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Early Access Program Results From Turkey and a Literature Review on Daratumumab Monotherapy Among Heavily Pretreated Patients With Relapsed/Refractory Myeloma
No full textThe present study investigated the efficacy and safety profile of
daratumumab monotherapy in 42 patients with relapsed refractory multiple
myeloma through a Turkish early access program. The current findings
have confirmed the efficacy of daratumumab monotherapy in heavily
pretreated patients with refractory multiple myeloma because of the deep
and durable responses and favorable safety and tolerability profile.
Background: In countries where frontline drug approval is limited to
first-generation proteasome inhibitors or immunomodulatory drugs,
relapses have been both more frequent and less durable. We investigated
real world data on the efficacy and safety of daratumumab monotherapy
among patients with relapsed refractory multiple myeloma (RRMM) from
Turkey using a prospective early access program. Patients and Methods: A
total of 42 patients with RRMM after a minimum of 3 previous lines of
proteasome inhibitor/immunomodulatory drug-based treatments were
included from 25 centers across Turkey. Daratumumab monotherapy was
administered intravenously at a dose of 16 mg/kg weekly (cycles 1-2), on
alternate weeks (cycles 3-6), and monthly thereafter. Results: The
median daratumumab monotherapy duration was 5.5 months (range, 0.2-28.7
months). The overall response rate was 45.2\%, including 14 (33.3\%)
partial responses, 4 (9.5\%) very good partial responses, and 1 (2.4\%)
complete response. The median duration of response was 4.9 months. The
median progression-free survival (PFS) was 5.5 (95\% confidence
interval, 2.6-8.4 months) with 12- and 18-month PFS rates of 35.7\% and
31.0\%, respectively. The median overall survival was not reached; the
12- and 18-month overall survival rates were 64.3\% and 59.5\%,
respectively. The depth of response had a significant effect on PFS
(log-rank test, P = .026). Overall, of the 76 adverse events reported,
33 (43.4\%) were grade >= 3; only 4 (9.52\%) were grade 3
infusion-related reactions. No infusion-related reactions or adverse
events led to treatment discontinuation. Conclusion: The present
findings from our daratumumab early access program have confirmed the
efficacy and safety profile of daratumumab monotherapy in heavily
pretreated Turkish patients with RRMM
Thalamocortical network interruption: A fresh view for migraine symptoms
No full textMigraine is a multifaceted brain disorder where multisensory
disturbances are associated with headache. Yet sensory symptoms are
conventionally justified by dysfunctions confined to the cerebral
cortex, a perspective through the complex interplay of thalamocortical
network would provide the entire picture, more pertinent to the central
sensory processing. It is important to consider thalamus as a hub that
integrates multiple domains via extensive connections among anatomically
and functionally separate cortical areas. Accordingly, cortical
spreading depression (CSD), implicated in migraine pathophysiology can
be seen as a tool to disconnect thalamocortical network by functionally
eliminating cerebral cortex. Hence, including thalamic reticular nucleus
and higher order thalamic nuclei, which conveys the information
transthalamically among visual, somatosensory, language and motor
cortical areas, would greatly improve our current understanding of
migraine
Antidepressant Potential of Lotus corniculatus L. subsp. corniculatus: An Ethnobotany Based Approach
No full textAs a Turkish traditional medicinal plant, aerial parts of Lotus
corniculatus L. subsp. corniculatus (Fabaceae) are used as a painkiller,
antihemoroidal, diuretic and sedative. In this study, the antidepressant
potential of the plant has been attempted to clarify. Extracts with
water, n-Hexane, ethyl acetate, and methanol were prepared respectively
from the aerial parts. Antidepressant activity of the extracts were
researched by using three different in vivo test models namely a tail
suspension test, antagonism of tetrabenazine-induced hypothermia,
ptosis, and suppression of locomotor activity and forced swimming test
on male BALB/c mice and in vitro monoamine oxidase (MAO)-A and B
inhibition assays. The results were evaluated through comparing with
control and reference groups, and then active compounds of the active
extract have been determined. Bioassay-guided fractionation of active
fraction led to the isolation of three compounds and structures of the
compounds were elucidated by spectroscopic methods. The data of this
study demonstrate that the MeOH extract of the aerial parts of the plant
showed remarkable in vivo antidepressant effect and the isolated
compounds medicarpin-3-O-glucoside, gossypetin-3-O-glucoside and
naringenin-7-O-glucoside (prunin) from the active sub-fractions could be
responsible for the activity. Further mechanistic and toxicity studies
are planned to develop new antidepressant-acting drugs
Sacroiliitis associated with familial Mediterranean fever in childhood: a case series and review of literature
No full textBackground and objectives. Familial Mediterranean fever (FMF) is an
autosomal-recessive auto-inflammatory disorder characterized by
recurrent episodes of fever with serositis. Sacroiliitis associated with
FMF is very rare, especially in children. We aimed to describe the
demographic, clinical, laboratory features, and treatment responses of
pediatric patients with FMF-related sacroiliitis.
Methods. The study consisted of seven pediatric patients younger than 16
years, diagnosed with sacroiliitis associated with FMF between 2010 and
2017. Medical records of patients were retrospectively evaluated.
Sacroiliitis was diagnosed based on magnetic resonance imaging. We also
reviewed previous studies of FMF related sacroiliitis.
