Demans Hastalarının Ayırıcı Tanısında Kullanılan Tanısal Testlerin Karşılaştırılması

Dementia is a clinical diagnosis characterized by a progressive deterioration in cognitive function. The most common type of dementia is Alzheimer's disease (AD). The aim of this study is to evaluate the possible relation and correlation between comprehensive geriatric assessment tests, metabolic function of brain determined by positron emission tomography (FDG PET CT) and volumetric analysis and atrophy symmetry measured by magnetic resonance imaging (MRI) in AD patients. 37 patients who had diagnosis of AD and admitted to Hacettepe University Faculty of Medicine Department of Internal Medicine Division of Geriatrics between 1 November 2012 and 1 November 2015 included. In addition to baseline demographic, clinical and laboratory characteristics, comprehensive geriatric assessment tests, metabolic measurements in 8 different localization by using FDG PET CT in all patients and volumetric analysis in 14 different regions by using cranial MRI in 16 patients were performed. Moderate to severe hypometabolic activity was most frequently observed in left temporal lobe (37 patients, 43,2% of all population). Thereafter, right temporal lobe (37,8%) and right and left parietal lobes (32,4%) followed left temporal lobe. On the other hand, normal metabolic activity was most frequently seen in right frontal lobe (75,7%). In 16 patients, mean ± SD right hippocampal volume was 3128,1 ± 732,2 mm3, mean ± SD left hippocampal volume was 3088,8 ± 791,5 mm3 and mean ± SD total hippocampal volume 6217,0 ± 1459,2 mm3. MOCA was found to be significantly lower in patients with moderate to severe hypometabolism in left temporal, right and left parietal lobes than that of mild hypometabolic and normometabolic patients (p = 0,033, p = 0,032 and p = 0,028). In patients with moderate to severe hypometabolism in right parietal, forward digit span test was found to be lower (p = 0,031) and geriatric depression scale was found to be higher (p = 0,023). There was no relationship between prekuneal and frontal hypometbolism and comprehensive geriatric assessment tests. It was also not found any relationship between hypometabolic status and volumetric analysis except right precuneal hypometabolism and left entorhinal cortex volume. Similarly, there was no significant relation between atrophy symmetry in MRG, volumetric analysis and comprehensive geriatric assessment tests. In correlation analysis, there were significant and negative correlations between right temporal lobar hypometabolism and forward digit span test (r = -0,304, p = 0,047) , mini mental state examination test (MMSE) (r = -0,301, p = 0,048) and MOCA (r = -0,296, p = 0,050); between left temporal lobar hypometabolism and forward digit span test (r = -0,324, p = 0,050), three word recall test (r = -0,369, p = 0,025), MMSE (r = -0,394, p = 0,016) and MOCA (r = -0,353, p = 0,032); between right parietal lobar hypometabolism and forward digit span test (r = -0,427, p = 0,008), perseveration (r = -0,360, p = 0,029), MMSE (r = -0,324, p = 0,050) and MOCA (r = -0,433, p = 0,007); left parietal lobar hypometabolism and forward digit span test (r = -0,377, p = 0,021), MMSE (r = -0,325, p = 0,047) and MOCA (r = -0,439, p = 0,007) and between both right and left prekuneal hypometabolism and MMSE (r = -0,356, p = 0,031 and r = -0,332, p = 0,044, respectively). There