Effect of Adiponectin on Acute Experimental Cerebral Ischemia/Reperfusion Injury.

AIM: To examine the effect of adiponectin administration on acute brain injury in an experimental model of cerebral ischemia/ reperfusion (I/R) in rats. MATERIAL AND METHODS: The study animals were divided into the following four groups: group I, sham (did not undergo surgical intervention and did not receive drugs); group II, the I/R model (received the intervention, but did not receive drugs); group III (I/Radiponectin) (the I/R model was used, and the animals were treated with 5 mg/kg adiponectin peritoneally 30 minutes after the ischemia); and group IV (I/R-tirofiban)( the I/R model was used, and the animals were treated with 0.5 mg/kg tirofiban peritoneally 30 minutes after the ischemia). RESULTS: Tumor necrosis factor-? (TNF-?) and interleukin (IL)-1? levels were statistically higher in the I/R group (group II) than in other groups. In the post-hoc (Tukey) test analysis, groups I, III, and IV had significantly lower TNF-? and IL-1? levels after treatment with both tirofiban and adiponectin than group II. No statistically significant difference was found between groups III and IV in terms of TNF-? levels. However, the decreased IL-1? level was more pronounced in group IV (tirofiban) than in other groups. The mean neurologic deficit scores were statistically significantly different among the groups. In the post-hoc (Tukey) test analysis, neurologic deficit scores were statistically significantly lower in groups III and IV than in group II. CONCLUSION: Adiponectin has anti-inflammatory and cerebral protective effects in experimental cerebral I/R injury.

How to manage MuSK antibody-positive myasthenic crisis during pregnancy?

Myasthenia gravis (MG) is an autoimmune disease that is characterised by the formation of antibodies against acetylcholine receptors in the postsynaptic membrane of the neuromuscular junction. The course of the disease cannot be predicted during pregnancy. A subtype of MG with positive muscle-specific receptor tyrosine kinase (anti-MuSK) antibodies exhibits more localised clinical characteristics and a poor response to treatment compared with the disease subtype that involves positivity for acetylcholine receptor antibodies. Myasthenic crisis is more frequently observed in anti-MuSK-positive myasthenia patients. Anti-MuSK-positive myasthenic crisis management is very difficult and a risky situation during pregnancy. The reported case was 30 years old, female, 9 weeks pregnant and musk antibody positive. She stopped her treatment without asking her doctor because she was planning pregnancy in the 6-month period before her hospitalization. She was intubated for a long time in the intensive care unit due to myasthenic crisis and was very resistant to treatment. During this period, her pregnancy was terminated due to fetal anomaly. Plasmapheresis, IVIg and immunosuppressive treatments were applied. Our patient was discharged after a period of about 10 weeks. We share our treatment management.

The role of atopy in the pathogenesis of bleomycin pulmonary toxicity.

INTRODUCTION: Bleomycin pulmonary toxicity (BPT) is a potentially life-threatening consequence of bleomycin usage in patients. An overproduction of epithelium-derived cytokines, habitually linked to allergic inflammation, has been recently revealed in experimental models of BPT. METHODS: We assessed retrospectively our cohort of patients with Hodgkin Lymphoma treated with bleomycin between 2014 and 2016 for their demographic, clinical features, including BPT development, atopy status and risk factors for BPT. Then they were invited for allergy testing and blood sample collection. The samples were stimulated with different stimuli (Bleomycin, IL-33, TSLP) for 24 h on cell culture. The culture supernatants were analysed for TGF-ß, Galectin3, Arginin, Amphiregulin, Eotaxin, IFNγ, TNFα, IL1ß, 4, 5, 6, 10, 13, 17, MIP-1α, and bleomycin hydrolase (BLH) levels. RESULTS: The cohort consisted of 51 patients showed that atopy was the only significant risk factor for BPT occurrence (OR: 7.2, p = 0.007). Fourteen subjects were included for blood analysis. The analysis of supernatants at the unstimulated condition revealed that BLH and Amphiregulin were significantly lower in patients who had BPT than controls. The BLH cut-off that best identified a history of BPT was 175.31 (Sensitivity: 62.5%, specificity: 100%). Following the stimulation, BLH reduced compared to the unstimulated condition and the difference between groups remained significant (p < 0.05). CONCLUSION: Our study is the first to report that low levels of bleomycin hydrolase in allergic individuals may be predisposing to a possible pathway of fibrosis.

