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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 Novel vaginal cerclage assisted laparoscopic cervico-sacropexy technique for uterovaginal prolapse(SAGE Publications Ltd, 2024) Aydın, Serdar; Çekiç, Sebile Güler; School of Medicine; Koç University HospitalAim Laparoscopic hysteropexy is a complicated procedure that requires specialized surgical skills, including precise dissection and suturing. The aim is to describe the technical considerations for performing a new, feasible, and minimally invasive technique to correct apical and concurrent apical and anterior vaginal wall defects.Method A retrospective analysis was conducted on 70 consecutive women who underwent surgery for stage >= 3 uterovaginal prolapse. As a part of the technique, an anterior 2-cm long transverse incision was made at the anterior cervicovaginal junction, and the bladder was dissected through blunt and sharp dissection to the level of the isthmus. A posterior colpotomy was performed. A polypropylene tape was inserted into the cervical connective tissue, and the free arms of the tape were inserted into the peritoneum via the posterior colpotomy. Two arms of the tape were passed from the tunnel parallel and medial to a right sacrouterine fold, then fixed to the anterior longitudinal ligament via the laparoscopic route.Results The tape can be inserted into the cervix in a median of 15 min, and the laparoscopy procedure can be completed in 24 min. No mesh erosion or long-term complications occurred. At a 1-year control, there were no cases of recurrence.Conclusions This novel cervico-sacrocolpopexy technique is a feasible and safe, minimally invasive way to correct apical or multicompartment defects, with a short operation time and an anatomical result that mimics the normal sacrouterine ligament.Publication Metadata only What is hot and new in basic and translational science in liver transplantation in 2022? Report of the basic and translational research committee of the international liver transplantation society(Lippincott Williams & Wilkins, 2023) Bhat, Mamatha; Dondossola, Daniele; Varghese, Rhea; Czigany, Zoltan; Emamaullee, Juliet; Ghinolfi, Davide; Al-Adra, David; Bonaccorsi-Riani, Eliano; Pang, Li; Boteon, Yuri L.; Brueggenwirth, Isabel; Pavan-Guimaraes, Juliana; Ho, Cheng-Maw; Zarrinpar, Ali; Abdelrahim, Maen; Barbas, Andrew S.; Mas, Valeria; Selzner, Markus; Martins, Paulo N.; Yüksel, Muhammed; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM)N/APublication Metadata only Prognostic significance of pathologic lymph node invasion in metastatic renal cell carcinoma in the immunotherapy era(Springer, 2023) Scheipner, Lukas; Barletta, Francesco; Garcia, Cristina Cano; Incesu, Reha-Baris; Morra, Simone; Baudo, Andrea; Assad, Anis; Tian, Zhe; Saad, Fred; Shariat, Shahrokh F.; Briganti, Alberto; Chun, Felix K. H.; Longo, Nicola; Carmignani, Luca; Pichler, Martin; Ahyai, Sascha; Karakiewicz, Pierre I.; Tilki, Derya; School of Medicine; Koç University HospitalBackground: This study aimed to test the prognostic significance of pathologically confirmed lymph node invasion in metastatic renal cell carcinoma (mRCC) patients in this immunotherapy era. Methods: Surgically treated mRCC patients were identified in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2018. Kaplan-Meier plots and multivariable Cox-regression models were fitted to test for differences in cancer-specific mortality (CSM) and overall mortality (OM) according to N stage (pN0 vs pN1 vs. pNx). Subgroup analyses addressing pN1 patients tested for CSM and OM differences according to postoperative systemic therapy status.Results: Overall, 3149 surgically treated mRCC patients were identified. Of these patients, 443 (14%) were labeled as pN1, 812 (26%) as pN0, and 1894 (60%) as pNx. In Kaplan-Meier analyses, the median CSM-free survival was 15 months for pN1 versus 40 months for pN0 versus 35 months for pNx (P < 0.001). In multivariable Cox regression analyses, pN1 independently predicted higher CSM (hazard ratio [HR], 1.88; P < 0.01) and OM (HR, 1.95; P < 0.01) relative to pN0. In sensitivity analyses addressing pN1 patients, postoperative systemic therapy use independently predicted lower