were significant and negative correlations between left temporal hypometabolism and left hippocampal (r = -0,420, p = 0,005) and total hippocampal (r = -0,254, p = 0,017); between right prekuneal hypometabolism and total hippocampal (r = -0,410, p = 0,005) and right parahippocampal (r = -0,435, p = 0,007) and between left prekuneal hypometabolism and total hippocampal (r = -0,406, p = 0,008) and right parahippocampal (r = -0,439, p = 0,007) volume. In conclusion, this study showed the relationship between 14 different geriatric assessment tests, hypometabolic activity of 8 different anatomic localizations and volumetric analysis of 14 different brain regions.TEŞEKKÜR…………………………………………………………………………iv ÖZET………………………………………………………………………..……….v ABSTRACT………………………………………………………..……………….vii İÇİNDEKİLER…………………………………………………………………...….ix SİMGELER VE KISALTMALAR…………………………………………………..xi TABLOLAR VE ŞEKİLLER DİZİNİ…………….………………….…………….xiii 1. GİRİŞ VE AMAÇ…………………………………………………...……….1 2. GENEL BİLGİLER………………………………………………….………3 2.1. Hafif Bilişsel Bozukluk……………………………..…………….…3 2.1.1. Amnestik Hafif Bilişsel Bozukluk:……………………..………3 2.1.2. Amnestik Olmayan Hafif Bilişsel Bozukluk…………………..4 2.2. Demans Sendromları………………………………………………4 2.2.1. Demansta Tanı ve Ayırıcı Tanı……………………..…………6 2.2.2. Alzheimer Hastalığı………………………………………….…6 2.2.3. Lewy Cisimcikli Demans………………………………...……10 2.2.4. Frontotemporal Demans……………………………..….……13 2.3. Demans Sendromlarında Görüntüleme…………...……………16 2.3.1. Yapısal Görüntüleme…………………………………………17 2.3.2. Moleküler Görüntüleme………………………………………20 2.4. Nöropsikiyatrik Değerlendirme……………………………..……22 2.4.1. Mini Mental Durum Değerlendirme Testi…………………...23 2.4.2. Saat Çizme Testi………………………………………………24 2.4.3. Montreal Bilişsellik Değerlendirme Ölçeği (MOCA)……….24 2.4.4. Geriatrik Depresyon Skalası……………………….………...25 3. HASTALAR VE YÖNTEM…………………………………………..……26 3.1. Hastaların Seçimi ve Genel Özellikleri………………………….26 3.2. Hastaların Nöropsikiyatrik Değerlendirilmesi……..……………27 3.3. Kranial Görüntüleme……………………………..……………….28 3.4. İstatistiksel Değerlendirme……………………………………….30 3.5. Etik Onay……………………………………………………….….30 4. BULGULAR………………………………………………….…………….31 4.1. Temel Demografik Özellikler……………………………………..31 4.2. Kranial Metabolik Aktivite ve Kapsamlı Geriatrik Değerlendirme Testleri……………………………………………...………………36 4.3. Kranial Metabolik Aktivite ve Volümetrik Ölçümler………….…45 4.4. Manyetik Rezonans Görüntülemede Atrofi Simetrisi ve Kapsamlı Geriatrik Değerlendirme Testleri………………...…..53 4.5. Manyetik Rezonans Görüntülemede Atrofi Simetrisi ve Volümetrik Ölçümler………………………………………………54 4.6. Kranial Metabolik Aktivite ile Nöropsikiyatrik Testlerin Korelasyon Analizi………………………………………………...55 4.7. Kranial Metabolik Aktivite ile Volümetrik Ölçümlerin Korelasyon Analizi………………………………………………………………55 4.8. Fazekas Skoru, Kortikal Beyaz Madde T1 Hipointensitesi ve Günlük Yaşam Aktivitesi Değerlendirmesinin Korelasyon Analizi………………………………….…………………………...59 5. TARTIŞMA…………………………………………………………….…..62 6. ÇALIŞMANIN KISITLILIKLARI…………………………………………..69 7. SONUÇLAR VE ÖNERİLER………………………………..……………70 8. KAYNAKLAR…………………………………………...………………….71 9. EKLER……………………………………………………….