Implementation of an antimicrobial stewardship program for patients with febrile neutropenia.

BACKGROUND: We aimed to describe the effectiveness of our standardized protocol for febrile neutropenia (FN), which was targeted to minimize unintended outcomes and reduce antimicrobial consumption. METHODS: The study was performed in a private hospital with 300 beds. We included all adult hematologic and oncologic cancer inpatients admitted between January 1, 2015-December 31, 2015, and January 1, 2016-May 31, 2017. The outcomes of the study were fatality, infections, and adherence to the antimicrobial stewardship program (ASP). RESULTS: We included 152 FN attacks of 95 adult inpatients from hematology and oncology wards; of these, 43% were women, and the median age was 57 years. The case fatality rate was 30% in the pre-ASP period and decreased to 11% in the post-ASP period (P = .024). The appropriate adding or changing (P = .006) and appropriate continuation or de-escalation or discontinuation of antimicrobials improved (P < .001). In the post-ASP period, Staphylococcus spp infections (from 22% to 8%, P = .02) and gram-negative infections decreased (from 43% to 20%, P = .003). In the multivariate analysis, appropriate continuation or de-escalation or discontinuation was increased in the post-ASP period (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.82-10.41; P = .001), and gram-positive infections were decreased (OR, 0.32; 95% CI, 0.11-0.95, P = .041). Vancomycin and fluoroquinolone use decreased significantly. CONCLUSIONS: After implementation of the ASP, the case fatality rate among the patients with FN decreased. Appropriate antimicrobial use increased and overall antimicrobial consumption was reduced. Bacterial infections and Candida infections decreased.

Rituximab desensitization in three patients with severe rituximab allergy.

Rituximab is a chimeric monoclonal antibody that targets CD20 positive B cells and has a positive effect on both overall and progression-free survival in B-cell lymphoid malignancies. Combination rituximab with chemotherapy treatment provide survival improvement. Although rituximab is an important treatment option in hematological malignancies, the risk of allergic reactions is high. These reactions are usually IgE-mediated and can be varied in regard of severity from urticaria to anaphylaxis. It is an option to interrupt the treatment and ommit rituximab therapy who had allergic reactions. Drug desensitization is another option and successful results have been reported by applying desensitization to such reactions. Drug desensitization alters the immune response to induce a state of temporary clinical tolerance to the allergic drug by giving gradual increasing of doses of drug at fixed time intervals. Herein, we present 3 cases successfully treated with rituximab desensitization. The cases were using rituximab with the diagnosis of Burkitt lymphoma, follicular lymphoma, and marginal zone lymphoma, respectively. Two cases had grade 2 and 1 case had grade 3 systemic allergic reaction with rituximab. There was no known allergy history in all 3 cases. All patients tolerated the desensitization protocol. The subsequent treatments of the patients were also given by desensitization protocol. A total of 12 desensitizations were administered to 3 cases. No severe or life-threating reactions were observed in subsequent applications. To date applying desensitization protocols ensure rituximab treatment safely. Rituximab desensitization can be performed at trained allergy centers, and it may be an appropriate option for rituximab allergic patients.

Iron deficiency and anemia in heart failure.

