This exploratory study evaluated the safety/efficacy of nintedanib or sunitinib as first-line therapy in patients with advanced renal cell carcinoma (RCC).−1 once daily ). Primary endpoint was progression-free survival (PFS) at 9 months. P-values reported are descriptive only; the study was not powered for such comparisons.Ninety-six patients were randomised (2:1) to either nintedanib (200 mg twice daily) or sunitinib . Median PFS was 8.4 months in each group (hazard ratio (HR), 1.12; 95% confidence interval (CI): 0.70–1.80; P=0.64). Median overall survival was 20.4 and 21.2 months for nintedanib and sunitinib, respectively . Overall incidence of any grade adverse events (AEs) was comparable (90.6% vs 93.8%); AEs grade ⩾3 were lower with nintedanib than sunitinib (48.4% vs 59.4%). Nintedanib was associated with lower incidences of some AEs typical of antiangiogenic tyrosine kinase inhibitors (TKIs): hypertension, hypothyroidism, hand–foot syndrome, cardiac disorders and haematological abnormalities.Progression-free survival at 9 months was comparable between nintedanib and sunitinib (43.1% In patients with advanced RCC, nintedanib has promising efficacy and similar tolerability to sunitinib, and a manageable safety profile with fewer TKI-associated AEs. NintedaClinical experience with nintedanib monotherapy in RCC has been reported from a Phase I study of patients with various solid tumour types, including metastatic RCC  evaluated the safety and efficacy of nintedanib as first-line therapy for previously untreated patients with advanced RCC. The study design included co-primary safety and efficacy objectives. The co-primary safety data for the nintedanib group have been reported previously . Adults (age ⩾18 years) with a histologically confirmed diagnosis of unresectable or metastatic RCC with clear cell component, and measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 were eligible for inclusion  Harmonized Tripartite Guideline on Good Clinical Research Practice (1997) and with the principles of the Declaration of Helsinki.vs sunitinib ahead of potential Phase III clinical evaluation. However, this comparison was exploratory, and the study was not powered to allow a formal statistical comparison between the treatment arms.This randomised, multicentre, open-label, parallel-group Phase II study evaluated the safety and efficacy of nintedanib. The primary objective was to investigate the cardiac safety of nintedanib in terms of its effect on patients' QT interval, as reported previously (−1) once daily in 6-week cycles (4 weeks of sunitinib followed by 2 weeks without treatment). Randomisation was performed using a telephone Interactive Voice/Web-based Randomization System (IVRS/IWRS). Randomisation was stratified according to each patient's Memorial Sloan-Kettering Cancer Center (MSKCC) risk score (favourable/intermediate vs poor) (vs no). Patients were treated until disease progression (according to RECIST version 1.1), death, unacceptable AEs, or withdrawal of consent for any other reasons. Two dose-reduction levels were available for patients experiencing drug-related AEs: 150 and 100 mg bid for nintedanib and 37.5 and 25 mg/kg once daily for sunitinib. Dose reductions in the nintedanib group were indicated for patients with diarrhoea grade 2 for >7 days despite optimal management; vomiting grade ⩾2; elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels grade ⩾2 together with elevated bilirubin levels grade >1; or any other AE grade 3/4. Dose reductions in the sunitinib group were indicated for patients with any AE grade 3/4. Treatment was discontinued if a third event occurred despite dose reductions. Where appropriate, patients were permitted to receive full supportive care, including transfusion of blood and blood products, and treatment with antibiotics, antiemetics, antidiarrhoeal agents, analgesics, erythropoietin or bisphosphonates. Additional chemo-, immuno-, radio- or hormone therapy was not permitted during the trial (with the exception of hormone replacement therapy). Palliative radiotherapy to control symptoms was permitted although radiated target lesions were no longer to be considered as target lesions.Given the exploratory nature of the treatment comparison, patients were randomised in a 2 : 1 ratio to receive either oral nintedanib (200 mg bid) continuously in 4-week cycles or oral sunitinib  would be >10 ms  in favour of the alternative hypothesis that the two means were equivalent, when the expected mean difference was 2.70 ms with a SD of 19 ms  with the exception of baseline characteristics and AEs, for which version SAS version 9.4 was used.The primary efficacy endpoint of 9-month PFS was derived from Kaplan–Meier (KM) estimates in order to take account of patients who were censored before 9 months  and compared between treatments using a normal approximation test. OR was assessed according to RECIST version 1.1. The number and percentage of responders was summarised along with the duration of response; the objective response rate was compared using a logistic regression model stratified by Motzer risk score and previous surgery for RCC. Additional efficacy endpoints of TTP, TTF and OS were evaluated using KM analysis; OS was calculated as the time to death in days. All patients were followed up for survival until death due to any cause, withdrawal of consent or 3 years following enrolment of the final subject. Progression-free survival and OS were analysed using a stratified log-rank test while HRs and CIs for PFS, TTP, TTF and OS were obtained from stratified Cox proportional hazards models; in both cases, the stratification factors were Motzer risk score and previous surgery for RCC. n=64) or sunitinib (n=32) (vs 93.8%), and had undergone prior nephrectomy (87.5% in both groups). The number of metastatic sites showed a similar pattern between the groups, but a higher proportion of patients in the nintedanib vs the sunitinib group had metastases in the bone (43.8% (n/N=28/64) vs 25.0% (8/32)) or liver (34.4% (22/64) vs 25.0% (8/32)).Of the 113 patients enrolled between 11 March 2010 and 14 December 2010, 99 were randomised and 96 received either nintedanib (b (n=32) ; Table 1As of the analysis cut-off date of 21 February 2014, 93.8% and 90.6% of patients treated with nintedanib and sunitinib, respectively, had discontinued treatment, whereas the remaining four (6.3%) and three (9.4%) patients in the nintedanib and sunitinib groups, respectively, were continuing treatment. Treatment discontinuation due to progressive disease occurred in 71.9% of patients, and treatment discontinuation owing to the other AEs occurred in 12.5% of patients, in both groups. The mean  duration of study treatment exposure was 348  and 391  days for patients in the nintedanib and sunitinib groups, respectively. Dose reductions occurred in 25.0% of patients in each treatment group, with a mean time to first dose reduction of 209 days with nintedanib and 186 days with sunitinib.P=0.85 for the intergroup comparison). Post hoc sub-analysis revealed PFS at 9 months for patients with liver or bone metastases at baseline to be 29.0% and 43.9%, respectively, with nintedanib and 14.3% and 25.0% with sunitinib. Median investigator-assessed PFS in the overall treatment groups was 8.4 months in each group . Progression-free survival was comparable in both treatment groups for patients with bone metastases at baseline. In the overall treatment groups, median TTP was 8.5 months  and median TTF was 8.4 months . At the cut-off date for this 3-year analysis, disease progression was recorded for 49 (76.6%) and 25 (78.1%) patients in the nintedanib and sunitinib groups, respectively, and treatment failure for 58 (90.6%) and 28 (87.5%) patients, respectively.The primary efficacy endpoint of PFS at 9 months was 43.1% for patients treated with nintedanib and 45.2% for sunitinib, derived from KM estimates . For patients with bone metastases at baseline, median OS was 18.3 months with nintedanib and 11.0 months with sunitinib . Post-study anticancer therapy was more common in the nintedanib group (39.1% vs 25.0% vs sunitinib group received interferon (14.1% vs 3.1%).At the cut-off date for the 3-year analysis, 42 (65.6%) and 21 patients (65.6%) in the nintedanib and sunitinib groups, respectively, had died. Median OS was 20.4 and 21.2 months for patients treated with nintedanib and sunitinib, respectively, with an HR of 0.92 , AST (any grade: 9.4% vs 0%) and ALT(7.8% vs 0%). Adverse events reported more frequently by patients receiving sunitinib vs nintedanib were: stomatitis, hand–foot syndrome (HFS), dyspepsia, anaemia, hypertension, hypothyroidism, dyspnoea and increased lipases.The most common AEs of any grade reported with nintedanib were diarrhoea, nausea and fatigue . Adversevs 15.6%) and hypothyroidism (3.1% vs 15.6%) were lower in the nintedanib arm than the sunitinib arm. There were no recorded events of gastrointestinal (GI) perforation in either group  in the nintedanib patients . Haematovs 6.3% with sunitinib), stomatitis (0.0% vs 9.4%), fatigue (0.0% vs 6.3%) and lethargy (0.0% vs 6.3%). Discontinuations due to AEs occurred in 17.2% and 15.6% of patients treated with nintedanib and sunitinib, respectively. Adverse events leading to death occurred for one patient in the nintedanib group  and one in the sunitinib group (ascites), which were not considered by the investigator to be drug-related.The most frequent AEs (⩾5%) leading to dose reduction in either group were diarrhoea , serious AEs (46% vs 56%), AEs leading to dose reductions (19% vs 59%) and drug discontinuation , nausea (37.5% vs 34.4%) and fatigue (25.0% vs 25.0%); however, the majority of these AEs were grade 1 or 2, and the incidence of grade ⩾3 events for nintedanib was comparable to that for sunitinib. The rate of patients with AEs of increased GGT, ALT and AST liver enzymes was higher with nintedanib than with sunitinib, while AEs of increased lipases were higher with sunitinib than for nintedanib.In the current study, the most frequent any-grade AEs associated with nintedanib Although treatment with antiangiogenic TKIs has been associated with certain specific AEs, including, bleeding, GI perforation and thromboembolism, nintedanib showed only moderate frequencies of hypertension, hypothyroidism and any cardiac AEs and there were no signs and symptoms for HFS, stomatitis or any haematological laboratory abnormalities. HypertenAs previously reported, treatment with nintedanib in this study was not associated with QT prolongation  inhibitor (Previously reported data from this Phase II study demonstrated that there was no prolongation of the QTcF interval with nintedanib (


