A case of tracheobronchial amyloidosis presenting with acute myeloid leukemia

Localized tracheobronchial amyloidosis (TBA) is a rare form of pulmonary amyloidosis that is characterized by amyloidosis accumulation in the trachea and main bronchus submucosa. TBA is usually localized in the lung and is not associated with systemic amyloidosis. Although patients may be asymptomatic at first, they may develop dyspnea, recurrent cough, and hemoptysis attacks as the lesions narrow the tracheobronchial tree. Histochemical examination of biopsies taken with flexible bronchoscopy after thorax CT findings is usually used to make the diagnosis. There has never been a case reported in which TBA and acute myeloid leukemia (AML) coexisted. We report the first case of TBA in a patient diagnosed with AML

Lenalidomide-based treatment results in patients with relapsed/refractory lymphoma (excluding mantle cell lymphoma): A multi-centre experience

Amaç: Lenfomalar, çoğunlukla B hücre kökenli heterojen bir hastalık grubunu temsil eder. Lenalidomid, kemo-immünoterapötik ajanlara talidomidin yapısal bir analoğu olarak dahil edilmiştir. Bu çalışmada amaç, mantle hücreli lenfoma dışı lenfomalarda, lenalidomid ile ilgili gerçek yaşam verilerimizi ortaya çıkarmaktır. Hastalar ve Yöntem: Ocak 2018- Ocak 2020 tarihleri arasında lenfoma tanısı alan hastalar geriye dönük olarak incelendi. Lenalidomid kombine rejimleri şu şekilde gruplandırılmıştır: Lenalidomi -deksametazon (Len-D); lenalidomid-bendamustin (Len-B); lenalidomid-rituksimab (Len-R). Bulgular: On beş (%60.9) hasta Len-D, 6 (%30.4) hasta Len-B ve 2 (%8.7) hasta Len-R aldı. En yaygın yanıt 13 (%56.5) hasta ile progresif hastalık idi, sadece 2 (%8.7) hastada tam yanıt vardı. Sonuç: Lenalidomid, diffüz büyük B hücreli lenfomalar (DBBHL), folliküler lenfoma (FL) ve indolen relaps/refrakter lenfomalar ile relaps/refrakter Hodgkin lenfomada (HL) yeni tedavi seçenekleri arasında yer almaktadır.Objective: Lymphomas represent a heterogeneous group of diseases, mostly of B-cell origin. Lenalidomide is included in chemo-immunotherapeutic agents as a structural analog of thalidomide. In this study, the goal is to reveal our real-life data on lenalidomide. Patients and Methods: Patients diagnosed with lymphoma between January 2018-2020, were retrospectively analyzed. Lenalidomide combined regimens were grouped as: Lenalidomidedexamethasone (Len-D); lenalidomide-bendamustine (Len-B); lenalidomide-rituximab (Len-R). Results: Fifteen (60.9%) patients received Len-D, 6 (30.4%) patients received Len-B and 2 (8.7%). patients received Len-R Most common response was progressive disease with 13 (56.5%) patients, only 2 (8.7%) patients had a complete remission. Conclusion: Lenalidomide appears as new treatment options in relapsed/refractory Hodgkin lenfoma (HL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and indolent lymphomas

Have COVID-19 pandemic restrictions impacted the functioning of the hematology clinic?

