Germline genetic variants in Turkish familial multiple myeloma/monoclonal gammopathy of undetermined significance cases.

Multiple myeloma (MM) is a haematological malignancy primarily affecting the elderly, with a striking male predilection and ethnic disparities in incidence. Familial predisposition to MM has long been recognized, but the genetic underpinnings remain elusive. This study aimed to investigate germline variants in Turkish families with recurrent MM cases. A total of 37 MM-affected families, comprising 77 individuals, were included. Targeted next-generation sequencing analysis yielded no previously reported rare variants. Whole exome sequencing analysis in 11 families identified rare disease-causing variants in various genes, some previously linked to familial MM and others not previously associated. Notably, genes involved in ubiquitination, V(D)J recombination and the PI3K/AKT/mTOR pathway were among those identified. Furthermore, a specific variant in BNIP1 (rs28199) was found in 13 patients across nine families, indicating its potential significance in MM pathogenesis. While this study sheds light on genetic variations in familial MM in Turkey, its limitations include sample size and the absence of in vivo investigations. In conclusion, familial MM likely involves a polygenic inheritance pattern with rare, disease-causing variants in various genes, emphasizing the need for international collaborative efforts to unravel the intricate genetic basis of MM and develop targeted therapies.

Case of Prolonged Viral Shedding: Chronic, Intermittan COVID-19?

COVID-19 is a pandemic that has been affecting the entire world and has caused the death of approximately 2.8 million people. Although the duration of viral shedding varies, an average of 7-10 days is accepted. It is still unclear whether prolonged viral shedding means prolonged contagious period and whether COVID-19 will become chronic or not. This article presents a case with hematological malignancy (lymphoma) with the longest polymerase chain reaction positivity that we could find in the literature (110 days in total).

A biomarker and therapeutical target in immune thrombocytopenia: TNF receptor-associated factor 6.

BACKGROUND: Immune thrombocytopenia (ITP) is an acquired disease characterized by various pathogenetic mechanisms. We aimed to evaluate the value of TRAF6 as a biomarker of pathogenesis in ITP. METHODS: 85 newly diagnosed ITP patients and 85 controls were included. RESULTS: In the patient group, mean TRAF6 level was 2348 pg/ml and in the control group, TRAF6 level was 25.57 pg/ml. In corticosteroid-responding patients, TRAF6 levels were lower than nonresponding patients. DISCUSSION: TRAF6 levels were observed to be higher than healthy controls, which suggest a solid relation with ITP pathogenesis. The observation that in patients who present with high TRAF6 levels, there was a significant corticosteroid refractoriness and responsiveness.

Fusarium Endophthalmitis, Unusual and Challenging Infection in an Acute Leukemia Patient.

Invasive fungal infections bring serious mortality and morbidity during the treatment of acute myeloid leukemia. Especially, mold infections are challenging, and each case is unique in feature. These cases are usually fatal, and there is no consensus regarding optimal treatment. AML patients receive antifungal prophylaxis and may further require IFI (invasive fungal infection) treatments, but fusarium mold infections are often unrecognized and could be overlooked. In this case report, we try to emphasize the importance of this infection with a high-risk AML patient.

Is JAK2V617F Mutation the Only Factor for Thrombosis in Philadelphia-Negative Chronic Myeloproliferative Neoplasms?

The most common genetic disorder in Philadelphia negative chronic myeloproliferative neoplasms is the JAK2-V617F mutation. In the present study, we aimed to determine risk factors for thrombosis in patients with essential thrombocytosis and polycythemia vera. We screened the medical records of 101 patients. Risk factors which may predict thrombosis were recorded. Venous thrombosis (VT) before diagnosis was significantly higher in JAK2 positive patients. VT after diagnosis was similar in JAK2 positive and negative groups, and was significantly higher in elderly patients. Treatment places importance on the JAK2 mutation under unmodifiable cardiovascular risk factors such as advanced age after diagnosis.

Fibroblast Growth Factor-23 and Carotid Artery Intima Media Thickness in Chronic Kidney Disease.

