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Publication Metadata only 423.11: Long-term compromised immune regulation after rituximab induction in blood group incompatible living-donor renal transplantation-5 year results of a prospective pilot study(Lippincott Williams & Wilkins, 2022) Weimer, Rolf; Karakizlis, Hristos; Renner, Fabrice; Dietrich, Hartmut; Daniel, Volker; Schüttler, Christian; Kämper, Daniel; Leicht, Dominik; Wörlen, Michael; Renner, Lene; Milchsack, Katrin; Padberg, Winfried; Opelz, Gerhard; Süsal, Caner; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 351800Background: An increased frequency of severe infectious diseases and BK viremia has been described after ABOi renal transplantation. As rituximab induction may alter immunoregulation in these patients, we analyzed clinically relevant immune parameters in a prospective renal transplant study up to 5 years posttransplant. Materials and Methods: Mononuclear cell subsets (peripheral blood; lymph nodes taken during transplant surgery), intracellular cytokine responses, CD4 helper function and in-vitro B cell responses were assessed pretransplant and up to 5 years posttransplant in 85 renal transplant recipients (living donation: n=25 ABO incompatible (ABOi) and n=30 ABO compatible (ABOc); deceased donation (DD): n=30, all ABO compatible). Results: Severe infectious diseases occurred more often in ABOi than ABOc recipients within 2 years posttransplant (11/24 (46%) versus 6/30 (20%), P=0.042) but not beyond. The incidence of BK viremia was significantly enhanced in rituximab versus non-rituximab treated patients (1 year: 9/29 (31%) versus 4/54 (7%), P=0.009; 5 years: 10/30 (33%) versus 7/53 (13%), P=0.029). After rituximab induction in ABOi recipients, counts of peripheral blood B cell subsets were profoundly downregulated even 3 years posttransplant and reached the level of non-ABOi recipients after 4 years (memory B cells after 5 years). T-dependent and T-independent B cell responses were significantly impaired in ABOi patients up to 2 years posttransplant (P=0.010 and P=0.053, respectively) whereas CD4 helper activity was not compromised. CD4+ T cell counts were significantly lower in ABOi compared to ABOc recipients at 3 and 6 months (P=0.025 and P=0.046, respectively), but showed no differences in the percentage of Tregs. In regional lymph nodes of ABOi patients, we found a significant downregulation of CD20+ but not CD19+ B cells (P<0.0005), of naive B cells (P=0.031) and short lived plasma cells (P<0.0005) at the time of transplantation. Conclusion: An increased frequency of severe infectious diseases and BK viremia in rituximab treated ABOi renal transplant recipients may be explained by significantly downregulated CD4+ T cell counts up to 6 months and a profoundly delayed B cell repopulation, most pronounced with regard to memory B cells, together with compromised B cell responses up to 2 years posttransplant. IL-10, as a key player in chronic BK virus infection, was not upregulated in rituximab-treated ABOi transplant recipients.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 A new technique of doppler dearterialization for hemorrhoidal disease: arterial detection ligation (ADL)(Springer, 2021) Zenger, Serkan; Gürbüz, Bülent; Can, Uğur; Yaltı, Mehmet Tunç; Faculty Member; School of Medicine; 221690Purpose: We describe the arterial detection ligation (ADL) technique, designed to find arteries at time-appropriate depth for ligating, and report our preliminary results of using this technique to treat patients with the hemorrhoidal disease (HD). Methods: The subjects of this retrospective analysis were patients with symptomatic grades 2 or 3 HD. We analyzed the clinical characteristics, postoperative complications, recurrence, and patient satisfaction of the patients treated with ADL. Results: A total of 75 patients were included in the study (male/female ratio 1.88; mean age 48 ± 19 years; mean BMI 24 ± 3 kg/m2). Thirty-nine patients (52%) did not require hospitalization and were discharged from the day clinic approximately 4 h postoperatively. Four patients (5.3%) suffered tenesmus for about 1 week postoperatively and two (2.7%) suffered temporary rectal bleeding. The mean VAS scores 1 day postoperatively, then at 1 week, 1 month and 1 year were 2.9, 1.5, 0.4, and 0, respectively. At the 1-month follow-up, there was no sign of recurrence and the satisfaction rate was 78.6% (n = 59). At the 1-year follow-up, three patients (4%) had a recurrence and the satisfaction rate was 86.7% (n = 65). Conclusion: Based on our preliminary findings, ADL is an effective technique for treating HD, generally as an outpatient procedure, without serious morbidity. We anticipate that the incidence of tenesmus, which is encountered frequently after other dearterialization methods, will be lower after the ADL