Genetic disorders enter the differential diagnosis of common neurologic diseases, but their overall prevalence is not known. We set out to determine their minimum prevalence.Meta-analysis of epidemiologic data gathered from the same geographic region in the North of England.Monogenic neurologic disorders affect at least 90.9/100,000 , or 1 in 1,100 of the population in Northern England.As a group, neurogenetic disorders are not rare. These findings have implications for clinical service delivery. The possibility of a highly penetrant mutation in a single gene enters the differential diagnosis of the most common neurologic disorders. If the inherited disorder presents late in life, or has a reduced penetrance, then there may be no affected relatives, so the absence of a family history does not preclude a genetic diagnosis. The widespread availability of inexpensive DNA tests has made it easier than ever to reach a molecular diagnosis in a patient with a suspected neurogenetic disorder, but the overall prevalence of these diseases has not been established. Herein, we present the results of a systematic review of neurogenetic disorders in the North of England, where the stable population has provided an ideal substrate for genetic epidemiology.We reviewed the reported prevalence of neurogenetic disorders, here defined as neurologic conditions known to be caused by highly penetrant mutations in a single gene . We did not include data on common neurologic conditions, such as Alzheimer disease, Parkinson disease, motor neuron disease , or inherited dystonias, in which only a minority of cases are caused by a single highly penetrant gene defect, although their likely contribution is discussed later in the article.Neurology® Web site at Neurology.org) for the precise census date in each study.2 Exact 95% confidence intervals (CIs) were calculated by the Clopper-Pearson method.A systematic literature review was undertaken by searching PubMed (MEDLINE) listings from January 1966 to April 2015 for relevant articles using the following terms: “ataxia,” “neuropathy,” “muscle disease,” “myopathy,” “dystrophy,” “Huntington,” “mitochondrial,” “optic atrophy,” or “hereditary spastic paraparesis” combined with the terms “epidemiology,” “prevalence,” or “incidence.” There was no language restriction. The final reference list was generated on the basis of relevance to the topics covered in this review. Priority was given to studies based on a molecular genetic diagnosis rather than those based on clinical or biochemical criteria alone. Articles containing disease prevalence statistics for the North of England  was established. The 5 main conditions represented in the population were myotonic dystrophy with a point prevalence of 10.6/100,000 (95% CI 9.6–11.6), dystrophinopathies at 8.5/100,000 (95% CI 7.6–9.4), facioscapulohumeral muscular dystrophy of 3.9/100,000 (95% CI 3.3–4.7), limb-girdle muscular dystrophy 2.3/100,000 (95% CI 1.8–2.9), and spinal muscular atrophy 1.9/100,000 (95% CI 1.4–2.4). Twelve further muscle disorders made up the remaining diagnoses including congenital muscular dystrophy with a point prevalence of 0.90/100,000 (95% CI 0.60–1.3) and 4 patients had X-linked Emery-Dreifuss muscular dystrophy giving a point prevalence of 0.13 (95% CI 0.04–0.34).3The point prevalence of all causes of genetic muscle disease was determined by Norwood et al.GNE (glucosamine [UDP-N-acetyl]-2-epimerase/N-acetylmannosamine kinase) myopathy, a rare distal myopathy with inclusion bodies estimated under the category of “distal myopathies,”3 was recently assessed separately in a Northern England cohort.4 Cases were identified from referral records to the Newcastle MRC Neuromuscular GNE diagnostic service, also based in the Northern Genetic Service. Genetics testing became available in 2010, after which the center received 87 referrals—64% from England, 13% Scotland, 14% from Northern Ireland, and the remaining referrals from abroad. Twenty-six cases of GNE myopathy were identified, 7 of these from England , 10 from Scotland, 8 from Northern Ireland, and 1 from the Republic of Ireland. Using these population estimates, a point prevalence of GNE myopathy in Northern England can be calculated as 1/million (95% CI 0.0–2.9) and for the UK as 0.4/million (95% CI 0.0–0.6).The prevalence of 5 The authors calculated the point prevalence of Charcot-Marie-Tooth (CMT) disease and hereditary neuropathy with liability to pressure palsy (HNPP) in a Northern England cohort using 3 databases, identifying cases using clinical, molecular diagnostic, and electrophysiologic criteria. From these, 352 individuals from 275 families were identified with a clinical diagnosis of CMT disease or HNPP. A minimum prevalence of CMT disease in the Northern region was estimated at 9.8/100,000 (95% CI 8.7–11.0) and for HNPP at 2.0/100,000 (95% CI 1.5–2.5), giving a combined minimum prevalence of 11.8/100,000 (95% CI 10.6–13.1).The most recent UK epidemiologic study of inherited neuropathies was published in 2012.SCA6 and SCA17 mutations, which both cause autosomal dominant cerebellar ataxia (ADCA). The first of these evaluated the prevalence of SCA6 mutations,6 which lead to an adult-onset progressive syndrome of ataxia, dysarthria, and nystagmus. Twenty-six cases heterozygous for the CAG repeats were identified from 16 genealogically distinct families. Using their data, a minimum prevalence of ADCA due to SCA6 can be estimated as 1.3/100,000 (95% CI 1.0–1.8) and in adults aged 45 years or older as 3.2/100,000 (95% CI 2.1–4.3). Because SCA6 mutations account for approximately 20% of ADCA in the region, the minimum prevalence of ADCA in the general population can be calculated as 5.2/100,000 (95% CI 4.3–6.1). The same group conducted a further study assessing the prevalence of SCA17,7 a dominantly inherited ataxia with extrapyramidal features and dementia presenting with a Huntington disease (HD)-like phenotype. Ninety families with suspected HD and 192 families with undiagnosed ataxia were included and screened for SCA17 mutations. Two of the 192 patients with undiagnosed ataxia, but none of the HD-like patients, were found to have (CAG/CAA)n expansions larger than the control range. Using these data, a minimum prevalence of SCA17 was estimated as 0.12/100,000 (95% CI 0.00–0.35). There were no UK studies specifically studying the prevalence of autosomal recessive ataxia, apart from one focused on SPG7 in North East England,8 which reported a prevalence of 0.80/100,000 (95% CI 0.00–0.13).Two studies in the North of England region calculated point prevalence of 9 Patients older than 21 years with a diagnosis of HD were included (n = 1136), and prevalence rates were calculated annually between 1990 and 2010. The prevalence of HD increased considerably between with this period, with a prevalence of 5.4/100,000 (95% CI 3.8–7.5) in 1990 up to a prevalence of 12.3/100,000 (95% CI 11.2–13.5) in 2010. These increased rates over time were predominantly represented in patients older than 60 years, whereby a prevalence in the 60 to 69 age group of 12.6/100,000 (95% CI 9.1–17.1) in 1990 rose to 24.2/100,000 (95% CI 21.1–27.5) in 2010 and in the 70+ group a prevalence of 7.2/100,000 (95% CI 4.8–10.4) in 1990 rose to 15.6/100,000 (95% CI 13.2–18.3) in 2010. Results were further analyzed on a regional basis showing that the North East of England and Scotland had the highest prevalence rates  while the lowest rates were found in London .The prevalence of HD in a UK cohort was estimated using the UK's General Practice research database, the world's largest computerized database of primary care medical records.10 and subsequently revised,12 based on referrals to a national diagnostic service for rare mitochondrial diseases in Newcastle upon Tyne in the North of England. The minimum prevalence of mitochondrial disease was established through molecular genetics testing for mitochondrial DNA (mtDNA) point mutations and deletions, and nuclear-genetic causes of mitochondrial disease in adults .12 Both adults and children were included to establish those at risk of mitochondrial disease. By excluding mtDNA mutations that cause Leber hereditary optic neuropathy , the minimum prevalence of non-LHON mitochondrial disease mutations in the population was calculated as 7.8/100,000 (95% CI 6.8–9.0) and the minimum prevalence of non-LHON mitochondrial disease as 7.6/100,000 (95% CI 6.5–8.9).The prevalence of mitochondrial disease was initially estimated in 2000,The 2 principal inherited optic neuropathies are LHON and autosomal dominant optic atrophy (DOA).12 Within this population, the prevalence of LHON was calculated as 3.7/100,000 (95% CI 2.9–4.6), while the prevalence of mtDNA LHON mutations, representing those “at risk” within the population, was 4.4/100,000 (95% CI 3.7–5.3).The prevalence of LHON was established through the prospective mtDNA genetic testing of patients with unexplained visual failure or suspected LHON in the Northern Genetic Service over a 21-year period (January 1990 to May 2011).13 Seventy-six patients from 22 families were identified with a clinical diagnosis of DOA, and OPA1 gene sequencing was performed on this group. Those found to be negative for this were further screened for OPA1 rearrangements and OPA3 mutations. The majority  of families with DOA carried OPA1 mutations while OPA1 rearrangements were only found in one family and no OPA3 mutations were detected in the study cohort. The calculated point prevalence estimate from this data for clinically determined DOA was 2.9/100,000 (95% CI 2.3–3.5) with the point prevalence of molecularly confirmed OPA1-positive DOA as 2.1/100,000 (95% CI 1.6–2.7). A recent update from the same group included a further 8 OPA1-positive and 5 OPA1-negative families resulting in a revised point prevalence estimate for DOA of 4.1/100,000 (95% CI 3.7–4.5).14The same center previously established the prevalence of DOA using North of England neurogenetic and ophthalmology clinical databases.SPG7 who were identified through their ataxic presentation and were included in the ataxia section above.We found no published UK epidemiologic data on the prevalence of HSP. We identified cases in the North of England using the Northern Genetics Service database to identify patients with suspected and genetically confirmed HSP. All patients had brain and spinal cord imaging to exclude a structural or inflammatory cause for the spastic paraparesis, and all had normal CSF examination. From a population of 2.61 million (mid-2013 estimate) in the North East region, 176 individual cases from 55 genealogically distinct families with clinical HSP were identified. Of this group, 74 cases (44.3%) had a confirmed genetic diagnosis giving a minimum point prevalence of confirmed HSP of 2.8/100,000 (95% CI 2.2–3.6). This did not include patients with 15 Second, some of the studies did not incorporate comprehensive genetic testing, raising the possibility that some of the cases were misdiagnosed as a noninherited disorder because there was no family history, and missed altogether. Family history is not a reliable guide to monogenic disease because a positive family history depends on the degree of relative affected,16 and even high penetrance mutations frequently present without a family history.17 Finally, it is also important to note that here we describe the results of several different studies performed at different time points. Most, but not all, of the studies were performed in the same geographic region but had subtly different forms of case ascertainment and encompassed different age groups  were not obtainable for our region but can be estimated from a study in South Wales, UK, a region with a stable population and similar demographic.20 From a group of 76 cases with late-onset cerebellar ataxia identified from general practice, hospital and health authority databases, as well as through personal notification from consultant neurologists, 4 were classified as ARCA, giving a prevalence estimate of 0.53/100,000 (95% CI 0–1.38). We note, when comparing these data with the worldwide review,19 the prevalence estimate for ARCAs represents the lower end of a worldwide range spanning from 0.1 to 7.2/100,000. As noted by the authors of the Welsh study,20 this is likely attributable to methodologic limitations in case ascertainment as well as the challenge of classifying patients with an undetermined family history. It was further restricted in considering only “late-onset” cerebellar ataxia (symptom onset at age 18 years or older), which is likely to significantly underestimate the overall prevalence of ARCA. In a similar way, estimates of the prevalence of mitochondrial disorders12 did not include affected pediatric cases. In the age group younger than 16 years, the minimum prevalence of mitochondrial disorders has been estimate at 5.0/100,000 (95% CI 4.0–6.2),21 indicating that, for these conditions, our quoted figures provide an underestimate. Likewise, with the almost exponential increase in disease gene discovery, the number of “single gene” neurogenetic disorders is on the increase,22 further emphasizing that the figures we report here are likely to be a conservative underestimate.Could our results be an overestimate? This is unlikely because most of the studies we included were performed in the North of England, which has a well-defined outbred stable population of largely white European extraction.23), Parkinson disease , motor neuron disease , and DYT1 dystonia , the combined overall minimum prevalence of neurogenetic disorders increases to ∼234/100,000, or at least 1 in 423 of the UK population. This figure does not include sporadic neurodegenerative diseases with a complex genetic architecture involving many different genetic