Research Outputs
Permanent URI for this communityhttps://hdl.handle.net/20.500.14288/2
Browse
251 results
Filters
Advanced Search
Filter by
Settings
Search Results
Publication Metadata only 268th ENMC workshop - Genetic diagnosis, clinical classification, outcome measures, and biomarkers in Facioscapulohumeral Muscular Dystrophy (FSHD): Relevance for clinical trials(Elsevier B.V., 2023) Montagnese F, de Valle K, Lemmers RJLF, Mul K, Dumonceaux J, Voermans N; 268th ENMC workshop participants.; Oflazer, Piraye; ; School of Medicine;Highlights This ENMC workshop has seen the participation of many important stakeholders working together to improve trial readiness in FSHD: patients and patients’ organizations (FSHD-Europe, FSHD-Society and FSHD Global), neuromuscular clinicians, geneticists, basic researchers, representatives of the TREAT-NMD network, the FSHD-CTRN and EMA. COMs represent useful tools for the standardized collection of clinical features but need to be selected to match the clinical setting of use. For patient care, they need to be informative, with practical and time efficient utility so as not to detract from clinical care. For clinical trial purposes, the need to be reliable, valid, meaningful and sensitive to change to better depict therapeutic responses. An optimized clinical evaluation and genetic test form is one of the goals of WG1 and 2. A diagnostic flowchart for FSHD1 and FSHD2 has been proposed. Another important unmet need for clinical trial readiness in FSHD is the identification of good therapeutic biomarkers, which ideally should be quantitative, non-invasive, applicable across the entire range of disease severity, sensitive to change, reliable and clinically meaningful. The WG 3 will produce standard operating procedures (SOPs) for DUX4 detection. Similarly, large differences in the reporting of studies performed on animal models, thus hindering interpretation, repeatability and comparison of the results need to be addressed. Guidelines regarding minimum information for publication of work including animal models for FSHD will therefore be published.Publication Metadata only A 52-year-old man with progressive weakness and incontinence(Sage, 2022) Danyeli, Ayca Ersen; Bozkurt, Subutay Berke; Uysal, Sanem Pinar; Akpek, Sergin; Kahyaoglu, Bulent; Peker, Selcuk; Altıntaş, Ayşe; Aygün, Murat Serhat; Akay, Olga Meltem; Üre, Ümit Barbaros; Ferhanoğlu, Ahmet Burhan; Faculty Member; Teaching Faculty; Faculty Member; Faculty Member; Faculty Member; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; Koç University Hospital; 11611; 291692; 170966; N/A; 18320Here we report a challenging case of a 52-year-old man presenting with subacute constipation, urinary retention, impotence, absent Achilles reflexes, and hypoesthesia in S2-S5 dermatomes. We review the clinical decision-making as the symptoms evolved and diagnostic testing changed over time. Once the diagnosis is settled, we discuss the sign and symptoms, additional diagnostic tools, treatment options and prognosis.Publication Metadata only A biallelic mutation links myorg to autosomal-recessive primary familial brain calcification(Oxford University Press (OUP), 2019) Forouhideh, Yalda; Mueller, Kathrin; Ruf, Wolfgang; Assi, Muhannad; Seker, Tuncay; Knehr, Antje; Strom, Tim M.; Gorges, Martin; Schradt, Falk; Meitinger, Thomas; Ludolph, Albert C.; Pinkhardt, Elmar H.; Kassubek, Jan; Uttner, Ingo; Weishaupt, Jochen H.; N/A; Tunca, Ceren; Başak, Ayşe Nazlı; Researcher; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; School of Medicine; N/A; 1512N/APublication Metadata only A case of drop foot due to piriformis syndrome(Springer Heidelberg, 2015) Yıldırım, Pelin; Güler, Tuba; Özer, Tülay; Gündüz, Osman Hakan; N/A; Mısırlıoğlu, Tuğçe Özekli; Doctor; N/A; Koç University Hospital; 175999N/APublication Metadata only A case with new-onset neuromyelitis optica spectrum disorder following COVID-19 mRNA BNT162b2 vaccination(Lippincott Williams & Wilkins, 2022) Afşar, Nazire; N/A; N/A; N/A; Çalışkan, İlay; Buluş, Eser; Polat-Altıntaş, Sevgi; Master Student; Doctor; Researcher; N/A; N/A; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine; N/A; N/A; N/A; 150017Introduction: In the midst of the coronavirus disease of 2019 pandemic, active immunization by effective vaccination gained utmost importance in terms of global health. The messenger RNA (mRNA) vaccines are novel strategies requiring clinical surveillance for adverse events. Case Report: We report a 43-year-old previously healthy female with an optic neuritis attack 24 hours following immunization with the second dose of coronavirus disease of 2019 mRNA BNT162b2 vaccine. A second transverse myelitis attack together with an elevated anti-AQP-4 antibody titer confirmed the diagnosis of neuromyelitis optica spectrum disorder. Conclusion: Our case identifies the BNT162b2 vaccine as a possible trigger for neuromyelitis optica spectrum disorder. This rare and potentially coincidental event has no implications for vaccine administration practices. However, further research is needed to elucidate the effects of mRNA vaccines on humoral and cell-mediated immunity.Publication Metadata only A genetic cause for intractable seizures: atypical Gaucher disease with a novel pathological variant(WILEY, 2024) Üçem, Selen; Avcı, Şahin; Gürses, Rabia Candan; School of Medicine; Koç University HospitalPublication Metadata only A multi-centre longitudinal study analysing multiple sclerosis disease-modifying therapy prescribing patterns during the Covid-19 pandemic(Springer Science and Business Media Deutschland GmbH, 2024) Lal, Anoushka P.; Foong, Yi Chao; Sanfilippo, Paul G.; Spelman, Tim; Rath, Louise; Levitz, David; Fabis-Pedrini, Marzena; Foschi, Matteo; Habek, Mario; Kalincik, Tomas; Roos, Izanne; Lechner-Scott, Jeannette; John, Nevin; Soysal, Aysun; D’Amico, Emanuele; Gouider, Riadh; Mrabet, Saloua; Gross-Paju, Katrin; Cárdenas-Robledo, Simón; Moghadasi, Abdorreza Naser; Sa, Maria Jose; Gray, Orla; Oh, Jiwon; Reddel, Stephen; Ramanathan, Sudarshini; Al-Harbi, Talal; Hardy, Todd A.; Ozakbas, Serkan; Alroughani, Raed; Kermode, Allan G.; Surcinelli, Andrea; Laureys, Guy; Eichau, Sara; Prat, Alexandre; Girard, Marc; Duquette, Pierre; Hodgkinson, Suzanne; Ramo-Tello, Cristina; Maimone, Davide; McCombe, Pamela; Spitaleri, Daniele; Sanchez-Menoyo, Jose Luis; Yetkin, Mehmet Fatih; Baghbanian, Seyed Mohammad; Karabudak, Rana; Al-Asmi, Abdullah; Jakob, Gregor Brecl; Khoury, Samia J.; Etemadifar, Masoud; van Pesch, Vincent; Buzzard, Katherine; Taylor, Bruce; Butzkueven, Helmut; Van der Walt, Anneke; Altıntaş, Ayşe; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of MedicineBackground: The COVID-19 pandemic raised concern amongst clinicians that disease-modifying therapies (DMT), particularly anti-CD20 monoclonal antibodies (mAb) and fingolimod, could worsen COVID-19 in people with multiple sclerosis (pwMS). This study aimed to examine DMT prescribing trends pre- and post-pandemic onset. Methods: A multi-centre longitudinal study with 8,771 participants from MSBase was conducted. Two time periods were defined: pre-pandemic (March 11 2018–March 10 2020) and post-pandemic onset (March 11 2020–11 March 2022). The association between time and prescribing trends was analysed using multivariable mixed-effects logistic regression. DMT initiation refers to first initiation of any DMT, whilst DMT switches indicate changing regimen within 6 months of last use. Results: Post-pandemic onset, there was a significant increase in DMT initiation/switching to natalizumab and cladribine [(Natalizumab-initiation: OR 1.72, 95% CI 1.39–2.13;switching: OR 1.66, 95% CI 1.40–1.98), (Cladribine-initiation: OR 1.43, 95% CI 1.09–1.87;switching: OR 1.67, 95% CI 1.41–1.98)]. Anti-CD20mAb initiation/switching decreased in the year of the pandemic, but recovered in the second year, such that overall odds increased slightly post-pandemic (initiation: