angiopoietin-2, a lung distension-responsive endothelial proinflammatory marker associated with increased cardiovascular risk. We investigated whether CPAP has unanticipated proinflammatory effects in patients with OSA and cardiovascular disease. Methods: Patients with OSA (apnoea-hypopnea index [AHI] ≥15 events/h without excessive sleepiness) in the Randomized Intervention with CPAP in Coronary Artery Disease and OSA study were randomized to CPAP or usual care following coronary revascularization. Changes in plasma levels of biomarkers of endothelial (angiopoietin-2, Tie-2, E-selectin, vascular endothelial growth factor [VEGF-A]) and lung epithelial (soluble receptor of advanced glycation end-products [sRAGE]) function from baseline to 12-month follow-up were compared across groups and associations with cardiovascular morbidity and mortality assessed. Findings: Patients with OSA (n = 189; 84% men; age 66 ± 8 years, BMI 28 ± 3.5 kg/m2, AHI 41 ± 23 events/h) and 91 patients without OSA participated. Angiopoietin-2 remained elevated whereas VEGF-A declined significantly over 12 months in the CPAP group (n = 91). In contrast, angiopoietin-2 significantly declined whereas VEGF-A remained elevated in the usual care (n = 98) and OSA-free groups. The changes in angiopoietin-2 and VEGF-A were significantly different between CPAP and usual care, whereas Tie-2, sRAGE and E-selectin were similar. Greater 12-month levels of angiopoietin-2 were associated with greater mortality. Greater CPAP levels were associated with worse cardiovascular outcomes. Interpretation: Greater CPAP levels increase proinflammatory, lung distension-responsive angiopoietin-2 and reduce cardioprotective angiogenic factor VEGF-A compared to usual care, which may counteract the expected cardiovascular benefits of treating OSA. Funding: National Institutes of Health/ National Heart, Lung, and Blood Institute; Swedish Research Council; Swedish Heart-Lung Foundation; ResMed Foundation.Publication Metadata only Current standards for training in robot-assisted surgery and endourology: a systematic review(Elsevier B.V., 2024) Basile, Giuseppe; Gallioli, Andrea; Diana, Pietro; Gallagher, Anthony; Larcher, Alessandro; Graefen, Markus; Harke, Nina; Traxer, Olivier; Van Der Poel, Henk; Emiliani, Esteban; Angerri, Oriol; Wagner, Christian; Montorsi, Francesco; Wiklund, Peter; Somani, Bhaskar; Buffi, Nicolò; Mottrie, Alex; Liatsikos, Evangelos; Breda, Alberto; Tilki, Derya; School of MedicineBackground and objective: Different training programs have been developed to improve trainee outcomes in urology. However, evidence on the optimal training methodology is sparse. Our aim was to provide a comprehensive description of the training programs available for urological robotic surgery and endourology, assess their validity, and highlight the fundamental elements of future training pathways. Methods: We systematically reviewed the literature using PubMed/Medline, Embase, and Web of Science databases. The validity of each training model was assessed. The methodological quality of studies on metrics and curricula was graded using the MERSQI scale. The level of evidence (LoE) and level of recommendation for surgical curricula were awarded using the educational Oxford Centre for Evidence-Based Medicine classification. Key findings and limitations: A total of 75 studies were identified. Many simulators have been developed to aid trainees in mastering skills required for both robotic and endourology procedures, but only four demonstrated predictive validity. For assessment of trainee proficiency, we identified 18 in robotics training and six in endourology training; however, the majority are Likert-type scales. Although proficiency-based progression (PBP) curricula demonstrated superior outcomes to traditional training in preclinical settings, only four of six (67%) in robotics and three of nine (33%) in endourology are PBP-based. Among these, the Fundamentals of Robotic Surgery and the SIMULATE curricula have the highest LoE (level 1b). The lack of a quantitative synthesis is the main limitation of our study. Conclusions and clinical implications: Training curricula that integrate simulators and PBP methodology have been introduced to standardize trainee outcomes in robotics and endourology. However, evidence regarding their educational impact remains restricted to preclinical studies. Efforts should be made to expand these training programs to different surgical procedures and assess their clinical impact. Patient summary: Simulation-based training and programs in which progression is based on proficiency represent the new standard of quality for achieving surgical proficiency in urology. Studies have demonstrated the educational impact of these approaches. However, there are still no standardized training pathways for several urology procedures.