Results. Five of the seven patients (male:female ratio of 5:2) had a
M694V (homozygous) mutation, one patient had a M694V (heterozygous)
mutation, and one patient had a V726A (heterozygous) mutation. All
patients were HLA-B27 negative. One of the cases achieved remission with
colchicine plus non-steroidal anti-inflammatory drug treatment, and one
patient's symptoms were managed by the addition of sulfasalazine. Four
patients responded to etanercept treatment, and one patient's symptoms
were suppressed with canakinumab.
Conclusion. Sacroiliitis can be seen in pediatric FMF patients suffering
with inflammatory back pain. This manifestation generally occurs in FMF
patients who have M694V mutation. Etanercept could likely show a
beneficial effect in patients who are resistant to disease modifying
anti-rheumatic drugs and non-steroidal anti-inflammatory drugs. In
addition, canakinumab treatment should be considered as a successful
alternative therapy in this rare group of patients
Systemic steroid treatment of rarely seen genitourinary system manifestation in children with Henoch Schönlein purpura: Case report and literature analysis
No full textDetermination of prognostic factors of surgically treated pathological Stage IIIA non-small cell lung cancer
No full textSynchrophasor Measurement Method Based On Quadrature Amplıtude Modulatıon
No full textMerkezi olmayan enerji üretim kaynaklarının yaygınlaşmasıyla birlikte tüm Dünyada şebekeler konvensiyonel yapıdan, dağıtık yapıya geçmektedir. Bu değişim, güç sistemi altyapısının daha detaylı izlenmesi ve otomasyonu gerekliliğini ön plana çıkmaktadır. Senkrofazör ölçümü, elektrik güç sistemlerinde arızaları tespit etmek ve sistem kararlılığını izlemek için yaygın bir araçtır ve senkrofazör ölçümleri için çeşitli Fazör Ölçüm Birimleri (PMU'lar) tasarlanmıştır. PMU’lar koordineli evrensel zamana senkronize edilmiş gerilim veya akım dalga biçimlerinin genliklerini, fazını, frekansını ve frekansın değişim oranını ölçebilen cihazlardır. Elektrik iletim seviyesinde, birden fazla PMU tarafından hesaplanan ve geniş alan izleme sistemleri aracılığıyla toplanan ölçüm verileri, şebeke durumunu belirli bir zamanda tahmin etmek için veri yoğunlaştırıcıları tarafından zamana göre toplanmaktadır. Bu şekilde, iletim sistemi operatörleri, sürekli şebeke dengesini izleyebilmekte, dinamik yükler ve hat koşul arızalarını tespit edip analiz edebilmekte ve güç sistemi hatlarının onarımı sağlamaktadır. Doğrusal olmayan dinamik yüklerin neden olduğu, hızlı bir şekilde zamanla değişen güç sistemi frekans durumları için özel olarak tasarlanmış PMU parametre hesaplama yöntemleri bulunmaktadır. Literatürde fazör kestirimi için, Ayrık Fourier Dönüşümü (DFT), ara değerli DFT, Kalman filtre, faz kilitlemeli döngü, Taylor Fourier filtre ve dalgacık dönüşüm algoritmaları yaygın olarak kullanılmaktadır. Bu çalışmada, IEEE Std. C37.118.1 standardında tanımlanan M sınıfı doğruluk kriterlerine uygun bir şekilde sinyallerin anlık genlik ve faz açılarını kestirmek amacıyla Dördün Genlik Modülasyonu ve Senkron Referans Çerçeve Analizi’ne dayalı yeni bir yöntem tasarlanmıştır. Önerilen yöntem, düşük hesaplama yükü ve hızlı tepki ile kolayca uygulanabilmesiyle öne çıkmaktadır. Önerilen yöntem, zamanda değişen gerilim verileri kullanılarak doğrulanmıştır. Simülasyon sonuçlar ise önerilen yöntemin IEEE Std. C37.118.1 standardında tanımlanan doğruluk kriterlerini karşıladığı gösterilmiştir.Power grids haverecently beenchangingfromconventional to distributed structure alloverthe globe dueto theincreasing penetration ofdecentralized resourcesinto the grids, which brings arequirement to haveadvanced automation and monitoring structures specified for power systems. Phasor measurement Units(PMUs)havebeen designed forsynchrophasor measurements and they aremainly used for fault detection and trackingnetwork stability inpower systems.PMUs aredevices measuringmagnitude, phase,frequency,and frequencydeviation rateofvoltageand current waveforms synchronized to universal time. At thetransmission system levelPMU measurements aregathered via wideareamonitoringsystems, and theyarecollected bydata concentrators in order to estimategrid stateata specifictime. Hence, transmission system operators can continuouslymonitor stabilityofthe grid, detect and analyzedynamicloads and line condition faults, and mitigate powersystem faults. Thereareseveral PMU parameter calculation methods specificallydesignedforrapidlytime-varyingpower system frequencies caused bynonlinear dynamicloads in theliteraturesuch as Discrete Phasor Transform(DFT), Interpolation DFT, Kalman Filter,phase-locked loop, Taylor Fourier filterand wavelet transform. This thesis proposes anovel design to estimateinstantaneous magnitudesand phasesof signals defined in IEEE StandardC37.118.1 with Mclass accuracybased on QuadratureAmplitude Modulation andSynchronousReferenceFrameAnalysis. Theproposed methodologyistested on simulated time-varyingvoltagedataand is shown to havelow computational complexityandfastresponse. Besides, simulation results of themethodologysatisfytheaccuracylimits definedin IEEE Standard C37.118.1