Heart failure is an important community health problem. Prevalence and incidence of heart failure have continued to rise over the years. Despite recent advances in heart failure therapy, prognosis is still poor, rehospitalization rate is very high, and quality of life is worse. Co-morbidities in heart failure have negative impact on clinical course of the disease, further impair prognosis, and add difficulties to treatment of clinical picture. Therefore, successful management of co-morbidities is strongly recommended in addition to conventional therapy for heart failure. One of the most common co-morbidities in heart failure is presence of iron deficiency and anemia. Current evidence suggests that iron deficiency and anemia are more prevalent in patients with heart failure and reduced ejection fraction, as well as those with heart failure and preserved ejection fraction. Moreover, iron deficiency and anemia are referred to as independent predictors for poor prognosis in heart failure. There is strong relationship between iron deficiency or anemia and severity of clinical status of heart failure. Over the last two decades, many clinical investigations have been conducted on clinical effectiveness of treatment of iron deficiency or anemia with oral iron, intravenous iron, and erythropoietin therapies. Studies with oral iron and erythropoietin therapies did not provide any clinical benefit and, in fact, these therapies have been shown to be associated with increase in adverse clinical outcomes. However, clinical trials in patients with iron deficiency in the presence or absence of anemia have demonstrated considerable clinical benefits of intravenous iron therapy, and based on these positive outcomes, iron deficiency has become target of therapy in management of heart failure. The present report assesses current approaches to iron deficiency and anemia in heart failure in light of recent evidence.

Use of fluorodeoxyglucose positron emission tomography for diagnosis of bleomycin-induced pneumonitis in Hodgkin lymphoma.

Bleomycin is an antineoplastic agent causing fatal pulmonary toxicity. Early diagnosis of bleomycin-induced pneumonitis is crucial to prevent irreversible damage. Pulmonary function tests are unreliable for identifying risk of bleomycin toxicity. Fluorodeoxyglucose PET/CT scanning can reveal inflammation secondary to pneumonitis but is not sufficiently specific for diagnosis. We retrospectively analyzed scans from 77 patients with Hodgkin lymphoma (median age 41 years, mean bleomycin dose 134 mg) to evaluate bleomycin-induced pneumonitis. We identified 13 patients with abnormal lung uptake of fluorodeoxyglucose. Tracer activity was predominantly diffuse, bilateral, in the lower lobes and subpleural areas. Interim scanning during treatment revealed pneumonitis in eight of 13 patients (asymptomatic in six). One asymptomatic patient died of bleomycin toxicity. For remaining 12 patients, bleomycin was discontinued and methylprednisolone given, all showed resolution of the pneumonitis. These findings suggest that routine interim or end-of-treatment FDG-PET/CT scanning could be beneficial for alerting clinicians to asymptomatic bleomycin-induced toxicity.

Diagnosis and treatment of iron deficiency anemia in patients with inflammatory bowel disease and gastrointestinal bleeding: iron deficiency anemia working group consensus report.

Iron deficiency (ID) and iron deficiency anemia (IDA) are important signs of gastrointestinal (GI) hemorrhage. Therefore, the evaluation of the GI tract should be a part of the diagnostic protocol in patients with IDA. GI hemorrhage is not a disease but a symptom, which might have different underlying causes. ID and IDA have significant negative impacts on the life quality and work ability, and they may lead to frequent hospitalization, delay of discharge, and increased healthcare costs. Therefore, an optimal management of the disease causing GI hemorrhage should include iron replacement therapy, along with the treatment of the underlying condition. IDA in inflammatory bowel disease (IBD) has received particular attention owing to its high prevalence, probably due to a number of other factors such as chronic hemorrhage, reduced dietary iron intake, and impaired absorption of iron. Historically, in IBD and in patients with GI hemorrhage, the diagnosis and management of IDA have been suboptimal. Options for iron replacement include oral and intravenous (IV) iron supplementation. Oral iron supplementation frequently results in GI side effects, and theoretically, it may exacerbate IBD activity; therefore, IV iron supplementation is usually considered in patients not responding to or not complying with oral iron supplementation or patients having low hemoglobin concentration and requiring prompt iron repletion. The aim of this report was to review the diagnostic and therapeutic considerations of IDA in IBD and GI hemorrhage with a multidisciplinary group of experts and to formulate necessary practical recommendations.