Amaç: Çalışmamızın amacı, kısıtlamaların uygulandığı COVID-19 pandemi sürecinde hematoloji klinik işleyişinin değerlendirilmesidir. Hastalar ve Yöntem: Pandeminin ilk döneminde sokağa çıkma kısıtlamalarının uygulandığı 13.03.2020-15.05.2020 ile bu tarih aralığına karşılık gelen 2019 döneminde Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi ve İstanbul Medipol Üniversitesi Tıp Fakültesi Erişkin Hematoloji kliniklerine yatışı yapılan hastalar retrospektif olarak değerlendirildi. Bulgular: Her iki dönemde de yatan hasta sayısı 266 idi. 65 yaş üstü hasta oranı anlamlı olmamakla birlikte 2020’de daha düşük saptandı (%33.1’e kaşın %40.6, p= 0.72). Pandemi döneminde 2019’a göre tanısal amaçlı yatışı yapılan hasta sayısı anlamlı olarak yüksek (OR: 2,1, %95 GA: 1.35-3.26, p< 0.001); herhangi bir enfeksiyon nedeniyle yatış oranı ise düşük (OR: 0,44, %95 GA: 0.27-0.71, p< 0.001) bulundu. Tanısal amaçlı yatış yapılan hastalarda 2020 yılında hem erkek hasta oranı yüksek (OR: 0.4, %95 GA: 0.18-0.92, p= 0.031) hem de yatış süresi daha uzun (medyan 7’ye 14 gün, p= 0.007) bulundu. Kemoterapi, destek ve mobilizasyon amaçlı yatışlar arasında fark saptanmadı. Replasman ihtiyacı nedeniyle yatışı yapılan hasta oranı yine pandemic döneminde yüksek iken (OR: 4.7, %95 GA: 1.7-12.6, p< 0.001), tüm hastalar değerlendirildiğinde kan ürünü kullanımı sıklığı iki yıl arasında farklı değildi. Sonuç: Çalışmamız, kısıtlamalar sürecinde hematoloji hasta yönetiminin önemini ve işlevselliğinin değişmediğini vurgulamaktadır.Objective: The aim of our study is to assess the clinical functioning of hematology during the COVID-19 pandemic when lockdown restrictions are enforced. Patients and Methods: Patients who were admitted to Necmettin Erbakan University Meram Medical Faculty and Istanbul Medipol University Medical Faculty Adult Hematology clinics between March 13, 2020, and May 15, 2020, when lockdown restrictions were enforced in the first phase of the pandemic were evaluated retrospectively by comparing them with those who were admitted to same clinics between March 13, 2019, and May 15, 2019. Results: The number of inpatients during both periods was 266. It was determined that during the period of the pandemic, the number of patients hospitalized for diagnostic purposes was significantly higher compared to 2019 (OR: 2.1, 95% CI: 1.35-3.26, p< 0.001), whereas the rate of hospitalization due to any infection was significantly lower (OR: 0.44, 95% CI: 0.27-0.71, p<0.001). Of the patients who were hospitalized for diagnostic purposes in 2020, both the rate of male patients was higher (OR: 0.4, 95% CI: 0.18-0.92, p= 0.031) and the duration of hospitalization was longer (7 vs. 14 days; p= 0.007) found. While the rate of patients hospitalized due to the need for replacement was also higher during the period of pandemic (OR: 4.7, 95% CI; 1.7-12.6, p< 0.001), when all patients were assessed, the frequency of blood product use was not different between two years. Conclusion: Our study highlights the cruciality and functionality of hematology patient management during the period of lockdown restrictions

Türkiye akademik CAR-T hücre (ISIKOK-19) klinik çalışması ön raporu: Ürün karakterizasyonu ve klinik uygulama sonuçları

