Anil Tombak

Low efficacy rate of moxifloxacin-containing Helicobacter pylori eradication treatment: in an observational study in a Turkish population.

Background:  Standard triple therapy for Helicobacter pylori has an eradication rate of about 50% in Turkey. It may be due to an increased resistance of H. pylori to antibiotics. Therefore, we aimed to investigate the effectiveness of a new second‐generation fluoroquinolone, moxifloxacin‐containing triple therapy in H. pylori eradication.

Bloodstream infections and mortality-related factors in febrile neutropenic cancer patients

Summary Background We performed a prospective observational cohort study to evaluate the causative bacteria and to identify risk factors for mortality in febrile neutropenic (FN) patients with blood stream infection (BSI). Material/Methods We conducted a prospective data collection on all patients with bacteremia or fungemia. The patients were assigned into low-risk and high-risk groups in accordance with the Multinational Association for Supportive Care in Cancer (MASCC) Risk Index. Results Throughout the study period, the patients developed 420 FN episodes. Out of 420 episodes, only 90 (21.4%) were found to have bloodstream infection. The mean age of the patients was 45.6±18.4 years and 55.6% of the patients were male. A total of 98 isolates were recovered from the cases of BSI. Coagulase-negative Staphylococcus spp (CoNS) were the most common isolates overall (33.7%). There was a significant increase in the rate of gram-negative bacteria throughout the study period (p=0.028). Overall mortality was 33%. Multivariate analyses showed that MASCC risk scores (p=0.0001, OR=15.1, CI%95 4.5–50.7), ICU wards (p=0.0002, OR= 8.6, Cl%95 1.101–68,157) and CoNS (p=0.004, OR=12.12, CI%95 2.3–64.7) were independent risk factors associated with mortality. BSI due to CoNS was associated with lower mortality; however, MASCC high risk score and ICU stay were associated with higher mortality. Conclusions The MASCC risk-index score and emergence of CoNS in positive blood cultures are valuable tools in the management of FN.

Mean Platelet Volume and Related Factors in Patients at Different Stages of Diabetic Nephropathy A Preliminary Study

Introduction: Mean platelet volume (MPV) is an independent cardiovascular disease predictor, and characteristics of MPV in patients with diabetic nephropathy (DN) are not well known. Aim: To determine the MPV levels in patients at different stages of DN. Patients and Methods: The MPV levels were investigated in healthy participants (group 1, n = 157), patients with type 2 diabetes mellitus without complication (group 2, n = 160), diabetic patients with clinical proteinuria (group 3, n = 144), and in patients with chronic kidney disease due to DN (group 4, n = 160). Findings: The MPV level was higher in all diabetic patients than that in normal participants (P < .05). The MPV values had a positive correlation with the serum creatinine and proteinuria, and a negative correlation with the glomerular filtration rate ([GFR] P < .001 for all, r values; .72, and .82, and −.92, respectively). Conclusion: The MPV values were higher in diabetic groups than that in normal participants. Both GFR and proteinuria were the most powerful determinants of MPV.

Therapeutic plasma exchange in patients with thrombotic thrombocytopenic purpura: A retrospective multicenter study

UNLABELLED Thrombotic thrombocytopenic purpura (TTP) is a particular form of thrombotic microangiopathy typically characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological abnormalities, and renal dysfunction. TTP requires a rapid diagnosis and an adapted management in emergency. Daily sessions of therapeutic plasma exchange (TPE) remain the basis of management of TTP. Also, TTP is a rare disease that is fatal if it is not treated. TPE has resulted in excellent remission and survival rates in TTP patients. AIM We aimed to present our experience in 163 patients with TTP treated with TPE during the past 5years from 10 centers of Turkey. PATIENTS AND METHODS One hundered and sixty-three patients with TTP treated with TPE during the past 5years from 10 centers of Turkey were retrospectively evaluated. TPE was carried out 1-1.5times plasma volume. Fresh frozen plasma (FFP) was used as the replacement fluid. TPE was performed daily until normalization of serum lactate dehydrogenase (LDH) and recovery of the platelet count to >150×10(9)/dL. TPE was then slowly tapered. Clinical data, the number of TPE, other given therapy modalities, treatment outcomes, and TPE complications were recorded. RESULTS Fifty-eight percent (95/163) of the patients were females. The median age of the patients was 42years (range; 16-82). The median age of male patients was significantly higher than female (53 vs. 34years; p<0.001). All patients had thrombocytopenia and microangiopathic hemolytic anemia. At the same time, 82.8% (135/163) of patients had neurological abnormalities, 78.5% (128/163) of patients had renal dysfunction, and 89% (145/163) of patients had fever. Also, 10.4% (17/163) of patients had three of the five criteria, 10.4% (17/163) of patients had four of the five criteria, and 6.1% (10/163) of patients had all of the five criteria. Primary TTP comprised of 85.9% (140/163) of the patients and secondary TTP comprised of 14.1% (23/163) of the patients. Malignancy was the most common cause in secondary TTP. The median number of TPE was 13 (range; 1-80). The number of TPE was significantly higher in complete response (CR) patients (median 15.0 vs. 3.5; p<0.001). CR was achieved in 85.3% (139/163) of the patients. Similar results were achieved with TPE in both primary and secondary TTP (85% vs. 87%, respectively; p=0.806). There was no advantage of TPE+prednisolone compared to TPE alone in terms of CR rates (82.1% vs. 76.7%; p=0.746). CR was not achieved in 14.7% (24/163) of the patients and these patients died of TTP related causes. There were no statistical differences in terms of mortality rate between patients with secondary and primary TTP [15% (21/140) vs. 13% (3/23); p=0.806]. But, we obtained significant statistical differences in terms of mortality rate between patients on TPE alone and TPE+prednisolone [14% (12/86) vs. 3% (2/67), p<0.001]. CONCLUSIONS TPE is an effective treatment for TTP and is associated with high CR rate in both primary and secondary TTP. Thrombocytopenia together with microangiopathic hemolytic anemia is mandatory for the diagnosis of TTP and if these two criteria met in a patient, TPE should be performed immediately.