CSM (HR, 0.73; P < 0.01) and OM (HR, 0.71; P < 0.01). Conclusion: Pathologically confirmed lymph node invasion independently predicted higher CSM and OM for surgically treated mRCC patients. For pN1 mRCC patients, use of postoperative systemic therapy was associated with lower CSM and OM. Consequently, N stage should be considered for individual patient counseling and clinical decision-making.Publication Metadata only In-hospital venous thromboembolism and pulmonary embolism after major urologic cancer surgery(Springer, 2023) Garcia, Cristina Cano; Tappero, Stefano; Piccinelli, Mattia Luca; Barletta, Francesco; Incesu, Reha-Baris; Morra, Simone; Scheipner, Lukas; Baudo, Andrea; Tian, Zhe; Hoeh, Benedikt; Chierigo, Francesco; Sorce, Gabriele; Saad, Fred; Shariat, Shahrokh F.; Carmignani, Luca; Ahyai, Sascha; Longo, Nicola; Briganti, Alberto; De Cobell, Ottavio; Dell'Oglio, Paolo; Mandel, Philipp; Terrone, Carlo; Chun, Felix K. H.; Karakiewicz, Pierre I.; Tilki, Derya; School of Medicine; Koç University HospitalBackground: This study aimed to test for temporal trends of in-hospital venous thromboembolism (VTE) and pulmonary embolism (PE) after major urologic cancer surgery (MUCS). Methods: In the Nationwide Inpatient Sample (NIS) database (2010-2019), this study identified non-metastatic radical cystectomy (RC), radical prostatectomy (RP), radical nephrectomy (RN), and partial nephrectomy (PN) patients. Temporal trends of VTE and PE and multivariable logistic regression analyses (MLR) addressing VTE or PE, and mortality with VTE or PE were performed. Results: Of 196,915 patients, 1180 (1.0%) exhibited VTE and 583 (0.3%) exhibited PE. The VTE rates increased from 0.6 to 0.7% (estimated annual percentage change [EAPC] + 4.0%; p = 0.01). Conversely, the PE rates decreased from 0.4 to 0.2% (EAPC - 4.5%; p = 0.01). No difference was observed in mortality with VTE (EAPC - 2.1%; p = 0.7) or with PE (EAPC - 1.2%; p = 0.8). In MLR relative to RP, RC (odds ratio [OR] 5.1), RN (OR 4.5), and PN (OR 3.6) were associated with higher VTE risk (all p < 0.001). Similarly in MLR relative to RP, RC (OR 4.6), RN (OR 3.3), and PN (OR 3.9) were associated with higher PE risk (all p < 0.001). In MLR, the risk of mortality was higher when VTE or PE was present in RC (VTE: OR 3.7, PE: OR 4.8; both p < 0.001) and RN (VTE: OR 5.2, PE: OR 8.3; both p < 0.001). Conclusions: RC, RN, and PN predisposes to a higher VTE and PE rates than RP. Moreover, among RC and RN patients with either VTE or PE, mortality is substantially higher than among their VTE or PE-free counterparts.Publication Metadata only Regional differences in total hospital costs for radical cystectomy in the United States(Elsevier Sci Ltd, 2023) Hoeh, Benedikt; Flammia, Rocco Simone; Hohenhorst, Lukas; Sorce, Gabriele; Chierigo, Francesco; Panunzio, Andrea; Tian, Zhe; Saad, Fred; Gallucci, Michele; Briganti, Alberto; Terrone, Carlo; Shariat, Shahrokh F.; Graefen, Markus; Antonelli, Alessandro; Kluth, Luis A.; Becker, Andreas; Chun, Felix K. H.; Karakiewicz, Pierre I.; Tilki, Derya; School of Medicine; Koç University HospitalObjectives: To test for regional differences in total hospital costs (THC) across the United States in bladder cancer patients treated with open radical cystectomy (ORC) or robotic-assisted radical cystectomy (RARC). Materials: We relied on the National Inpatient Sample (NIS) database (2016-2019) and stratified RC patients according to census region (Midwest, Northeast, South, West). Primary statistical analyses consisted of THC-trend analyses and multivariable log-link linear regression models, after adjustment for hospital clustering (Generalized Estimating Equation function) and discharge disposition weighting. Finally, sensitivity analysis, relying on most favorable patient cohort, was performed. Results: Of 5280 eligible patients, 1441 (27%), 1031 (20%), 1854 (35%) and 954 (18%) underwent RC in the Midwest, Northeast, South and West, respectively. Median THC was 28,915$ and differed significantly between regions (Midwest: 28,105$; Northeast: 28,886$; South: 26,096$; West: 38,809$; p < 0.001). After stratification between ORC and RARC, highest THC was invariably recorded in the West: ORC 36,137$ vs 23,941-28,850$ and RARC 