technique, which avoids both mass ligation of hemorrhoidal arteries deeper than 12 mm and running a long mucopexy suture line.Publication Open Access A novel and simple machine learning algorithm for preoperative diagnosis of acute appendicitis in children(Springer, 2020) Türkmen, İnan Utku; Namlı, Gözde; Özturk, Çiğdem; Esen, Ayşe B.; Eray, Y. Nur; Akova, Fatih; Aydın, Emrah; Eroğlu, Egemen; Faculty Member; faculty Member; School of Medicine; 32059; N/AIntroduction: there is a tendency toward nonoperative management of appendicitis resulting in an increasing need for preoperative diagnosis and classification. For medical purposes, simple conceptual decision-making models that can learn are widely used. Decision trees are reliable and effective techniques which provide high classification accuracy. We tested if we could detect appendicitis and differentiate uncomplicated from complicated cases using machine learning algorithms. Materials and methods: we analyzed all cases admitted between 2010 and 2016 that fell into the following categories: healthy controls (Group 1); sham controls (Group 2); sham disease (Group 3), and acute abdomen (Group 4). The latter group was further divided into four groups: false laparotomy; uncomplicated appendicitis; complicated appendicitis without abscess, and complicated appendicitis with abscess. Patients with comorbidities and whose complete blood count and/or pathology results were lacking were excluded. Data were collected for demographics, preoperative blood analysis, and postoperative diagnosis. Various machine learning algorithms were applied to detect appendicitis patients. Results: there were 7244 patients with a mean age of 6.84 +/- 5.31 years, of whom 82.3% (5960/7244) were male. Most algorithms tested, especially linear methods, provided similar performance measures. We preferred the decision tree model due to its easier interpretability. With this algorithm, we detected appendicitis patients with 93.97% area under the curve (AUC), 94.69% accuracy, 93.55% sensitivity, and 96.55% specificity, and uncomplicated appendicitis with 79.47% AUC, 70.83% accuracy, 66.81% sensitivity, and 81.88% specificity. Conclusions: machine learning is a novel approach to prevent unnecessary operations and decrease the burden of appendicitis both for patients and health systems.Publication Open Access A novel Fontan Y-graft for interrupted inferior vena cava and azygos continuation(Oxford University Press (OUP), 2022) Çicek, Murat; Köse, Banu; Yılmaz, Emine Hekim; Aydemir, Numan Ali; Özkök, Serçin; Yurtseven, Nurgül; Erdem, Hasan; Sasmazel, Ahmet; Department of Mechanical Engineering; Lashkarinia, Seyedeh Samaneh; Pekkan, Kerem; Rezaeimoghaddam, Mohammad; Rasooli, Reza; Faculty Member; Researcher; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; 161845; N/A; N/AObjectives: to evaluate the hemodynamicdynamic advantage of a new Fontan surgical template that is intended for complex single-ventricle patients with interrupted inferior vena cava-azygos and hemi-azygos continuation. The new technique has emerged from a comprehensive pre-surgical simulation campaign conducted to facilitate a balanced hepatic flow and somatic Fontan pathway growth after Kawashima procedure. Methods: for 9 patients, aged 2 to 18 years, majority having poor preoperative oxygen saturation, a pre-surgical computational fluid dynamics customization is conducted. Both the traditional Fontan pathways and the proposed novel Y-graft templates are considered. Numerical model was validated against in vivo phase-contrast magnetic resonance imaging data and in vitro experiments. Results: the proposed template is selected and executed for 6 out of the 9 patients based on its predicted superior hemodynamic performance. Pre-surgical simulations performed for this cohort indicated that flow from the hepatic veins (HEP) do not reach to the desired lung. The novel Y-graft template, customized via a right- or left-sided displacement of the total cavopulmonary connection anastomosis location resulted a drastic increase in HEP flow to the desired lung. Orientation of HEP to azygos direct shunt is found to be important as it can alter the flow pattern from 38% in the caudally located direct shunt to 3% in the cranial configuration with significantly reversed flow. The postoperative measurements prove that oxygen saturation increased significantly (P-value = 0.00009) to normal levels in 1 year follow-up. Conclusions: the new Y-graft template, if customized for the individual patient, is a viable alternative to the traditional surgical pathways. This template addresses the competing hemodynamic design factors of low physiological venous pressure, high postoperative oxygen saturation, low energy loss and balanced hepatic growth factor distribution possibly assuring adequate lung development.Publication Metadata only A