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Item Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease(2021) Ozen, Ahmet; Kasap, Nurhan; Vujkovic-Cvijin, Ivan; Apps, Richard; Cheung, Foo; Karakoc-Aydiner, Elif; Akkelle, Bilge; Sari, Sinan; Tutar, Engin; Uygun, Dilara Kocacik; Islek, Ali; Akgun, Gamze; Selcuk, Merve; Sezer, Oya Balci; Ozcay, Figen; Zhang, Yu; Kutluk, Gunsel; Topal, Erdem; Sayar, Ersin; Celikel, Cigdem; Houwen, Roderick H.J.; Bingol, Aysen; Ogulur, Ismail; Eltan, Sevgi Bilgic; Snow, Andrew L.; Lake, Camille; Fantoni, Giovanna; Alba, Camille; Sellers, Brian; Chauvin, Samuel D.; Dalgard, Clifton L.; Harari, Olivier; Ni, Yan G.; Wang, Ming-Dauh; Devalaraja-Narashimha, Kishor; Subramanian, Poorani; Ergelen, Rabia; Artan, Reha; Guner, Sukru Nail; Dalgic, Buket; Tsang, John; Belkaid, Yasmine; Ertem, Deniz; Baris, Safa; Lenardo, Michael J.; https://orcid.org/0000-0002-8402-8208; https://orcid.org/0000-0002-5214-516X; 33398182; AAI-9346-2021; ABG-5684-2020CHAPLE disease is a lethal syndrome caused by genetic loss of the complement regulatory protein CD55. Lenardo, Ozen and their colleagues report that blockade of C5 complement activation in a small cohort of pediatric patients with CHAPLE disease reduced gastrointestinal pathology and restored their immunity and growth. Complement hyperactivation, angiopathic thrombosis and protein-losing enteropathy (CHAPLE disease) is a lethal disease caused by genetic loss of the complement regulatory protein CD55, leading to overactivation of complement and innate immunity together with immunodeficiency due to immunoglobulin wasting in the intestine. We report in vivo human data accumulated using the complement C5 inhibitor eculizumab for the medical treatment of patients with CHAPLE disease. We observed cessation of gastrointestinal pathology together with restoration of normal immunity and metabolism. We found that patients rapidly renormalized immunoglobulin concentrations and other serum proteins as revealed by aptamer profiling, re-established a healthy gut microbiome, discontinued immunoglobulin replacement and other treatments and exhibited catch-up growth. Thus, we show that blockade of C5 by eculizumab effectively re-establishes regulation of the innate immune complement system to substantially reduce the pathophysiological manifestations of CD55 deficiency in humans.Item A Comparison between Mygind and Kaiteki positions in administration of drops to the olfactory cleft(2021) Milk, Dafna G.; Khong, Grace C.; Cam, Osman H.; Alfaro-Iraheta, Fernando; Tierney, Claire; Kassem, Firas; Leong, Samuel C.; https://orcid.org/0000-0002-2785-4474; 33326692Objectives Topical nasal steroids are a common treatment intervention for olfactory dysfunction. Penetration of topic treatment to the olfactory cleft (OC), such as nasal drops, is greatly dependent on the position of the head when the treatment is administered. We aimed to examine the penetrance of nasal drops to the OC in two different head positions: the Mygind (lying head back) position and the Kaiteki position. Design and Setting The specimens were firstly positioned in Mygind, and thereafter in Kaiteki positions. Nasal drops mixed with blue food dye were administered into the nostrils in each of the head position. Endoscopic videos were recorded, and two blinded observers scored the extent of olfactory cleft penetration (OCP) using a 4-point scale (0 = none, 3 = heavy). Participants Twelve fresh-frozen cadaver specimens. Main outcome measures Penetration of the dye into the OC. Results The mean score of nasal drops penetrance to the OC in the Mygind position was 1.34 (standard deviation, SD = 0.92), as compared to 1.76 (SD = 0.65) in the Kaiteki position. The difference in the OCP score between the two groups was not statistically significant (P > .05). Conclusion Both Mygind and Kaiteki head positions are reasonable options for patients considering topical nasal drops for olfaction impairment. The preference of one position over the other should be determined by patient's preference and comfort.Item Focusing on the big picture while observing the concerns of both managers and passengers in the post-covid era(2021) Samanci, Simge; Atalay, Kumru