BACKGROUND: The cause of early-accelerated atherosclerosis development observed in Chronic Kidney Disease (CKD) is not fully understood. The determination of the relationship between the levels of fibroblast growth factor 23 (FGF-23) and the development of endothelial dysfunction, left ventricular hypertrophy, and myocardial infarction lends support to the possibility that FGF-23 plays a role in the development of atherosclerosis in CKD. Only a few studies, however, have been conducted that analyze the relationship between FGF-23 levels in the progression of CKD and the development of atherosclerosis, and these studies have generally been limited to those patients receiving dialysis therapy due to end stage renal disease (ESRD). METHODS: In the present study, carotid artery intima-media thicknesses (IMT) were measured ultrasonically as a marker of atherosclerosis in 91 patients with CKD stage 3 - 4 (61 female and 30 male, age between 19 - 65 years, glomerular filtration rate [GFR] 15 - 60 mL/min 1.73 m2, CKD was not related to diabetes mellitus, and without cardiovascular-cerebral disease) in contrast to 36 healthy volunteers (26 female and 10 male, age between 19 - 65 years, GFR > 90 mL/min 1.73 m2, and without any diagnoses of acute or chronic disease), and a possible role of FGF-23 on atherosclerosis was analyzed. RESULTS: Patients were similar to controls with respect to age, gender, smoking status, body mass index, and plasma glucose and lipid profile. On the other hand, IMT measurements (p < 0.00001) and FGF-23 levels (p = 0.00012) were significantly higher in patients than controls. IMT was measured above the subclinical atherosclerosis limit of 0.750 mm in 54% of the patients. Multivariate regression analysis showed that patients' age, high sensitive c-reactive protein (hsCRP), and FGF-23 levels were independent predictors of IMT (p < 0.00001, r = 0.559). Independent of other variables, every 1 µmol/L increase in FGF-23 levels resulted in 0.444 mm increase of IMT measurements in patients with CKD. CONCLUSIONS: Our findings suggest that monitoring serum FGF-23 may be useful as a non-invasive indicator of subclinical atherosclerosis in patients with chronic kidney disease.

Immune thrombocytopenia: epidemiological and clinical features of 216 patients in northwestern Turkey.

We evaluated the clinical features, treatment modalities, treatment responses, and prognosis of our patients with immune thrombocytopenia (ITP). Furthermore, we estimated the frequency of ITP in the Thrace region of Turkey. Two hundred sixteen patients diagnosed with ITP between 2000 and 2012 at our center were retrospectively evaluated. Patients' clinical features, treatments, and responses to treatment modalities were recorded. The mean annual incidence of ITP was 2.92/100,000 (95%CI: 1.57-4.27). The overall prevalence of ITP was 35.1/100,000 (95%CI: 30.3-39.8). The administration of first-line therapy resulted in complete remission (CR) in 76.5 % of patients and partial remission (PR) in 13.6 %. After 5 years, 33 % of patients who were responsive to first-line therapy were still in relapse-free remission. Of patients who were given second-line therapy, CR was obtained in 71.3 % and PR in 14.9 %. The duration of relapse-free remission was longer with splenectomy than with steroids (p < 0.001). Five years after splenectomy, 62 % of patients were in relapse-free remission; contrarily, this was lower with steroids (36 % at 5 years). The annual incidence and prevalence of ITP in northwestern Turkey was similar to data from western countries-at the lower limit for some countries. Effective treatment strategies seem to be steroids as first-line therapy and splenectomy in refractory cases.

The alteration of NTproCNP plasma levels following anaerobic exercise in physically active young men.

OBJECTIVE: Amino-terminal propeptide of C-type natriuretic peptide (NTproCNP) is a synthesis product of C-type natriuretic peptide (CNP). In this study, plasma levels of NTproCNP were compared before and after exercise in healthy young subjects who are physically active (PA) or not physically active (NPA). METHODS: The study was carried on PA group (n=10) who defined the exercise duration more than 2.5 hours per week for at least one year and NPA group (n = 10) whose exercise duration was lower than 1.5 hours per week. The level of maximal oxygen consumption was determined. Wingate exercise test was applied on the following day. Plasma NTproCNP levels were measured before the exercise and at the 1st, 5th and 30th minute after the exercise. RESULTS: Exercise duration of physically active group was reported as 11.3 ± 5.0 hours per week. Basal NTproCNP levels of the groups were found to be comparable. NTproCNP levels in the 5th minute (0.93 ± 0.23 pmol/L; p<0.05) and in the 30th minute (0.77 ± 0.21 pmol/L p < 0.05) after exercise were higher than the levels before exercise (0.64 ± 0.29 pmol/L) in PA group. Additionally, the plasma levels of NTproCNP after 5th minute of exercise were higher in PA group (0.93 ± 0.23 pmol/L) than NPA group (0.74 ± 0.16 pmol/L, p<0.05). CONCLUSION: Being physically active may be a fact affecting the secretion of CNP, which plays a protective role in endothelium, following exercise.

