Αρχειοθήκη ιστολογίου

Δευτέρα 28 Δεκεμβρίου 2015

SARC009: Phase 2 study of dasatinib in patients with previously treated, high-grade, advanced sarcoma

BACKGROUND

Dasatinib exhibited activity in preclinical models of sarcoma. The Sarcoma Alliance for Research through Collaboration (SARC) conducted a multicenter, phase 2 trial of dasatinib in patients with advanced sarcoma.

METHODS

Patients received dasatinib twice daily. The primary objective was to estimate the clinical benefit rate (CBR) (complete response or partial response within 6 months or stable disease duration of ≥6 months) with a target of ≥25%. Patients were enrolled into 1 of 7 different cohorts and assessed by imaging every 8 weeks using Choi criteria tumor response and a Bayesian hierarchical design. For each subtype, enrollment was stopped after a minimum of 9 patients were treated if there was a <1% chance the CBR was ≥25%.

RESULTS

A total of 200 patients were enrolled. Accrual was stopped early in 5 cohorts because of low CBR. The leiomyosarcoma (LMS) and undifferentiated pleomorphic sarcoma (UPS) cohorts fully accrued and 6 of 47 and 8 of 42 evaluable patients, respectively, exhibited clinical benefit. The probability that the CBR was ≥25% in the LMS and UPS cohorts was 0.008 and 0.10, respectively. The median progression-free survival ranged from 0.9 months in patients with rhabdomyosarcoma to 2.2 months in patients with LMS. The median overall survival was 8.6 months. The most frequent adverse events were constitutional, gastrointestinal, and respiratory, and 36% of patients required dose reduction for toxicity. Serious adverse events attributed to therapy occurred in 11% of patients.

CONCLUSIONS

Dasatinib may have activity in patients with UPS but is inactive as a single agent in the other sarcoma subtypes included herein. The Bayesian design allowed for the early termination of accrual in 5 subtypes because of lack of drug activity. Cancer 2015. © 2015 American Cancer Society.



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Identification of patient subgroups with markedly disparate rates of MYCN amplification in neuroblastoma: A report from the International Neuroblastoma Risk Group project

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BACKGROUND

MYCN gene amplification (MNA) is a hallmark of aggressive neuroblastoma. This study was performed to determine univariate and multivariate predictors of tumor MNA.

METHODS

Data from the International Neuroblastoma Risk Group were analyzed for a subset of 7102 patients with known MYCN status. Chi-square testing and logistic regression were used to identify univariate and multivariate predictors of MYCN status. Recursive partitioning was used to identify groups of patients with maximal differences in rates of MNA.

RESULTS

All clinical features (age ≥ 18 months, high ferritin levels, high lactate dehydrogenase [LDH] levels, International Neuroblastoma Staging System stage 4, and adrenal sites) and pathological/biological features (DNA index ≤ 1, high mitosis-karyorrhexis index [MKI], undifferentiated/poorly differentiated grade, unfavorable histology according to the International Neuroblastoma Pathology Classification, and segmental chromosomal aberrations [SCAs]) were significantly associated with MNA. LDH (odds ratio [OR], 8.4; P < .001) and chromosomal 1p loss of heterozygosity (OR, 19.8; P < .001) were the clinical and biological variables, respectively, most strongly associated with MNA. In logistic regression, all variables except chromosome 17q aberration and pooled SCAs were independently predictive of MNA. Recursive partitioning identified subgroups with disparate rates of MNA, including subgroups with 85.7% MNA (patients with high LDH levels who had poorly differentiated adrenal tumors with chromosome 1p deletion) and 0.6% MNA (localized tumors having hyperdiploidy and low MKIs and lacking chromosome 1p aberrations).

CONCLUSIONS

MNA is strongly associated with other clinical and biological variables in neuroblastoma. Recursive partitioning has identified subgroups of neuroblastoma patients with highly disparate rates of MNA. These findings can be used to inform investigations of molecular mechanisms of MNA. Cancer 2015. © 2015 American Cancer Society.



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Oncolytic reovirus in combination with chemotherapy in metastatic or recurrent non–small cell lung cancer patients with KRAS-activated tumors

BACKGROUND

The type 3 Dearing reovirus (Reolysin) is a naturally occurring virus that preferentially infects and causes oncolysis in tumor cells with a Ras-activated pathway. It induces host immunity and cell cycle arrest and acts synergistically with cytotoxic agents.

METHODS

This study evaluated Reolysin combined with paclitaxel and carboplatin in patients with metastatic/recurrent KRAS-mutated or epidermal growth factor receptor (EGFR)–mutated/amplified non–small cell lung cancer.

RESULTS

Thirty-seven patients were treated. Molecular alterations included 20 KRAS mutations, 10 EGFR amplifications, 3 EGFR mutations, and 4 BRAF-V600E mutations. In total, 242 cycles (median, 4; range, 1-47) were completed. The initial doses were area under the curve (AUC) 6 mg/mL/min for carboplatin, 200 mg/m2 for paclitaxel on day 1, and 3 × 1010 50% tissue culture infective dose for Reolysin on days 1 to 5 of each 21-day cycle. Because of diarrhea and febrile neutropenia (in the first 2 patients), subsequent doses were reduced to 175 mg/m2 for paclitaxel and AUC 5 mg/mL/min for carboplatin. Toxicities included fatigue, diarrhea, nausea/vomiting, neutropenia, arthralgia/myalgia, anorexia, and electrolyte abnormalities. Response Evaluation Criteria in Solid Tumors 1.0 responses included the following: partial response for 11 patients, stable disease (SD) for 20 patients, progressive disease for 4 patients, and not evaluable for 2 patients (objective response rate, 31%; 90% 1-sided lower confidence interval, 21%). Four SD patients had >40% positron emission tomography standardized uptake value reductions. The median progression-free survival, median overall survival, and 12-month overall survival rate were 4 months, 13.1 months, and 57%, respectively. Seven patients were alive after a median follow-up of 34.2 months; they included 2 patients without disease progression at 37 and 50 months.