loci, such as APOE, which has a moderately strong influence on the risk of developing Alzheimer disease. It also cannot include genetic forms of neurodegenerative disease due to hitherto unknown genes. This is important to recognize, given the recent unexpected finding that hexanucleotide repeat expansions in C9ORF72 cause a substantial proportion of cases of ALS and other neurodegenerative diseases.29 For these reasons, even the prevalence of 1 in 423 is likely to be an underestimate.We deliberately did not include genetic forms of common neurodegenerative diseases in our review because of the difficulty in diagnosing inherited forms of the disorder, which may be clinically indistinguishable from sporadic cases. However, using UK prevalence data for the principal neurodegenerative disorders Alzheimer disease (UK prevalence 1,100/100,000, of which ∼110/100,000 [∼1%] are monogenic30 and with an aging population, these figures are likely to increase. Moreover, a UK neurologist will have on average 80 patients with a neurogenetic disorder within their referral area.31 The majority of the disorders discussed here have no treatment and cause progressive disability, often over several decades. The effect on families and medical and social services will be substantial. Second, our estimates do not account for the impact of the genetic diagnoses on at-risk family members, who may request genetic counseling and prenatal and preimplantation diagnosis to prevent recurrence. Finally, with the mainstream introduction of exome and whole genome sequencing in clinical practice, the number of unexpected predictive tests will also increase, placing even greater strain on clinical service provision, and emphasizing the need to develop treatments that can slow down or prevent these disorders.These findings have major implications. For example, the average UK primary care practice will have at least 16 patients with single gene neurogenetic disorders on their records


Purpose. Triple-negative breast cancer (TNBC) is defined by the loss of expression of ER, PR, and Her2neu expressions. The aim of this study was to examine the expression of the EGFR, CK5, and Ki-67 among triple-negative breast cancer cases and to correlate the expression of the basal markers with the clinicopathological prognostic parameters. Materials and Methods. Thirty-six female patients with TNBC based on ER, PR, and the HER2neu negativities were studied by immunohistochemistry for EGFR, CK5, and Ki-67 expression. Statistical analysis was done using the SPSS software version 20. Results. The mean and median ages were 45.18 years and 46.70 years, respectively. Infiltrating ductal carcinoma NOS was the predominant histopathological type (29/36 [80.6%]). The commonest histological grade was grade 2 (17/36 [47.2%]). Tumour necrosis was seen in 16/36 (44.4%) patients. Infiltrative margins were shown in 69.44% (25/36) cases. Ki-67 was positive in 80.56% (29/36) cases, 61.11% (22/36) were CK5-positive, and 86.11% (31/36) were EGFR-positive. The only significant positive association observed was between the CK5 and histological grade (P < 0.05). Conclusion. CK5 shows a statistically significantly correlation with TNBC histological grade. The majority of the specimens show EGFR expression. Therefore TNBCs could potentially benefit from EGFR-targeted therapeutic strategies. The antibody clones which were used were for the estrogen receptor , the progesterone receptor , Her2neu , EGFR , CK5 , and Ki-67 . All antibodies are ready to use. After bringing the section to water, antigen retrieval was done by boiling the section in either citrate buffer  or EDTA buffer . For EGFR, antigen retrieval was done by heat induced epitope retrieval. Tissue controls were used for IHC assays. The section was washed with deionized water for 2 to 3 minutes followed by peroxide blocking for 30 minutes using 4% hydrogen peroxide in methanol; then the section was washed by Tris buffer (pH 7.5) for 2 to 3 minutes. Background blocking was done by horseradish peroxidase (HRP) for 10 minutes followed by primary antibody overnight. Next day wash with Tris buffer for 2 to 3 minutes was followed by secondary antibody (Biotin) for 30 minutes; then again wash with Tris buffer and tertiary antibody (Streptavidin) was applied for 30 minutes. Wash with Tris buffer twice and D.A.B. was applied for 10 to 15 minutes and reaction was stopped by using distilled water. Counterstain Hematoxylin was applied for 2 minutes and washed with distilled water.The tissue sections were used for all the immunohistochemical analyses . In a majority of the patients, the tumour size was between 2.1 and 5 cm  followed by <2 cm . The commonest histological grade was grade 2  followed by grade 3  and grade 1  . In gradBreast cancer is a biologically heterogeneous disease and clinical outcomes of patients with the same diagnostic and clinical prognostic profiles are markedly different possibly due to molecularly distinct diseases into group into classes based mainly on morphology . Breast


No adverse events were implant-related and none required device removal. Three patients (2.9%) experienced procedure-related complications. The overall adjacent fracture rate up to 1 year after surgery was 2.9%. The SpineJack procedure is an effective, low-risk procedure for patients with traumatic VCF allowing a fast and sustained improvement in quality of life over 1 year after surgery.This prospective, consecutive, multicentre observational registry aimed to confirm the safety and clinical performance of the SpineJack system for the treatment of vertebral compression fractures (VCF) of traumatic origin. We enrolled 103 patients (median age: 61.6 years) with 108 VCF due to trauma, or traumatic VCF with associated osteoporosis. Primary outcome was back pain intensity (VAS). Secondary outcomes were Oswestry Disability Index (ODI), EuroQol-VAS, and analgesic consumption. 48 hours after surgery, a median relative decrease in pain intensity of 81.5% was observed associated with a significant reduction in analgesic intake. Improvements in disability (91.3% decrease in ODI score) and in quality of life (increase 21.1% of EQ-VAS score) were obtained 3 months after surgery. All results were maintained at 12 months. A reduction in the kyphotic angulation was observed postoperatively (−5.4 ± 6.3°;  Vertebroplasty and kyphoplasty are minimally invasive accepted procedures in the therapy of painful osteoporotic compression fractures –5. Both Balloon kyphoplasty has been used for the treatment of fresh traumatic fractures , 7. Seve “Patients age > 18 years presenting a mobile spinal fracture that may result from trauma  and/or osteoporosis (IFU), with a minimum internal pedicle diameter > 5.8 mm to allow placement of the device.” In order to ensure overall homogeneity and relevance of the results, we decided to include patients with acute fresh traumatic VCF, a traumatic fracture being defined as a fracture of the VB resulting from a high or low-energy impact occurring during a traumatic event. In this registry, data of interest  were collected without requiring the physician to perform additional investigations. As surgeons must follow their own standard care practice follow-up, the patients analyzed might have no complete datasets at 3 or 12 month.Between October 2011 and December 2012, 103 patients from 14 centers throughout Europe were enrolled in this prospective, consecutive, multicenter observational registry. All of them met the indication as listed on the products' labelling, namely,Local Ethics Committee submissions were performed as per local regulations requirements. All patients gave their informed consent in accordance with ISO 14155 and the Declaration of Helsinki.The 5 mm diameter SpineJack was implanted using a percutaneous or minimally invasive posterior surgical approach using surgical tools supplied with the device . With thA simple mechanism locks the implant into the desired position as controlled by the physician. Once the desired expansion obtained, the device was left in place inside the restored vertebra and polymethylmethacrylate (PMMA) bone cement was injected into and around the implant. Regular fluoroscopic controls throughout the operative procedure ensured correct implantation . PostopeThe main outcome was pain evolution over time as assessed using a 10-cm visual analogue scale (VAS) where 0 is no pain and 10 is the worst imaginable pain. Secondary outcomes included analgesic intake, functional capacity   and qualX-rays were performed following routine clinical practice at each study site  and performed as per described in the protocol imaging. All available X-ray images were collected to assess the evolution of vertebral kyphotic angle.Quantitative radiographic analysis was done on X-ray by an independent, qualified core lab using the validated FXA software developed by ACES Ing. -GmbH, Filderstadt, Germany . This inStatistical analyses were performed at the 0.05 global significance level using two-sided tests . Within-group tests were used to test evolution between visits. Depending on the normality of the distribution, Wilcoxon's test or Student's test for pairwise comparisons were used.Assuming a mean evolution of pain from baseline to 12 months of 5 (SD 2.5) with a precision of 0.6 and a relative precision of 12%, 66 evaluable patients were required.Considering a lost-to-follow-up rate of 20%, 80 patients were to be included.2. Eight patients (7.8%) presented with previous traumatic VCF; 5 of them had been already treated surgically at a level different from the one treated in this study. For 77 patients (74.8%), a previous treatment had been administered: bed rest (65.1%), bracing (9.7%), and walking aid (4.9%). A total of 108 VCF were treated . Most fractures were due to high energy trauma  and the remaining were traumatic fractures with associated osteoporosis . As osteoporosis evaluation by DEXA was not performed in routine practice, it was not requested by the protocol. Osteoporotic patients were already known by the investigator, but patients with severe osteoporosis were excluded from the study. Median time from trauma to surgery was 6 days for pure traumatic fractures and 12 days in osteoporotic patients. The Magerl classification [The 103 patients analyzed  had a median age of 61.6 years, with a median BMI of 25.8 kg/mfication  showed tMean duration of hospital stay was 4.3 ± 3.5 days. Prolonged hospitalization (27 days) was observed in one obese, osteoporotic patient treated out of IFU indications at the time of this registry as he presented with a severe A3.3 fracture. He underwent decompression and posterior instrumentation after dislocation of posterior wall at Day 4 (procedure-related); cut-out of screws in L3 occurred at 3 months, but the patient refused revision surgery. Mean follow-up period of the 103 patients was 13.1 ± 3 months. Twenty-three (23) patients withdrew from the study before the 12-month visit: 2 patients died due to renal failure and acute respiratory syndrome, respectively; 11 patients refused medical follow-up because of complete relief of their symptoms; 1 patient was withdrawn because of severe aggravation of a preexisting osteoporosis at inclusion, with four consecutive spontaneous fractures after surgery on Day 19, Day 49 and two fractures on Day 86; 9 patients were lost to follow-up. Flowchart of visits according to type and age of fracture is presented in All surgeries were performed by surgeons, according to their standard procedures. Most fractures (94.2%) were treated under general anesthesia, 3.9% under local anesthesia, 1% by both local and general anesthesia, and the remaining 1% by spinal anesthesia. Mean duration of general anesthesia was 79.7 ± 34.7 min; all local anesthesia lasted 60 min. Of the 108 treated vertebrae, 106 (98.1%) were treated by a percutaneous approach, while 2 (1.9%) were treated by open surgery. Mean operating time was 38.3 ± 15.1 min (range: 17–105). Mean quantity of cement injected was 6.7 mL ± 2.2 mL (range: 3.0–10.8).p < 0.001). This change corresponded to a median relative decrease in pain intensity of 81.5%. This improvement was maintained over the 12-month follow-up period. Mean changes in