novel modification of tongue in groove technique (auto-septal projection graft) in rhinoplasty(Springer, 2021) Koçak, İlker; N/A; Gökler, Ozan; Teaching Faculty; School of Medicine; 311179Introduction Derotation of the nasal tip with narrow nasolabial angle is a common nasal deformity that leads to a long nose appearance, named drooping nose. In these patients, there are various techniques described to fix droopy tip and to achieve a desirable nasal tip rotation such as caudal septal extension graft, extended columellar strut graft, tongue in groove, columellar strut graft, and tip rotation sutures. This study aimed to evaluate changes in nasal tip support after modified tongue-in-groove technique (auto-septal projection graft). Materials and Methods Forty-two patients who underwent a primary open approach septorhinoplasty using the modified tongue-in-groove technique between June 2017 and March 2019 were retrospectively analyzed. Postoperative and preoperative photographs were analyzed, and nasolabial angle and the nasal tip projection ratio were recorded and compared before and average of 17.3 months after the surgery. Results Forty-two patients (33 female and 9 male) were included the study. The mean nasolabial angle was 85.7 degrees preoperatively and 99.3 degrees postoperatively. The nasal tip projection ratio was 0.60 preoperatively and 0.64 postoperatively. Both the tip rotation and the tip projection increased significantly after the modified tongue in groove (p<0.05). Conclusion It seems that modified tongue-in-groove method (auto-septal projection graft) is an effective technique in maintaining tip projection and rotation in rhinoplasty and safe method to correct droopy nasal tip in selected cases.Publication Metadata only Abo and rh blood groups and risk of myelomeningocele(Turkish Neurosurgical Soc, 2020) Isik, Semra; Cevik, Serdar; Turhan, Ali Haydar; Hanimoglu, Hakan; N/A; Baygül, Arzu Eden; Faculty Member; School of Medicine; 272290AIM: To investigate the relationship between the distribution of ABO or Rhesus (Rh) blood group antigens and the incidence of myelomeningocele. MATERIAL and METHODS: A retrospective data was reviewed for all myelomeningocele patients operated at a tertiary academic hospital between years 2014 and 2019. Age, sex, delivery method, physical and neurological examination findings, and radiological findings alongside with blood type of each patient were recorded. The data of blood group distribution among the study patients was compared to the data of healthy individuals in the same region. RESULTS: Patients with group B and AB showed a higher chance of developing myelomeningocele. Rh-positive blood group was associated with high incidence of myelomeningocele (93.5%), whereas Rh-negative blood group showed least association (6.5%). Rh-positive blood group was also found to be more frequent in patients with myelomeningocele with hydrocephalus and Chiari malformation. CONCLUSION: The findings of this study show that ABO and Rh blood groups have an effect on the development of myelomeningocele under the influence of environmental or genetic factors.Publication Metadata only Acinar cystic transformation of the pancreas(Lippincott Williams and Wilkins (LWW), 2023) Luchini, Claudio; Mattiolo, Paola; Basturk, Olca; Mafficini, Andrea; Ozcan, Kerem; Lawlor, Rita T.; Hong, Seung-Mo; Brosens, Lodewijk A.; Marchegiani, Giovanni; Pea, Antonio; Manfrin, Erminia; Sciacca, Giuseppe; Zampieri, Federica; Polati, Rita; De Robertis, Riccardo; Milella, Michele; D'Onofrio, Mirko; Malleo, Giuseppe; Salvia, Roberto; Scarpa, Aldo; N/A; Adsay, Nazmi Volkan; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Koç University Hospital; 286248Acinar cystic transformation (ACT) of the pancreas, previously called acinar cell cystadenoma, is a poorly understood and rare entity among pancreatic cystic lesions. This study aims to clarify its real nature. This research cohort included 25 patients with pancreatic ACT, representing the largest series in the literature. We describe their clinicopathological features and molecular profile using next-generation sequencing. ACT arose more often in women (F/M similar or equal to 2:1), in the body-tail region, with a mean size of similar to 4 cm. At the latest follow-up, all patients were alive and disease free. Histologically, a typical acinar epithelium lined all cysts, intermingled with ductal-like epithelium in 11/25 (44%) cases. All the cases lacked any evidence of malignancy. Three ACT showed peculiar features: 1 showed an extensive and diffuse microcystic pattern, and the other 2 harbored foci of low-grade pancreatic intraepithelial neoplasia (PanIN) in the ductal-like epithelium. Next-generation sequencing revealed the presence of 2 pathogenic/likely pathogenic mutations in 2 different cases, 1 with ductal-like epithelium and 1 with