Immature platelet fraction as a useful marker in Crimean-Congo hemorrhagic fever.

The aim of this study is to evaluate the clinical significance and diagnostic performance of the immature platelet fraction (%IPF) in Crimean-Congo hemorrhagic fever (CCHF). Samples obtained from 32 healthy control subjects and 40 CCHF patients (9 positive and 31 negative radiological findings) were evaluated in the study. The samples obtained from CT-positive subjects demonstrated higher IPF% values which also exhibited a positive correlation with mean platelet volume (MPV) and platelet size deviation width (PDW) values.The patient group IPF% values were positively correlated with the duration of hospital stay. The ROC analysis also suggested the potential importance of IPF values higher than 10.5% in diagnosing CCHF patients with positive radiological findings.The results of our study showed that % IPF can be considered as a useful parameter in the follow-up of the disease course in patients with CCHF.

Risk of hepatitis B virus reactivation during immunosuppressive treatment.

OBJECTIVE: In this study, we aimed to rate Hepatitis B Virus (HBV) reactivation, risk factors for reactivation and compare the efficacy of prophylactic antiviral therapy in patients who initiated immunosuppressive therapy. PATIENTS AND METHODS: A total of 177 patients with Chronic Hepatitis B or resolved HBV infection who had received immunosuppressive treatment were analyzed in this retrospective study. Demographic features, relevant liver tests, prophylactic treatment type, duration of treatment, transaminase levels and HBV serology and clinical conditions were recorded from all patients who received prophylactic treatment. RESULTS: Eleven reactivation occurred in all groups. The mean age of patients who developed reactivation was statistically significantly lower (p=0.049). Three (27.3%) of the patients were male and 8 (72.7%) were female (p=0.66). Eight (36.36%) of 22 HB surface antigen (HBsAg) positive patients developed reactivation, 3 (155%) of 155 HBsAg negative patients developed reactivation. HBsAg positivity was determined as a risk factor for reactivation (p<0.001). There was no significant difference neither in reactivation, nor in the type of antiviral treatment (p=0.2) according to anti-HBs serology (p=0.366). CONCLUSIONS: As a result, early age, baseline HBsAg positivity, moderate risk group, baseline HBV DNA positivity were associated with reactivation. Gender, immunosuppressive therapy type, preemptive antiviral therapy type, and anti-HBs titers were not associated with reactivation.

Immature platelet fraction as a useful marker in Crimean-Congo hemorrhagic fever

@#The aim of this study is to evaluate the clinical significance and diagnostic performance of the immature platelet fraction (%IPF) in Crimean-Congo hemorrhagic fever (CCHF). Samples obtained from 32 healthy control subjects and 40 CCHF patients (9 positive and 31 negative radiological findings) were evaluated in the study. The samples obtained from CT-positive subjects demonstrated higher IPF% values which also exhibited a positive correlation with mean platelet volume (MPV) and platelet size deviation width (PDW) values.The patient group IPF% values were positively correlated with the duration of hospital stay. The ROC analysis also suggested the potential importance of IPF values higher than 10.5% in diagnosing CCHF patients with positive radiological findings.The results of our study showed that % IPF can be considered as a useful parameter in the follow-up of the disease course in patients with CCHF.

Which Tyrosine Kinase Inhibitor Must We Apply Before? A Case Report of Crizotinib-resistant Patient with Concomitant EGFR and EML4-ALK Gene Mutations

ABSTRACT The concomitant epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocations in lung adenocancers are very rare scenarios. Until now, 42 cases described in the literature have all been treated by different drugs. There is no overall consensus regarding the treatment for this adenocarcinoma subgroup. We report here a case of lung adenocarcinoma with concomitant EGFR mutation in exon 21 (L858R) and ALK rearrangement in primary tumour, EGFR mutation in exon 21 (L858R) and no ALK rearrangement in its synchronous metastasis. We treated this patient with crizotinib as the second-line therapy (after the first line docetaxel-cisplatin chemotherapy), but no response was obtained. The therapeutic choice for the lung adenocancer patients with concomitant EGFR mutation and ALK rearrangement is unclear. Examination of c-ros oncogene 1 mutation can be used as an indicator in the prediction of the crizotinib treatment success. The ALK mutation may not responsible for the resistance to EGFR-tyrosine kinase inhibitors (TKI), and EGFR-TKI can be initiated to EGFR and ALK dual mutant patients as the first treatment.