43,119$ vs 28,425-29,952$ (both p < 0.05). In multivariable log-link linear regression models, surgery in the West was independently associated with higher THC: ORC (Exponent beta (Exp(beta]]: 1.39; 95%-CI: 1.32-1.47; p < 0.001) and RARC (Exp(beta]: 1.46; 95%-CI: 1.38-1.55; p < 0.001). Results remained unchanged when analyses were refitted in most favorable patient subgroup. Conclusions: Important regional differences in ORC and RARC THC distinguish the West from other United States regions. The THC discrepancy clearly requires closer examination to identify underlying processes that contribute to inflated costs in the West.Publication Metadata only A multinational cohort study examining sex differences in excess risk of death with graft function after kidney transplant(Lippincott Williams and Wilkins, 2024) Vinson, A.J,; Zhang, X.; Dahhou, M.; Döhler, B.; Sapir-Pichhadze, R.; Cardinal, H.; Melk, A.; Wong, G.; Francis, A.; Pilmore, H.; Foster, B.J.; Süsal, Caner; Koç University Transplant Immunology Research Centre of Excellence (TIREX); School of Medicine; Koç University HospitalBackground: Kidney transplant recipients show sex differences in excess overall mortality risk that vary by donor sex and recipient age. However, whether the excess risk of death with graft function (DWGF) differs by recipient sex is unknown. Methods: In this study, we combined data from 3 of the largest transplant registries worldwide (Scientific Registry of Transplant Recipient, Australia and New Zealand Dialysis and Transplant Registry, and Collaborative Transplant Study) using individual patient data meta-analysis to compare the excess risk of DWGF between male and female recipients of a first deceased donor kidney transplant (1988-2019), conditional on donor sex and recipient age. Results: Among 463 895 individuals examined, when the donor was male, female recipients aged 0 to 12 y experienced a higher excess risk of DWGF than male recipients (relative excess risk 1.68; 95% confidence interval, 1.24-2.29); there were no significant differences in other age intervals or at any age when the donor was female. There was no statistically significant between-cohort heterogeneity. Conclusions: Given the lack of sex differences in the excess risk of DWGF (other than in prepubertal recipients of a male donor kidney) and the known greater excess overall mortality risk for female recipients compared with male recipients in the setting of a male donor, future study is required to characterize potential sex-specific causes of death after graft loss.Publication Metadata only Impact of gut microbiota on liver transplantation(Elsevier Science Inc, 2023) Basarir, Kerem E.; Mihaylov, Plamen; Lee, Jason T. C.; Fridell, Jonathan A.; Emamaullee, Juliet A.; Ekser, Burcin; Sucu, Serkan; Balık, Emre; School of MedicineThe gut microbiota has been gaining attention due to its interactions with the human body and its role in pathophysiological processes. One of the main interactions is the "gut-liver axis," in which disruption of the gut mucosal barrier seen in portal hypertension and liver disease can influence liver allograft function over time. For example, in patients who are undergoing liver transplantation, preexisting dysbiosis, perioperative antibiotic use, surgical stress, and immunosuppressive use have each been associated with alterations in gut microbiota, potentially impacting overall morbidity and mortality. In this review, studies exploring gut microbiota changes in patients undergoing liver transplantation are reviewed, including both human and experimental animal studies. Common themes include an increase in Enterobacteriaceae and Enterococcaceae species and a decrease in Faecalibacterium prausnitzii and Bacteriodes, while a decrease in the overall diversity of gut microbiota after liver transplantation.Publication Metadata only Donor-derived cell-free DNA (dd-cfDNA) in kidney transplant recipients with indication biopsy-results of a prospective single-center trial(Frontiers Media Sa, 2023) Benning, Louise; Morath, Christian; Fink, Annette; Rudek, Markus; Speer, Claudius; Kaelble, Florian; Nusshag, Christian; Beimler, Joerg; Schwab, Constantin; Waldherr, Ruediger; Zeier, Martin; Suesal, Caner; Tran, Thuong