OR 1.26, 95% CI 1.06–1.49;Switching: OR 1.15, 95% CI 1.02–1.29. Initiation/switching of fingolimod, interferon-beta, and alemtuzumab significantly decreased [(Fingolimod-initiation: OR 0.55, 95% CI 0.41–0.73;switching: OR 0.49, 95% CI 0.41–0.58), (Interferon-gamma-initiation: OR 0.48, 95% CI 0.41–0.57;switching: OR 0.78, 95% CI 0.62–0.99), (Alemtuzumab-initiation: OR 0.27, 95% CI 0.15–0.48;switching: OR 0.27, 95% CI 0.17–0.44)]. Conclusions: Post-pandemic onset, clinicians preferentially prescribed natalizumab and cladribine over anti-CD20 mAbs and fingolimod, likely to preserve efficacy but reduce perceived immunosuppressive risks. This could have implications for disease progression in pwMS. Our findings highlight the significance of equitable DMT access globally, and the importance of evidence-based decision-making in global health challenges. © The Author(s) 2024.Publication Metadata only A multidisciplinary clinical approach to facioscapulohumeral muscular dystrophy orthopedic surgery in facioscapulohumeral dystrophy(Literatura Medica, 2018) N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; Çakmak, Özgür Öztop; Eren, İlker; Aslanger, Ayça Dilruba; Günerbüyük, Caner; Kayserili, Hülya; Oflazer, Piraye; Şar, Cüneyt; Demirhan, Mehmet; Özdemir, Yasemin Gürsoy; Faculty Member; Faculty Member; Doctor; Teaching Faculty; Faculty Member; Faculty Member; Doctor; Faculty Member; Faculty Member; School of Medicine; School of Medicine; N/A; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; Koc University Hospital; 107818; 168021; N/A; 380939; 7945; N/A; N/A; 9882; 170592Background - Impaired shoulder function is the most disabling problem for daily life of Fascioscapulohumeral muscular dystrophy (FSHD) patients. Scapulothoracic arthrodesis can give a high impact to the functionality of patients. Here we report our experience with scapulothoracic arthrodesis and spinal stenosis surgery in FSHD patients. Patients and methods - 32 FSHD patients were collected between 2015-2016. Demographical and clinical features were documented. All the patients were neurologically examined. The Medical Research Council (MRC) and the FSHD evaluation scale was used to assess muscle involvement(1). Scapulothoracic arthrodesis and spinal stenosis surgeries were performed in eligible patients. Results - There were 16 male and 16 female (mean age 34.4 years; range 12-73) patients. 6 shoulders of 4 patients aged between 2132 years underwent scapulothoracic arthrodesis (two bilateral, one left and one right sided). Only one 63 years old female patient with severe hyperlordosis had spinal fusion surgery. All of the patients undergoing these corrective surgeries have better functionality in daily life, as well as superior shoulder elevation. Conclusion - Until the emergence and clinical use of novel therapeutics, surgical interventions are indicated in carefully selected patients with FSHD to improve arm movements, the posture and the quality of life of patients in general. Scapulothorosic arthrodesis is a management with good clinical results and patient satisfaction. In selected cases other corrective orthopedic surgeries like spinal fusion may also be considered.Publication Metadata only A new lumbar fixation device alternative to pedicle-based stabilization for lumbar spine: in vitro cadaver investigation(Taylor & Francis, 2020) Gomleksiz, Cengiz; Erbulut, Deniz Ufuk; Can, Halil; Kodigudla, Manoj Kumar; Kelkar, Amey, V; Kasapoglu, Eser; Ozer, Ali Fahir; Goel, Vijay K.; Özer, Ali Fahir; Faculty Member; School of Medicine; 1022Context: To evaluate the stability provided by a new bilateral fixation technique using an in vitro investigation for posterior lumbar segmental instrumentation. Design: Experimental cadaver study. In this study, we propose an alternative technique for a posterior lumbar fixation technique called "inferior-oblique transdiscal fixation" (IOTF). Setting: Study performed at Engineering Center for Orthopedic Research