VAS scores versus baseline at 48 hours after surgery, 3 months, and 12 months are shown in As early as 48 hours after surgery, a significant improvement in back pain was obtained with a mean VAS score decreasing from 6.6 ± 2.6 cm at baseline to 1.4 ± 1.3 cm  or moderate (51.5%) analgesics. Two days after surgery, these percentages decreased to 1% and 5.8%, respectively. Evolution in analgesic requirement is illustrated in p < 0.001). This change corresponded to a median relative decrease of 91.3%. This improvement was maintained at 12 months. Mean changes in ODI scores at 3 months and 12 months versus baseline are shown in A marked improvement in disability was observed at 3 months with a mean ODI score decreasing from 76.2 ± 20.0 at baseline to 14.2 ± 16.6 . This change corresponded to a median relative increase in quality of life of 21.1%. A slightly further improvement was observed at 12 months. Mean changes in EQ-VAS scores at 3 months and 12 months versus baseline are shown in A clear improvement in quality of life was observed at 3 months with a mean EQ-VAS score increasing from 53.4 ± 25.4 at baseline to 71.5 ± 24.8 . Despite a lower reduction observed at 3 and 12 months, the improvement of kyphosis remained statistically significant compared to baseline . Similar results were observed for both types of fractures.A significant and immediate reduction in the kyphotic angulation was observed 48 hours after the procedure  experienced a total of 21 adverse events which are detailed in Among these adverse events, 13 serious adverse events concerning 10 patients (9.7%) were reported. Two patients died because of renal failure with lower limb vascular obliteration on Day 52 in one patient and acute respiratory syndrome at 6.8 months in the other patient.Three patients (2.9%) experienced procedure-related complications. Eight subsequent compression fractures concerning 3 osteoporotic patients were reported. The overall adjacent fracture rate up to 1 year after surgery was 2.9% (4 fractures concerning 3 out of 103 patients). The adjacent fracture rate in the osteoporotic group was 13.6% (4 fractures concerning 3 out of 22 patients).Cement leakage was shown in 43 out of 108 (39.8%) treated vertebrae with no clinical consequences. Leaks were detected by peroperative fluoroscopy (28.6% of cases), postoperative X-rays (28.6% of cases) or CT scans (42.8% of cases). inter alia of an average 4–6-week bed rest and an additional 6–12-week TLSO bracing. There is a consensus in the aims of operative treatment. Operative treatment should prevent neurologic symptoms, minimize spinal deformity and complications, allow fracture healing, and insure the best possible function.Treatment of traumatic VCF without neurological symptoms and intact posterior ligament complex is still controversial. Vaccaro et al. proposed a classification system that should be helpful for decision making . One majOperative treatment ranges from combined anteroposterior approaches to minimal invasive procedures like cement augmentation . BalloonThe study implant is designed to work as an intravertebral reduction device directing its forces in the craniocaudal direction. The technical possibilities and improved height restoration have been shown in several biomechanical studies –30. All In patients with VCF, clinical and radiological results of this minimal invasive technique have to be balanced against its complications. In the study performed by the Task Force “Wirbelsäule”  German Society of Trauma Surgery, the complication rates (recessing and nonrecessing complications) of the different procedures varied between 14.1 and 29.7% –34. CompThe present study supports the growing interest in minimally invasive techniques in the management of spinal injuries with no neurological deficit. These long-term results confirm the stability of the correction over time. The device described allows an effective, low-risk procedure for patients with vertebral fractures of traumatic origin with a significant reduction in pain and analgesic consumption achieved immediately after surgery and maintained over time. Additionally, this procedure allows a fast and sustainable improvement in quality of life. Main complications included asymptomatic cement extravasation and adjacent fractures, which were caused by the cementation technique or resulted from underlying osteoporosis but were not due to the procedure itself. One-year results from this registry are very promising and will be confirmed with the 2-year outcomes and have to be further proven by comparative randomized study results.


Infection is widespread but most prevalent among young, rural residents with fever. Rickettsia felis has been reported to be a cause of fever in sub-Saharan Africa, but this association has been poorly evaluated in Gabon. We assessed the prevalence of this bacterium among children <15 years of age in 4 areas of Gabon; the locations were in urban, semiurban, and rural areas. DNA samples from 410 febrile children and 60 afebrile children were analyzed by quantitative PCR. Overall, the prevalence of R. felis among febrile and afebrile children was 10.2% (42/410 children) and 3.3% (2/60 children), respectively. Prevalence differed among febrile children living in areas that are urban , semiurban , and rural . Furthermore, in a rural area (Fougamou), R. felis was significantly more prevalent in febrile (39.7% [23/58]) than afebrile children (5.0% [1/20]). Additional studies are needed to better understand the pathogenic role of R. felis in this part of the world. Over the past decade, reported cases of malaria and associated deaths have declined in Africa  than that in urban areas of sub-Saharan African, such as Franceville, Gabon (10%) . Written informed consent forms and questionnaires were completed by parents or legal guardians upon a child’s enrollment in the study.During April 2013–January 2014, a total of 525 children <15 years of age were recruited for the study; 465 of the children were febrile (axillary temperature >37.5°C), and 60 were afebrile (controls). Febrile children were recruited from the pediatric outpatient clinics at the 4 health care centers. The control group was recruited from children who had accompanied their sick parents to the health care centers. Children in the control group had to be free of fever for at least 1 week before study inclusion. Molecular analyses were performed on DNA extracts from blood samples from each child; blood smears, serologic testing, and culture were not done. After a child’s parent or legal guardian was interviewed, a blood sample was collected into an EDTA tube. World Health Organization guidelines for blood collection were followed, including guidelines for hand hygiene, use of sterile tubes, and skin disinfection with 70% alcohol. The International Center of Medical Research of Franceville, which has a well-trained staff with expertise in infectious diseases, performed DNA extraction by using the E.Z.N.A. Blood DNA Maxi Kit  according to the manufacturer’s protocol (R. felis DNA) and negative  controls were also systematically used for each PCR assay. All samples were screened by Rickettsia spp.–specific qPCR targeting the gltA gene and by R. felis–specific qPCR targeting the bioB, orfB, and vapB1 genes (Specific quantitative PCR (qPCR) was performed by using a CFX96 Touch Real-Time PCR Detection System . qPCR Master Mix  was prepared according to the manufacturer’s instructions; for each reaction, 15 μL of Master Mix was added to 5 μL of DNA. The quality of extracted DNA and the lack of PCR inhibitors were systematically checked by targeting a housekeeping gene, human β-actin , seasons, and geographic areas and by the participants’ sex and age. A 2-tailed p value <0.05 was considered statistically significant.Data were analyzed by using Epi Info software version 7.0.8.0 . Mantel-Haenszel χA total of 465 febrile children were recruited from Franceville (n = 80), Koulamoutou (n = 167), Lastourville (n = 155), and Fougamou (n = 63) . HoweverR. felis DNA was detected in 42 (10.2%) of 410 analyzed samples from febrile children  among children 0–1 year of age, 15.2% (16/105) among children >1– 3 years of age, 11.5% (10/87) children >3–5 years of age, 7.7% (3/39) among children >5–7 years of age, 6.7% (2/30) among children >7–9 years of age, and 0 (0/20) among children >9–15 years of age  to Koulamoutou (2.1% [3/141]) to Lastourville (11.2% [15/134]) to Fougamou (39.7% [23/58]); however, no adjustments were made when testing these pairs , in Franceville than in Fougamou , in Koulamoutou than in Lastourville , in Koulamoutou than in Fougamou , and in Lastourville than in Fougamou . Overall, the prevalence of R. felis among febrile children was significantly higher in the rural areas  than in the urban area . Among the 60 afebrile children, only 2  were positive for R. felis; the girls were 1 and 3 years of age and were from Fougamou and Franceville, respectively. In all, R. felis DNA was detected in 10.2% (42/410) of febrile children and in 3.3% (2/60) of afebrile children; this difference was not significant (p = 0.09).children . The bacs of age , panel Ase pairs , panel BR. felis DNA was detected in 23 (39.7%) of 58 febrile children at this rural location  and girls (28.6% [8/28]) did not differ significantly (p = 0.11). R. felis prevalence also did not differ significantly by age, even though prevalence was higher among 1- to 3-year-old children (R. felis DNA was detected significantly more frequently in febrile (39.7% [23/58]) than afebrile (5.0% [1/20]) children (p = 0.004).location . Prevalechildren . OverallR. felis DNA was detected in 15 (11.2%) of 134 febrile children in this rural location  was higher than that during the dry season (5.2% [3/58 children]), but the difference was not statistically significant (p = 0.05). Prevalence among boys (7.6% [6/79]) and girls (16.4% [9/55]) did not differ significantly (p = 0.17). Prevalence also did not differ significantly by age (R. felis DNA was detected in 15 (11.2%) of 134 febrile children and in 0 of 16 afebrile children; this difference was not statistically significant (p = 0.3).location . R. feliy by age . R. feliR. felis DNA was detected in 3 (2.1%) of 141 febrile children in this semiurban location (R. felis DNA was detected in 1 (1.6%) of 63 boys and in 2 (2.6%) of 78 girls (p<1); 2 of these children were 4 years of age, and 1 was 5 years of age. As stated above, no afebrile children were enrolled from Koulamoutou.location . PrevaleR. felis DNA was detected in 1 (1.3%) of 77 febrile children and in 1 (4.2%) of 24 afebrile children (p = 0.3) in this urban area  to assess the prevalence of Rickettsia spp.–specific qPCR targeting the highly conservative gltA gene and an R. felis–specific qPCR targeting the bioB, orfB, and vapB1 genes. The Rickettsia spp.–specific assay can amplify almost all Rickettsia spp., including R. conorii and R. rickettsii, but it is less sensitive than the R. felis–specific assay. When a sample in our study was positive by the Rickettsia spp.