Objective: Chimeric antigen receptor T (CAR-T) cell therapies have already made an impact on the treatment of B-cell malignancies. Although CAR-T cell therapies are promising, there are concerns about commercial products regarding their affordability and sustainability. In this preliminary study, the results of the first production and clinical data of an academic CAR-T cell (ISIKOK-19) trial in Turkey are presented. Materials and Methods: A pilot clinical trial (NCT04206943) designed to assess the safety and feasibility of ISIKOK-19 T-cell therapy for patients with relapsed and refractory CD19+ tumors was conducted and participating patients received ISIKOK-19 infusions between October 2019 and July 2021. The production data of the first 8 patients and the clinical outcome of 7 patients who received ISIKOK-19 cell infusions are presented in this study. Results: Nine patients were enrolled in the trial [5 with acute lymphoblastic leukemia (ALL) and 4 with non-Hodgkin lymphoma (NHL)], but only 7 patients could receive treatment. Two of the 3 participating ALL patients and 3 of the 4 NHL patients had complete/ partial response (overall response rate: 72%). Four patients (57%) had CAR-T-related toxicities (cytokine release syndrome, CAR-T-related encephalopathy syndrome, and pancytopenia). Two patients were unresponsive and had progressive disease following CAR-T therapy. Two patients with partial response had progressive disease during follow-up. Conclusion: Production efficacy and fulfillment of the criteria of quality control were satisfactory for academic production. Response rates and toxicity profiles were also acceptable for this heavily pretreated/refractory patient group. ISIKOK-19 cells appear to be a safe, economical, and efficient treatment option for CD19+ tumors. However, the findings of this study need to be supported by the currently ongoing ISIKOK-19 clinical trial.Amaç: Kimerik antijen reseptör T (CAR-T) hücre uygulamaları B-hücreli malignitelerin tedavisinde etkili olmaktadır. CAR-T hücre uygulamalarının sonuçları umut vaadedici olsa da, ticari CAR-T ürünlerinin yükek maliyetleri nedeniyle ulaşılabilirlik açısından ciddi sorunlar yaşanmaktadır. Bu ön raporda, Türkiye’deki ilk akademik CAR-T hücre çalışmasının üretim ve klinik uygulama sonuçları sunulmuştur. Gereç ve Yöntemler: Relaps refrakter CD 19+ hematolojik maligniteli hastalarda ISIKOK-19 T-hücre tedavisinin güvenliği ve etkinliğini değerlendirmek amacıyla yürütülen klinik çalışmaya (NCT04206943) Ekim 2019-Temmuz 2021 tarihleri arasındaki hastalar dahil edilmiştir. Bu raporda ilk 8 hastanın üretim bilgileriyle, ISIKOK-19 hücre infüzyonu yapılan 7 hastanın klinik sonuçları sunulmuştur. Bulgular: Çalışmaya toplam 9 hasta dahil edilmiştir (5 akut lenfoblastik lösemi [ALL] ve 4 non-hodgkin lenfoma [NHL]), ancak sadece 7 hastaya hücre infüzyonu yapılabilmiştir. Hücre infüzyonu alan 3 ALL hastasından 2’sinde ve 4 NHL hastasının 3’ünde tam/kısmi cevap gözlenmiştir (toplam yanıt oranı %72). Dört hastada (%57) CAR-T ilişkili toksisite (sitokin salınım sendromu, immün efektör hücre ilişkili nörotoksisite sendromu ve pansitopeni) tespit edilmiştir. İki hastada ise CAR-T hücre uygulaması sonrası cevapsızlık ve progresif hastalık izlenmiştir. Kısmi cevap veren hastalardan 2’sinde de takip sırasında progresif hastalık tespit edilmiştir. Sonuç: Akademik CAR-T üretimimiz, üretim etkinliği ve kalite kontrol kriterlerinin tam olarak karşılanması açısından tatmin edici sonuçlara sahiptir. Çalışmaya dahil edilen hastaların tedavi yükü hesaba katıldığında tedaviye cevap oranı ve toksisite profili açısından da sonuçlar kabul edilebilir düzeydedir. Bu sonuçlarla, ISIKOK-19 hücrelerinin güvenli, ekonomik ve etkili bir tedavi seçeneği olduğu düşünülebilir. Ancak bu ön sonuçların halen devam eden ISIKOK-19 klinik çalışmasıyla desteklenmesi beklenmektedir

Spatial and temporal heterogeneity in human mobility patterns in Holocene Southwest Asia and the East Mediterranean