……………..93Demans, bilişsel işlevlerde ilerleyici bozulma ile karakterize klinik bir tanıdır. En sık demans tipi Alzheimer Hastalığıdır (AH). Bu çalışmanın amacı, AH’de kapsamlı geriatrik değerlendirme testleri, pozitron emisyon tomografi (FDG PET BT) ile değerlendirilen beynin metabolik işlevleri ve kranial manyetik rezonans görüntüleme (MRG) ile ölçülen volümetrik analizler ve atrofi simetrisi arasındaki olası ilişkileri ve korelasyonları incelemektir. Çalışmaya Hacettepe Üniversitesi Tıp Fakültesi İç Hastalıkları Ana Bilim Dalı Geriatri Bilim Dalına 01 Kasım 2012 – 01 Kasım 2015 tarihleri arasında Alzheimer Hastalığı tanısı ile başvuran 37 hasta alındı. Tüm hastalarda temel demografik, klinik ve laboratuvar bilgilerinin yanı sıra kapsamlı geriatrik değerlendirme testleri, 8 farklı lokalizasyonda FDG PET BT ile metabolik ölçümler ve 16 hastada kranial MRG ile 14 farklı bölgenin volümetrik analizi yapıldı. Sol temporal lob, 37 hastanın %43,2’si (16 hasta) ile orta – ağır hipometabolizmanın en sık görüldüğü bölgeydi. Bunu %37,8 ile sağ temporal lob ve %32,4 ile sağ paryetal ve sol paryetal loblar izledi. Normal metabolik aktivitenin en sık izlendiği bölge ise %75,7 ile sağ frontal bölgeydi. 16 hastada ortalama ± SD sağ hipokampüs volümü 3128,1 ± 732,2 mm3, sol hipokampüs volümü 3088,8 ± 791,5 mm3 ve total hipokampüs volümü 6217,0 ± 1459,2 mm3 olarak bulundu. Montreal Bilişsel Değerlendirme (MOCA), sol temporal, sağ ve sol paryetal loblarında orta – ağır hipometabolizma görülen hastalarda hafif hipometabolizma görülen ve hipometabolizma görülmeyen hastalara göre anlamlı olarak daha düşüktü (p = 0,033, p = 0,032 ve p = 0,028). Sağ paryetal orta – ağır hipometabolizma olan hastalarda ileri menzil test skoru daha düşük (p = 0,031) ve geriatrik depresyon skalası (p = 0,023) daha yüksek bulundu. Prekuneal ve frontal hipometabolizma ile testler arasında anlamlı ilişki saptanamadı. Sağ prekuneus metabolik aktivitesi ile sol entorhinal korteks volüm dışında hipometabolik durum ile volümetrik analizler arasında ilişki saptanmadı. Yine MRG’de atrofi simetrisi ile volümetrik ölçümler, kapsamlı geriatrik değerlendirme testleri arasında anlamlı ilişki bulunmadı. Korelasyon analizinde sağ temporal lob hipometabolizması ile ileri menzil (r = -0,304, p = 0,047) , mini mental durum değerlendirme (MMSE) (r = -0,301, p = 0,048) ve MOCA (r = -0,296, p = 0,050) arasında, sol temporal lob hipometabolizması ile ileri menzil (r = -0,324, p = 0,050), üç kelime test (r = -0,369, p = 0,025), MMSE (r = -0,394, p = 0,016) ve MOCA (r = -0,353, p = 0,032) arasında, sağ paryetal lob hipometabolizması ile ileri menzil (r = -0,427, p = 0,008), perseverasyon (r = -0,360, p = 0,029), MMSE (r = -0,324, p = 0,050) ve MOCA (r = -0,433, p = 0,007) arasında, sol paryetal lob hipometabolizması ile ileri menzil (r = -0,377, p = 0,021), MMSE (r = -0,325, p = 0,047) ve MOCA (r = -0,439, p = 0,007) arasında ve hem sağ hem sol prekuneus ile MMSE arasında (r = -0,356, p = 0,031 ve r = -0,332, p = 0,044, sırasıyla) negatif yönde anlamlı korelasyon saptandı. Sol temporal lob hipometabolizması ile sol hipokampal (r = -0,420, p = 0,005) ve total hipokampal (r = -0,254, p = 0,017), sağ prekuneus lob hipometabolizması ile total hipokampal (r = -0,410, p = 0,005) ve sağ parahipokampal (r = -0,435, p = 0,007) ve sol prekuneus lob hipometabolizması ile total hipokampal (r = -0,406, p = 0,008) ve sağ parahipokampal (r = -0,439, p = 0,007) volüm arasında negatif yönde anlamlı korelasyon saptandı. Bu çalışma ile 14 farklı geriatrik değerlendirme testi, 8 farklı anatomik bölge hipometabolizması ve 14 farklı beyin bölgesinin volümetrik analizi arasındaki ilişki gösterilmiştir