Didem; Isin, Feride BaharThis study reveals how to improve and define the issues of service quality in the airline sector after the outbreak of COVID-19, to what extent customer needs (important issues) and expectations (expected performances) will differ, and the priorities of airline sector managers in terms of resource allocation, costs, planned strategies, and operational efficiency and effectiveness. It offers a systematic and interactive perspective by simultaneously providing the perspective of both airline managers and passengers by using a new hybrid method, namely Fuzzy Importance, Expected Performance, and Priority Analysis (FIEPA) with VIKOR. This method allows the use of different perspectives of different managers in the analysis, which can be prioritized with different weights. According to the results of the study, in which 449 passengers participated on Twitter, the attributes on which airline managers should focus were determined, having three distinctive characteristics of being important for customers, having high priority according managers, and having low expected performance according customers. Twenty-two attributes related to the service quality of airlines during outbreak periods were classified into three main dimensions as "social distance and hygiene during flight", "information awareness and concern", and "infection alert procedure".Item A note on habit: Veblen and Dewey(2021) Araz, Bahar; Aydin, Derya Guler; AAC-8845-2021Thorstein B. Veblen is one of the most prominent economists, who emphasizes human nature and social reality. For Veblen, habit and institutions constitute crucial categories. However, there is a conflicting interpretation of habit in the institutionalist literature. While some claim that Veblen uses the notion of habit to indicate human dispositions, propensities, proclivities and even capacities, others argue that habit in Veblen is repeated action. This discussion is so crucial since it gives rise to the question of whether Veblen can be considered as a pragmatist (C) 2020 Elsevier B.V. All rights reserved.Item Does the sexual function of the spouses change after the TOT procedure?(2021) Turgut, Hasan; Hasirci, Eray; https://orcid.org/0000-0002-4147-2966; 33386954; AAI-7997-2021Aim This prospective study aimed to evaluate sexual function in women who underwent transobturator tape (TOT) sling surgery and their male sexual partners compared to before the procedure. Materials and methods The study included a total of 202 women with stress urinary incontinence who underwent the TOT procedure between April 2018 and February 2020, and their partners. All of the women completed the Incontinence Impact Questionnaire (IIQ-7), Urogenital Distress Inventory (UDI-6), and Female Sexual Function Index (FSFI) questionnaire while their partners completed the International Index of Erectile Function (IIEF-5) questionnaire before and 6 months after the procedure. Results Mean IIQ-7 and UDI-6 scores were significantly lower at postoperative month 6 compared to preoperative values (p < 0.001). Mean FSFI scores were 22.5 +/- 1.7 preoperatively and 27.8 +/- 1.6 at postoperative month 6 (p < 0.001). Pain score did not change significantly (p = 0.4), but there were significant increases in the other FSFI domains of desire, arousal, lubrication, and satisfaction (p < 0.001, p < 0.001, p < 0.001, p < 0.001). The partners' mean IIEF score was 50.05 +/- 5.4 preoperatively and increased to 59.7 +/- 6.8 postoperatively (p < 0.001). No significant differences were detected in erectile or orgasmic function (p = 0.16, p = 0.67), whereas desire, intercourse satisfaction, and overall satisfaction scores increased significantly (p < 0.001, p < 0.001, p < 0.001). Conclusion TOT surgery improves sexual function not only in women but also their partners.Item Efficacy of beta-lactam/beta-lactamase inhibitors to treat extended-spectrum beta-lactamase-producing Enterobacterales bacteremia secondary to urinary tract infection in kidney transplant recipients (INCREMENT-SOT Project)(2021) Hamiyet Demirkaya, Melike; 33222379Background Whether active therapy with beta-lactam/beta-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear. Methods