PanIN, and affecting KRAS (c.34G>C, p.G12R) and SMO (c.1685G>A, p.R562Q) genes, respectively. The other case with PanIN was not available for sequencing. Overall, our findings support that ACT is a benign entity, potentially arising from heterogeneous conditions/background, including: (1) acinar microcysts, (2) malformations, (3) obstructive/inflammatory setting, (4) genetic predisposition, (5) possible neoplastic origin. Although all indications are that ACT is benign, the potential occurrence of driver mutations suggests discussing a potential role of long-term surveillance for these patients.Publication Metadata only Acute-onset hemiparkinsonism secondary to subacute-chronic subdural hematoma(Turkish Neurosurgical Soc, 2022) Özekmekçi, Sibel; Şenel, Gülçin Benbir; N/A; Ertan, Fatoş Sibel; Çakmak, Özgür Öztop; Peker, Selçuk; Faculty Member; Faculty Member; Faculty Member; School of Medicine; School of Medicine; School of Medicine; Koç University Hospital; 112829; 299358; 11480Subdural hematomas constitute rare causes of secondary Parkinsonism in elderly. Subacute or chronic subdural hematomas occur in the elderly following minor head trauma or even without a remarkable history of trauma. A 69-year-old woman admitted with a rapidly progressive acute-onset hemiparkinsonism on the left side of her body. She denied any precipitating event before the onset of her symptoms, and her medical history was unremarkable. The anti-Parkinsonian therapy showed no benefit, but gradually worsening of the symptoms was observed. Her brain magnetic resonance imaging revealed a large subacute-chronic subdural hematoma on the right side with a mass effect on the basal ganglia structures, contralateral to her symptomatology. On thorough questioning, she confessed to having fallen out of the bed at night almost four weeks ago, three-weeks before the onset of her symptomatology. She had no complications associated with this fall and merely remembered this event. She denied any history of rapid eye movements (REM) sleep behavior disorder. The anti-Parkinsonian treatment was discontinued; the subdural hematoma was evacuated via burr hole drainage surgery. Her symptoms disappeared instantly after the surgery, with a normal neurologic examination one week after the surgery.Publication Metadata only Adjuvant versus on-progression Gamma Knife radiosurgery for residual nonfunctioning pituitary adenomas: A matched-cohort analysis(Amer Assoc Neurological Surgeons, 2023) Mantziaris, Georgios; Pikis, Stylianos; Chytka, Tomas; Liscak, Roman; Sheehan, Kimball; Sheehan, Darrah; Bindal, Shray K.; Niranjan, Ajay; Lunsford, L. Dade; Kaur, Rupinder; Madan, Renu; Tripathi, Manjul; Pangal, Dhiraj J.; Strickland, Ben A.; Zada, Gabriel; Langlois, Anne-Marie; Mathieu, David; Warnick, Ronald E.; Patel, Samir; Minier, Zayda; Speckter, Herwin; Xu, Zhiyuan; Anand, Rithika Kormath; Sheehan, Jason P.; Peker, Selçuk; Samancı, Mustafa Yavuz; School of MedicineOBJECTIVE Radiological progression occurs in 50%-60% of residual nonfunctioning pituitary adenomas (NFPAs). Stereotactic radiosurgery (SRS) is a safe and effective management option for residual NFPAs, but there is no consen-sus on its optimal timing. This study aims to define the optimal timing of SRS for residual NFPAs. METHODS This retrospective, multicenter study involved 375 patients with residual NFPAs managed with SRS. The patients were divided into adjuvant (ADJ;treated for stable residual NFPA within 6 months of resection) and progression (PRG) cohorts (treated for residual NFPA progression). Factors associated with tumor progression and clinical deteriora-tion were analyzed.RESULTS Following propensity-score matching, each cohort consisted of 130 patients. At last follow-up, tumor con-trol was achieved in 93.1% of patients in the ADJ cohort and in 96.2% of patients in the PRG cohort (HR 1.6, 95% CI 0.55-4.9, p = 0.37). Hypopituitarism was associated with a maximum point dose of > 8 Gy to the pituitary stalk (HR 4.5, 95% CI 1.6-12.6, p = 0.004). No statistically significant difference was noted in crude new-onset hypopituitarism rates (risk difference [RD] = -0.8%, p > 0.99) or visual deficits (RD = -2.3%, p = 0.21) between the two cohorts at the last follow-up. The median time from resection to new hypopituitarism was longer in the PRG cohort (58.9 vs 29.7 months, p = 0.01).CONCLUSIONS SRS at residual NFPA progression does not appear to alter the probability of tumor control or hormon-al/visual deficits compared with adjuvant SRS. Deferral of radiosurgical management to the time of radiological progres- sion could significantly prolong the time to radiosurgically induced pituitary dysfunction. A lower maximum point dose (< 8 Gy) to the pituitary stalk portended a more favorable chance of preserving pituitary function after SRS. https://thejns.org/doi/abs/10.3171/2022.10.JNS221873