We present a spatiotemporal picture of human genetic diversity in Anatolia, Iran, Levant, South Caucasus, and the Aegean, a broad region that experienced the earliest Neolithic transition and the emergence of complex hierarchical societies. Combining 35 new ancient shotgun genomes with 382 ancient and 23 present-day published genomes, we found that genetic diversity within each region steadily increased through the Holocene. We further observed that the inferred sources of gene flow shifted in time. In the first half of the Holocene, Southwest Asian and the East Mediterranean populations homogenized among themselves. Starting with the Bronze Age, however, regional populations diverged from each other, most likely driven by gene flow from external sources, which we term “the expanding mobility model.” Interestingly, this increase in inter-regional divergence can be captured by outgroup-f$_3$-based genetic distances, but not by the commonly used F$_{ST}$ statistic, due to the sensitivity of F$_{ST}$, but not outgroup-f$_3$, to within-population diversity. Finally, we report a temporal trend of increasing male bias in admixture events through the Holocene

H2S biosynthesis and catabolism: new insights from molecular studies

Hydrogen sulfide (H2S) has profound biological effects within living organisms and is now increasingly being considered alongside other gaseous signalling molecules, such as nitric oxide (NO) and carbon monoxide (CO). Conventional use of pharmacological and molecular approaches has spawned a rapidly growing research field that has identified H2S as playing a functional role in cell-signalling and post-translational modifications. Recently, a number of laboratories have reported the use of siRNA methodologies and genetic mouse models to mimic the loss of function of genes involved in the biosynthesis and degradation of H2S within tissues. Studies utilising these systems are revealing new insights into the biology of H2S within the cardiovascular system, inflammatory disease, and in cell signalling. In light of this work, the current review will describe recent advances in H2S research made possible by the use of molecular approaches and genetic mouse models with perturbed capacities to generate or detoxify physiological levels of H2S gas within tissue

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Power quality in electrical energy systems