–specific qPCR, it was also positive by the R. felis qPCR. Several samples had positive results for only 2 of the 3 genes targeted by the R. felis–specific qPCR. This discrepancy might be explained by possible genetic diversity of the R. felis strains. The 3 genes used for the R. felis–specific assay are not all conservative, so it is possible that some strains have a certain degree of genetic diversity that may occasionally cause false-negative PCR results. Our results were also systematically validated by using rigorous criteria. To check the quality of each PCR run, we used negative controls  with every tenth sample, and we used 2 positive controls (R. felis DNA) per run. In addition, we required that all negative and positive controls be systematically correct  before validating each PCR run, and a sample was not considered R. felis–positive unless confirmed by at least 2 of the 4 sequences of targeted DNA. Thus, we consider our results to be valid. The fact that R. felis DNA has not been detected in samples (from febrile patients in France and Tunisia) previously analyzed in our laboratory  and increases in southern Africa countries   were previously assessed in Gabon by using standard culture methods  and rural (39.7%) areas of Gabon showed that R. felis is unequally distributed in the country. Differences in the prevalence of a possible vector or reservoir, or both, and disparate health care–associated conditions, including environmental conditions, poverty, and the availability and quality of health care facilities, between rural and urban areas may influence the distribution of R. felis in Gabon; however, these factors have not been determined. An increased prevalence of R. felis was observed during the rainy season. This same finding was described in Senegal, where the prevalence of infection in the rural areas was 24 times higher than that in urban areas of Algeria . In a rural area of Senegal (Dielmo and Ndiop), the incidence of R. felis infection has also been reported to be higher (reaching 36%) among febrile children 1–3 years of age, but the incidence was lower (0.1%) in persons >15 years of age  than afebrile (6.3%) persons  than afebrile (3.3%) children, but the difference was not statistically significant (p = 0.09). Of more interest, in rural Fougamou, the difference in prevalence was significantly higher in similarly aged children with and without fever . Therefore, the presence of R. felis in febrile and afebrile persons should not exclude that this bacterium is a cause of fever in sub-Saharan Africa.Most of the fever-associated studies conducted in Africa failed to use a control group of afebrile persons. Consequently, when a pathogen was detected in febrile patients, it was systematically and automatically considered as the cause of fever (R. felis in blood specimens from febrile patients in 2 different areas of Africa (eastern and western) (R. felis was 2.2 times higher in blood specimens from febrile persons compared with afebrile persons in Kenya (R. felis was significantly higher in febrile (15.0%) than afebrile (4.0%) persons in Senegal (R. felis infection after treatment with doxycycline (R. felis has also been observed in blood specimens from febrile patients in Asia (R. felis among febrile persons compared with healthy persons in our study led us to suspect that this microorganism plays the role of pathogen. However, the presence of the microorganism may be a cofactor or the cause of a previous event not yet determined. Another hypothesis would be that blood specimens may be contaminated by surface bacteria, including R. felis, which has been detected on the skin of healthy persons in Senegal (In 2010, independent research teams detected R. felis bacterium is widespread in Gabon, but it primarily occurs in rural areas and is most prominent during the rainy season. R. felis is also more prevalent among febrile than afebrile children in rural areas of Gabon. More studies will help to better understand the pathogenic role of R. felis in this part of the world.In summary, the


Objectives: Oral lichen planus is chronic inflammatory disease with a high prevalence in the population. This study describes the epidemiological and clinical characteristics of group of patients with oral lichen planus in the Czech Republic.Material and Methods: Data was taken from the medical records of 171 patients referred to the Oral Medicine Unit at the University Hospital in Hradec Králové with histologically confirmed clinical diagnosis of oral lichen planus in the period 2003 – 2013. The data were retrospectively reviewed. Results: Of the 171 patients, 116 (67.8%) were women and 55 (32.2%) were men. The mean age was 55.2 ± 12.4 years (range of 85.0 – 20.9). The reticular form was the most frequent 93.6% (160 pts.), desquamative gingivitis was 12.9% (22). The buccal mucosa was the site most affected 89.5% (153 pts.). The lesions were asymptomatic in 52 patients (30.4%). Extraoral lesions were observed in 20.5% (35 pts.) of the patients, skin involvement was in 16.4% (28 pts.). Smokers were 29 patients. Local treatment used 116 (67.8%), only 6 patients used systemic short tome corticoid therapy. No evidence between OLP and malignant transformation was observed. Conclusions: This retrospective study show very similar profile and clinical features of the patients with OLP as in other studies. Key words:Oral lichen planus, clinical features, extraoral manifestation. Oral lichen planus (OLP) is chronic inflammatory disorder that affects the oral mucous membrane. It is a common disease affecting 0.1% to 4% of the population . The etiP value < 0.05 was considered statistically significant.The study was approved by local Ethics Committee. The study group comprises 171 patients examined at the Oral Medicine Unit at Department of Dentistry Clinic Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Králové in the Czech Republic in the period 2003-2013 with histologically confirmed clinical diagnosis of OLP according to the diagnostic criteria of World health Organization (WHO) of 1978 modified by van der Meij et al. in 2003 . We excl-Patient´s gender and ethnic origin.A total of 171 charts of patients with confirmed diagnosis of OLP were retrospectively analyzed, of whom, 116/171 (67.8%) were women and 55/171 (32.2%) were men, giving a female to male ratio of 2.11:1. All of affected patients were white Caucasian.-Age of onset of oral lichen planus. The mean age of the patients at presentations was 55.2 ±12.4 years , with an overall range of 85.0 – 20.9 years. The highest prevalence for women was found in the age group 50-59 years , for men in the age group 60-69  . Age distribution plot is shown in figure -Systemic diseases, medication, smoking.Positive history for medication and systemic diseases was found in 117 patients (68.4%). The most prevalent systemic disorders included arterial hypertension , thyroid gland disorders , diabetes mellitus , hypercholesterolemia , other cardiovascular diseases , hypothyroidism , anxiety/depression , rheumatological diseases  and hypeurikemia . Positive allergy history was in 36/171 patients (21.1%). The medications taken by the patients are shown in figure -Chief symptoms associated with oral lichen planus.The presence of the symptoms was reported by the 109/171 patients (63.7%). Severe sustained pain occurred only in 37/171 (21.6%) patients, mild and moderate pain in 72/171 pts. (42.1%). Only 3/171 patients (3.8%) had severe pain in white forms (reticular a plaque lesions), 34/171 patients (37.0%) in red forms (erosive and erythematous lesions). Comparison of erythematous and erosive forms (red lesions) versus the others is shown in -Clinical types of oral lichen planus and distribution.The most common type was reticular form of the oral lichen planus which was observed in 160/171 (93.5%) patients. 11/171 (6.4%) patients did not show any reticula and were presented only by other clinical forms without reticula. Erosive form was the second most common type with a prevalence of 80/171 (46.8%) pts. Prevalence of the erythematous lesions was 66/171(38.6%) and plaque form was in 56/171 (32.7%) pts. Desquamative gingivitis was present in 22/171 (12.9%) pts. In all cases of desquamation, there was a combination with another form of OLP. 107/171 patients (62.6%) had combination of more types of OLP.Most of the patients  exhibited multiple sites of involvement, with the buccal mucosa being the most common location in each clinical form , followed by the tongue , gingiva and alveolar mucosa , lips . Lesions on the palate  and floor of the mouth  were uncommon. No malignant transformation was observed during the observation period.-Extraoral manifestaion:Extraoral lesions were observed in 20.5% (35/171 patients) of the patients, skin problems were in 16.4% (28/171 patients). Another 7/171 patients (4%) had genital involvement or the involvement of nails.-Treatment.Topical steroids alone were prescribed to 116/171 (67.8%) and in combination with systemic steroids to 6/171 (3.5%) of the patients. 55/171 (32.2%) patients didn´t use the drugs . In the local treatment we used dexamethasone gel, which patients applied a several times per day to the most symptomatic areas. In 61/171 (35.7%) cases we used combination dexamtehasone gel and depot form of corticosteroid intralesional.p<0.0001). Also considering systemic treatment with steroids, all 6 patients who received oral steroid therapy were from the red lesion group (p=0.02). The same is true for intralesional application of corticoids. The patients with red lesions were treated with intralesional application in 61% of cases, where only 6% of patients with white lesions required this procedure (p<0.0001). There is also an interesting fact regarding the distribution of lesions in the oral cavity. Red lesions are more frequently found on less common places especially palate and alveolar ridge . Also the recurrence of symptoms after treatment is much higher in red lesions than in white lesions . From this point of view it is clear that occurrence of red lesion is related to clinically much more aggressive behavior and need for further treatment. We have not observed any malignant transformation of OLP in our group of patients. We have to admit that the period of follow up is relatively short and it cannot be excluded that such event might occur in the future. Given the fact, that about 0.5–2% patients with longstanding oral lichen planus may develop a squamous cell carcinoma (This is as we know the first retrospective analysis of patients with OLP conducted in the east Bohemia. As all retrospective data, it has its major limitations. The biggest bias could potentially be produced by the fact, that our hospital is a tertiary care facility and there is a possibility, that not all the patients from the general practitioners are reported. In general, the results of the present study of OLP are compatible with other previous studies, but we also found some differences which are a matter for discussion. In our study the women were affected in 67.8%, representing the ratio 2.1:1. This number of affected women is similar to the one showed the other studies published by . The firarcinoma , the per


Scores higher than the proposed cut-score on SCL-90R scale were observed on depression, obsessions-compulsions, paranoid ideation, anxiety, anger-hostility, somatization, interpersonal sensitivity, and psychoticism subscales. In sum, 42.9% of our sample exhibited depressive symptomatology, 34.9% obsessive-compulsive symptoms, 29.1% somatization, 27.2% anxiety symptoms, 22.2% paranoid ideation, 19% phobic anxiety, 15.1% psychoticism, and 15.1% hostility and 11.9% presented with symptoms of interpersonal sensitivity. Mean score on AUDIT scale was 6.9 ± 7.9. 63.0% of our participants scored below cut-off and were classified as having a low level of alcohol-related problems; 24.4% scored in the range of 8–15 which is an indication of alcohol abuse whereas 12.6% scored 16 and above indicative of serious abuse/addiction. Scores on AUDIT scale were positively correlated with length of time on methadone treatment, but not with length of time on drug use or age of our participants. Positive correlations were observed among AUDIT and SCL-90R scores, namely, with global severity index score, positive symptom distress index, positive symptom total, and all primary symptom dimensions subscales except phobic anxiety. Substance abuse and dependence, especially opioid dependence, contribute significantly to the global burden of disease in Greece . AccordiApplying harm reduction policies and attempting to aid drug users who failed to benefit from abstinence “drug-free” treatment programs led to the development of the Organisation against Drugs (OKANA) in 1995, with 54 Substitution Treatment Units and a total of 9.878 persons in substitution treatment in Greece in 2012. 