Hypovitaminosis D is Associated with Endothelial Dysfunction in Patients with Metabolic Syndrome.

OBJECTIVES: Recent research has shown that hypovitaminosis D may increase the risk of hypertension, vascular disease, diabetes mellitus, obesity and Metabolic Syndrome (MetS). Endothelial Dysfunction (ED) is one of the key components of MetS which is associated with an imbalance between vasoactive substances such as Nitric Oxide (NO) and Endothelins (ET). In this study, we assessed the association of 25(OH) D3 level with endothelial dysfunction and subclinical atherosclerosis in MetS patients. DESIGN AND METHODS: 105 MetS patients and 48 controls were included. 25(OH) D3 levels were measured using Ultra-High Performance Liquid Chromatography (UHPLC). NOx (NO2 plus NO3) and Endothelin- 1(ET-1) concentrations were determined along with routine biochemical tests. Flow-Mediated Dilatation (FMD) and carotid Intima-Media Thickness (cIMT) were measured by ultrasonography. RESULTS: In MetS patients, vitamin D and NOx levels were significantly lower (p<0.001), while ET-1 levels were higher than controls (p<0.005). MetS patients with ED exhibited significantly lower vitamin D levels than their counterparts free of ED. Vitamin D levels were correlated positively with FMD and NOx, and negatively with systolic blood pressure and body mass index. Subclinical atherosclerosis as assessed by the cIMT did not associate with low vitamin D levels. CONCLUSION: Vitamin D deficiency seen in MetS patients is more prominent in the presence of ED. Hypovitaminosis D may affect endothelial cells, and participate in the development of hypertension.

Low concentrations of adropin are associated with endothelial dysfunction as assessed by flow-mediated dilatation in patients with metabolic syndrome.

BACKGROUND: In individuals with atherosclerotic risk factors, endothelial dysfunction (ED) appears as an early phase in the development of clinical symptoms. Recent studies indicate that adropin, a newly identified peptide, participates in cardiovascular health through the regulation of several metabolic events including angiogenesis and blood flow. In this study, we aimed to determine the relation of adropin with biochemical and radiologic parameters which reflect ED such as endothelial nitric oxide synthase (eNOS), endothelin 1 (ET-1), nitric oxide (NO) and flow-mediated dilatation (FMD) along with the routine biochemical measurements in patients recently diagnosed with metabolic syndrome (MetS). METHODS: Fasting blood samples from 110 patients with MetS diagnosed according to the NCEP ATP III-2005 criteria were collected to measure the concentrations of adropin and other parameters including the lipid profile, insulin and glucose. Serum NOx concentrations were determined by measuring NO2 plus NO3. FMD test was performed by ultrasonography, and patients were stratified as FMD (+) or (-). Data were compared between these two subgroups and also with matching healthy controls (n=50). Biochemical data were evaluated using Student's t or Mann-Whitney U tests. RESULTS: Fifty-nine subjects had ED (+) and the remaining 101 subjects were ED (-). In the first group, adropin levels were significantly lower than the latter (2.13±1.05 vs. 3.41±1.63 ng/mL, respectively; p<0.001) and independently associated with FMD positivity as assessed by the logistic regression analysis. CONCLUSIONS: Low adropin level in circulation is related to ED and has a close association with FMD. Any alterations in its level may be of help in order to assess the development of ED before the occurrence of clinical symptoms in patients with metabolic syndrome.

Dentists' knowledge of occlusal splint therapy for bruxism and temporomandibular joint disorders.