Tez (Yüksek Lisans) -- İstanbul Teknik Üniversitesi, Fen Bilimleri Enstitüsü, 1995Thesis (M.Sc.) -- İstanbul Technical University, Institute of Science and Technology, 1995Yarıiletken güç elektroniği devrelerinin gelişmesi beraberinde bazı sorunları da getirmiştir. Bu nedenle teknolojinin gelişimine paralel olarak şebekedeki dalga şekli distorsiyonlan da artmıştır. Yarıiletken devreler yapı olarak şebekeden dalgalı akım çektiği için harmoniklere yol açar. Aynı zamanda şebekedeki anahtarlama olayları, kısadevreler, yıldırım düşmesi, kesintiler gibi etkenler de güç kalitesini olumsuz yönde etkiler. Günümüzde güç kalitesi sorunlarının çözümlenmesi hem verimlilik açısından ve hem de ekonomik nedenlerden dolayı bir zorunluluk haline gelmiştir. Bu sorunları çözmek için önce sistemli bir çalışma yapılması gereklidir. Daha sonra ihtiyaca ve elde edilen verilere bağlı olarak değişik yöntemler kullanılarak güç kalitesi problemleri giderilmeye çalışılır."Electrical power qualify" is a term which has captured increasing attention in power engineering in recent years. The term broadly refers to maintaining the near sinusoidal waveform of power distribution bus voltages at rated voltage magnitude and/or frequency. Power quality is not a new phenomenon, but what is new is the increasing severity of power quality problems in terms of customer sensitivity. Power quality is a term which has many interpretations, but can be generally be classified as an area that deals with intermittent and steady state voltage and current waveform distrtion from normal operating conditions. Historically, power quality phenomena can be traced to the early parts of this century, as a real world condition that electrical equipment is subjected to in most installations. There are three stages in history of power quaUty which summarize the development and level of interest in the area. The first stage is represented by Steinmetz, who found a solution for third harmonic currents resulting from saturated iron in machines and transformers. In the early 1900's, Steinmetz suggested using delta and undergrounded-wye connections to stop the third harmonics from spreading into the power system. With this problem, harmonics were put aside for several years until the 1930's and 1940's, which represents the second stages in its history. During this period, power and telephone circuits often shared the same paths. Audio interference was (and still is) a common problem because of harmonic currents that coupled inductively into nearby telephone circuits. These harmonics were produced by, among others, arc furnaces, large rectifiers, or power supply rectifiers. Harmonics aroses as an area of study once again. The new problems were lessened by filtering where necessary and by learning to limit the magnetizing current harmonics produced by distribution transformers. vn The third stages started in the late 1950's with the advent of power semiconductor devices. The emerging dependence on power electronic based devices has given rise to a renewed interest in harmonics again, in which turn has broadened to an interest in overall power quality, since power quality includes in addition to harmonics, non-periodic waveform. This renewed interest in power quality is of greater importance today for two reasons: firstly, there are many more harmonic producing technologies today (i.e.: alternate energy converters, static var compensators, motor control devices, flexible AC transmission systems-FACTS, direct energy conversion devices, and so forth), and secondly, there are devices and loads that are sensitive to waveform distortions (i.e.: word-processors, computers, relays, meters and industrial process controllers). A recent study on power system harmonic has identified power quality problems as: i. The failure capacitor banks due to dielectric breakdown or reactive power overload. ii. Interference with ripple control and power line carrier systems, causing misoperation of systems which accomplish remote switching, load control, and metering iii. Excessive losses resulting in heating of induction and synchronous machines. iv. Overvoltages and excessives currents on the system from resonance to harmonic voltages or currents on the network. v. Dielectric breakdown of insulated cables resulting from harmonic voltages. vi. Inductive interference with eommunications systems. vii. Errors in meter reading. viii. Signal interference and relay malfunction, particularly in solid state and microprocessor controlled systems. ix. Interference with