CONCLUSIONS

Reolysin in combination with paclitaxel and carboplatin was well tolerated. The observed response rate suggests a benefit of the reovirus for chemotherapy. A follow-up randomized study is recommended. The proportion of patients surviving longer than 2 years (30%) suggests a second/third-line treatment effect or possibly the triggering of an immune response after tumor reovirus infiltration. Cancer 2015. © 2015 American Cancer Society.



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Disparities in the use of screening magnetic resonance imaging of the breast in community practice by race, ethnicity, and socioeconomic status

BACKGROUND

Uptake of breast magnetic resonance imaging (MRI) coupled with breast cancer risk assessment offers the opportunity to tailor the benefits and harms of screening strategies for women with differing cancer risks. Despite the potential benefits, there is also concern for worsening population-based health disparities.

METHODS

Among 316,172 women aged 35 to 69 years from 5 Breast Cancer Surveillance Consortium registries (2007-2012), the authors examined 617,723 negative screening mammograms and 1047 screening MRIs. They examined the relative risks (RRs) of MRI use by women with a <20% lifetime breast cancer risk and RR in the absence of MRI use by women with a ≥20% lifetime risk.

RESULTS

Among women with a <20% lifetime risk of breast cancer, non-Hispanic white women were found to be 62% more likely than nonwhite women to undergo an MRI (95% confidence interval, 1.32-1.98). Of these women, those with an educational level of some college or technical school were 43% more likely and those who had at least a college degree were 132% more likely to receive an MRI compared with those with a high school education or less. Among women with a ≥20% lifetime risk, there was no statistically significant difference noted with regard to the use of screening MRI by race or ethnicity, but high-risk women with a high school education or less were less likely to undergo screening MRI than women who had graduated from college (RR, 0.40; 95% confidence interval, 0.25-0.63).

CONCLUSIONS

Uptake of screening MRI of the breast into clinical practice has the potential to worsen population-based health disparities. Policies beyond health insurance coverage should ensure that the use of this screening modality reflects evidence-based guidelines. Cancer 2015. © 2015 American Cancer Society.



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Polymorphisms of CASR gene increase the risk of primary hyperparathyroidism

Abstract

Objective

To evaluate correlations between polymorphisms of calcium-sensing receptor (CASR) gene [A986S (rs1081725), R990G (rs1042636) and Q1011E (rs1801726)] and the risk of primary hyperparathyroidism (PHPT) among human population.

Methods

Relevant studies were retrieved from online databases using computer-based search strategies, which were then supplemented by manual search strategies. Case–control studies related to our topic were identified based on strict inclusion and exclusion criteria. Statistical analyses were conducted using the Comprehensive Meta-analysis 2.0 (Biostat Inc., Englewood, NJ, USA).

Results

We retrieved 202 studies from online databases and other sources initially and eventually enrolled six studies into our meta-analysis. These six studies contained a sum of 693 PHPT patients and 1252 healthy controls. Our meta-analysis results showed that single nucleotide polymorphisms (SNPs) of CASR gene A986S (rs1081725) and R990G (rs1042636), but not Q1011E (rs1801726), may increase the risk of PHPT [A986S (rs1081725): allele model: P = 0.013; dominant model: P = 0.044; R990G (rs1042636): allele model: P = 0.023; dominant model: P = 0.026)]. Subgroup analyses based on ethnicity showed that among Asians, A986S (rs1081725) increased the PHPT risk (P = 0.04) under the allele model, but not under the dominant model. Among Caucasians, there was no association between gene frequencies and PHPT under both the allele and dominant model. In Asians, no significant association was observed between R990G (rs1042636) and PHPT risk, but in Caucasians, R990G (rs1042636) significantly increased the incidence of PHPT [R990G (rs1042636): allele model: P = 0.015; dominant model: P = 0.009)].

Conclusion

Our results indicate that SNPs of CASR gene A986S (rs1081725) and R990G (rs1042636) may increase the risk of PHPT, and the polymorphisms can potentially be used as important biological markers for early diagnosis of PHPT.



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Efficacy and safety of growth hormone treatment in children with short stature: the Italian cohort of the GeNeSIS clinical study

Abstract

Purpose

We examined auxological changes in growth hormone (GH)-treated children in Italy using data from the Italian cohort of the multinational observational Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS) of pediatric patients requiring GH treatment.

Methods

We studied 711 children (median baseline age 9.6 years). Diagnosis associated with short stature was as determined by the investigator. Height standard deviation score (SDS) was evaluated yearly until final or near-final height (n = 78). Adverse events were assessed in all GH-treated patients.

Results

The diagnosis resulting in GH treatment was GH deficiency (GHD) in 85.5 % of patients, followed by Turner syndrome (TS 6.6 %). Median starting GH dose was higher in patients with TS (0.30 mg/kg/week) than patients with GHD (0.23 mg/kg/week). Median (interquartile range) GH treatment duration was 2.6 (0.6–3.7) years. Mean (95 % confidence interval) final height SDS gain was 2.00 (1.27–2.73) for patients with organic GHD (n = 18) and 1.19 (0.97–1.40) for patients with idiopathic GHD (n = 41), but lower for patients with TS, 0.37 (−0.03 to 0.77, n = 13). Final height SDS was >−2 for 94 % of organic GHD, 88 % of idiopathic GHD and 62 % of TS patients. Mean age at GH start was lower for organic GHD patients, and treatment duration was longer than for other groups, resulting in greater mean final height gain. GH-related adverse events occurred mainly in patients diagnosed with idiopathic GHD.