Clinical characteristics of haematological malignancy patients diagnosed with leukaemia cutis: Experience of a single centre.

BACKGROUND/OBJECTIVES: We evaluated the clinical characteristics of patients with haematological malignancies at our centre who were diagnosed with leukaemia cutis (LC). In addition, we describe the spectrum of other skin lesions, including, secondary skin malignancies and nonspecific benign skin lesions in haematological malignancy patients. METHODS: We defined 58 skin lesions that developed in 54 inpatients hospitalised in the Department of Haematology, Trakya University Medical Faculty, Turkey. All skin lesions that developed in inpatients between 2006 and 2012 had been evaluated by a dermatologist. The patients' clinical features, skin biopsy results and therapies were obtained from hospital files. The diagnosis of LC was based on clinical features and histopathological examinations of the skin biopsy. RESULTS: There were 11 patients with LC. Six (54.5%) had acute myeloblastic leukaemia. In nine patients (82%), LC was present at the initial presentation. Secondary skin malignancy was detected in 11 patients (five basal cell carcinoma, four Kaposi's sarcoma, one squamous cell carcinoma, one malignant melanoma); and malignancy was present in two patients (18%) at the initial presentation. Nonspecific benign skin lesions, the most frequent of which were drug eruptions, were determined in 32 of our patients. LC had a significantly higher likelihood of being present at initial presentation than other skin lesions (P < 0.01). The median survival in LC patients was quite short (4.5 months). CONCLUSIONS: LC was usually diagnosed at the initial presentation of the patient or during the early course of the disease. Having LC was a poor prognostic factor.

Evaluation of the Practice Pattern of Medical Patients' VTE Prophylaxis With a Standard Risk Assessment Model Form: MERAM Study.

Hospitalized acutely ill patients face high risk for venous thromboembolism (VTE) unless appropriate thromboprophylaxis is applied. This study aimed to determine VTE prophylaxis practices for inpatients in Turkey and to evaluate the impact of physicians' training via a modified "Standard Medical Patients' VTE Risk Assessment Model (MERAM)." A total of 607 inpatients included in this national multicenter noninterventional observational registry were evaluated in terms of demographics, VTE risk, and preventive measures at 2 consecutive cross-sectional visits. Physicians were asked to complete a questionnaire on current VTE method risk assessment and other models including MERAM. The VTE prophylaxis rates significantly increased from 49.4% to 62.4% between visits (P < .05). The lack of risk evaluation decreased from 74.6% to 19.5% (P < .001). Percentage of physicians using prophylaxis and use of MERAM increased between visits. Physician training proved effective for providing general "awareness" of VTE prophylaxis and led to higher rates of risk assessment model-based appropriate VTE prophylaxis.

Sticky platelet syndrome in patients with uninduced venous thrombosis.

OBJECTIVE: Sticky platelet syndrome (SPS) is a common autosomal dominant inherited platelet disorder. SPS is characterized by platelet hyperreactivity and is associated with arterial and venous thrombosis. The aim of this study was to determine the role of SPS in patients with uninduced venous thrombosis. MATERIAL AND METHODS: The study included 28 patients (15 male and 13 female) with uninduced venous thrombosis. SPS was defined according to Mammen's aggregation method, which is described in detail elsewhere. RESULTS: According to the defined ranges for platelet hyperreactivity, 3 (50%) patients, 2 (33%), and 1 (17%) (n =6 [21%]) with a confirmed diagnosis were classified as type II, I, and III SPS, respectively. In 1 patient SPS was the only hereditary abnormality noted. The other 5 patients carried other inherited coagulation defects, in addition to SPS. CONCLUSION: The present findings indicate that the prevalence of SPS was 21% in the patients with uninduced venous thrombosis. We therefore suggest that SPS should be considered in the differential diagnosis of such cases. CONFLICT OF INTEREST: None declared.

Turkish Chronic Myeloid Leukemia Study: Retrospective Sectional Analysis of CML Patients.

OBJECTIVE: here have been tremendous changes in treatment and follow-up of patients with chronic myeloid leukemia (CML) in the last decade. Especially, regular publication and updating of NCCN and ELN guidelines have provided enermous rationale and base for close monitorization of patients with CML. But, it is stil needed to have registry results retrospectively to evaluate daily CML practices. MATERIALS AND METHODS: In this article, we have evaluated 1133 patients' results with CML in terms of demographical features, disease status, response, resistance and use of second-generation TKIs. RESULTS: The response rate has been found relatively high in comparison with previously published articles, and we detected that there was a lack of appropriate and adequate molecular response assessment. CONCLUSION: We concluded that we need to improve registry systems and increase the availability of molecular response assessment to provide high-quality patient care. CONFLICT OF INTEREST: None declared.