Complete Remission of Burkitt Lymphoma After Surgical Excision: A Case Report.

Burkitt lymphoma (BL) is a highly aggressive B cell non-Hodgkin lymphoma that has a high proliferation rate. The prognosis for BL is generally favorable, with cure rate of 75-90 % with modern chemoimmunotherapy regimens. Prompt administration of multiagent immunochemotherapy regimens is critical, because BL is almost always fatal if left untreated. Nevertheless here we report a case of BL that is still in complete remission after more than 4 years without any further treatment after surgical excision of the involved lymph node.

Novel Masters of Erythropoiesis: Hypoxia Inducible Factors and Recent Advances in Anemia of Renal Disease.

Anemia seen in patients with chronic kidney disease is a particular form of 'anemia of chronic disease'. Although multifactorial in origin, erythropoiesis-stimulating agents (ESAs) and adjuvant iron therapy represent the primary treatment for anemia in chronic kidney disease. Subsequent clinical observations revealed that these ESA hyporesponsive patients often had increased systemic inflammation as a consequence of their comorbidities. Use of high ESA doses to overcome this ESA hyporesponsiveness posed some concerns regarding associated adverse events of therapy and increased mortality in this special patient population. Recognizing the pivotal roles of hypoxia inducible factors (HIFs) in orchestrating elements of erythropoiesis opened new avenues in the management of renal anemia. Several phase 1 and 2 studies confirmed the results of early experimental studies supporting the beneficial role of augmenting HIFs for erythropoiesis. In this review, we describe the physiologic functions of HIF in erythropoiesis with special emphasis on interactions with iron and hepcidin metabolism and inflammation.

The Clinical and Urodynamic Results of Percutaneous Posterior Tibial Nerve Stimulation on Neurogenic Detrusor Overactivity in Patients With Parkinson's Disease.

OBJECTIVE: To investigate the effect of percutaneous posterior tibial nerve stimulation (PTNS) treatment after 12 weeks on urodynamic and clinical findings in patients with Parkinson's disease (PD) with neurogenic detrusor overactivity. METHODS: A total of 47 patients with PD with neurogenic detrusor overactivity were enrolled in the study. Urodynamic studies before and after 12-week PTNS treatment were performed. International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), Overactive Bladder Questionnaire (OAB-V8), and Overactive Bladder Questionnaire Short Form (OAB-q SF) have been assessed before and after PTNS treatment. RESULTS: The mean first involuntary detrusor contraction volume (1st IDCV) on standard cystometry was 133.2 ± 48.1 (24-265) mL, whereas it was 237.3 ± 43.1 (145-390) mL after PTNS. The mean maximum cystometric capacity (MCC) on standard cystometry was 202.2 ± 36.5 (115-320) mL, whereas it was 292.1 ± 50.6 (195-395) mL after stimulation. The improvements in the first involuntary detrusor contraction volume and maximum cystometric capacity were statistically significant after stimulation. The mean Pdetmax at first involuntary detrusor contraction, maximal detrusor pressure at maximum cystometric capacity, PdetQmax, Qmax, and post-void residual volume were statistically significant after 12-week stimulation. Mean parametric improvements at 12-week PTNS treatment from baseline included daytime frequency decreased by 5.6 voids daily, urge incontinence decreased by 3.1 episodes daily, urgency episodes decreased by 6.3 episodes daily, nocturia decreased by 2.7 voids, and voided volume improved by a mean of 92.6 mL. The change from baseline on the ICIQ-SF, OABv8, and OAB-q at 12-week PTNS treatment demonstrated statistically significant improvements. CONCLUSION: These results have demonstrated that PTNS improves the lower urinary tract symptoms and urodynamic parameters in patients with PD.

GnRH agonist leuprolide acetate does not confer any protection against ovarian damage induced by chemotherapy and radiation in vitro.