AIMS: The aim of this study was to investigate dentist's approaches to the use of splint therapy for myofascial pain, bruxism, and temporomandibular joint (TMJ) disorders and to assessment of treatment modalities. MATERIALS AND METHODS: A 12-item questionnaire was developed to determine dentists' knowledge of TMJ disorders and approaches for occlusal splint treatments. The researchers spoke with each dentist included in the study at his/her clinic or by telephone to assess their immediate knowledge and approach to the TMJ disorders. Chi-squared test was performed to analyze the values. The confidence interval was set as 95%. RESULTS: A total of 370 dentists working in Turkey were participated in this study. The most common splint application reason for occlusal splint treatment was bruxism (77.8%) while TMJ pain was very rare (%1.4). The use of hard splint ratios for 0-5 years of professional experience was 57.0%, 42.4.0%, and 26.8% for the experience of 5-15 years and over 15 years groups, respectively (P < 0.001). While the dentists' with sufficient knowledge soft splint application rates were 11.6%, hard splint application rates were 43.4% for the dentists with sufficient knowledge. Occlusion adjustment rate of dentists who practice in all three groups was under 16.0%. CONCLUSIONS: The knowledge of the dentists about TMJ disorders and occlusal splint therapy were found to be insufficient. Their knowledge decreased with increasing experience.

Giant thrombus on apical wall of left ventricle due to HIT syndrome after anterior MI.

Heparin-induced thrombocytopenia (HIT) is the most important and the most frequent drug-induced, immune-mediated type of thrombocytopenia. It is associated with significant mortality and morbidity if unrecognized. We describe a patient with a giant thrombus on the apical wall of the left ventricle that occurred due to HIT syndrome after anterior myocardial infarction.

Clinical and prognostic importance of XIAP and USP8 in advanced stages of non-small cell lung cancer.

PURPOSE: To investigate the relationship of the apoptosis regulators X-linked inhibitor of apoptosis (XIAP) and ubiquitin specific protease 8 (USP8) with clinical parameters, survival and response to chemotherapy in patients with advanced stages of non-small cell lung cancer (NSCLC). METHODS: The study included 34 NSCLC patients (28 females, 6 males) and 44 healthy individuals (17 males, 27 females) as a control group. XIAP and USP8 levels were determined by ELISA. RESULTS: The median serum XIAP level of the patients and the control group showed no significant difference. USP8 level was higher in patients than in controls (p<0.0001). In univariate analysis, there was no significant relationship between XIAP and USP8 serum levels and age, sex, performance status, weight loss, stage of disease, histopatological type and response to chemotherapy. Response to chemotherapy did not differ between the high and low XIAP and USP8 groups . There was no significant difference in progression- free survival (PFS) (p=0.432 and p=0.50, respectively) and overall survival (OS) (p=0.989 and p=0.90, respectively) between the low and high XIAP and USP8 groups. CONCLUSION: No relationship was found in serum XIAP and USP8 levels with clinical parameters, response to chemotherapy, PFS and OS in patients with advanced stages of NSCLC.

Percutaneous coronary intervention vs. optimal medical therapy--the other side of the coin: medication adherence.

WHAT IS KNOWN AND OBJECTIVE: Although many studies have examined medication adherence in patients with coronary artery disease (CAD), no prospective trial has compared medication adherence between patients treated with percutaneous coronary intervention (PCI) or with optimal medical therapy (OMT) in real life. This study sought to compare the adherence to evidence-based secondary preventive medications in patients with documented CAD treated with PCI and OMT, or OMT alone. METHODS: We evaluated adherence to statins, beta-blockers, and angiotensin converting enzyme inhibitors (ACEI) during a 6-month follow-up in 232 patients with documented CAD, comparing patients treated with PCI and those receiving medical therapy alone. Medication adherence was measured with reference to national reimbursement database records. RESULTS AND DISCUSSION: Of the 232 patients who survived the 6-month follow-up, the percentages of adherent patients according to prescription records (prespecified primary endpoint) were 53·6% (n = 82) in the PCI group and 33·8% (n = 27) in the OMT group (P = 0·004). Analysis of the individual medication classes revealed similar results for beta-blockers (86·0% in PCI group vs. 72·5% in OMT group, P = 0·006) and statins (64·5% in PCI group vs. 44·0% in OMT group, P = 0·003). Adherence to ACEI was also higher in the PCI group, but the difference was not statistically significant (77·6% vs. 69·3%, P = 0·17). By logistic regression analysis, belonging to the PCI group was an independent predictor of medication adherence [B = 2·20 (1·06-4·50), P = 0·03)]. WHAT IS NEW AND CONCLUSION: In the present study we demonstrated that adherence to evidence-based medication therapies in patients treated with PCI is significantly higher than in patients treated with OMT alone. Medication adherence should be followed carefully in CAD patients treated with OMT.