Successful use of fondaparinux in a child with heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a well described side effect of heparin therapy. A 12-year-old boy developed deep-vein thrombosis. Risk factors for initial thrombosis are antiphospholipid syndrome and heterozygous mutation for prothrombin G20210A. Anticoagulant therapy with warfarin for 12 months was effective, but discontinuation of warfarin after 12 months resulted in recurrence of thrombosis. Unfractionated heparin (UFH) was initiated during the acute period, but heparin-induced thrombocytopenia developed. Transition from UFH to fondaparinux resulted in successful anticoagulation for a period of platelet recovery. We report a case of HIT developing with a background of prothrombotic genetic risk factors and antiphospholipid syndrome. This case study highlights several difficulties in pediatric HIT cases.

Inflammatory bowel disease and thrombosis.

Inflammatory Bowel Disease (IBD) is a group of chronic and relapsing inflammatory disorders of the gastrointestinalsystem. In these cases, findings are detected in extraintestinal systems also. There is a tendency for thrombotic eventsin IBD, as in the other inflammatory processes. The pathogenesis of this thrombotic tendency is multidimensional,including lack of natural anticoagulants, prothrombotic media induced via the inflammatory process, long-termsedentary life style, steroid use, surgery, and catheter placement. The aim of this review was to highlight the positiverelationship between IBD and thrombotic events, and the proper treatment of at-risk patients.

Does anti-TNF therapy cause any change in platelet activation in ankylosing spondylitis patients? A comparative study.

Recently, it has been reported that ankylosing spondylitis (AS) was characterised by endothelial dysfunction and the development of atherosclerotic complications. In this study, we evaluated platelet and endothelial activation parameters in AS patients. Fiftynine AS patients and 22 healthy controls were included. The clinical features and acute phase parameters were evaluated. In all patients and healthy controls, platelet-monocyte complexes (PMC), platelet-neutrophil complexes, basal and ADP-stimulated P-selectin (CD62P) expression were determined by flow cytometry; soluble E-selectin (sE-selectin) and soluble CD40L (sCD40L) were determined by ELISA. AS patients were divided into two groups as active and inactive by using BASDAI. In 15 AS patients, the evaluated parameters were assessed before and after 12 weeks of anti-TNF therapy. PMC and sCD40L levels in AS patients were significantly higher than in the control group (P values 0.013 and 0.016). The evaluated variables were similar in active and inactive AS groups (P > 0.05). There were no significant changes in platelet and endothelial activation parameters in AS patients after anti-TNF therapy (P > 0.05). Platelet activation which is reflected by high levels of PMC and sCD40L might be responsible for the increased frequency of atherosclerosis in AS. The platelet activation in our AS patients was not associated with disease activity and did not improve after anti-TNF therapy.

[Effect of the levels of vascular endothelial growth factor-A and C on the prognosis of patients with laryngeal carcinoma]. / Larenks kanserli hastalarda vasküler endotelyal büyüme faktörü A ve C düzeylerinin prognoza etkisi.

OBJECTIVES: In this study, we determined the prognostic importance of vascular endothelial growth factor (VEGF)-A and C values and their relationship with tumor stages and neck lymp node involvement and also, the relationship between microvessel density and tumor stage in the pathologic specimens. PATIENTS AND METHODS: Thirty-three male patients (mean age 57.8±7.2 years; range 49 to 69 years) who underwent surgical treatment for laryngeal squamous cell carcinoma and a control group of 13 healthy male subjects (mean age 54.2±6.1 years; range 41 to 62 years) were included in the study. Patients were divided into two groups: the early-stage group consisting of patients with T1 and T2 stage tumors and the advanced stage group including patients with T3 and T4 stage tumors. Patients are evaluated in terms of plasma VEGF-A and C levels before and six months after the surgery. In the pathologic specimens, CD 31 was used for immunohistochemical staining. For each patient the number of microvessels per millimeter square (microvessel density) was determined. RESULTS: The preoperative plasma VEBF-A levels of the patients with early-stage tumors were significantly lower compared to those of the control group, while there was no significant difference between the preoperative levels of the patients with advanced stage tumors and the levels of the control group. There was no significant difference between the preoperative and postoperative 6th month VEGF-A levels of the patients both in the early-stage and the advanced stage groups. The preoperative plasma VEGF-C values of the patients with lymph node involvement were significantly lower than those of the patients with early-stage tumors. There was no significant difference between the VEGF-C levels in pre- and postoperatively at six months after the operation of patients with lymph node involvement. There was no significant difference between the preoperative VEGF-C levels of the patients with lymph node involvement and those without lymph node involvement. No significant difference was found in microvessel density between the cases with early and advanced stage tumors. CONCLUSION: It was seen that the plasma VEGF-A value did not increase in patients with laryngeal cancer and rather it is low in patients with early-stage disease. No relationship was found between the plasma VEGF-C values and cervical lymph node involvement.