Azacitidine versus decitabine in patients with refractory anemia with excess blast—Results of multicenter study

The present study aimed to compare the efficacy and safety of azacitidine and decitabine in patients with myelodysplastic syndrome (MDS). A total of 88 patients diagnosed with refractory anemia with excess blast (RAEB) treated with azacitidine (n=57) or decitabine (n=31) were evaluated. Comparisons between azacitidine and decitabine groups were performed in the whole cohort, and in a 1:1 propensity score-matched cohort in order to reduce the simple selection bias. Patients who received azacitidine or decitabine had comparable overall response rates in both the unmatched (49.1% vs. 64.5%, p=0.166) and the propensity-matched cohorts (52% vs. 68%, p=0.248). The cumulative incidence of AML transformation at one year was comparable between azacitidine and decitabine in the unmatched (24.0% vs. 31.3%, p=0.26) and in the propensity-matched cohorts (18.7% vs. 31.5%, p=0.11). There was no difference in terms of transfusion requirement, febrile neutropenia episodes or the need for antifungal use during the treatment cycles in the propensity-matched cohort. The median overall survival was 20.4 months for azacitidine and 16.8 months for decitabine (p=0.59). Finally, we found that at least a four-cycle treatment with any HMA was a favorable factor. In conclusion, both azacitidine and decitabine have similar efficacy and toxicity profiles in the treatment of MDS-RAEB.

Seasonal Association of Immune Thrombocytopenia in Adults

BACKGROUND Immune thrombocytopenia (ITP) is an autoimmune disorder. It is characterized by thrombocytopenia due to thrombocyte destruction mediated by autoantibodies; however, cytotoxic and defective regulatory T-lymphocytes play an important role in its pathogenesis. While childhood ITP is usually acute, self-limiting and generally seasonal in nature, ITP in adults is usually chronic; its relation with seasons has not been studied. AIMS We investigated whether months and/or seasons have triggering roles in adults with ITP. STUDY DESIGN Descriptive study. METHODS A retrospective case review of adult patients with primary ITP diagnosed at various University Hospitals in cities where Mediterranean climate is seen was performed. Demographic data, date of referral and treatments were recorded. Corticosteroid-resistant, chronic and refractory cases were determined. Relation between sex, corticosteroid-resistant, chronic and refractory ITP with the seasons was also investigated. RESULTS The study included 165 patients (124 female, mean age=42.8±16.6). Most cases of primary ITP were diagnosed in the spring (p=0.015). Rates of patients diagnosed according to the seasons were as follows: 35.8% in spring, 23% in summer, 20.6% in fall, and 20.6% in winter. With respect to months, the majority of cases occurred in May (18.2%). Time of diagnosis according to the seasons did not differ between genders (p=0.699). First-line treatment was corticosteroids in 97.3%, but 35% of the cases were corticosteroid-resistant. Steroid-resistant patients were mostly diagnosed in the spring (52.1%) (p=0.001). ITP was chronic in 52.7% of the patients and they were also diagnosed mostly in the spring (62.7%) (p=0.149). CONCLUSION This is the first study showing seasonal association of ITP in adults and we have observed that ITP in adults is mostly diagnosed in the spring. The reason why more patients are diagnosed in the spring may be due to the existence of atmospheric pollens reaching maximum levels in the spring in places where a Mediterranean climate is seen.