large motor controllers and powerplant excitation systems. x. Mechanical oscillations of inductions and synchronous machines. xi. Unstable operations of firing circuits based on zero crossing detecting or latching xii. Excessive heating of transformers due to the frequency dependence core vui xiii. Change in TV picture size and brightness if harmonics affect the peak voltages xiv. Effects on computer and computerized automation production. Electric Power Quality " Harmonics Modelling and Analysis Component models Stochastic Methods Instrument Metering -Measurements Waveform Analysis Voltage Support -Software Solutions -SWCc Passive Filtreler -SVCs Active Filters Fundamental I Concepts I Effects Standards Definitions User Issues Protection Figure 1. Main aspects of electrical power quality IX Figure 1 is a pictorial of the main aspects of electric power quality. There are six areas shown are: Modelling and analysis : Analysis of nonsinusoidal waveforms in power distribution systems may be accomplished by time domain methods; transformed domain methods; simulation of the existing circuit. Time domain metodologies are primarily based on numerical integration techniques. Perhaps the most popular of these techniques is that used in the Electromagnetic Transients Programs (EMTP). This techniques entails a resolution of energy storage elements in power systems (e.g., V s, C's ) to a parallel combination of a fixed resistance and a time-varying current source. The time varying current source is found iteratively and recursively. Under this resolution, the power network may be modeled as a fixed bus conductance matrix, G^, and the injections currents, 1^(0, to the network are calculated at each time step, This metodology is complete and as detailed as the models used to obtain G^t) and I^Ct). Typically data requirements as well as computational requirements are intensive. Effects of power quality problems : The proliferation of non-lineer loads and sources, such as power electronic based equipment, has largely ocurred in the absence of complete standards which limit the harmonic signals that the power system should be able to withstand and that utilities can absorb. This situation is leading to an emerging problem of power quality for both utilities and their customers. The requirements of sensitive loads for "clean power", the characterization of sources of "dirty power", and the establishment of interface guidelines and standards require considerable technical and economic evaluation. Mitigation of power quality problem : Power quality problems span such a wide range of characteristics that it is difficult to summarize and prioritize research areas for this topic. Among these topics are : i. Novel efficient means of voltage regulation- Especially with rapid response time. ii. Optimal passive filter design iii. Practical active filter theory iv. Power electronic solutions to power qualty problems. v. Efficient power conditioning Measurements : Measurements of power quality problems may consist of testing in some or all of the following areas: i. Voltage / current / frequency / N-phase unbalance : Steady state deviations from normal utility voltage, current, frequency and phase operating points can be caused by many factors within the utility grid: customer loadsvariations, improper grounding, tap changing, and insertion of compensation elements. Test standards which may apply are : ANSI C84. 1, ANSI C37. 106, and IEEE 141 ii. Harmonics : No-lineer devices or loads cause voltage and current waveform distortions. These distortions which may be periodic in nature can cause problems. Voltage notching and flicker are also problems that may be caused by by the electronic devices. Test standards which may apply are : IEEE 519-D5, ANSIC57.106, and IEEE 141 XI iii. Energy usage : It is well known that power quality affects the real and the reactive power demans of equipment. This results in high cost of operation, losses, and voltage and current regulation problems. Test standards which may apply are : IEEE 519, IEEE 141, IEEE 389 and IEC 555 iv. Surge tests : Lightning or switching transients can cause damage or misoperation of devices not capable of handling such surges. Test standards which may apply are : ANSI / IEEE C62.4 1, and ANSI / IEEE C37.90. 1 v. Over and under voltage : Sags and swells in voltage over aperiod of several cycles are a phenomenon arising due to phase delays in the power system. Test standards which may apply are : IEEE 141, and ANSI C37Yüksek LisansM.Sc