Sequential adjuvant docetaxel and anthracycline chemotherapy for node positive breast cancers: a retrospective study.

PURPOSE: Anthracyclines and taxanes are the most active agents in the adjuvant treatment of breast cancer (BC). They can be used simultaneously or sequentially. The optimal schedule and duration for their administration is unknown. We analyzed the efficacy of sequential adjuvant anthracycline and docetaxel administration in node positive BC patients. METHODS: Node positive BC patients (N=539) from 6 medical oncology centers in Turkey who received sequential adjuvant anthracycline-based regimens and taxane chemotherapy were included in this study between 2006 - 2010. One-hundred and thirty-eight (25%) patients received 3 cycles of anthracycline-based chemotherapy followed by 3 cycles of docetaxel (3+3) and 401 (75%) patients received 4 cycles of anthracycline-based chemotherapy followed by 4 cycles of docetaxel (4+4). Prognostic factors analyzed were estrogen receptor (ER), progesterone receptor (PR), HER2, tumor grade, and nodal status in relation to disease free survival (DFS) and HER2 status in relation to overall survival (OS). RESULTS: The patient median age was 48 years (range 18-79). Most common grade 3-4 toxicities were neutropenia, mucositis and arthralgia. No treatment-related toxic deaths were seen. With a median follow up of 26 months (range 1-115) 61 (11.3%) recurrences and 11 (2%) deaths were registered. Three-year DFS was 81% and OS 96% for all patients. There was no statistically significant difference between 3+3 and 4+4 groups in terms of survival (3-year DFS 88% and 79% [p=0.28] and OS 97% and 95% [p=0.60), respectively). CONCLUSION: Sequential chemotherapy with 4+4 cycles of anthracycline and docetaxel every 3 weeks is an acceptable regimen for adjuvant treatment of node positive BC patients. Duration of chemotherapy should be planned depending on prognostic factors. In this study there was no difference between 3+3 and 4+4 groups in DFS and OS despite the presence of good prognostic factors in the 3+3 group.

Phonon bottleneck in graphene-based Josephson junctions at millikelvin temperatures.

We examine the nature of the transitions between the normal and superconducting branches in superconductor-graphene-superconductor Josephson junctions. We attribute the hysteresis between the switching (superconducting to normal) and retrapping (normal to superconducting) transitions to electron overheating. In particular, we demonstrate that the retrapping current corresponds to the critical current at an elevated temperature, where the heating is caused by the retrapping current itself. The superconducting gap in the leads suppresses the hot electron outflow, allowing us to further study electron thermalization by phonons at low temperatures (T≲1 K). The relationship between the applied power and the electron temperature was found to be P∝T3, which we argue is consistent with cooling due to electron-phonon interactions.

Universal features of counting statistics of thermal and quantum phase slips in nanosize superconducting circuits.

