Emel Gönüllü

Acute severe cardiac failure in a myeloma patient due to proteasome inhibitor bortezomib

We present here a case of severe congestive cardiac failure, in a 47-year-old patient with myeloma who had no prior cardiac history, after receiving bortezomib. Bortezomib is a boron-containing molecule, which reversibly inhibits the proteasome, an intracellular organelle, which is central to the breakdown of ubiquitinated proteins and consequently crucial for normal cellular homeostasis. Phase II clinical trials demonstrate that it is effective for the treatment of relapsed refractory myeloma. Acute development of congestive cardiac failure associated with bortezomib therapy occurs very rarely or may be underestimated. Inhibition of proteasome activity may impair cardiac function due to accumulation of unfolded, damaged and undegraded proteins in myocytes. Patients with or without cardiac disease or previously received anthracycline-containing regimes should be closely monitored when being subjected to treatment with bortezomib.

The Association Between Gene Polymorphisms and Leukocytosis with Thrombotic Complications in Patients with Essential Thrombocythemia and Polycythemia Vera

Objective: Vascular events are a common complication in patients with polycythemia vera (PV) and essential thrombocythemia (ET). This study aimed to analyze the association between PAI-1 4G/5G and ACE I/D gene polymorphisms, and leukocytosis with thrombosis in patients with PV and ET. Material and Methods: In total, 64 patients with ET and PV were evaluated. Arterial or venous thrombosis, such as cerebral transient ischemic attack, ischemic stroke, myocardial infarction, peripheral arterial thrombosis, deep venous thrombosis, and pulmonary embolism, were defined as a vascular event. DNA samples were screened for mutations via reverse hybridization strip assay. Results: In terms of PAI-1 gene polymorphism, the frequency of the 4G and 5G allele was 48.5% and 51.5%, respectively. The ACE allele frequency was 51.2% and 48.8% for D and I, respectively. There wasn’t an association between occurrence of vascular events and the frequency of any allele. In terms of occurrence of vascular events, there weren’t any significance differences between the patients that were carrying the ACE D/D homozygous allele to ACE I/D and those that carried the I/I allele (P = 0.93). There wasn’t a significant difference in occurrence of vascular events between the PAI-1 5G/5G homozygote allele carriers, and the 4G/5G and 4G/4G allele carriers (P = 0.97). Vascular events were significantly more common in the patients with leukocytosis (leukocyte count >10 × 109 L–1) than in those without leukocytosis (leukocyte count ≤10 × 109 L–1) (P = 0.00). Age >60 years was also a significant risk factor for occurrence of vascular events(P = 0.008). Conclusion: PAI-1 and ACE gene polymorphisms were not considered new risk factors for thrombosis in PV and ET patients. On the other hand, leukocytosis at diagnosis was associated with the occurrence of vascular events in the patients with ET and PV.

Effect of heat shock protein-90 (HSP90) and vascular endothelial growth factor (VEGF) on survival in acute lymphoblastic leukemia: an immunohistochemical study

Background The significance of vascular endothelial growth factor (VEGF) and heat shock protein-90 (HSP90) has received only limited attention especially in acute lymphoblastic leukemia (ALL). In this study, we assessed expressions of HSP90 and VEGF in bone marrow samples of patients with ALL and effect of these expression quantities on the mean overall survival. Patients and methods Using immunohistochemical methods, we assessed expression of HSP90 and VEGF in 22 cases of ALL. Results Expression of HSP90 was detected in 19/22 (86.4%) and 3/22 (13.6%) of patients with ALL, for strongly positive and moderate-weakly positive, respectively. Negative HSP90 expression was not detected in patients with ALL. Expression of HSP90 in patients with ALL and in control group were statistically significant (Pxa0<xa00.001), however, did not reflect the mean overall survival (Pxa0=xa00.910). Mean OS was evaluated 992xa0±xa0181 and 724.8xa0±xa088.2xa0days for moderate-weak and high HSP90 expression, respectively. VEGF expressions were not significantly different between ALL and control groups (Pxa0<xa00.087). We did not find any relationship between HSP90 and VEGF expressions in bone marrow specimens of patients with ALL. Conclusion This study demonstrated that HSP90 expression grades in patients with ALL were significantly higher than that in controls and presence of strong HSP90 expression was associated with worse overall survival. VEGF expression in patients with ALL was not different from that in control samples. Determination HSP90 with immunohistochemical method in bone marrow can provide information about prognosis.