The Role of Azacitidine in the Treatment of Elderly Patients with Acute Myeloid Leukemia: Results of a Retrospective Multicenter Study

Objective: In this study, we aimed to investigate the efficacy and safety of azacitidine (AZA) in elderly patients with acute myeloid leukemia (AML), including patients with >30% bone marrow (BM) blasts. Materials and Methods: In this retrospective multicenter study, 130 patients of ≥60 years o ld who were ineligible for intensive chemotherapy or had progressed despite conventional treatment were included. Results: The median age was 73 years and 61.5% of patients had >30% BM blasts. Patients received AZA for a median of four cycles (range: 1-21). Initial overall response [including complete remission (CR)/CR with incomplete recovery/partial remission] was 36.2%. Hematologic improvement (HI) of any kind was documented in 37.7% of all patients. HI was also documented in 27.1% of patients who were unresponsive to treatment. Median overall survival (OS) was 18 months for responders and 12 months for nonresponders (p=0.005). In the unresponsive patient group, any HI improved OS compared to patients without any HI (median OS was 14 months versus 10 months, p=0.068). Eastern Cooperative Oncology Group performance status of <2, increasing number of AZA cycles (≥5 courses), and any HI predicted better OS. Age, AML type, and BM blast percentage had no impact. Conclusion: We conclude that AZA is effective and well tolerated in elderly comorbid AML patients, irrespective of BM blast count, and HI should be considered a sufficient response to continue treatment with AZA.

Multicenter retrospective analysis regarding the clinical manifestations and treatment results in patients with hairy cell leukemia: twenty-four year Turkish experience in cladribine therapy

In this multicenter retrospective analysis, we aimed to present clinical, laboratory and treatment results of 94 patients with Hairy cell leukemia diagnosed in 13 centers between 1990 and 2014. Sixty‐six of the patients were males and 28 were females, with a median age of 55. Splenomegaly was present in 93.5% of cases at diagnosis. The laboratory findings that came into prominence were pancytopenia with grade 3 bone marrow fibrosis. Most of the patients with an indication for treatment were treated with cladribine as first‐line treatment. Total and complete response of cladribine was 97.3% and 80.7%. The relapse rate after cladribine was 16.6%, and treatment related mortality was 2.5%. Most preferred therapy (95%) was again cladribine at second‐line, and third line with CR rate of 68.4% and 66.6%, respectively. The 28‐month median OS was 91.7% in all patients and 25‐month median OS 96% for patients who were given cladribine as first‐line therapy. In conclusion, the first multicenter retrospective Turkish study where patients with HCL were followed up for a long period has revealed demographic characteristics of patients with HCL, and confirmed that cladribine treatment might be safe and effective in a relatively large series of the Turkish study population. Copyright

Change in plasma a disintegrin and metalloprotease with thrombospondin type-1 repeats-13 and von Willebrand factor levels in venous thromboembolic patients

Objectives: Venous thromboembolism (VTE) is an important cause of morbidity and mortality. A disintegrin and metalloprotease with thrombospondin type-1 repeats-13 (ADAMTS-13) is a metalloprotease that cleaves plasma von Willebrand factor (VWF) multimers. The presence of large VWF multimers in the plasma due to ADAMTS-13 deficiency is the main factor in the pathogenesis of thrombotic thrombocytopenic purpura. The present study aimed to investigate the relation of plasma levels of ADAMTS-13 and VWF antigen with VTE. Methods: The present study included 30 patients with VTE and age- and gender-matched 30 healthy subjects. Patients with any condition (diabetes, icterus, hyperlipidemia, physical, or surgical trauma, acute coronary syndrome, pregnancy, renal insufficiency, liver disease, malignancy, collagen tissue disease, chronic or acute inflammation, drug use affecting thrombocyte function) that could affect plasma VWF antigen or ADAMTS-13 levels were excluded. Plasma ADAMTS-13 and VWF antigen levels in the VTE and control groups were quantitatively determined by enzyme-linked immunosorbent assay method. Results: The median ADAMTS-13 level was 280 ng/ml (minimum–maximum, 70–1120 ng/ml) in the VTE group and 665 ng/ml (minimum–maximum, 350–2500 ng/ml) in the control group; the difference between the groups was significant (P < 0.0001). The mean VWF antigen level was 1750 ± 616 mU/ml in the patient group, which was significantly higher than that of the control group (950 ± 496 mU/ml) (P < 0.0001). Conclusion: Significantly lower ADAMTS-13 levels and significantly higher VWF antigen levels were concluded to be the result of a pathological process rather than an etiological factor for VTE.

Complete recovery of pyoderma gangrenosum after successful treatment of underlying hairy cell leukemia with cladribine.