We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively. Results Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count <= 500 cells/mu L at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes. Conclusions Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902).Item Long-term clinical and angiographic follow-up results of the dual-layer flow diverter device (FRED) for the treatment of intracranial aneurysms in a multicenter study(2021) Dinc, Hasan; Saatci, Isil; Oguz, Sukru; Baltacioglu, Feyyaz; Yildiz, Altan; Donmez, Halil; Belet, Umit; Onal, Baran; Andic, Cagatay; Koc, Osman; Kocak, Omer; Koroglu, Mert; Cetin, Mustafa; Cekirge, H. Saruhan; https://orcid.org/0000-0001-8581-8685; 33392735; AAM-3180-2021Purpose Our aim was to determine the long-term safety and efficacy of the Flow Re-Direction Endoluminal Device (FRED) in this multicenter study with prospective design. Materials-method This study included 136 consecutive patients with 155 aneurysms treated between March 2013 and June 2016 in 10 centers. Twenty-two (16.2%) patients presented with rupture of the index aneurysm. Large/giant aneurysms comprised 1/3 of the cohort. Adjuvant coil use during the treatment was 15.5%. The effectiveness measure in the study was the percentage of aneurysms with stable occlusion at follow-up. Results Vascular imaging follow-up was performed at least once in 131/136 (96.3%) patients with 148/155 (95.5%) aneurysms up to 75 months (mean: 37.3 months; median: 36 months according to latest follow-up), and 102/155(65.8%) aneurysms in 90/136 (66.2%) patients had >= 24-month control. According to the latest controls, the overall stable occlusion rate was 91.9% (95% CI, 87.5 to 96.3%). Three out of 148 aneurysms with follow-up were retreated (2%, 95% CI 0.0 to 4.3%). Adverse events were noted in 19/136 (14%, 95% CI, 9 to 21%) patients with a morbidity of 1.5% (95% CI, 0.0 to 3.5%). Mortality was 1/136 (0.7%, 95% CI, 0.02 to 2.2%) and was unrelated to aneurysm treatment. In-stent stenosis (ISS) was detected in 10/131 of the patients with follow-up (7.6%, 95% CI; 3.1 to 12.2%), only one being symptomatic. No adverse events have occurred in any of the patients with follow-up after 24 months, except the one resulting from ISS. Conclusion In the treatment of cerebral aneurysms which were candidates for flow diversion technique, this study showed long-term efficacy of FRED with good safety and occlusion rates.Item High-grade endometrial stromal sarcoma versus undifferentiated uterine sarcoma: a Turkish uterine sarcoma group study-001(2021) Ayhan, Ali; Tunc, Mehmet; Boran, Nurettin; Khatib, Ghanim; Gokcu, Mehmet; Simsek, Tayup; Ozen, Ozlem Isiksacan; Toptas, Tayfun; Yalcin, Ibrahim; Meydanli, Mehmet Mutlu; https://orcid.org/0000-0002-9082-1317; 33392719; AAK-4468-2021Objective Prognostic factors associated with high-grade endometrial stromal sarcoma (HGESS) and undifferentiated uterine sarcoma (UUS) have not been distinctly determined due to the repetitive changes in the World Health Organization (WHO) classification. We aimed to compare clinicopathologic features and outcomes of patients with HGESS with those of patients with UUS. Methods A multi-institutional, retrospective, cohort study was conducted including 71 patients, who underwent surgery at 13 centers from 2008 to 2017. An experienced gynecopathologist from each institution re-evaluated the slides of their own cases according to the WHO2014 classification. Factors associated with refractory/progressive disease, recurrence or death were examined using logistic regression analyses. Kaplan-Meier method and log-rank test were used for survival comparisons. Results The median disease-free survival (DFS) for HGESS and UUS was 12 months and 6 months, respectively. While the median overall survival was not reached in HGESS group, it was 22 months in the UUS group. Kaplan-Meier analyses revealed that patients with UUS had a significantly poorer DFS than those with HGESS (p = 0.016), although OS did not differ between the groups (p = 0.135). Lymphovascular-space involvement (LVSI) was the sole significant factor associated with progression, recurrence or death for HGESS (Hazard ratio: 9.353, 95% confidence interval: 2.539-34.457, p = 0.001), whereas no significant independent factor was found for UUS. Conclusions UUS has a more aggressive behavior than HGESS. While no significant predictor of prognosis was found for UUS, LVSI is the sole independent prognostic factor for HGESS, with patients 9.3 times more likely to experience refractory/progressive disease, recurrence or death.Item Can MitoTEMPO protect rat sciatic nerve against ischemia-reperfusion injury?