Risk factors for urolithiasis in patients with ankylosing spondylitis: a prospective case–control study

It has been reported that renal stone formation increased in patients with ankylosing spondylitis (AS). However, its reason remains unclear. The aim of this study was to evaluate serially the possible risk factors for renal stone formation in AS patients. Two groups consisted of AS patients with renal stone (nxa0=xa030), AS patients without renal stone (nxa0=xa030), and 20 healthy controls (HC) were included to the study. Parathyroid hormone, calcium, magnesium, phosphorus and immunoglobulin A levels and 24xa0h urine were evaluated at baseline, and three times monthly. Serum calcium levels were higher in AS patients with urolithiasis than those without at baseline and third-month evaluation (baseline: 9.53xa0±xa00.3 vs 9.32xa0±xa00.3xa0mg/dl; pxa0<xa00.03; at third-month evaluation: 9.74xa0±xa00.2 vs 9.56xa0±xa00.3xa0mg/dl; pxa0<xa00.01). No significant differences were found between groups in terms of PTH and magnesium levels. In all evaluation times, although urinary calcium excretion was higher in AS patients with urolithiasis than in those without, it did not reach a statistical significance. IgA levels were significantly higher in renal stone sufferers than HC patients in all evaluation times.AS patients with urolithiasis also had high IgA levels compared with AS patients without renal stone at the second-month evaluation time (276xa0±xa0102 vs 219xa0±xa0104xa0mg/dl, pxa0<xa00.002). Increased levels of serum calcium and IgA levels as well as family history for urolithiasis may be an indicator of the development of urolithiasis in AS patients.

Continuous passive motion in adhesive capsulitis patients with diabetes mellitus: A randomized controlled trial

BACKGROUNDnThe aim of this study was to clarify the effects of continuous passive motion (CPM) treatment on adhesive capsulitis (AC) in diabetes mellitus (DM) patients.nnnMETHODSnForty-one DM patients with AC were randomized to two treatment groups. The first group (n= 20) (CPM group) received CPM treatments; the second group (n= 21) had conventional physical therapy (CPT group), including active stretching, range of motion (ROM) and pendulum exercises. All patients received electrotherapy. After a four-week-long physical therapy program, the patients were instructed to continue with an eight-week home exercise program. The patients rated the pain they felt at night, both while at rest and in motion, in the past week using the visual analogue scale (VAS). Functional outcome evaluations were performed using the Constant Shoulder Score (CSS) and Shoulder Pain and Disability Index (SPADI). All patients were evaluated at baseline, and during the fourth and twelfth weeks of the study.nnnRESULTSnThere were significant improvements in both groups active and passive ROM for the shoulder, VAS measures, SPADI pain and disability scores and CSS, and excluding the active and passive internal and external rotation of shoulder increased with both treatment methods (CPM or CPT) over time (p< 0.001), however these differences were found to be prominent in patients receiving CPM therapy.nnnCONCLUSIONSnBoth the CPM and CPT therapies seemed to be beneficial for the treatment of AC in DM patients, however CPM revealed more distinctive improvements in the function and pain levels of the AC patients.

Exon 2: Is it the good police in familial mediterranean fever?

Objective Familial Mediterranean fever (FMF) is the most common autoinflammatory disease. Most of the identified disease-causing mutations are located on exon 10. As the number of studies about the effect of the exonal location of the mutation and its phenotypic expression is limited, we aimed to investigate whether the exonic location of the Mediterranean fever (MEFV) mutation has an effect on the clinical manifestation in patients with FMF. Methods Study population was derived from the main FMF registry that included 2246 patients from 15 different rheumatology clinics. We categorized the mutations according to their exon locations and retrieved the clinical and demographic information from the database. Results Patients having the MEFV mutations on exon 2 or 10 (n:1526) were divided into three subgroups according to the location of the MEFV mutations: Group 1 (exon 2 mutations), Group 2 (exon 10 mutations), and Group 3 (both exon 2 and exon 10 mutations). Group 2 patients were of a significantly younger age at onset, and erysipel-like erythema, arthritis, amyloidosis, and a family history of FMF were more common in this group. Conclusion Patients with FMF and exon 10 mutations show more severe clinical symptoms and outcome. Exon 2 mutations tend to have a better outcome.