Exellence (ECORE) in Toledo University-Ohio. Participants: Six human lumbar cadaveric specimen used in this study. Interventions: In this study, we propose an alternative technique for a posterior lumbar fixation technique called "inferior-oblique transdiscal fixation" (IOTF). As a novel contribution to the classical technique, the entry point of the screw is the supero-lateral point of the intersecting line drawn between the corpus and the pedicle of the upper vertebra. This approach enables the fixation of two adjacent vertebrae using a single screw on each side without utilizing connecting rods. Outcome Measures: Flexion (Flex), extension (Ext), right and left lateral bending (LB & RB), and right and left axial rotation (LR & RR), and the position data were captured at each load step using the Optotrak motion measurement system and compared for IOTF and posterior transpedicular stabilization. Results: The Posterior stabilization system (PSS) and IOTF significantly reduced the ROM of L4-L5 segment compared to intact segment's ROM. During axial rotation (AR) IOTF fused index segment more than PSS. Besides this, addition of transforaminal lumbar interbody fusion (TLIF) cage improved the stabilization of IOTF system during flexion, extension and lateral bending. Whereas, PSS yielded better fusion results during extension compared to IOTF with and without interbody fusion cages. Conclusions: We hypothesized that the new posterior bilateral system would significantly decrease motion compared to the intact spine. This cadaver study showed that the proposed new posterior fusion technique IOTF fused the index segment in a similar fashion to the classical pedicle screw fusion technique.Publication Metadata only A novel BHLHE41 variant is associated with short sleep and resistance to sleep deprivation in humans(Oxford University Press (OUP), 2014) Pellegrino, Renata; Goel, Namni; Cardinale, Christopher J.; Dinges, David F.; Kuna, Samuel T.; Maislin, Greg; Van Dongen, Hans P. A.; Tufik, Sergio; Hogenesch, John B.; Hakonarson, Hakon; Pack, Allan I.; Department of Chemical and Biological Engineering; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; Department of Molecular Biology and Genetics; Kavaklı, İbrahim Halil; Faculty Member; College of Engineering; 40319Study Objectives: Earlier work described a mutation in DEC2 also known as BHLHE41 (basic helix-loop-helix family member e41) as causal in a family of short sleepers, who needed just 6 h sleep per night. We evaluated whether there were other variants of this gene in two well-phenotyped cohorts. Design: Sequencing of the BHLHE41 gene, electroencephalographic data, and delta power analysis and functional studies using cell-based luciferase. Results: We identified new variants of the BHLHE41 gene in two cohorts who had either acute sleep deprivation (n = 200) or chronic partial sleep deprivation (n = 217). One variant, Y362H, at another location in the same exon occurred in one twin in a dizygotic twin pair and was associated with reduced sleep duration, less recovery sleep following sleep deprivation, and fewer performance lapses during sleep deprivation than the homozygous twin. Both twins had almost identical amounts of non rapid eye movement (NREM) sleep. This variant reduced the ability of BHLHE41 to suppress CLOCK/BMAL1 and NPAS2/BMAL1 transactivation in vitro. Another variant in the same exome had no effect on sleep or response to sleep deprivation and no effect on CLOCK/BMAL1 transactivation. Random mutagenesis identified a number of other variants of BHLHE41 that affect its function. Conclusions: There are a number of mutations of BHLHE41. Mutations reduce total sleep while maintaining NREM sleep and provide resistance to the effects of sleep loss. Mutations that affect sleep also modify the normal inhibition of BHLHE41 of CLOCK/BMAL1 transactivation. Thus, clock mechanisms are likely involved in setting sleep length and the magnitude of sleep homeostasis.