Conclusions

Data from the Italian cohort of GeNeSIS showed auxological changes and safety of GH therapy consistent with results from international surveillance databases.



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Absence of the BRAF V600E mutation in pheochromocytoma

Abstract

Purpose

Pheochromocytomas (PCCs) are rare endocrine tumors originating from the adrenal medulla. These tumors display a highly heterogeneous mutation profile, and a substantial part of the causative genetic events remains to be explained. Recent studies have reported presence of the activating BRAF V600E mutation in PCC, suggesting a role for BRAF activation in tumor development. This study sought to further investigate the occurrence of the BRAF V600E mutation in these tumors.

Methods

A cohort of 110 PCCs was screened for the BRAF V600E mutation using direct Sanger sequencing.

Results

All cases investigated displayed wild-type sequences at nucleotide 1799 in the BRAF gene.

Conclusions

Taken together with all previously screened tumors up to date, only 1 BRAF V600E mutation has been found among 361 PCCs. These findings imply that the BRAF V600E mutation is a rare event in pheochromocytoma.



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Immunoexpression of Ki-67, MCM2, and MCM3 in Ameloblastoma and Ameloblastic Carcinoma and Their Correlations with Clinical and Histopathological Patterns

Cell proliferation assays are performed using antibodies against nuclear proteins associated with DNA replication. These nuclear proteins have gained special interest to predict the biological and clinical behaviors of various tumors. The aim of this study was to analyze the presence of Ki-67 protein and the minichromosome maintenance-2 (MCM2) and maintenance-3 (MCM3) proteins in ameloblastoma. Materials and Methods. Cell proliferation marker expression levels were assessed via immunohistochemistry in 111 ameloblastoma cases (72 unicystic ameloblastoma samples, 38 solid/multicystic ameloblastoma samples, and 1 ameloblastic carcinoma). The label index was performed as described previously. Results. MCM2 and MCM3 showed higher proliferation indexes in all variants of ameloblastoma compared to the classic marker Ki-67. No correlation between the proliferation index and the clinical and protein expression data was observed. Conclusion. The results suggest that clinical features do not directly affect tumor cell proliferation. Moreover, the high levels of cellular proliferation of MCM2 and MCM3 compared with Ki-67 may indicate that MCM2 and MCM3 are more sensitive markers for predicting the growth rate and eventually might be helpful as a tool for predicting aggressive and recurrent behaviors in these tumors.

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Thief steals equipment from Okla. fire dept. ambulance

The thief was caught on camera wearing a camouflage hoodie and beanie opening the ambulance and removing a bag

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Thief steals equipment from Okla. fire dept. ambulance

The thief was caught on camera wearing a camouflage hoodie and beanie opening the ambulance and removing a bag

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Time to contrast enema and ileostomy closure rates following low anterior resection: does laparoscopic surgery make a difference? A prospective cohort study



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Child Asthma Rates Leveling Off, Except Among Poor and Older Kids: Study

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MONDAY, Dec. 28, 2015 -- Rates of childhood asthma appear to have plateaued, except among the poor and kids aged 10 to 17, U.S. health officials report. Researchers found that childhood asthma rates increased from 2001 to 2009 -- a trend that began...

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Health Tip: Start a Group Training Session

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-- Participating in a group training session lets you use the services of a professional trainer at a lower cost than private lessons. The American Council on Exercise mentions these other potential benefits: Finding workout partners with the same...

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Health Tip: Four Simple Steps for Healthier Eating

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-- For better health and weight management, four simple steps can help you stick with a more nutritious eating plan. The Academy of Nutrition and Dietetics advises: Eat foods lower in fat, such as lean meats and foods that aren't fried. Avoid...

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Toxins, Vol. 8, Pages 5: Development of an Enzyme-Linked Immunosorbent Assay Method Specific for the Detection of G-Group Aflatoxins

To detect and monitor G-group aflatoxins in agricultural products, we generated class-specific monoclonal antibodies that specifically recognized aflatoxins G1 and G2. Of the final three positive and stable hybridomas obtained, clone 2G6 produced a monoclonal antibody that had equal sensitivity to aflatoxins G1 and G2, and did not cross-react with aflatoxins B1, B2, or M1. Its IC50 values for aflatoxins G1 and G2 were 17.18 ng·mL−1 and 19.75 ng·mL−1, respectively. Using this new monoclonal antibody, we developed a competitive indirect enzyme-linked immunosorbent assay (CI-ELISA); the method had a limit of detection of 0.06 ng·mL−1. To validate this CI-ELISA, we spiked uncontaminated peanut samples with various amounts of aflatoxins G1 and G2 and compared recovery rates with those determined by a standard HPLC method. The recovery rates of the CI-ELISA ranging from 94% to 103% were comparable to those of the HPLC (92% to 102%). We also used both methods to determine the amounts of G-group aflatoxins in five peanut samples contaminated by aflatoxin B1-positive, and their relative standard deviations ranged from 8.4% to 17.7% (under 20%), which demonstrates a good correlation between the two methods. We further used this CI-ELISA to assess the ability of 126 fungal strains isolated from peanuts or field soils to produce G-group aflatoxins. Among these, seven stains producing different amounts of G-group aflatoxins were identified. Our results showed that the monoclonal antibody 2 G6-based CI-ELISA was suitable for the detection of G-group aflatoxins present in peanuts and also those produced by fungi.