We perform measurements of phase-slip-induced switching current events on different types of superconducting weak links and systematically study statistical properties of the switching current distributions. We employ two types of devices in which a weak link is formed either by a superconducting nanowire or by a graphene flake subject to proximity effect. We demonstrate that independently of the nature of the weak link, higher moments of the distribution take universal values. In particular, the third moment (skewness) of the distribution is close to -1 both in thermal and quantum regimes. The fourth moment (kurtosis) also takes a universal value close to 5. The discovered universality of skewness and kurtosis is confirmed by an analytical model. Our numerical analysis shows that introduction of extraneous noise into the system leads to significant deviations from the universal values. We suggest using the discovered universality of higher moments as a robust tool for checking against undesirable effects on noise in various types of measurements.

Trabectedin in advanced soft tissue sarcoma: case series.

The prognosis of advanced soft tissue sarcomas (STS) is poor. The median overall survival (OS) is 6 months in unresectable and metastatic STS that progress after treatment with anthracyclines and ifosfamide. Trabectedin is an alkylating agent, effective in advanced STS, especially in leiomyosarcoma and liposarcoma. In the present study, the effectiveness and safety of trabectedin was retrospectively evaluated in 8 unresectable and metastatic STS patients. Their median age was 47 years. The median progression free survival (PFS) was 3.75 months and the median OS 15 months in relapse or progression after anthracyclines and/or ifosfamide. Toxicities were mainly hematologic. In the present study, trabectedin showed efficacy in different histological subtypes of sarcomas like liposarcoma and leiomyosarcoma.

Long term experience in high grade glial tumors with temozolomide.

PURPOSE: Temozolomide is used concurrently with radiotherapy (RT) and as consolidation therapy in high grade gliomas (HGGs). In the present study we present our experience of long-term efficacy and toxicity of temozolomide in HGGs. METHODS: After surgery, temozolomide was administered at 75 mg/m(2) daily concurrently with RT, followed by 6 courses of consolidation therapy (150-200 mg/m(2) for 5 days every 28 days). RESULTS: A total of 172 patients with either glioblastoma multiforme (GBM) (n= 142; 82.6%) or anaplastic astrocytoma (AA) (n= 30; 17.4%) were studied. The objective response rate (ORR) was 42.5%, including 12 (7%) complete responses (CRs) and 61 (35.5%) partial responses (PRs). In the GBM group, median progression free survival (PFS) and overall survival (OS) were 9 and 16 months, respectively. In the AA group, median PFS and OS were 16 and 24 months, respectively. Three-year OS was 18.2% for GBM, and 39.4% for AA. In elderly patients (14.5%), median PFS and OS were 8 and 11 months respectively for both HGGs. Serious toxicities were mainly hematologic. CONCLUSION: Temozolomide is an effective agent in HGGs with favorable outcome and low toxicity profile even in advanced age.

Distribution of supercurrent switching in graphene under the proximity effect.

We study the stochastic nature of switching current in hysteretic current-voltage characteristics of superconductor-graphene-superconductor junctions. We find that the dispersion of the switching current distribution scales with temperature as σ(I) proportional to T(α(G)) with α(G) as low as 1/3. This observation is in sharp contrast to the known Josephson junction behavior where σ(I) proportional to T(α(J)) with α(J)=2/3. We propose an explanation using a generalized version of Kurkijärvi's theory for the flux stability in rf-SQUID and attribute this anomalous effect to the temperature dependence of the critical current which persists down to low temperatures.

Hypoxia inducible factor-1 alpha and carbonic anhydrase IX overexpression are associated with poor survival in breast cancer patients.