STUDY QUESTION: Is there any in vitro evidence for or against ovarian protection by co-administration of a GnRH agonist with chemotherapy in human? SUMMARY ANSWER: The co-administration of GnRH agonist leuprolide acetate with cytotoxic chemotherapy agents does not preserve ovarian reserve in vitro. WHAT IS KNOWN ALREADY: Randomized controlled trials of the co-administration of gonadotrophin-releasing hormone (GnRH) agonists with adjuvant chemotherapy to preserve ovarian function have shown contradictory results. This fact, together with the lack of a proven molecular mechanism of action for ovarian protection with GnRH agonist (GnRHa) places this approach as a fertility preservation strategy under scrutiny. We therefore aimed in this study to provide in vitro evidence for or against the role of GnRHa in the prevention of chemotherapy-induced damage in human ovary. STUDY DESIGN, SETTINGS, SIZE AND DURATION: This translational research study of ex vivo and in vitro models of human ovary and granulosa cells was conducted in a university hospital between 2013 and 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian cortical pieces (n = 15, age 14-37) and mitotic non-luteinized (COV434 and HGrC1) and non-mitotic luteinized human granulosa cells (HLGC) expressing GnRH receptor were used for the experiments. The samples were treated with cyclophosphamide, cisplatin, paclitaxel, 5-FU, or TAC combination regimen (docetaxel, adriamycin and cyclophosphamide) with and without GnRHa leuprolide acetate for 24 h. DNA damage, apoptosis, follicle reserve, hormone markers of ovarian function and reserve (estradiol (E2), progesterone (P) and anti-mullerian hormone (AMH)) and the expression of anti-apoptotic genes (bcl-2, bcl-xL, bcl-2L2, Mcl-1, BIRC-2 and XIAP) were compared among control, chemotherapy and chemotherapy + GnRHa groups. MAIN RESULTS AND THE ROLE OF CHANCE: The greatest magnitude of cytotoxicity was observed in the samples treated with cyclophosphamide, cisplatin and TAC regimen. Exposure to these drugs resulted in DNA damage, apoptosis and massive follicle loss along with a concurrent decline in the steroidogenic activity of the samples. GnRHa co-administered with chemotherapy agents stimulated its receptors and raised intracellular cAMP levels. But it neither activated anti-apoptotic pathways nor prevented follicle loss, DNA damage and apoptosis induced by these drugs. LIMITATIONS, REASONS FOR CAUTION: Our findings do not conclusively rule out the possibility that GnRHa may offer protection, if any, through some other mechanisms in vivo. WIDER IMPLICATIONS OF THE FINDINGS: GnRH agonist treatment with chemotherapy does not prevent or ameliorate ovarian damage and follicle loss in vitro. These data can be useful when consulting a young patient who may wish to receive GnRH treatment with chemotherapy to protect her ovaries from chemotherapy-induced damage.

Diagnosis and treatment of iron deficiency anemia during pregnancy and the postpartum period: Iron deficiency anemia working group consensus report.

According to the World Health Organization (WHO), anemia is the most common disease, affecting >1.5 billion people worldwide. Furthermore, iron deficiency anemia (IDA) accounts for 50% of cases of anemia. IDA is common during pregnancy and the postpartum period, and can lead to serious maternal and fetal complications. The aim of this report was to present the experiences of a multidisciplinary expert group, and to establish reference guidelines for the optimal diagnosis and treatment of IDA during pregnancy and the postpartum period. Studies and guidelines on the diagnosis and treatment of IDA published in Turkish and international journals were reviewed. Conclusive recommendations were made by an expert panel aiming for a scientific consensus. Measurement of serum ferritin has the highest sensitivity and specificity for diagnosis of IDA unless there is a concurrent inflammatory condition. The lower threshold value for hemoglobin (Hb) in pregnant women is <11 g/dL during the 1st and 3rd trimesters, and <10.5 g/dL during the 2nd trimester. In postpartum period a Hb concentration <10 g/dL indicates clinically significant anemia. Oral iron therapy is given as the first-line treatment for IDA. Although current data are limited, intravenous (IV) iron therapy is an alternative therapeutic option in patients who do not respond to oral iron therapy, have adverse reactions, do not comply with oral iron treatment, have a very low Hb concentration, and require rapid iron repletion. IV iron preparations can be safely used for the treatment of IDA during pregnancy and the postpartum period, and are more beneficial than oral iron preparations in specific indications.