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Influence of the Alcohol Present in a Phytotherapic Tincture on Male Rat Lipid Profiles and Renal Function

This study evaluated the influence of the alcohol present in a formulation of the antiophidic phytotherapic tincture, Específico-Pessôa, on rat blood biochemical and hematological parameters, and on organ histology. Three groups of rats were treated orally for 10, 15, or 30 days; one group received the tincture, the other received alcohol alone, and the third was a control group. The results of this study indicated that cholesterol levels were significantly increased after 10 days in the alcohol and tincture groups, although these decreased after 30 days in the tincture group. Triglyceride levels were significantly reduced after 15 days in the tincture group and after 30 days in the alcohol and tincture groups. A higher creatinine level was observed in the alcohol and tincture groups after 15 and 30 days. The uric acid levels in these groups were reduced at 10 and 30 days, although this metabolite was elevated at 15 days in the alcohol group. Hydropic multifocal degeneration with lymphohistiocytic infiltration and some polymorphonuclear cells was observed in the livers of rats treated with either the tincture or alcohol. These data demonstrate the importance of considering the potential actions of the alcohol present in pharmaceutical formulations.

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Behavior of melanocytes and keratinocytes in reticulate acropigmentation of Kitamura

Abstract

Reticulate acropigmentation of Kitamura (RAK, OMIM 615537) is a rare genetic pigmentary disorder that usually shows an autosomal dominant pattern of inheritance with high penetrance. The disorder was first described by Kitamura and Akamatsu in 1943, and then reported worldwide in 1953 (Kitamura et al., 1953). RAK patients typically present within the first or second decade of life with angulated and slightly depressed reticulate hyperpigmentation on the dorsum of the extremities without hypopigmented macules.

This article is protected by copyright. All rights reserved.



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Remodelling of elastic fibres in striae gravidarum



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News and Notices



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Fragrance contact allergy in the population



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Burden of disease scoring in epidermolysis bullosa



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The clinical relevance of dermoscopic naevus patterns



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Growth and hormonal profiling in children with congenital melanocytic naevi



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Navigating uncertainty: a valuable cost-effectiveness analysis in the rapidly changing field of metastatic melanoma treatment



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Can we trust questions about self-reported and caregiver-reported eczema in epidemiological studies?



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Does systemic antipsoriatic therapy affect the cardiovascular risk?



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Occupational contact urticaria: a diagnosis not to be missed



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British Society for Paediatric Dermatology Annual Meeting, October 2nd 2015, Keble College, Oxford, U.K.



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BJD in translation



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Chilblain lesions associated with inherited autoimmune disease



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Conflicts of interest in dermatology: a medical student and mentor perspective

Summary

Conflict of interest (COI) in medicine is well defined, but is seldom discussed in the field of dermatology. This perspective sheds light on this topic in dermatology and provides suggestions on how better to approach COI in medical school and residency.



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Editor's Choice



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Plain language summaries



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Next-generation antipsoriatic drugs: small molecules join



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Paraneoplastic pemphigus: an entity still in search of an identity?



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Treatment regimens in vulval lichen sclerosus



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A Case of Tinea Incognito

2015-12-28T04-57-51Z
Source: Medicine Science | International Medical Journal
Ragip Ismail Engin.
A 62-year-old male farmer presented to our clinic with eruption and mild itching on the right hand. He stated that this eruption had begun 15 days previously and that he had presented to the local general practitioner. Dermatological examination revealed a lesion containing maculopapules approximately 6x7 cm in size on the dorsum of the right hand with mild margin activation and a very few occasional red squamae. Dermatophyte infection was primarily suspected. We learned from anamnesis that the drug previously administered was clobetasol dipropionate, raising the possibility of tinea incognito (TI). Native preparate was performed from the squamae on the lesion. Fungal hyphae were observed at microscopic examination. In describing this case diagnosed as TI, we wish to emphasize that specimens should be taken for microscopic examination with KOH in patients with a similar clinical appearance at differential diagnosis, and that treatment should be administered accordingly.


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Wnt5a-Ror2 signaling in mesenchymal stem cells promotes proliferation of gastric cancer cells by activating CXCL16-CXCR6 axis

Summary

Wnt5a-Ror2 signaling has been shown to play important roles in promoting aggressiveness of various cancer cells in a cell-autonomous manner. However, little is known about its function in cancer-associated stromal cells, including mesenchymal stem cells (MSCs). Thus, we examined the role of Wnt5a-Ror2 signaling in bone marrow-derived MSCs in regulating proliferation of undifferentiated gastric cancer cells. Co-culture of a gastric cancer cell line, MKN45 cells, with MSCs either directly or indirectly promotes proliferation of MKN45 cells, and suppressed expression of Ror2 in MSCs prior to co-culture inhibits enhanced proliferation of MKN45 cells. In addition, conditioned media from MSCs, treated with control siRNA, but not siRNAs against Ror2, can enhance proliferation of MKN45 cells. Interestingly, it was found that expression of CXCL16 in MSCs is augmented by Wnt5a-Ror2 signaling, and that recombinant CXCL16 protein can enhance proliferation of MKN45 cells in the absence of MSCs. In fact, suppressed expression of CXCL16 in MSCs or an addition of a neutralizing antibody against CXCL16 fails to promote proliferation of MKN45 cells in either direct or indirect co-culture with MSCs. Importantly, we show that MKN45 cells express CXCR6, a receptor for CXCL16, and that suppressed expression of CXCR6 in MKN45 cells results in a failure of its enhanced proliferation in either direct or indirect co-culture with MSCs. These findings indicate that Wnt5a-Ror2 signaling enhances expression of CXCL16 in MSCs and as a result enhanced secretion of CXCL16 from MSCs might act on CXCR6 expressed on MKN45, leading to the promotion of its proliferation.