Dizygotic Twin With Congenital Av Block

PubMe

Unclassifiable non-CML classical myeloproliferative diseases with microcytosis

Background/aim Polycythemia Vera (PV) is a myeloproliferative disorder characterized by overproduction of morphologically normal red blood cells (RBCs), granulocytes, and platelets, a phenotype that is caused by a mutation (V617F) in Janus kinase 2 (JAK2). However, JAK2 V617F is also found in approximately 50% of patients with essential thrombocytosis and primary myelofibrosis, rendering its presence nonspecific as a diagnostic test. An increased red cell mass is a major criterion for the diagnosis of PV according to World Health Organization (WHO) 2016 criteria. High hemoglobin (Hgb) or Hematocrit (Hct) are universally used as indicators of an increased red cell mass for the diagnosis of PV. However, conditions such as iron deficiency (ID) with decreased mean cell volume may mask the diagnosis due to nonelevated Hct level. The aim of this study was to investigate the clinical characteristics of the patients with unclassifiable non-CML classical myeloproliferative disease with microcytosis (MPD/M) and nonelevated Hgb and Hct levels at diagnosis and to determine if some of these cases could be real PV cases masked due to ID-related microcytosis. Materials and methods There were 23 MPD/M cases among 208 non-CML classical MPD cases (11%). Among 22 patients who had adequate test results related to the cause of microcytosis, ID and beta-thalassemia trait (TT) were the apparent causes of microcytosis in 15 and 1 cases, respectively. Results Clinicopathological correlations revealed consistently positive JAK2 V617F mutation status (20/20, 100%), frequently elevated RBC count (17/23, 73.9%), and PV-compatible bone marrow findings (10/12, 83.3%). These findings are compatible with PV instead of essential thrombocytopenia or primary myelofibrosis. In spite of frequent cytoreductive treatment, 3 patients developed increased Hgb/Htc levels during median 58.2 (279–63) months’ follow-up. Conclusion These data show that the majority of MPD/M cases are PV patients masked due to ID-related microcytosis.PubMedWoSScopu

Comparison of Myeloablative Versus Reduced-Intensity Conditioning Regimens for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia: A Cohort Study

Objective: Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective treatment modality for a variety of malignant and non-malignant hematologic disorders. Myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC) regimens could have different clinical outcomes. This purpose of this study was to assess the long-term outcome of MAC versus RIC regimens in patients with acute myeloid leukemia (AML) undergoing allogeneic HSCT. Materials and Methods: We retrospectively compared long-term outcomes with MAC and RIC regimens in patients with AML who underwent allo-HSCT at our tertiary transplantation center. Results: We analyzed survival outcomes after MAC-HSCT versus RICHSCT among 107 adult patients with AML diagnosed from 2001 through 2017. Of those, 44 patients underwent a MAC regimen, whereas 63 patients received a RIC regimen. The median follow-up time was 37 months (range: 6-210) for the entire group. The 3-year overall survival (OS) for RIC and MAC patients was 67% and 60%, respectively (p>0.05). The 3-year progression-free survival (PFS) for RIC and MAC patients was 88% and 77%. In multivariate analysis, the type of conditioning regimen (RIC vs. MAC) did not influence PFS (p=0.24). Acute graft-versus-host disease (GVHD) was seen in five of the RIC patients and 9 of the MAC patients. Chronic GVHD was seen in 16 of the RIC patients and 6 of the MAC patients. There was no significant difference between the two groups in terms of acute GVHD (p=0.089), but there was a significant difference between the two groups in terms of chronic GVHD (p=0.03). Conclusion: This retrospective analysis confirmed that MAC and RIC regimens had a consistently equivalent rate of OS and PFS in AML patients who underwent allo-HSCT. The choice of MAC versus RIC conditioning regimen might be decided on the basis of patient and disease characteristics

Mitoxantrone-Melphalan Conditioning Regimen For Autologous Stem Cell Transplantation In Relapsed/Refractory Lymphoma