Differences in platelet-leukocyte aggregates among subtypes of acute cerebral ischemia.

BACKGROUND: Acute cerebral ischemia is caused by different pathophysiological mechanisms. The role of platelets and other blood cells can be different among the stroke subtypes. METHODS: Seventy-two patients with acute ischemic cerebrovascular disease, including 31 patients with large vessel disease, 21 patients with cardioembolic disease, and 20 patients with small vessel disease, were evaluated. P-selectin (CD62P) expression and platelet leukocyte aggregates were measured with flow cytometry at the acute phase after the ischemic event. Markers were also measured in 37 control subjects. In all subjects, the serum high-sensitivity C-reactive protein (CRP) was also measured. RESULTS: The platelet-monocyte aggregates (PMA) and platelet-granulocyte aggregates (PGA) in the large vessel disease group were higher than in control group (P=0.002, and P<0.0001, respectively). The PMA and PGA in the small vessel disease group were also higher than in the control group (P=0.004 and P<0.0001, respectively). In contrast, in the cardioembolic disease group, the PMA and PGA were not significantly different from the control group. CD62P expression was higher in all of the patient groups relative to the control group (P<0.05 for all comparisons). Serum CRP levels were also higher in all of the patient groups than in the control group (P<0.0001 for all comparisons). CONCLUSIONS: In contrast to large vessel and small vessel disease, it seems that platelet-leukocyte association does not play a crucial role in the pathogenesis of cardioembolic stroke.

Soluble CD40 ligand and prolactin levels in migraine patients during interictal period.

The relationship of migraine with cardiovascular diseases has been clarified by many studies, and currently, migraine is suggested to be a systematic vasculopathy. Inflammation, thrombosis and impaired vascular reactivity are the underlying pathophysiological mechanisms of the vasculopathy. In the present study, we aimed to investigate the relationship between prolactin levels and subclinical atherosclerosis risk factors such as soluble CD40 ligand (sCD40L) and high-sensitivity CRP (hsCRP) in migraine patients during interictal period. Fifty female migraine patients and age-matched 25 female control cases were enrolled in the study. Migraine diagnosis was settled according to the ICHD-II diagnostic criteria. A questionnaire was completed about the existence of vascular risk factors. Serum samples were used to measure sCD40L, hsCRP and prolactin levels. No difference was found between the prolactin levels of the migraine patients and the controls. The sCD40L levels were significantly higher in migraine patients (p < 0.001). High-sensitivity CRP levels showed no difference between the groups. There was no correlation between prolactin, sCD40L, and hs-CRP levels in migraine patients. We consider that the migraine patients are prone to subclinical atherosclerosis, but this tendency is independent of prolactin levels.

Low levels of protein Z are associated with HELLP syndrome and its severity.

Protein Z (PZ) was found to be associated with pregnancy complications. There are no data implying an association between hemolysis (H), elevated liver enzymes (EL), and low platelet counts (LP) (HELLP) syndrome and changes in plasma levels of PZ. The aim of this study is to investigate whether HELLP syndrome is associated with plasma concentrations of PZ. Protein Z levels in 29 women with HELLP syndrome were compared with 29 healthy, nulliparous and 25 normal pregnant women. The median PZ levels in patients with HELLP syndrome were found to be significantly lower than those of pregnant women. No significant difference was found between HELLP and healthy groups. Protein Z levels correlated with platelet counts, lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) levels in patients with HELLP syndrome. Median PZ level was higher in partial HELLP than in complete HELLP. We calculated 1330 ng/mL as a cutoff value for PZ level to discriminate HELLP syndrome from normal pregnancy. Low PZ levels are associated with the pathobiology of HELLP syndrome.