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FOXA1 expression affects to the proliferation activity of luminal breast cancer stem cell populations

Abstract

The expression of estrogen receptor (ER) is the key in most breast cancers (BC) and binding of ER to the genome correlates to Forkhead protein (FOXA1) expression. We herein assessed the correlation between the cancer stem cell (CSC) population and FOXA1 expression in luminal breast cancer (BC). We established luminal BC cells derived from metastatic pleural effusion and analyzed the potency of CSC and related factors with established luminal BC cell lines. We also confirmed that mammosphere cultures have an increased aldehyde dehydrogenase (ALDH)-positive population, which is one of the CSC markers, compared with adherent culture cells. Using a qPCR analysis, we found that mammosphere forming cells showed a higher expression of FOXA1 and stemness-related genes compared with adherent culture cells.

Furthermore, the growth activity and colony-forming activity of 4-hydroxytamoxifen (4-OHT)-treated BC cells were inhibited in a mammosphere assay. Interestingly, 4-OHT -resistant cells had significantly increased FOXA1 gene expression levels. Finally, we established short hairpin RNA of FOXA1 (shFOXA1) MCF-7 cells and investigated the relationship between self-renewal potential and FOXA1 expression. As a result, we found no significant difference in the number of mammospheres but decreased colony formation in shFOXA1 MCF-7 cells compared with control. These results suggest that the expression of FOXA1 appears to be involved in the proliferation of immature BC cells rather than the induction of stemness-related genes and self-renewal potency of CSCs.

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New Roles for Lysine Demethylase KDM4A

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Lysine methyltransferases and lysine demethylases are two examples of chromatin-modifying enzymes inside the nucleus. While past researchers have focused on how these enzymes target nuclear proteins, Rechem et al. posit that there are also important roles for chromatin-modifying enzymes outside the nucleus.1  Adding weight to this argument, the team also explained that earlier data has implicated Read the rest of this article

The post New Roles for Lysine Demethylase KDM4A appeared first on Accelerating Science.



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Maternal dietary fat intake during pregnancy is associated with infant temperament

ABSTRACT

Research with rodents and nonhuman primates suggests that maternal prenatal dietary fat intake is associated with offspring behavioral functioning indicative of risk for psychopathology. The extent to which these findings extend to humans remains unknown. The current study administered the Automated Self-Administered 24 hr Dietary Recall Questionnaire three times in pregnancy (n = 48) to examine women's dietary fat intake in relation to infant temperament assessed using the Infant Behavior Questionnaire at 4-months old. The amount of saturated fat that the mother consumed was considered as a moderator of the association between total fat intake and child temperament. Results from a series of multiple linear regressions indicate that greater total fat intake was associated with poorer infant regulation and lower surgency. However, this second effect was moderated by maternal saturated fat intake, such that total fat intake was only related to infant surgency when mothers consumed above the daily recommended allowance of saturated fat. Under conditions of high total fat and high saturated fat, infants were rated as lower on surgency; under conditions of low total fat yet high saturated fat, infants were rated as higher on surgency. There were no associations between maternal prenatal fat intake and infant negative reactivity. These findings provide preliminary evidence that pregnant women's dietary fat intake is associated with infants' behavioral development, though future research is needed to address this report's limitations: a relatively small sample size, the use of self-report measures, and a lack of consideration of maternal and infant postnatal diet. © 2015 Wiley Periodicals, Inc. Dev Psychobiol 9999: 1–8, 2015.



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Spatial variation in osteon population density at the human femoral midshaft: histomorphometric adaptations to habitual load environment

Abstract

Intracortical remodeling, and the osteons it produces, is one aspect of the bone microstructure that is influenced by and, in turn, can influence its mechanical properties. Previous research examining the spatial distribution of intracortical remodeling density across the femoral midshaft has been limited to either considering only small regions of the cortex or, when looking at the entirety of the cortex, considering only a single individual. This study examined the spatial distribution of all remodeling events (intact osteons, fragmentary osteons, and resorptive bays) across the entirety of the femoral midshaft in a sample of 30 modern cadaveric donors. The sample consisted of 15 males and 15 females, aged 21–97 years at time of death. Using geographic information systems software, the femoral cortex was subdivided radially into thirds and circumferentially into octants, and the spatial location of all remodeling events was marked. Density maps and calculation of osteon population density in cortical regions of interest revealed that remodeling density is typically highest in the periosteal third of the bone, particularly in the lateral and anterolateral regions of the cortex. Due to modeling drift, this area of the midshaft femur has some of the youngest primary tissue, which consequently reveals that the lateral and anterolateral regions of the femoral midshaft have higher remodeling rates than elsewhere in the cortex. This is likely the result of tension/shear forces and/or greater strain magnitudes acting upon the anterolateral femur, which results in a greater amount of microdamage in need of repair than is seen in the medial and posterior regions of the femoral midshaft, which are more subject to compressive forces and/or lesser strain magnitudes.



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Clinical significance of accounting for tissue heterogeneity in permanent breast seeds implant brachytherapy planning