Diagnostic contribution of (18)F-FDG-PET/CT in fever of unknown origin.

OBJECTIVES: Fever of unknown origin (FUO) remains one of the most compelling diagnostic issues in medicine. We aimed to evaluate the potential clinical contribution of 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) in the identification of the underlying cause of FUO. METHODS: Fifty consecutive patients (27 men and 23 women; age range 16-88 years) with FUO based on the revised definition criteria were included in the study. A diagnostic protocol including biochemistry, histopathology, and microbiological tests was performed and the patients were followed up. FDG-PET was performed in 25 of the 50 patients (12 males and 13 females; age range 16-88 years) in order to determine the etiology of the patient's fever. PET-CT images were obtained with the Gemini Philips TF (18)F-FDG-PET/CT camera after a 60-min 'standard uptake' period following an injection of a mean 330 MBq (range 290-370 MBq) intravenous (18)F-FDG. RESULTS: A total of 21 patients were available for analysis of the diagnostic contribution of PET/CT (two patients were undiagnosed and two had non-contributory PET/CT findings). (18)F-FDG-PET/CT was able to precisely detect the cause of fever in 60% of the cases (n=15). The accuracy, sensitivity, and specificity of this imaging modality were 90.5%, 93.8%, and 80%, respectively. Among the cases with a true-positive (18)F-FDG-PET/CT finding (i.e., 15 cases), the identified underlying causes of FUO included localized infection (n=7), non-infective inflammatory process (n=5), and malignancy (n=3). CONCLUSIONS: Further studies to confirm the high diagnostic yield of (18)F-FDG-PET/CT observed in the present study would lend support to the inclusion of this imaging modality in the initial diagnostic work-up of patients with suspected FUO.

Ischemia-modified albumin: could it be a new oxidative stress biomarker for colorectal carcinoma?

BACKGROUND/AIMS: An impaired oxidative/antioxidative status plays an important role in the pathogenesis of many diseases, including cancer. The aim of this study was to evaluate the levels of the novel marker ischemia-modified albumin (IMA) and albumin-adjusted IMA (Adj-IMA) in patients with colorectal cancer (CRC) and look for the associations of these with the total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI). METHODS: Forty patients with CRC (19 females and 21 males; mean age, 56.5±2.1 years) and 39 age- and sex-matched healthy people (22 females and 17 males; mean age, 56.0±1.7 years) were included in this study. Serum levels of IMA, TAS, and TOS were analyzed, and the OSI was calculated. RESULTS: Serum IMA, TOS, and OSI levels were significantly higher in patients with CRC than in controls (p<0.0001), whereas TAS levels were significantly lower in CRC patients (p=0.03). There was no significant difference in serum Adj-IMA levels between groups (p=0.32). CONCLUSIONS: In this study, the oxidative/antioxidant status was impaired in favor of oxidative stress in CRC patients. This observation was not confirmed by IMA measurement. Further studies are needed to establish the relationship between IMA and oxidative stress parameters in CRC and other cancers.

Nonleukemic ureteral granulocytic sarcoma presenting with unilateral urinary obstruction and hematuria.

Granulocytic sarcoma is an extramedullary tumor which is composed of myeloblasts and immature myeloid cells. It usually occurs in association with acute myeloid leukemia and most commonly involves skin, soft tissue, lymph nodes, bone, and periosteum. We report a case of isolated ureteral granulocytic sarcoma without hematologic manifestations. Our patient presented with bloody urine and left-sided lumbar pain. Preoperative clinical and radiologic features raised the suspicion of an upper urinary tract transitional cell carcinoma, and he was scheduled for nephroureterectomy. However, perioperative pathologic feedback and the unusual endoscopic appearance of the tumor altered our surgical strategy towards segmental ureterectomy and ureteroneocystostomy. Eventual pathologic diagnosis was granulocytic sarcoma of the ureter. Postoperative workup failed to demonstrate any sign of an accompanying hematologic disorder. He started receiving the chemotherapy protocol of acute myeloblastic leukemia. To our knowledge, this is the first documented case of nonleukemic ureteral granulocytic sarcoma which came to attention due to urologic complaints.