To the Editor, Hairy cell leukemia (HCL) is a chronic B-cell disorder characterized by the presence of typical hairy cells in the peripheral blood and marrow, pancytopenia, and splenomegaly. Cutaneous lesions referable to thrombocytopenia, such as ecchymoses and petechiae, infection, and vasculitis, are common during the disease course, but lesions caused by infiltration of the skin by hairy cells are unusual. Pyoderma gangrenosum (PG) is a rare idiopathic ulcerative neutrophilic inflammatory skin disease characterized by a variable clinical presentation. PG is often a cutaneous manifestation of a systemic disease [1]. Here, we report a patient who was diagnosed with HCL presenting with a PG lesion and recovered after treating the underlying disease with cladribine. A 43-year-old male was admitted to our hospital with a painful ulcer on his left tibial surface. The lesion had first appeared 4 weeks ago accompanied by 38oC to 39oC fever. A physical examination revealed blood pressure, 120/85 mmHg; heart rate, 92 beats per minute; respiration rate, 22 breaths per min; and body temperature, 36.5oC. Two painful ulcers were found on his left tibial surface; one was 5 × 12 cm and the other was 4 × 8 cm in size (Fig. 1). The liver was palpable under the costal margin, and the spleen was 20 cm in length. Laboratory tests revealed pancytopenia (leukocytes, 1,230/mm3; neutrophils, 180 /mm3; hemoglobin, 6.6 g/dL; platelets, 51,000 /mm3). Cells with abundant agranular cytoplasm and multiple cytoplasmic projections were seen on the peripheral smear. A bone marrow examination showed diffuse infiltration of hairy cells and immunophenotyping using flow cytometry showed that these cells were CD103 (+), CD19 (+), CD20 (+), CD25 (+), CD3 (−), CD5 (−), and CD10 (−). HCL was diagnosed based on these findings. Figure 1. Pyoderma gangrenosum before treatment of hairy cell leukemia on the left tibial surface of the patient. Cultures and biopsies of the ulcerated skin lesions on the tibial surface were taken. Local and parenteral antibiotics were applied and dressings and debridement were performed regularly. No bacterial growth was seen on the cultures. The histopathological examination of this skin lesion proved the diagnosis of PG (Fig. 2). Figure 2. Diffuse necrosis and inflammatory cell infiltration were seen in the histopathological examination of the skin lesion, and this was compatible with pyoderma gangrenosum (H&E, ×40). Cladribine was administered at a rate of 0.1 mg/kg/day for 7 days for the HCL. The neutropenia resolved after 20 days of cladribine monotherapy. The pancytopenia had resolved completely, and spleen size was normal at the follow-up. The PG resolved completely after the third month of cladribine treatment by treating the primary disease and changing the dressings regularly (Fig. 3). Figure 3. Pyoderma gangrenosum completely resolved after the cladribine treatment. PG is a disease with unclear etiology. It is probably a hyperergic reaction, connected with a systemic disease or with an immunological compound. Approximately 50% to 70% of patients with PG have an underlying systemic disease, and the most commonly associated conditions are inflammatory bowel disease, polyarthritis, hematological disease (acute myelogenous leukemia and HCL), monoclonal gammopathies, hepatitis, and collagen vascular diseases. PG can begin at any age, but is most common in 30- to 50-year-old patients of either sex [1]. The incidence of PG is approximately 3 per million people per year in the United States. The frequency of malignant neoplasms in cases of PG is not exactly known, but it has been assessed to be 7% [2]. These cases are most often associated with acute or chronic leukemia. PG skin lesions are painful, erythematous papules, sterile pustules, or fluctuant nodules that may progress to expanding ulcers. The lesions can develop individually at any cutaneous site but are typically found on the lower extremities and trunk [1]. The diagnosis of PG is based primarily on the clinical presentation, as immunohistopathological findings in patients with PG are nonspecific [1]. Biopsies may demonstrate edema, mixed inflammatory infiltrates (predominantly neutrophilic infiltrate), lymphocytic vasculitis, necrosis, and hemorrhage. A few reported cases of HCL have the presenting symptoms of PG [3-5]. Patients presenting with PG should be carefully examined for an underlying hematological malignancy with detailed anamnesis, a physical examination, and laboratory testing. HCL can be easily diagnosed in patients with pancytopenia, splenomegaly, and typical hairy cells, and skin ulcers can be related to PG, as in our patient. Although the histopathological changes are not specific to PG, biopsies of the lesions must be performed, as these lesions can also be related to infiltration of leukemic cells. Once HCL and PG are diagnosed, the main treatment target should be HCL, as PG will completely recover in a few months with the successful treatment of HCL using cladribine, as in our patient.