Publication date: Available online 23 December 2015
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Shahram Mashouf, Emmanuelle Fleury, Priscilla Lai, Tomas Merino, Eli Lechtman, Alex Kiss, Claire McCann, Jean-Philippe Pignol
PurposeThe Inhomogeneity Correction Factor (ICF) method provides heterogeneity correction for the fast calculation TG43 formalism in seeds brachytherapy. This study compared ICF corrected plans to their standard TG43 counterparts looking at their capacity to assess inadequate coverage and/or risk of any skin toxicities for patients who received Permanent Breast Seed Implant (PBSI).Methods and MaterialsThe 2 month post implant CT-scans and plans of 140 PBSI patients were used to calculate dose distributions using the TG-43U1 formalism and the ICF method. Multiple dose-volume histogram (DVH) parameters of clinical target volume (CTV) and skin were extracted and compared for both ICF and TG43 dose distributions. Short term (desquamation and erythema) and long term (telangiectasia) skin toxicity data were available on 125 and 110 of the patients, respectively, at the time of study. The predictive value of each DVH parameter of skin was evaluated using the area under the receiver operating characteristic (ROC) curve for each toxicity endpoint.ResultsThe DVH parameters of CTV calculated using the ICF method showed an overall decrease compared to TG43 while those of skin showed an increase confirming previously reported findings on the impact of heterogeneity with low energy sources. The ICF methodology enabled us to distinguish patients for whom the CTV V100 and V90 are up to 19% lower compared to TG43, which could present a risk of recurrence not detected when heterogeneity are not accounted for. The ICF method also led to an increase in the prediction of desquamation, erythema, and telangiectasia91% of skin DVH parameters studied.ConclusionsThe ICF methodology has the advantage to distinguish any inadequate dose coverage of CTV due to breast heterogeneity, which can be missed by TG43. The use of the ICF correction also led to an increase in prediction accuracy of skin toxicities in majority of cases.

Teaser

In this study we compared a tissue heterogeneity correction algorithm (ICF method) to the standard AAPM-TG43 protocol for a cohort of patients treated with permanent breast seed implants (PBSI). Using heterogeneity correction enabled distinguishing patients who received lower dose to the clinical target volume (CTV), who would otherwise go undetected using TG43. The use of the ICF correction also led to an increase in prediction accuracy of skin toxicities in the majority of the cases.


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The Best Medical Technologies of 2015

As we look back on the medtech developments of 2015 there's definitely a sense that we're living through revolutionary times. Nearly every day exciting and fascinating technologies are being unveiled by small and large companies, universities, and even tiny independent groups. Empowered by high-powered computers, 3D printers, and other technologies, researchers, scientists, and engineers are coming up with novel solutions to age-old medical problems. Everything from treating gunshot wounds to how fetuses inside the womb are monitored is going through change thanks to technologies developed by thousands of independent minds around the world.

And so we'd like to take you on a quick tour of amazing, inspiring, and long hoped for medical capabilities that have graced these pages over the last year.

Eyes-On Wearable Ultrasound and Infrared Glasses

Evena-wearable-ultrasound

Who would have thought we'd have hands-free and at-a-distance ultrasound technology in a pair of glasses? Evena Medical released their Eyes-On device that projects both ultrasound waves and infrared light to visualize both the peripheral and deeper vasculature for venipuncture procedures. The glasses feature Epson's Moverio technology that displays an image laid over the wearer's field of view. The computer that powers the glasses does image processing on the imaging data, detecting the vasculature and displaying it over the patient's skin within the glasses.

Here's what you would see wearing the glasses when imaging the peripheral vasculature using infrared:

 

Nanoparticles and Vascular Stents for Busting Brain Clots

clot-busting-nano-drugsThe field of nanomedicine has seen considerable progress this year in attacking its main target, cancer, but also in addressing other difficult conditions. Researchers at Harvard's Wyss Institute and University of Massachusetts' New England Center for Stroke Research combined a narrow stent with pressure activated nanoparticles to break up vessel occlusions in the brain that cause ischemic strokes. The technology addresses many cases for which clot retrieval is not appropriate and may prevent smaller pieces of the clot from causing damage further down the vasculature.

The stent is used to bore through the clot, creating a passage for a narrow stream of blood to flow through. Special nanoparticles carrying clot busting drugs are then released toward the clot. Designed to let go of their payloads when put under high pressure, the nanoparticles only become active when passing through the freshly made tunnel within the clot. Since the drug is released just near the clot, it sticks to it and dissolves it. Any pieces of the clot breaking away should also get a few of the millions of nanoparticles passing through attached to them, helping to break up any loose bits that may otherwise cause further damage.

 

ekso-stimulationParalyzed People Walk Again!

Last year we've seen real progress toward getting paralyzed folks back up on their feet again, and not by simply using exoskeletons. At UCLA researchers managed to non-invasively stimulate the spinal cords of paralyzed men who were then able to voluntarily move their legs. Though they weren't exactly walking and remained horizontal, one man out of the study went on with specialized rehab to be able to use a smart exoskeleton.

The UCLA researchers combined non-invasive spinal cord stimulation from NeuroRecovery Technologies with a powered exoskeleton from EKSO Bionics. The combination allowed the man to actually walk again, using his legs to push forward and take repeated steps while being supported by the exoskeleton.

Coincidentally, last year we got a chance to visit EKSO's research lab and try out an exoskeleton for ourselves. Though the new prototype device we tried was designed for able bodied people operating heavy handheld equipment, the trip allowed us to experience the potential of exoskeletons for medical applications.

 

 

XstatXStat

Can the same device make it to our "Best Of" list two years in a row? If it's the XStat Rapid Hemostasis System, indeed it can. While originally developed for battlefield medics to stop bleeding from gunshot wounds, only this month has it been approved by the FDA for civilian use.

The XStat is a syringe filled with tablets made of an absorbent material. It's inserted into the wound and the sponge tablets that are pushed inside rapidly swell on contact with blood. Since their new volume is many times their original size, the soaked sponges end up filling the space of the wound, preventing further bleeding. Once the patient is delivered to the hospital and treated, X-rays can be used to make sure all the sponges are removed since they all have a small radiopaque marker within them.

 

Fetal Pacemaker

fetal-pacemaker-bigWhile adult pacemakers are getting tiny, some patients may benefit considerably more from pacemaker miniaturization. Children born with complete heart block, a condition in which electrical signals don't propagate properly throughout the heart, often don't make it before a pacemaker can be implanted. Moreover, external pacemakers that are often used can come with serious side effects.