PURPOSE: Hypoxia is common in many solid tumors such as breast, head-neck, and soft tissue malignancies. Hypoxia causes overexpression of hypoxia inducible factor-1 alpha (HIF-1α) and carbonic anhydrase IX (CA IX) which are associated with unfavorable prognosis in breast cancer. In our study, we evaluated HIF-1α and CA IX expression in patients with breast cancer. METHODS: Between June 1996 and June 2008, 111 women with breast cancer were evaluated. Estrogen receptor (ER) and progesterone receptor (PR) status and Her2/ neu expression were evaluated by immunohistochemical methods. Her-2/neu expression was also assessed by FISH method when needed. Two groups were created: ER and PR positive, Her-2/neu negative (group 1, n=56); and ER and PR negative, Her-2/neu positive (group 2, n=55). HIF-1α and CA IX expressions were investigated in both groups and results were compared. In addition, we investigated the association between HIF-1α and CA IX expressions with stage, grade, lymph node metastasis, tumor size, menopause status and survival. RESULTS: Median patient age in group 1 was 52 years (range 34-77), and in group 2 47 years (range 27-83). HIF-1α expression was detected in 26 (46.4%) of group 1 and in 46 (83.6%) of group 2 patients (p=0.0001). CA IX expression was detected in 25 (46.4%) of group 1 and in 37 (67.3%) of group 2 patients (p7equals;0.0137rpar;. In group 1, median disease free survival (DFS) was 97 months and in group 2 46 months (p=0.0308). In group 1, median overall survival (OS) was 108 months and in group 2 75 months (p=0.0339). CONCLUSION: HIF-1α and CA IX overexpressions are observed more often in ER and PR negative, Her-2/neu positive breast cancer and are associated with poor survival.

Gemcitabine and cisplatin combination chemotherapy in triple negative metastatic breast cancer previously treated with a taxane/anthracycline chemotherapy; multicenter experience.

This study was aimed to establish clinical efficacy and tolerability of gemcitabine and cisplatin combination in patients with metastatic triple negative breast cancer progressing after anthracycline and taxane based chemotherapies.Thirty-three patients who were given cisplatin and gemcitabine for triple negative and metastatic breast cancer were evaluated retrospectively. A total of 141 cycles were administered with a median 4 cycles per patient. Median follow-up time was 14 months (range, 2-36 months). Objective response rate was 27.3%. Total clinical benefit of the combination was 48.4%. The estimated median progression free survival and median overall survival were 5 months and 14 months, respectively. The most common Grade 3 and 4 toxicity were neutropenia and thrombocytopenia observed in 10 (27.7%) and 9 (24.9%) patients, respectively. The combination of the gemcitabine and cisplatin after taxane/anthracycline is well tolerated and seems to be effective with acceptable toxicity profile.

Phase diffusion in graphene-based Josephson junctions.

We report on graphene-based Josephson junctions with contacts made from lead. The high transition temperature of this superconductor allows us to observe the supercurrent branch at temperatures up to ∼2 K, at which point we can detect a small, but nonzero, resistance. We attribute this resistance to the phase diffusion mechanism, which has not been yet identified in graphene. By measuring the resistance as a function of temperature and gate voltage, we can further characterize the nature of the electromagnetic environment and dissipation in our samples.

Serum granulocyte colony-stimulating factor levels in gliomas.

PURPOSE: Apart from its known effects on granulopoiesis, granulocyte-colony stimulating factor (G-CSF) is also involved in growth and progression of malignant cells. In this study we report the serum G-CSF levels and their relationship with survival in patients with glial cell tumors. METHODS: Serum G-CSF levels of 17 patients (10 male, 7 female, median age 55 years, range 19-75), with histologically proven glial cell tumors and of 17 sex- and age-matched healthy controls were assayed by enzyme-linked immunosorbent assay (ELISA). RESULTS: All patients were treated with radiotherapy and concomitant temozolomide, followed by temozolomide alone. Eight patients were treated with carboplatin plus cyclophosphamide combination as second-line chemotherapy. The median follow-up was 21 months (4-42). The median OS was 36 months (95% CI, 15.7-56.4). Serum G-CSF levels in glioma patients and healthy controls were 44.14 ± 18.89 pg/ ml and 28.84±15.65 pg/ml, respectively (p=0.027). There was no significant correlation between survival time and serum G-CSF levels (r=0.384; p=0.217). CONCLUSION: Serum G-CSF levels were high in glioma patients compared with healthy controls and they may be involved in tumor progression, but the G-CSF role in prognosis was not clarified. Further studies with larger numbers of patients must be conducted to elucidate the role of G-CSF in glial cell tumors.