SAT0333 Hemostatic Mechanisms May Play A Role in The Development of Thrombosis in Male Patients with Behcet's Disease: A Thromboelastographic Analysis

Background In Behcets disease (BD), vascular involvement is seen frequently in young male BD patients. However, its reason is not well known. Objectives Our aim was to compare thrombotic tendency according to gender by using the modified Rotational Thromboelastography parameters and platelet-leucocyte complex levels. Methods 126 BD patients (71 male, 55 female; mean age:41±9 yrs) who met ISSG criteria for Behcets disease were included into study. This group was divided into 3 subgroups as non-thrombotic (n=73), acute thrombotic (n=25) and chronic thrombotic group (n=28). As disease control and healthy control group, 23 patients with vasculitis (16 female, 7 male; mean age 49±16 yrs), 8 patients with thrombosis (3 female, 5 male; mean age:55±11 yrs) and 25 healthy individuals (11 female, 14 male; mean age:37±10 yrs) were included to study. By using the modified rotation thromboelastogram, clotting time (CT), clot formation time (CFT) and maximum clot formation (MCF) were determined by INTEM and EXTEM analysis. Thrombocyte-leucocyte complexes and thrombocyte activation marker (p62) were investigated by flow-cytometric method. Results In terms of thrombocyte-leucocyte complexes and P62 levels, no significant difference was found in female BD patients vs male BD pts, active BD pts vs inactive BD pts and thrombotic BD pts vs non-thrombotic BD pts. Thrombocyte-leucocyte complexes levels were higher in vasculitis group than BD group (p<0.01) and HC group (p<0.04). I-MCF was significantly prolonged in male BD patients than female BD patients. E-CFT was found to be shorter in male BD patients compared to female BD patients. E-MCF was statistically prolonged in male BD patients. In inactive male BD patients, while I-CFT was shorter than HC individuals, I-MCF and E-MCF were statistically prolonged than HC (p<0.02, p<0.03), respectively. However, No significant differences were found between inactive female BD patients and HC in terms of all ROTEM parameters. In active BD patients, E-CFT was shorter (p<0.02) and E-MCF was significantly prolonged than those of inactive BD patients (p<0.005). Conclusions These results support that male BD patients have a hypercoagulable state compared to female BD patients which may be an explanation why male patients are prone to thrombotic complications. Disclosure of Interest None declared

Non-hodgkin lenfomalı bir hastada jejunumda arteriyovenöz malformasyona bağlı, hayatı tehdit eden alt gastrointestinal sistem kanaması

GIRIŞ Alt gastrointestinal sistem (GIS) kanamalarina en sik neden olan hastaliklar, anjiodisplaziler, divertikulosis, polipler, intestinal tumorler, inflamatuvar hastaliklar, radyasyon enteriti gibi durumlardir. Ama hematolojik malignitelerde, ilk akla gelenler genelde losemi tutulumu, kemik iligi supresyonuna bagli mukozal degisiklikler, enfeksiyonlar, peptik ulser gibi durumlardir (1). Alt GIS kanamalarinin cogu, ciddi kanamalar degildir ama bazen de cok ciddi tani ve tedavi problemlerine yol acabilirler (2). Bu nedenle bu kanamalarda hizli tani koymak ve hemostatik tedavi yontemlerine hizli baslamak bazen hayat kurtarici olmaktadir (1). Unutulmamasi gereken durum ozellikle hematolojik maligniteli hastalarda, alt GIS kanama tespit edildiginde, hemen bu durumu mukozal degisiklikler, trombositopeni gibi nedenlere baglamadan, hastayi cok hizli ve cok dikkatli degerlendirmektir. Burada, bizim olgumuzda alt gastrointestinal sistemde masif kanamaya bagli hayati tehdit eden hemorajik sok durumu, cerrahi yaklasimla duzeltilmis ve hastanin hayati kurtarilmistir. OLGU Otuz dort yasinda erkek hasta 3 aydir devam eden belde ve uylukta agri ve sag bacakta guc kaybi nedeniyle beyin cerrahi servisine basvurmus. Hastanin fizik muayenesinde sag kalca ve sag dizde 2/5 kas gucu saptanmis, duyu muayenesi normalmis. Istenen torakal magnetik rezonans goruntulemede, T11 ust end platodan baslayan T12-L1 disk duzeyine kadar devamlilik gosteren, epidural yerlesimli, spinal kanal sol lateral ve posterior komsulugunda en genis transvers capi 18 mm olculen metastatik kitle lezyonu izlenmesi uzerine operasyona karar verilmis ve bu kitle operasyonla cikarilarak patoloji laboratuvarina gonderilmis. Patoloji laboratuarina giden 2x2x0.9 cm boyutlu bejkahverengi tumor dokusu incelenerek diffuz buyuk B hucreli lenfoma tanisi konulmus ve hematoloji bolumune yonlendirilmis. Hasta degerlendirildi ve kemik iligi biyopsisi yapildi. Kemik iliginde diffuz buyuk B hucreli lenfoma infiltrasyonu saptandi. Hastanin boyun ve toraks bilgisayarli tomografi (BT) sonuclari normaldi. Tum karin BT ‘de alt torakal duzeyden gecen kesitlerde kostada 6x4 cm boyutlu, sag ilyak kemikte 10x7 cm boyutOLGU SUNUMU