A team from Children's Hospital Los Angeles and University of Southern California built and tested a pacemaker that can be implanted in utero into a fetus. Because the procedure can be done before birth and the pacemaker fully implanted into the child, we may soon witness complete heart block turn into a considerably less grave of a condition.

The device has already been tested with great success on sheep fetuses and the team behind the new pacemaker believes it's ready for clinical trials. These should commence soon since the device is already covered by the FDA's Humanitarian Use Device designation.

 

Light Powered Cardiac Pacemaker

Since we're on the subject of pacemakers, we might be seeing the way they work fundamentally change. At Israel's Technion-Institute of Technology researchers have been able to pace the rhythm of a rat's heart using a beam of light. This was accomplished by using a virus to make the rat express the Channelrhodopsin-2 transgene within its ventricular myocardium. This made the rat heart react to blue light effectively the same as to an electric pacemaker, contracting along with flashes of the light. Since there aren't any leads and the only device needed for pacing is a simple strobe light, the optogenetic technology may one day become common. One big next step to bringing light pacemakers closer to clinical practice is to figure out the optimal places within the heart where to express the transgene.

Check out this video of a rat heart beating to the rhythm of a light:

 

Light Producing Sleep Mask for Preventing Diabetic Retinopathy

Noctura

Diabetic retinopathy is an unfortunate, but very common way for people with diabetes to lose their eyesight. It's been a difficult to manage condition, but now there's a new night-time sleep mask that may help dramatically slow its onset. As a patient's diabetes progresses, the blood circulation worsens and the supply of oxygen to the retina is compromised. retinopathyThe retina is especially oxygen-starved at night since the rods, which are used primarily when the eyes dark-adjust, demand more oxygen than the light-activated cones. In response to this ischemia, the body signals for additional blood vessels to be formed in this region, but these new blood vessels are very weak and susceptible to microaneurysms and leaking.  This leaking leads to retinal edema and eventually macular edema, which destroys a patient's eyesight.

The Noctura 400 sleep mask from PolyPhotonix prevents the patient's eyes from dark-adapting while the patient is asleep. It continuously shines light at the user's closed eyelid, but the color and brightness of this light was selected such that it prevents the rods from dark-adapting but does not stimulate the patient's cones or other photoreceptive cells.  This prevents the therapy from adversely affecting the patient's quality of sleep.

 

EarLens Laser-based Hearing Device

headerImage_deviceThis year we also saw an FDA approval of the laser-based hearing aid from EarLens Corporation. The EarLens consists of two parts: a tympanic membrane transducer, which is non-surgically placed deep into the ear canal on the eardrum, and a behind-the-ear audio processor that is connected to a probe that's placed in the ear canal. Sounds are converted to electronic signals, digitally processed, amplified, and sent to the ear tip, which contains a laser diode sending out pulses of light. A photodetector in the tympanic membrane transducer converts the light back into electronic signals, transmitting sound vibrations directly to the eardrum by direct contact. Check out how this ingenious device works:

 

WiSE Wireless Technology for LV Heart Pacing Without Coronary Sinus Leads

WiSE-technology

Pacemakers typically deliver electric signals only to the right side of the heart because that's the easy route for lead placement. Now there's a way for pacing both sides of the heart using a conventional pacemaker coupled with an additional system. The WiSE technolory from EBR Systems includes an implanted pulse generator near the heart and a receiver-electrode attached to the endocardium of the left ventricle.

The generator detects the signal of the primary pacemaker and fires off an ultrasonic pulse toward the receiver-electrode as needed. The tiny device converts sound waves into an electrical signal, pacing the left ventricle. One of the main advantages of the system is that it allows the physician to place the electrode anywhere within the heart, optimizing pacing therapy for each patient.

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And there it is, 2015 is wrapping to a close, but on a high note. We are seeing revolutionary changes in how many diseases are managed, treated, and cured, and there's a definite sense that things are only heating up. Genetic technologies, better approaches to pacing and stimulation, new materials and their applications, and many other aspects of how medicine can be improved will paint the pages of Medgadget in the coming years.

The post The Best Medical Technologies of 2015 appeared first on Medgadget.

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Timing of routine infant vaccinations and risk of food allergy and eczema at one year of age

Abstract

Background

Epidemiological evidence suggests that routine vaccinations can have non-targeted effects on susceptibility to infections and allergic disease. Such effects may depend on age at vaccination, and a delay in pertussis vaccination has been linked to reduced risk of allergic disease. We aimed to test the hypothesis that delay in vaccines containing diphtheria-tetanus-acelullar pertussis (DTaP) is associated with reduced risk of food allergy and other allergic diseases.

Methods

HealthNuts is a population-based cohort in Melbourne, Australia. 12 month-old infants were skin prick tested to common food allergens, and sensitized infants were offered oral food challenges to determine food allergy status. In this data linkage study, vaccination data for children in the HealthNuts cohort were obtained from the Australian Childhood Immunisation Register. Associations were examined between age at the first dose of DTaP and allergic disease.

Results

109 of 4433 children (2.5%) received the first dose of DTaP one month late (delayed DTaP). Overall, delayed DTaP was not associated with primary outcomes of food allergy (adjusted odds ratio (aOR) 0.77; 95% CI 0.36-1.62, p=0.49) or atopic sensitization (aOR 0.66; 95% CI 0.35-1.24, p=0.19). Among secondary outcomes, delayed DTaP was associated with reduced eczema (aOR 0.57; 95% CI 0.34-0.97, p=0.04) and reduced use of eczema medication (aOR 0.45; 95% CI 0.24-0.83, p=0.01).