Background/aim High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become the standard approach for patients with relapsed/refractory Hodgkin’s lymphoma (HL) or non-Hodgkin’s lymphoma (NHL). In this study, we report the outcome of the mitoxantrone-melphalan conditioning regimen for lymphoma. Materials and methods The study group included 53 patients who were relapsed/refractory HL (n = 14) and NHL (n = 39) and received mitoxantrone and melphalan followed by ASCT. The transplant regimen consisted of mitoxantrone (60 mg/m2) and melphalan (180 mg/m2) followed by peripheral blood stem cell infusion (PBSC). Results Prior to high-dose chemotherapy, 37.7% of the patients were in complete remission (CR) and 45.3% were in partial remission (PR), and 17% had stable or progressive disease. After high-dose chemotherapy and PBSC, 44 out of 51 patients achieved CR (86.2%). CR was achieved in 24 out of 33 patients (72.7%) who were transplanted in a marginally active phase of the disease. At a median followup of 25.4 months (1.8–131.3 months) after ASCT, 13 patients relapsed/progressed and 8 patients died. The estimated 2-year overall survival (OS) was 81.9%, and event-free survival (EFS) was 59.3%. Conclusion High-dose chemotherapy followed by ASCT is an effective conditioning regimen in relapsed/refractory lymphoma patients who are undergoing ASCT.PubMedWo

A Spectrum of Clinical Findings from ALPS to CVID: Several Novel LRBA Defects

Introduction: Autosomal recessively inherited lipopolysaccharide-responsive beige-like anchor (LRBA) protein deficiency was shown to be responsible for different types of inborn errors of immunity, such as common variable immunodeficiency (CVID) and autoimmune lymphoproliferative syndrome (ALPS). The aim of this study was to compare patients with LRBA-related ALPS and LRBA-related CVID, to describe their clinical and laboratory phenotypes, and to prepare an algorithm for their diagnosis and management. Methods: Fifteen LRBA-deficient patients were identified among 31 CVID and 14 possible ALPS patients with Western blotting (WB), primary immunodeficiency disease (PIDD) gene, next-generation panel screening (NGS), and whole exome sequencing (WES). Results: The median age on admission and age of diagnosis were 7 years (0.3–16.5) and 11 years (5–44), respectively. Splenomegaly was seen in 93.3% (14/15) of the patients on admission. Splenectomy was performed to 1/5. Recurrent upper respiratory tract infections (93.3% (14/15)), autoimmune cytopenia (80% (12/15)), chronic diarrhea (53.3% (8/15)), lower respiratory tract infections (53.3% (8/15)), lymphoma (26.6% (4/15)), Evans syndrome (26.6% (4/15)), and autoimmune thyroiditis (20% (3/15)) were common clinical findings and diseases. Lymphopenia (5/15), intermittant neutropenia (4/15), eosinophilia (4/15), and progressive hypogammaglobulinemia are recorded in given number of patients. Double negative T cells (TCRαβ+CD4−CD8−) were increased in 80% (8/10) of the patients. B cell percentage/numbers were low in 60% (9/15) of the patients on admission. Decreased switched memory B cells, decreased naive and recent thymic emigrant (RTE) Thelper (Th) cells, markedly increased effector memory/effector memory RA+ (TEMRA) Th were documented. Large PD1+ population, increased memory, and enlarged follicular helper T cell population in the CD4+ T cell compartment was seen in one of the patients. Most of the deleterious missense mutations were located in the DUF1088 and BEACH domains. Interestingly, one of the two siblings with the same homozygous LRBA defect did not have any clinical symptom. Hematopoietic stem cell transplantation (HSCT) was performed to 7/15 (46.6%) of the patients. Transplanted patients are alive and well after a median of 2 years (1–3). In total, one patient died from sepsis during adulthood before HSCT. Conclusion: Patients with LRBA deficiency may initially be diagnosed as CVID or ALPS in the clinical practice. Progressive decrease in B cells as well as IgG in ALPS-like patients and addition of IBD symptoms in the follow-up should raise the suspicion for LRBA deficiency. Decreased switched memory B cells, decreased naive and recent thymic emigrant (RTE) Th cells, and markedly increased effector memory/effector memory RA+ Th cells (TEMRA Th) cells are important for the diagnosis of the patients in addition to clinical features. Analysis of protein by either WB or flow cytometry is required when the clinicians come across especially with missense LRBA variants of uncertain significance. High rate of malignancy shows the regulatory T cell’s important role of immune surveillance. HSCT is curative and succesful in patients with HLA-matched family donor