Azacitidine has limited activity in 'real life' patients with MDS and AML: a single centre experience.

Myelodysplastic syndrome (MDS) represents a heterogeneous group of potentially malignant diseases of bone-marrow stem cells. Acute myelogenous leukaemia (AML) is an inevitable outcome for many patients with MDS. Azacitidine has been reported to result in comparably higher response rates and improved survival than other treatment strategies. In this retrospective study, we report the results on 25 'real life' patients with MDS, CMML or AML treated with azacitidine between 2005 and 2009. All patients fulfilled the World Health Organization criteria for MDS and AML. No eligibility criteria other than diagnosis were considered. Complete response (CR) rate was observed in three of the 25 'real life' patients (12%) with a median duration of CR of 5 months (4-6 months). Seven patients (28%) had mono- or bi-lineage haematologic improvement and 15 patients (60%) showed neither morphologic nor haematologic response. Among 17 non-AML patients, the median time from onset of Aza-C treatment to AML transformation was 10 months (4-15 months). Overall death rate was 72%. All of the eight AML patients died. The death rate under Aza-C among non-AML patients was 59%. Unlike the results of the clinical trials, our data show that Aza-C has a limited activity in 'real-life' patients with MDS and AML. It is obvious that Aza-C can induce complete or partial responses in a considerable number of MDS patients but responses are usually not durable as we observed in our patients.

Bortezomib: a new therapeutic option for POEMS syndrome.

OBJECTIVE: POEMS syndrome with its classical five findings (Polyneuropathy, Organomegaly, Endocrinopathy, M protein, and Skin changes) is a rare multisystem disease. Proinflammatory and proangiogenic cytokines play important roles in its pathogenesis. Treatment options are still debated. METHODS: We present a 65-year-old man with POEMS syndrome who was successfully treated with bortezomib. RESULTS: After seven cycles of this protocol, serum M protein level declined to normal range, and near-to-complete remission was achieved. His symptoms of polyneuropathy improved dramatically. CONCLUSION: Bortezomib may be an effective and safe therapeutic option for patients with POEMS syndrome.

Osteonecrosis of the jaw in patients with multiple myeloma treated with zoledronic acid.

Intravenous bisphosphonates-the potent inhibitors of osteoclast-mediated bone resorption are among the most commonly prescribed drugs in the management of multiple myeloma (MM). Zoledronic acid (ZA) is a new generation potent intravenous bisphosphonate that has been approved for the treatment and prevention of bone lesions, and/or hypercalcemia associated with MM. Osteonecrosis of the jaw (ONJ) is an emerging serious side effect of the new generation bisphosphonates with a growing number of reports related to this pathological entity. ONJ usually appears following oral surgical and dental procedures but sometimes occur spontaneously. These cases are mostly seen and treated by dentists and oral surgeons. The aim of this study was to discuss the frequency, characteristics, risk factors, management and histopathological features of ZA induced ONJ based on the literature and illustrated with five own cases. Thirty-two patients with MM who received ZA for a median period of 26.5 +/- 18.7 months (min: 5 months, max: 76 months) were evaluated. ONJ was detected in five patients and mean drug duration time was 34 months. The frequency was 15% and the patients were usually symptomatic. There was no significant difference in terms of the duration of ZA in patients with and without ONJ. Management of these established cases were performed with medical treatment, minor debridement, sequestrectomy, and combining bone resection with autologous platelet rich plasma. Our data indicate that ZA therapy has a major role in the development of ONJ a fact that should be considered by physicians treating MM patients.