27.1% of individuals were in methadone and 72.9% in buprenorphine Substitution Treatment Units in 2012 . Most ofThe high prevalence of concomitant psychiatric disorders –10 and aAddiction and psychological disorders have bilateral correlation. Studies report that there are significant associations between the current measure of psychological distress on methadone maintained patients and both illegal substance use and alcohol use –20. HighSeveral other studies indicate that drug-dependent subjects with current problematic substance use and coexisting psychopathology undergoing methadone maintenance require higher methadone dosages on treatment programs –24 tend Coexisting psychopathology has a further negative influence on health-related quality of life  and it iStudies include psychiatric disorders as causes of addicts' rehabilitation failure –34. AccoThe present study aims at investigating the presence of psychopathological symptoms and alcohol use patterns among drug addicts receiving methadone maintenance treatment since relevant research in the Greek population has not extensively studied such issues.130 randomly selected individuals from a population list of 300 methadone maintenance patients treated in the 4th Substitution Unit of OKANA in Athens agreed to complete Symptoms Checklist 90-Revised (SCL-90R) and Alcohol Use Disorders Identification Test (AUDIT) self-report scales, during one year. Research Randomizer  was usedParticipants were informed that all study information would be kept confidential, participation (or lack thereof) would not affect their treatment, and participation was voluntary, based on verbal informed consent. All interviews were conducted by personnel separate from clinic staff in a private room at the outpatient clinic. Ethics approval was not necessary given that the nonexperimental design did not expose subjects to risks. Additionally, subjects were informed of the study's goals and procedures. Data were recorded and handled anonymously.The SCL-90R is a 90-item self-report symptom inventory designed to reflect psychological symptom patterns of psychiatric and medical patients. Each item of the questionnaire is rated on a 5-point scale of distress from 0 (none) to 4 (extreme). The SCL-90R consists of the following nine primary symptom dimensions: somatization , obsessions-compulsions , interpersonal sensitivity , depression , anxiety , hostility , phobic anxiety , paranoid ideation , and psychoticism  –46.α values for the nine symptom dimensions ranged from a low of 0.77 for psychoticism to a high of 0.90 for depression. Additionally, the few validity studies of the SCL-90R demonstrate that this scale has equal validity compared with other self-report inventories. The SCL-90R has been standardized and used in the Greek population and its reliability (Cronbach's α) for the total of the items is 0.97 [T scores have a normal mean of 50 and a standard deviation of 10. The cut-off level indicating clinically significant problems was set to T ≥ 70 [The SCL-90 takes between 12 and 20 min to complete. With regard to its reliability, the internal consistency coefficient  is 0.97 –50. The  is 0.97 . T scoreo T ≥ 70 , 53. TheThe inventory was completed in the presence of psychologists who provided clarifications when necessary.The Alcohol Use Disorders Identification Test (AUDIT) consists of 10 questions: three questions on use, four on dependence, and three questions about problems related to harmful alcohol use. Each response has a score ranging from 0 to 4. A total score of >8 is an indication of alcohol abuse and a score of >15 indicates serious abuse/addiction whilst a score between 8 and 10 is an indication of being at risk, according to the authors –57.t-test was run to determine whether AUDIT score in recruited subjects was significantly different to Greek general population, defined as AUDIT score of 3.79 [t-test was used to test for significance of difference between groups based on gender and employment status. One-way ANOVA was used to test for significance of difference among groups based on marital status. Pearson's correlation was used to measure the bivariate associations among continuous variables. To determine the best predictors of the dependent variable “AUDIT” we performed a stepwise multiple regression analysis with length of time on methadone treatment and (from the SCL-90R) whether or not there was psychopathology present as independent variables. Statistical significance was set at P < 0.05 (two-tailed). All analyses were carried out using the statistical package SPSS version 19.All variables are assessed with the use of descriptive statistics and values are expressed as the mean ± standard deviation for continuous variables. Kolmogorov-Smirnov test served as a goodness of fit test indicating the normality of the distribution of our data. A one-sample  of 3.79 . IndepenOf the 130 participants 98 (75.4%) were males and 32 (24.6%) females. 77 participants (59.23%) reported being single, 25 (19.23%) divorced, 23 (17.7%) married, and 5 (3.8%) widowed. 80 participants (61.5%) reported having no children whereas 50 (38.5%) of them reported having at least one. The vast majority of our sample stated being unemployed, 106 (81.53%), whereas only 24 (18.46%) reported having a job. Mean age of our sample was 43.34 ± 8.11, mean years of education were 10.34 ± 3.02, and mean length of time on drug use was 26.07 ± 7.93 years and on methadone treatment 6.69 ± 4.18 years.In almost all subscales of the SCL-90R mean scores were >1 . Highestt(126) = 4.421, and P < 0.0005) (Mean AUDIT score of our sampled population (6.91 ± 7.96) was higher than the Greek general population AUDIT score of 3.79 , a stati 0.0005) .Only 6.4% of our sample scored within normal range on all nine factors of the SCL-90R scale. On the contrary, 42.9% of our participants reported symptoms over the cut-score on depressive symptomatology, whereas 34.9% presented with obsessions-compulsions symptoms .24.4% of our sample scored in the range of 8–15 on AUDIT scale as an indication of alcohol abuse, and 12.6% scored >15 indicating serious abuse/addiction. 3.9% scored in the range of 16–19 indicating a high level of alcohol problems, and 8.7% scored >20 indicating possible dependence .P < 0.05) and had less mean length of time on drug use (23.5 versus 27.0 P < 0.05)  .N = 50) scored higher on depression (2.2 versus 1.8 P < 0.05) and somatization (1.6 versus 1.3 P < 0.05) compared to others without parental responsibilities.Drug addicts of our sample on parenthood (P < 0.05) and paranoid ideation  were noted among employed individuals of our sample (N = 24). Divorced or separated subjects exhibited higher rates on AUDIT scale versus married ones .Lower levels for anxiety  in the dependent variable. The final regression model showed that from all variables entered into the equation “somatization subscale from SCL-90R” and “years on methadone treatment” were significant predictors of “scores on AUDIT scale” . “Somatization subscale from SCL-90R” explained 9% of the variance and “years on methadone treatment” accounted for an additional 4% of the variance of AUDIT scores (β coefficient 0.36 P = 0.023).Stepwise multiple regression analysis was conducted to identify the best predictors of the dependent variable “scores on AUDIT scale” among the independent variables “scores on subscales of SCL-90R” and “length of time on methadone treatment” and to examine their contribution to the variation (expressed as The results from the present study are largely consistent with findings from other studies , 59 thatYet, unlike other reports , 64, ourThe fact that the largest proportion of our sample reported being unmarried or divorced and without any children highlights some of the social consequences of addiction, affecting their family environment . EarlierFurther studies , 59 rankCoexisting psychopathology substantially affects quality of life , 73 and The relationship between addictive disorders and other forms of psychopathology has long been debated since it may involve such a close interaction at neurobiological levels between predisposing factors, addictive processes, and addictive consequences that the attempt to clinically distinguish between addictive-related and independent psychopathological symptoms may turn out to be little more than an inconclusive theoretical exercise. This is the reason that the application of the classic model of psychiatric comorbidity in the field of addiction has been the target of criticism owing to the difficulty of disentangling supposedly independent psychiatric symptoms and syndromes from the core psychopathology of addiction –77.Another important issue is the prevalence of alcohol abuse and dependence which is increasingly acknowledged , 78–82 iIn the predictive model of our study, 9% of the variance of scores on AUDIT was attributed to somatization subscale from SCL-90R and years on methadone treatment explained an additional 4% of the variance. Somatization in drug addicts is distinguished by a number of somatic and anxious elements, which are usually a feature of opiate withdrawal. In the late 90s it was proposed that alcohol abuse during methadone maintenance treatment might result from inadequate methadone dose  or that Results from other studies , 84, 85 In sum, our study indicates the presence of high rates of psychopathological symptoms along with problematic alcohol use among drug addicts that hinders the positive outcome of therapeutic efforts in substitution programs. This should be taken into account during the therapeutic treatment process, so as to implement the most effective and most intensive interventions –94.The limited number of participants compared with the total number of drug addicts treated in all Substitution Units of our country may compromise the generalizability of our findings and additional extended surveys are required to conclude more accurately.It is also important to emphasize that the results of the present study evidence psychiatric symptomatology and not psychiatric diagnosis among drug addicts on methadone maintenance treatment owing to lack of necessary diagnostic tools but beyond this owing primarily to lack of information about concurrent substance abuse among participants leading them to experience relevant intoxication or withdrawal symptoms which might have affected their answers in applied questionnaires.High levels of psychological distress along with high prevalence of alcohol-related problems are evidenced among drug addicts on Methadone Substitution Treatment Programs, in Greece. Moreover the fact that our research was conducted in a time of economic crisis, with limited work opportunities, provides a further explanation for the high unemployment rates in our sample. Targeting ancillary psychosocial services –97 which


In 2013, a resurgence of measles occurred in Beijing, China. The outbreaks occurred among adults and were associated with endemic genotype H1 and imported genotype D8 viruses. Migrant workers were disproportionately represented in the outbreaks; thus, vaccinating such workers against measles may be an effective strategy toward the elimination of this disease. Serum and throat swab samples were collected from 97.3% and 96.8% of the suspected case-patients, respectively. The samples were tested for measles IgM by using the VIRION SERION ELISA Measles Virus IgM test  or for measles virus genes by using a real-time reverse transcription PCR kit . Of the 1,233 samples, 558 were positive, and 5 additional cases were confirmed by epidemiologic linkage. Thus, a total of 563 measles cases in Beijing were confirmed in 2013; this number represents a 6-fold increase from the number of cases in 2012.The number of reported cases was highest during March–May. Most cases occurred among a floating population of adult migrant workers and permanent adult residents and their children ; 67.3% o>15 years of age and defined as adult patients. The median age of the adult patients was 23.5 years (range 15.0–70.0 years). Vaccination history was unknown for 87.6% (324/370) of the adults. Among the 65 patients in the age group targeted for measles vaccination, 36.9% (24) had not been vaccinated because of contraindications.Among the persons with confirmed measles, 22.8% (128) were <8 months of age, 11.5% (65) were 8 months–14 years of age, and 65.7% (370) were We used real-time reverse transcription PCR–positive samples to try to isolate and genotype virus from 468 of the 563 positive samples. Genomic sequencing and phylogenetic analyses were based on N450 nucleotide sequences, as previously described .Measles viruses within a transmission chain had identical or nearly identical N450 sequences  reference sequences.