Conclusions

There was no overall association between delayed DTaP and food allergy, however children with delayed DTaP had less eczema and less use of eczema medication. Timing of routine infant immunizations may affect susceptibility to allergic disease.

This article is protected by copyright. All rights reserved.



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IJMS, Vol. 17, Pages 37: The Role of bFGF in the Excessive Activation of Astrocytes Is Related to the Inhibition of TLR4/NFκB Signals

Astrocytes have critical roles in immune defense, homeostasis, metabolism, and synaptic remodeling and function in the central nervous system (CNS); however, excessive activation of astrocytes with increased intermediate filaments following neuronal trauma, infection, ischemia, stroke, and neurodegenerative diseases results in a pro-inflammatory environment and promotes neuronal death. As an important neurotrophic factor, the secretion of endogenous basic fibroblast growth factor (bFGF) contributes to the protective effect of neuronal cells, but the mechanism of bFGF in reactive astrogliosis is still unclear. In this study, we demonstrated that exogenous bFGF attenuated astrocyte activation by reducing the expression of glial fibrillary acidic protein (GFAP) and other markers, including neurocan and vimentin, but not nestin and decreased the levels of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), via the regulation of the upstream toll-like receptor 4/nuclear factor κB (TLR4/NFκB) signaling pathway. Our study suggests that the function of bFGF is not only related to the neuroprotective and neurotrophic effect but also involved in the inhibition of excessive astrogliosis and glial scarring after neuronal injury.

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IJMS, Vol. 17, Pages 33: Targeted Radionuclide Therapy of Human Tumors

Targeted radionuclide therapy is one of the most intensively developing directions of nuclear medicine. Unlike conventional external beam therapy, the targeted radionuclide therapy causes less collateral damage to normal tissues and allows targeted drug delivery to a clinically diagnosed neoplastic malformations, as well as metastasized cells and cellular clusters, thus providing systemic therapy of cancer. The methods of targeted radionuclide therapy are based on the use of molecular carriers of radionuclides with high affinity to antigens on the surface of tumor cells. The potential of targeted radionuclide therapy has markedly grown nowadays due to the expanded knowledge base in cancer biology, bioengineering, and radiochemistry. In this review, progress in the radionuclide therapy of hematological malignancies and approaches for treatment of solid tumors is addressed.

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IJMS, Vol. 17, Pages 25: Interleukin-10 Protection against Lipopolysaccharide-Induced Neuro-Inflammation and Neurotoxicity in Ventral Mesencephalic Cultures

Interleukin (IL)-10, an anti-inflammatory cytokine, is expressed in the brain and can inhibit microglial activation. Herein, we utilized lipopolysaccharide (LPS)-induced inflammatory Parkinson's disease (PD) cell model to determine whether microglia and astrocytes are necessary targets for IL-10 neuroprotection. Primary ventral mesencephalic (VM) cultures with different composition of neurons, microglia and astrocytes were prepared. The cells were exposed to IL-10 (15, 50 or 150 ng/mL) 1 h prior to LPS (50 ng/mL) treatment. LPS induced dopaminergic and non-dopaminergic neuronal loss in VM cultures, VM neuron-enriched cultures, and neuron-microglia co-cultures, but not in neuron-astrocyte co-cultures. IL-10 reduced LPS-induced neuronal loss particularly in single VM neuron cultures. Pro-inflammatory mediators (TNF-α, IL-1β, inducible nitric oxide synthase and cyclooxygenase-2) were upregulated in both neuron-microglia and neuron-astrocyte co-cultures by LPS. In contrast, neurotrophic factors (brain-derived neurotrophic factor, insulin-like growth factor-1 or glial cell-derived neurotrophic factor) were downregulated in neuron-microglia co-cultures, but upregulated in neuron-astrocyte co-cultures by LPS. IL-10 reduced both the increase in production of the pro-inflammatory mediators and the decrease in production of the neurotrophic factors induced by LPS. These results suggest that astrocytes can balance LPS neurotoxicity by releasing more neurotrophic factors and that IL-10 exerts neuroprotective property by an extensive action including direct on neurons and indirect via inhibiting microglial activation.

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DAMS Participates in IMA-NATCON

It was a pleasure to be a part of IMA NATCON 2015 90th Annual National Conference of IMA (Indian Medical Association) Held on 27th & 28th December 2015 Hotel Le-Meridien, New Delhi. Thank you to Dr Ajay Lekhi President DMA for making us a part of the event. My topic was basics of cross sectional imaging for non-radiologists.

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Echinocandin to fluconazole step-down therapy in critically ill patients with invasive, susceptible Candida albicans infections

Summary

Invasive Candida spp. infections are increasingly diagnosed in critically ill patients. For initial treatment, an echinocandin is recommended with a possible step-down to fluconazole when the patients' condition is improving and the isolate appears susceptible, but there are no data to support such policy. We studied the safety and efficacy of step-down therapy in critically ill patients with culture proven deep seated or bloodstream infections by C. albicans susceptible to fluconazole. All patients admitted into the intensive care unit from January 2010 to December 2014, who had a culture proven invasive C. albicans infection and received initial treatment with an echinocandin for at least 4 days were included. Data on patient characteristics, treatment and vital outcomes were assessed. Of the 56 patients, 32 received step-down fluconazole therapy, at median day 5, whereas the echinocandin was continued in the other 24. No differences where seen in baseline characteristics or risk factors for invasive C. albicans infection between the two groups. Response rates were similar and no difference where seen in 28-day or 90-day mortality between the groups. Step-down therapy to fluconazole may be safe and effective in critically ill patients with invasive infections by C. albicans, susceptible to fluconazole, who have clinically improved as early as 4 days after start of treatment with an echinocandin.



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