Ülkemizdeki paroksismal nokturnal hemoglobinüri hastalarının klinik özelliklerinin ve tedavi sonuçlarının değerlendirilmesi çok merkezli bir çalışma

Amaç: Paroksismal nokturnal hemoglobinüri (PNH), kronik intravasküler hemoliz bulguları,kemik iliği yetersizliği ve trombozla kendini gösterebilen edinsel, klonal bir hematopoietikkök hücre hastalığıdır. Klinik bulguların çok değişken olması, tanıda gecikmelere vehastalığın morbi-mortalitesinde artışa yol açabilmektedir. Tanıda altın standart yöntem, temelmoleküler defektin, yani glukozilfosfotidilinozitol (GPİ) çıpası yardımıyla hücre membranınabağlanan proteinlerdeki eksikliğin akım sitometrik yöntemle ortaya konulmasıdır.Tedavisinde ise tek küratif yöntem allojeneik kök hücre naklidir. Ancak günümüzde PNHtedavisinde, hemoliz, transfüzyon bağımlılığı, organ hasarı ve semptomları azalttığı gösterilenve bir terminal kompleman inhibitörü olarak görev yapan eculizumab da yaygın olarakkullanılmaktadır. Bu çok merkezli çalışmada amacımız, ülkemizdeki PNH hastaların kliniközelliklerinin ve tedavi yönetimlerinin değerlendirilmesidir.Gereç ve yöntem: Çalışmamıza yirmi farklı merkezin hematoloji kliniğinde PNH tanısı alantoplam 60 olgu dahil edilmiştir. Tüm olguların retrospektif olarak dosyaları taranmış,hastaların demografik özellikleri, laboratuvar bulguları, gelişen komplikasyonlar, akımsitometri bilgileri, aldıkları tedaviler ve ölüm sebepleri kaydedilmiştir.Bulgular: Çalışmamıza alınan 60 hastanın ortanca yaşları 33 (17-77) idi. Kırkaltı hasta klasikPNH ve 14 hasta sekonder PNH (13 hasta aplastik anemi+PNH, 1 hasta myelodisplastiksendrom+PNH) idi. Hastaların temel demografik özellikleri, hematolojik parametreleri,semptom ve bulguları Tablo1’de özetlenmiştir. Halsizlik ve karın ağrısı en sık başvuruyakınmaları olup, organomegali sadece 7 hastada saptanmıştı. Akım sitometrik analizdeortanca granülosit ve monosit klonları klasik PNH olgularında sırasıyla %75 (23.1-99.5) ve%77 (14.2-99) ve sekonder PNH olgularında %70.5 (13.8-95) ve %61 (14-95.5) olarak izlendi. Tromboembolik olaylar 60 hastanın 18 inde (%30) gözlenmişti. Klasik ve sekonderPNH olguları arasında tromboembolik olay gelişimi açısından istatistiksel bir farkgözlenmemişti (sırasıyla %17.3 ve %14.2, p:0.57). Hastaların, 2009 yılında eculizumabülkemizde ulaşılabilir olana dek immünsupresif ilaçlarla tedavi gördükleri, bu tarihten sonraise olguların %67.4’ünde (31/46) eculizumab tedavisine geçildiği izlendi. Ortalama yaşamsüresi 42 ay (7-183) olarak belirlendi. 60 hastadan 4’ü (%6.6) infeksiyon, 2’si fungalpnömoni, 1’i sepsis ve diğer 1 hasta ise CMV enfeksiyonu nedenli kaybedildi.Tartışma: Çalışmamızda, nadir bir hematopoietik kök hücre hastalığı olan PNH’nin görülmeyaşının literatürle benzerlik gösterdiğini görülmüştür. Trombotik komplikasyon sıklığı %30olarak belirlenmiş olup, sıklıkla ve beklendiği üzere venöz tromboz şeklinde geliştiğigörülmüştür. Literatürden farklı olarak tromboz nedenli ölen hasta görülmemiş, en sık ölümsebebi enfeksiyon olarak belirlenmiştir.Çalışmamız, PNH hastalarının değerlendirildiği ve ülkemizde bugüne kadar yapılmışen kapsamlı çalışmadır. Bu ve benzer çalışmaların, nadir görülen PNH gibi hastalıklarda,ileriye yönelik olarak hastalık yönetimini de etkileyebilecek çok değerli bilgiler verebileceğinidüşünüyoruz.Anahtar kelimeler: Eculizumab, Paroksismal nokturnal hemoglobinüri, Tromboz&nbsp;</p