Enterococcus faecium and Pseudomonas aeruginosa are part of the ESCAPE pathogens, which have the ability to “escape” the currently available therapeutic options. For these germs alternatives are needed, as is the case of bacteriophage treatment.Pseudomonas spp. and Enterococcus spp. isolated and stored from patients treated in the Adults II ward of the National Institute for Infectious Diseases “Prof. Dr. Matei Balş”, Romania during April 2013 – July 2014.In this study we used a bacteriophage testing kit containing 4 types of Georgian products: PYO, INTESTI  and PHAGYO, PHAGESTI  to test the strains of Enterococcus  and 9 strains of Pseudomonas aeruginosa. The strains had been isolated mostly from cutaneous wounds (3/9) for Enterococcus spp. and from urine (5/9) for P. aeruginosa. For Enterococcus spp. the rate of susceptibility to PYO phages was 33.33% (3/9), to INTESTI 55.56% (5/9), to PHAGYO 44.44% (4/9) and to PHAGESTI 0% (0/9). We tested the Enterococcus ATTC, and it displayed susceptibility to PYO, INTESTI and PHAGYO.We identified 9 strains of Pseudomonas spp. the rate of susceptibility to PYO phages was of 66.67% (6/9), INTESTI 88.89% (8/9), PHAGYO 55.56% (5/9), PHAGESTI 44.44% (4/9). We tested the Pseudomonas ATTC, and it displayed susceptibility to all the bacteriophage products tested.For Enterococcus spp. we identified a statistically significant correlation between susceptibility to ampicillin vs. PYO phages (p=0.034) and vs. INTESTI phages (p=0.024). For P. aeruginosa a correlation was identified between susceptibility to ceftazidime and PYO phages (p=0.029).Performing the ANOVA test for Enterococcus spp., their activity against it was similar to that of INTESTI. PYO and PHAGYO showed activity on Enterococcus ATCC, too. For P. aeruginosa the rate of susceptibility was very high for phages, and quite low for almost all antibiotics tested. We intend to develop further studies for testing a higher number of strains and for assessing a potential synergy for co-administration of antibiotics and bacteriophages.Despite the fact that PYO and PHAGYO do not contain phages for


Dickeya dianthicola is one of the causative agents of soft rot and blackleg diseases, which are currently identified in European countries in a wide range of crops. Here, we report the draft genome sequence of D. dianthicola strain RNS04.9, which was isolated from a potato plant with blackleg symptoms in 2004. Pectobacterium and Dickeya are causative agents of soft rot and blackleg diseases that affect a wide range of field crops and ornamental plants . Sequence reads were trimmed based on quality (threshold 0.05), and minimum size (above 60 nucleotides). Scaffolding of the contig was processed using SSPACE basic version 2.0  comprised 35 contigs, the 11 remaining ones being included in the second scaffold . The in silico closure of some gaps was carried out by mapping (read length of 0.9 and similarity of 0.95) the mate-pair reads on each of the 5-kbp contig ends. Following this treatment, 36 gaps were elucidated. Then, the collected reads were used for de novo local assembling (read length of 0.5 and similarity of 0.8). This allowed the generation of one scaffold with 10 gaps, from 28 bp to 3,271 bp in size. Some gaps were resolved by Sanger sequencing of PCR amplicons.Genomic DNA of sion 2.0 . A totalD. dianthicola strain RNS04.9 revealed a circular chromosome consisting of 4,721,506 bp and comprised 7 contigs. No plasmid was detected. The G+C content was ~56%. Gene prediction using the RAST version 4.0 automated pipeline (Dickeya spp. genomes and draft genomes that are available in public databases.At the end, the genome sequence of pipeline , 23 reveAPVF00000000. The version described in this paper is the first version, APVF01000000.This draft genome sequence has been deposited at DDBJ/EMBL/GenBank under the accession number


Breast cancer is the most common malignancy tumor amongst Malagasy women registered at the pathology unit of the “Institut Pasteur de Madagascar”. In Madagascar, there is no laboratory practicing hormone receptors' status on these tumors. Until now no study about hormone receptors' status of Malagasy women with invasive breast cancer was performed. So it will be the first study talking about this topic. The aim of this study was to determine hormone receptors' status in Malagasy women with invasive breast cancer.This retrospective and descriptive study was based on patients' medical files from 2009 to 2011. It included all invasive breast cancer diagnosed in Malagasy women at the pathology laboratory located at the “Institut Pasteur de Madagascar”, in Antananarivo. Along this period this laboratory has sent paraffin blocks of invasive breast carcinoma in two pathological laboratories in France.We collected 77 cases of invasive breast cancer along this period. The mean age was 48.8 +/- 10.7, ranging from 26 years to 70 years. There were 46.8 % (n = 36) women with progesterone receptor positive (PR+), 53.2 % (n = 41) with progesterone receptor negative (PR-). For the estrogen receptor, 61.0 % (n = 47) were positive and 36.4 % (n = 28) were negative. ER+/PR+ represented 44.2 % (n = 34); ER-/PR- 33.8 % (n = 26); ER +/ PR- 16.8 % (n = 13); ER-/PR+ and ER-/PR- represented respectively 2.6 % (n = 2).Patients in our study had more important rate of ER-, PR- and a less important rate of ER+/PR+, PR+. These results suggest that more study related to Hormone Receptor profile should be conducted in Malagasy women with breast cancer. Breast cancer ranks first amongst cancers seen at the “Institut Pasteur de Madagascar” (IPM), either for women or for all locations combined . In MadaData collection: Patients were recruited according to the following steps:Patients registered in the cancer registry of the IPM from 2009 to 2011; Blocks were sent and analyzed in France; After Hematoxylin Erythrosine Safran study, block used for the immunohistochemical study were selected, it has been practiced ABC peroxidase, DAB revelation with Automate Ventana Benchmark in presence of the following antibodies: E-cadherin; Ki-67; Estrogen Receptor (ER); Progesteron Receptor (PR); Oncoprotein cerB2.Patients with immunohistochemistry results of at least one HR were retained; Patients with PR or ER staining more than 1 % were considered positive . The results were registered on EPI6-INFO version 3.5.3 of the Center Diseases Control and Prevention, Atlanta before analysis.Inclusion criteria: Breast tumors diagnosed in IPM during the study period ; Axillary lymph nodes sampling or other specimens with diagnosis of malignant invasive breast cancer; Blocks sent to IPM by other pathological laboratory for immunohistochemistry study.Non inclusion criteria: Blocks sent to France after December 31st, 2011; Axillary lymph nodes sample and tumors which were analyzed without malignant histology; Non-invasive breast tumors; Biopsy of permeation nodules or any other samples outside the mammary gland.Exclusion criteria: Patients whose specimens have been revised twice (first time for a biopsy and a second time for a mastectomy). They were taken into account for an exam; blocks sent to the IPM without pathology report or clinical information; Specimen in which the result of immunohistochemistry studies were not contributory; cases for which data were unavailable.We have collected 77 files of patients in our study during 3 years. The mean age was 48.8 years +/-10.7, ranging from 26 years to 70 years with a median age of 47 years. The mean age was respectively for patients with ER-, ER+, and ER- 47.7 years old, 50.7 and 47.5 without statistic differences . For the PR status, mean age was 46.8 years for PR- and 51.1 years for PR+; there was no statistic differences . The most frequent histological type was the ductal invasive carcinoma with 87.0 % (n= 67) .For all population: There were 46.8 % (n = 36) women with PR+, 53.2 % (n = 41) with PR-. For the ER, 61.0 % (n = 47) were ER+ and 36.4 % (n = 28) were ER-. We were unable to have ER status for two women. ER+/PR+ represented 44.2 % (n = 34); ER-/PR- 33.8 % (n = 26); ER+/PR- 16.8 % (n = 13); ER-/PR+ and ER-/PR- represented respectively 2.6 % (n = 2) of this population ; one of them was ER+ and PR+; the others (n = 6) were ER- and PR-. The HR status of the first patient was ER+/PR+ and the others were all ER-/PR-.For patients 35-50 years old: They represented 46.7 % (n = 36) of our population. There were 47.2 % (n = 17) women with PR+, 52.8 % (n = 19) with PR-. For the ER, 61.1 % (n = 22) were ER+ and 36.1 % (n = 13) were ER-. We were unable to have ER status for one patient for this category of age. ER+/PR+ represented 44.4 % (n= 16); ER-/PR- 33.3 % (n = 12); ER+/PR- 16.7 % (n = 6); ER-/PR+ and ER-/PR– represented respectively 2.8 % and 2,8 % (n = 1).For patients > 50 years old: This age group represented 44.1 % (n = 34) of our population. There were 52.9 % (n = 18) women with PR+, 47.1 % (n= 16) with PR-. For the ER, 70.6 % (n = 24) were ER+ and 26.5 % (n = 9) were ER-. We were unable to have ER status for one patient. ER+/PR+ represented 50.0 % (n= 17); ER-/PR- 23.5 % (n = 8); ER+/PR- 20.6 % (n = 7); ER-/PR+ and ER-/PR- represented respectively 2.9 % (n = 1) and 3.0 % (n = 1) of this age group.Analysis: Statistical analysis was performed between age and positivity of HR, but it was not possible because of insufficient patient number.Our study suggests that Malagasy women with breast cancer have more important rate of ER-, PR-; and less important rate of ER+/PR+ and PR+. This retrospective study we have conducted is the first document analyzing the status of Malagasy women with invasive breast cancer towards HR. The first explanation is that until now,, there officially is no laboratory in the Malagasy territory which practices HRS in this type of tumor while breast cancer ranks first in terms of frequency of cancers diagnosed at the IPM . This poThe hormonal profile of a population may change over time as it has been reported in the United States by Li