Covid-19 Pandemi Raporu (20 Mart-20 Kasım 2020)

31 Aralık 2019 tarihinde Çin’de ortaya çıkan ve kısa sürede tüm dünyayı etkileyen SARS-Coronavirus-2 etkenine bağlı COVID-19’un Dünya Sağlık Örgütü tarafından pandemi ilan edildiği dönem ile eş zamanlı olarak, ülkemizde 11 Mart 2020’de ilk vaka bildirilmiştir. Hacettepe Üniversitesi Türkiye’nin salgınla mücadelesinde tüm birimlerindeki akademik ve idari personeli ile titiz bir süreç yürütmüş, öncü rolü ile Türkiye’de yürütülen mücadeleye birçok açıdan ciddi katkıda bulunmuştur.Türkiye Cumhuriyeti Sağlık Bakanlığı COVID-19 Bilimsel Danışma Kurulu’nda Hacettepe Üniversitesi Tıp Fakültesi’nden dört öğretim üyesi yer almıştır. Türkiye’de yürütülen aşı çalışmalarında İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı öncülük etmiştir. İlk COVID-19 hastamızı kabul ettiğimiz 21 Mart 2020 tarihinden itibaren de poliklinikler, yataklı servisler ve yoğun bakım ünitemizde yoğun bir şekilde mücadeleye devam etmekteyiz.Bu süreçte ülkemizde olduğu gibi bizde de çok sayıda sağlık çalışanımız COVID-19’a yakalandı, ülkemizde ciddi sayıda sağlık çalışanı kayıpları yaşadık. Yaşadığımız bu dönem bir yandan hekimler başta olmak üzere sağlık çalışanları için tarifi zor, hazin bir dönemdir, ancak diğer yandan da birbirimizi koruma, hastalıkla mücadele için dayanışma ve hoşgörünün her zamandan daha önemli olduğunu anladığımız bir dönemdir.Yüzyılda bir görülen bu salgının halen ülkemizde yoğun olarak yaşandığı ve tam olarak ne zaman sonlanacağının öngörülemediği bir dönemde tarihe not düşmek, geleceğe katkıda bulunmak adına hizmet ve eğitim fonksiyonlarını bir bütün halinde yürüten Hacettepe Üniversitesi Tıp Fakültesi İç Hastalıkları, İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji, Göğüs Hastalıkları ve Kardiyoloji Anabilim Dalları olarak sekiz aylık dönemi bir rapor olarak sunmayı düşündük. Amacımız mücadele devam ederken, sınırlarımız dahilindeki bilgi birikimimiz ve tecrübelerimizi güncel bilgilerle birlikte derleyerek paylaşmak ve katkı sunmaktır.Üniversitemiz, Fakültemiz ve Hastane Yönetimleri ile bize destek olan araştırma görevlilerine, hemşirelerine ve tüm sağlık personeline, bu raporun hazırlanması ve düzenlenmesinde büyük emeği olan Prof. Dr. Ömrüm Uzun ve Prof. Dr. Mine Durusu Tanrıöver başta olmak üzere tüm öğretim elemanlarına ve de pandemi döneminin başından beri sosyal destek ve bu raporun basılması için kaynak sağlayan Hacettepe İç Hastalıkları Eğitim ve Sosyal Dayanışma Derneği’ne (kısa adıyla Hacettepe İç Hastalıkları Derneği) teşekkürü borç bilir, raporumuzun yararlı olmasını dileriz.Prof. Dr. Arzu Topeli İskitİç Hastalıkları (Yoğun Bakım Bilim Dalı) Anabilim Dalı BaşkanıHacettepe Üniversitesi Hastaneleri Pandemi Kurulu Yoğun Bakım SorumlusuProf. Dr. Serhat Ünalİnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı BaşkanıHacettepe Üniversitesi Erişkin ve Onkoloji Hastaneleri İnfeksiyon Kontrol Komitesi Başkanı ve Pandemi Kurulu İnfeksiyon Kontrol Sorumlus