Vitamin B12 levels in patients with Familial Mediterranean Fever (FWF) under regular colchicine treatment

GİRİŞ: Günümüzde FMF için standart tedavi düzenli kolşisin kullanımı olup bu tedavi çoğu hastada hastalığın tam remisyonu veya atakların sıklık ve şiddetinin azalmasına yol açmaktadır. Düzenli ve uygun dozlarda kolşisin kullanımının ataklar üzerinde etkisi olmasa bile, amiloidoz gelişiminden koruduğu hatta renal amiloidozun gerilemesine yol açtığı gösterilmiştir. Kolşisin tedavisinin B12 eksikliği yaptığına dair yayınlar ilk olarak 1960-1970'li yıllara aittir. Günümüzde düzenli kolşisin tedavisi alan hastaların B12 replasman tedavisi kullanma gerekliliği net değildir. B12 vitamin düzeyinin saptanmasında kullanılan biyokimyasal kitlerin gelişmesi de göz önüne alındığında son yıllarda bu konuda yapılmış bir çalışma bulunmamaktadır. Biz bu çalışmada düzenli kolşisin tedavisi kullanan hastalardaki vitamin B12 düzeyini saptamayı amaçladık. GEREÇLER VE YÖNTEM: Çalışmaya hastanemiz dahiliye kliniğinde düzenli takipleri yapılan 95 fmf hastası ve karşılık gelen yaş ve cinsiyet benzer 90 kontrol grubu dahil edilmiştir. Bütün hastaların hemoglobin, hematokrit, folik asit, ferritin ve vitamin B12 düzeyleri ölçülmüş; elde edilen ölçümlerin uzun süreli ve düzenli kolşisin kullanımı ile olan ilişkisi araştırılmıştır. BULGULAR: Çalışmamızda hasta grubununun ortalama vitamin B12 düzeyi 352,12 ± 171,62 olarak ölçülmüş; kontrol grubunda ise vitamin B12 düzeyi ortalaması 360,96 ± 146,53 olarak saptanmıştır. Her iki grup arasında ortalama vitamin B12 düzeyi açısından istatistiki anlamlı fark gözlenmemiştir (p = 0,707). Vitamin B12 düzeyinin 194 pg/ml'nin altında ölçülmesi olarak tanımlanan eksiklik açısından gruplar incelendiğinde hasta bireylerin % 12,6'sında; kontrol grubunun ise %3,3'ünde eksiklik saptanmıştır. Sonuç olarak düzenli kolşisin kullanan hastalarda kontrol grubu ile karşılaştırıldığında istatistiki olarak anlamlı düzeyde fazla kişide vitamin B12 eksikliği gözlenmiştir. Bu bireylerin ortalama hemoglobin, hematokrit, folik asit ve ferritin düzeyleri eksiklik saptanmayan hastalarla benzer özellikteydi. SONUÇ VE ÖNERİLER: Çalışmamız sonuçları doğrultusunda, uzun süreli ve düzenli kolşisin kullanan hastalarda klinik olarak asemptomatik vitamin B12 eksikliği gelişebileceğinden ve bu eksikliğin tedavi edilmemesi durumunda hastalarda vitamin eksikliğine bağlı ciddi hematolojik ve nöropsikiyatrik sorunlar ortaya çıkabileceğinden bu hastalarda belli aralıklarla serum vitamin B12 düzeylerinin ölçülmesi önerilebilir. Eksiklik durumunda kolşisin tedavisinin kesilmesi söz konusu olamayacağından vitamin B12 replasmanı gündeme gelebilir. Bu konuda daha önce yapılmış çalışmaların geniş insan serilerini içermemesi ileride yapılacak geniş çaplı çalışmaları gerekli kılmaktadır. Çalışmamız literatürde konu ile ilgili yapılmış en geniş erişkin insan çalışması olması özelliği ile diğer çalışmalara ışık tutacaktır. INTRODUCTION: Unremitting use of daily colchicine as a standard theurapeutic regimen for Familial Mediterranean Fever (FMF) warrants a decrease in frequency and intensity of acute episodes in a majority of patients. It is denoted that regular intake of colchicine in appropriate dosage; not only prevents from amyloidosis to develop, but also elicits a regression in renal involvement of amyloidosis; even though it is ineffective in the course of execarbetions. Initial articles blaming the colchicine treatment as a causative agent for B12 insufficiency were published at 60's and 70's. It is still debated that B12 replacement is required for patients under regular colchicine treatment. There is no recent data with large sample population when improvements in biochemical kits detecting B12 vitamin levels are taken into account. In this study we aimed to measure vitamin B12 levels in patients under regular colchicine treatment. MATERIALS AND METHOD: 95 FMFpatients with a close follow up by our outpatient clinics and a control group of 90 individuals sharing the same demographic characteristics were included in the study. Hemoglobin, folic acid, ferritin and B12 vitamin levels of all individuals were measured and relationship of the obtained data with regular colchicine intake was investigated. RESULTS: Mean vitamin B12 levels were measured as 352,12 ± 171,62 in the sample group and 360,96 ± 146,53 in the control group. No statistical significance between B12 vitamin levels of two groups were observed (p = 0,707). When two groups were compared for vitamin B12 deficiency defined as serum level of 194 pg/ml and below.; 12,6% of patients and 3,3% of control group was stated to be deficient. Consequently; vitamin B12 deficiency was significantly higher in patients under regular colchicine treatment in comparison to the control group. Hemoglobin, haematocrit, folic acid and ferritin levels were similar both in sample and control group. DISCUSSION: As a result of this study; long lasting and constant intake of colchicine may cause asymptomatic vitamin B12 deficiency and may lead to severe neuropsychiatric and haematological disorders if left untreated; we suggest to measure vitamin B12 levels in certain intervals. If a deficiency is determined because cessation of colchicine is not reliable; replacement of vitamin B12 may be considered. Absence of investigations about this topic involving large patient series necessitates further evaluation. Having the property of largest sample population in the literature; distinguishes our study from others and hopefully inspire the larger ones