et al. between 1992 and 1998. Indeed, the rate of ER+ and PR+ respectively rose from 75.4 % to 77.5 % and 65.0 % to 67.7 % between the two periods. The authors then discussed the role of hormonal factors .According to Huang, several risk factors are accompanied by an increased risk of breast cancer with ER+ and PR+ . These sIn contrast, the risk of breast cancer ER- and PR- increases if there is a family history of breast or ovarian cancer in the first degree, also there is no role of hormone in these cases . Our stuER+ is more frequent among women that live in developed countries than those who live in developing countries , 6. Dey Malagasy low socioeconomic level could explain the fact that there were fewer ER+/PR+ amongst women in our population. During our study period, according to the Malagasy National Institute of Statistics, the rate of Madagascar's real economic growth was negative (- 4.6 %) . The rurOur study highlighted a rate of 43 % of profile ER+/PR+ against 52 % in McGuire's series and 53 % in the Carolina Breast Cancer Study , 4. ProfFor patients with ER-/PR-, Korean women living in America have the more important percentage with 36.1 %. In practice, for this patients group, there is no indication of hormone therapy. Particularly in the adjuvant setting, it has been recognized for a long time that there is no need to prescribe hormone therapy in patients who do not have HR+ . AccordiRegarding hormonal profiles ER-/PR+, in our study, the rate of patient was very low; we saw only 2 of 77 patients nearly 3 % with this hormonal profile. This profile type represented 6 % of the study population in the McGuire's series and 8 % for the Carolina Breast Cancer Study , 4. In fAbout the proportion of HR+, the rate of ER+ is more important than the rate of PR+. Our series has a proportion of HR+ rate considerably lower than in other studies. Indeed, the rate of ER+ was 60.87 % against 75 % for Nadji, 69 % for McGuire and 64 % for the Carolina Breast Cancer Study. About PR+ rate, the difference is more pronounced. In our case, this rate was 46 % against 55 %, 58 % and 61 % respectively in the series of Nadji, McGuire and the Carolina Breast Cancer Study , 11, 4. These findings suggest that important studies should be conducted among Malagasy women with invasive breast cancer with consideration of their age. Here, hormone exposure and post-menopausal status of these patients could explain the high rate of HR+ among women more than 50 years .


TM ) allows feedback of the delivered flow rate from the targeted minimal alveolar concentration (MAC). Sedation is usually monitored by the RASS (Richmond Assessment Sedation Score).In ICU sedation, use of inhalated gaz has interesting qualities, but remains limited due to lack of available and appropriate material. a new medical device  in sedated patients.TM system. RASS was evaluated after 15 min of stability after changing the MAC. Statistical analysis was performed using STATA, p < 0.05 was considered significant.This prospective, interventional study was approved by the appropriate Institutional Review Board  and conducted in a 16-bed ICU. For each patient, the sevoflurane MAC were increased to 0.1 MAC every 30 minutes from MAC 0 until MAC 0.8 then reduced with the same steps. Sevoflurane was administered with the MirusThirty patients were included: 11 women and 19 men, median age was 57 years; 63% of patients were postoperatively, median IGSII was 29.7 and SOFA 5.6. Compared to MAC 0, RASS decreased significantly from MAC 0.1 (p < 0.001) then stabilized from MAC 0.6. From MAC 0.2, a significant correlation was noted between Bispectral index (BIS) and sevoflurane dose, and between the BIS and RASS. For a target of RASS -5, effective concentrations (EC) of sevoflurane were MAC 0.6 for EC50 and MAC 0.8 for EC95.TM system allows stable concentrations of sevoflurane and was well correlated to the targeted level of sedation. EC50 and EC95 can be expressed from RASS -1 until RASS -5.This study found a correlation between the RASS and also the FeSevo or MAC of sevoflurane. The decrease in the RASS was well correlated with the increase in the concentration of sevoflurane and decreased BIS. Sedation with inhalated sevoflurane administered by the Mirus


Background. We investigated the predictive value of morning blood pressure surge (MBPS) on the development of microalbuminuria in normotensive adults with a recent diagnosis of type 2 diabetes. Methods. Prospective assessments of 24-hour ambulatory blood pressure monitoring and urinary albumin excretion were performed in 377 adult patients. Multivariate-adjusted Cox regression models were used to assess hazard ratios (HRs) between baseline and changes over follow-up in MBPS and the risk of microalbuminuria. The MBPS was calculated as follows: mean systolic BP during the 2 hours after awakening minus mean systolic BP during the 1 hour that included the lowest sleep BP. Results. After a mean follow-up of 6.5 years, microalbuminuria developed in 102 patients. An increase in MBPB during follow-up was associated with an increased risk of microalbuminuria. Compared to individuals in the lowest tertile (−0.67 ± 1.10 mmHg), the HR and 95% CI for microalbuminuria in those in the highest tertile of change (24.86 ± 6.92 mmHg) during follow-up were 17.41 (95% CI 6.26–48.42); p for trend <0.001. Mean SD MBPS significantly increased in those who developed microalbuminuria from a mean [SD] of 10.6 [1.4] to 36.8 [7.1], p < 0.001. Conclusion. An increase in MBPS is associated with the risk of microalbuminuria in normotensive adult patients with type 2 diabetes.  Normoal102 patients that developed microalbuminuria had a significant increase in MBPS over time (from 10.9 ± 1.4 to 35.3 ± 9.2 mmHg), while the MBSP did not significantly change in those who remained normoalbuminuric over time  Figure .Lastly, proliferative retinopathy developed in 18 subjects , but none of the 18 subjects had clinical evidence of neuropathy.Hypertension is certainly a major determinant of microangiopathy in diabetes, but the relationship between hypertension and microalbuminuria in diabetes is complex. Hypertension and microalbuminuria often coexist in diabetic patients, and reducing blood pressure reduces microalbuminuria in type 1 diabetes . HoweverEarly documentation of an increase in morning pressure might warrant the use of agents such as angiotensin-converting enzyme inhibitors or angiotensin II-receptor blockers in a patient with type 2 diabetes. Documentation of normal morning blood pressure, on the other hand, might suggest that there is no need for early therapeutic interventions other than those designed to provide optimal glycemic control.What Is New? We for the first time evidenced that an increase in blood pressure during morning period, detected by ambulatory blood pressure monitoring, preceded the development of microalbuminuria in newly diagnosed type 2 diabetes. In contrast, in subjects in whom microalbuminuria did not develop during a follow-up period of more than five years, neither nighttime, daytime, nor morning blood pressure increased significantly.What Is Relevant? The evaluation of the blood pressure circadian rhythm at an early stage of type 2 diabetes would provide the best basis for choosing therapies designed to prevent the progression to microalbuminuria. Early documentation of an increase in morning pressure might warrant the use of agents such as angiotensin-converting enzyme inhibitors or angiotensin II-receptor blockers in a patient with type 2 diabetes. Summary. An increase in morning systolic blood pressure is associated with the risk of microalbuminuria in normotensive adult patients with type 2 diabetes.


Code systems are the emergency call and management systems for rapid response in healthcare institutions. The main aim of these systems is to provide common institutional understanding of what is necessary to be done immediately at the time of an event. Code Blue (CB), which is used throughout the world and was described in the 2008 service quality standards of Turkey, defines the necessary emergency intervention in cases of respiratory or cardiac arrest. This study aimed to evaluate the clinical and application data of patients for whom a CB call was made between 2009 and 2013.After approval of local ethics committee, retrospective examination was made of CB forms. The age and gender of the patient, diagnosis, department to which admitted, time of CB call, reason for CB, whether or not CB was appropriate, whether or not CPR was applied, duration of CPR if applied, APACHE II and PRISM scores and predicted mortality were recorded from the hospital automated record system and the CB form. Patients who refused treatment or who could not reach the necessary parameters for the calculation of APACHE II and PRISM scores were excluded.P < 0.01). There was no statistically significant relationship between the duration of CPR and age (P >0.05). The overall mean time taken to reach the patient was 102.71 ± 22.47 seconds, which reduced to 93.64 ± 19.91 seconds in 2013. The APACHE II-PRISM scores and mortality rates were low in the cases of erroneous CB (P < 0.05).From CB calls for a total of 1,195 patients over the 5-year period, 1,035 (86.6%) were evaluated. The rate of erroneous CB was 36.9%. Patients comprised 413 (39.9%) females and 622 (60.1%) males with a mean age of 59.73 ± 23.13 years . The distribution of total cases over the 5 years (2009 to 2013) was 15.5%, 25.2%, 26.5%, 19% and 13.8% respectively. Distribution according to clinic was emergency internal (37.5%), internal (16.5%) and emergency surgical (9.5%). Clinical diagnosis was cardiac 28.8%, neurological 15.6% and end-stage cancer 13.5%. A total 19.9% of the patients were those discharged from intensive care. The total survival rate was 59.6%. The duration of CPR in survivors was statistically longer than in nonsurvivors (The time taken to reach patients conformed with the global standard mean 2 to 3 minutes . The rat