Hien; Süsal, Caner; Koç University Transplant Immunology Research Centre of Excellence (TIREX); School of Medicine; Koç University HospitalDonor-derived cell-free DNA (dd-cfDNA) identifies allograft injury and discriminates active rejection from no rejection. In this prospective study, 106 kidney transplant recipients with 108 clinically indicated biopsies were enrolled at Heidelberg University Hospital between November 2020 and December 2022 to validate the clinical value of dd-cfDNA in a cohort of German patients. dd-cfDNA was quantified at biopsy and correlated to histopathology. Additionally, dd-cfDNA was determined on days 7, 30, and 90 post-biopsy and analyzed for potential use to monitor response to anti-rejection treatment. dd-cfDNA levels were with a median (IQR) % of 2.00 (0.48-3.20) highest in patients with ABMR, followed by 0.92 (0.19-11.25) in patients with TCMR, 0.44 (0.20-1.10) in patients with borderline changes and 0.20 (0.11-0.53) in patients with no signs of rejection. The AUC for dd-cfDNA to discriminate any type of rejection including borderline changes from no rejection was at 0.72 (95% CI 0.62-0.83). In patients receiving anti-rejection treatment, dd-cfDNA levels significantly decreased during the 7, 30, and 90 days follow-up compared to levels at the time of biopsy (p = 0.006, p = 0.002, and p < 0.001, respectively). In conclusion, dd-cfDNA significantly discriminates active rejection from no rejection. Decreasing dd-cfDNA following anti-rejection treatment may indicate response to therapy.Publication Metadata only Immune response to Covid-19 mRNA vaccination in previous nonresponder kidney transplant recipients after short-term withdrawal of mycophenolic acid 1 and 3 months after an additional vaccine dose(Lippincott Williams & Wilkins, 2023) Kuehn, Tessa; Speer, Claudius; Morath, Christian; Bartenschlager, Marie; Kim, Heeyoung; Beimler, Joerg; Buylaert, Mirabel; Nusshag, Christian; Kaelble, Florian; Reineke, Marvin; Toellner, Maximilian; Klein, Katrin; Blank, Antje; Parthe, Sylvia; Schnitzler, Paul; Zeier, Martin; Bartenschlager, Ralf; Tran, Thuong Hien; Schaier, Matthias; Benning, Louise; Süsal, Caner; Koç University Transplant Immunology Research Centre of Excellence (TIREX); School of Medicine; Koç University HospitalBackground: The impaired immune response to coronavirus disease 2019 (Covid-19) vaccination in kidney transplant recipients (KTRs) leads to an urgent need for adapted immunization strategies. Methods: Sixty-nine KTRs without seroconversion after =3 Covid-19 vaccinations were enrolled, and humoral response was determined after an additional full-dose mRNA-1273 vaccination by measuring severe acute respiratory syndrome coronavirus 2-specific antibodies and neutralizing antibody activity against the Delta and Omicron variants 1 and 3 mo postvaccination. T-cell response was analyzed 3 mo postvaccination by assessing interferon-? release. Mycophenolic acid (MPA) was withdrawn in 41 KTRs 1 wk before until 4 wk after vaccination to evaluate effects on immunogenicity. Graft function, changes in donor-specific anti-HLA antibodies, and donor-derived cell-free DNA were monitored in KTRs undergoing MPA withdrawal. Results: Humoral response to vaccination was significantly stronger in KTRs undergoing MPA withdrawal 1 mo postvaccination; however, overall waning humoral immunity was noted in all KTRs 3 mo after vaccination. Higher anti-S1 immunoglobulin G levels correlated with better neutralizing antibody activity against the Delta and Omicron variants, whereas no significant association was detected between T-cell response and neutralizing antibody activity. No rejection occurred during study, and graft function remained stable in KTRs undergoing MPA withdrawal. In 22 KTRs with Omicron variant breakthrough infections, neutralizing antibody activity was better against severe acute respiratory syndrome coronavirus 2 wild-type and the Delta variants than against the Omicron variant. Conclusions: MPA withdrawal to improve vaccine responsiveness should be critically evaluated because withdrawing MPA may be associated with enhanced alloimmune response, and the initial effect of enhanced seroconversion rates in KTRs with MPA withdrawal disappears 3 mo after vaccination.