(2021) Tuncer, Seckin; Akkoca, Ahmet; Celen, Murat Cenk; Dalkilic, Nizamettin; https://orcid.org/0000-0002-2306-4467; 33415504; AAD-6066-2021Abdominal ischemia-reperfusion (I/R) is known to cause both structural and functional damage to sciatic nerve which is related to the oxidative stress. We investigated the protective effects of mitochondria-targeted antioxidant (2-(2,2,6,6-tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl) triphenylphosphonium chloride (MitoTEMPO) on ischemia-reperfusion-induced nerve damage by using the conduction velocity distribution (CVD) calculations from in vitro compound nerve action potential (CNAP) recordings from rat sciatic nerve. Adult male Wistar albino rats were divided into three groups. The IR and IR + MT groups had aortic cross-clamping for 1 h followed by 2 h reperfusion, while SHAM group had the same procedure without cross-clamping. IR + MT group received 0.7 mg/kg/day MitoTEMPO injection for 28 days before I/R, while other groups received vehicle alone. Ischemia-reperfusion resulted in a significant decrease (p < .05) in maximum depolarizations (mV), areas (mV.ms), and maximum and minimum upstroke velocities (mV/ms) of CNAPs, while injection of MitoTEMPO showed a complete protective effect on these impairments. The histograms for CVD showed that I/R blocked the contribution of fast-conducting fibers (> 60 m/s). MitoTEMPO prevented that blockage and caused a shift in the CVD. Functional nerve damage caused by I/R can be prevented by MitoTEMPO, which can enter mitochondria, the main source of reactive oxygen species (ROS).Item Is the extent of lymphadenectomy a prognostic factor in International Federation of Gynecology and Obstetrics stage II endometrioid endometrial cancer?(2021) Cuylan, Zeliha Firat; Akilli, Huseyin; Gungorduk, Kemal; Demirkiran, Fuat; Oz, Murat; Salman, Mehmet Coskun; Sozen, Hamdullah; Celik, Husnu; Gokcu, Mehmet; Bese, Tugan; Meydanli, Mehmet Mutlu; Ozgul, Nejat; Topuz, Samet; Kuscu, Esra; Kuru, Oguzhan; Gokmen, Sibel; Gultekin, Murat; Ayhan, Ali; 33426779Aim This study aimed to evaluate the prognostic significance of adequate lymph node dissection (LND) (>= 10 pelvic lymph nodes (LNs) and >= 5 paraaortic LNs removed) in patients with International Federation of Gynecology and Obstetrics (FIGO) stage II endometrioid endometrial cancer (EEC). Methods A multicenter department database review was performed to identify patients who had been operated and diagnosed with stage II EEC at seven centers in Turkey retrospectively. Demographic, clinicopathological, and survival data were collected and analyzed. Results We identified 284 women with stage II EEC. There were 170 (59.9%) patients in the adequate lymph node dissection (LND) group and 114 (40.1%) in the inadequate LND group. The 5-year overall survival (OS) rate of the inadequate LND group was significantly lower than that of the adequate LND group (84.1% vs. 89.1%, respectively; p = 0.028). In multivariate analysis, presence of lymphovascular space invasion (LVSI) (hazard ratio [HR]: 2.39, 95% confidence interval [CI]: 1.23-4.63; p = 0.009), age >= 60 (HR: 3.30, 95% CI: 1.65-6.57; p = 0.001], and absence of adjuvant therapy (HR: 2.74, 95% CI: 1.40-5.35; p = 0.003) remained as independent risk factors for decreased 5-year disease-free survival (DFS). Inadequate LND (HR: 2.34, 95% CI: 1.18-4.63; p < 0.001), age >= 60 (HR: 2.67, 95% CI: 1.25-5.72; p = 0.011), and absence of adjuvant therapy (HR: 4.95, 95% CI: 2.28-10.73; p < 0.001) were independent prognostic factors for decreased 5-year OS in multivariate analysis. Conclusion Adequate LND and adjuvant therapy were significant for the improvement of outcomes in FIGO stage II EEC patients. Furthermore, LVSI was associated with worse 5-year DFS rate in stage II EEC.