Tall cell carcinoma with reversed polarity: A case report of a very rare breast tumor entity and mini-review

Tall cell carcinoma with reversed polarity (TCCRP) is a very rare variant of carcinoma of the breast, resembling the tall cell variant of papillary thyroid carcinoma, first described in 2003, recently recognized as a separate entity in the 5th edition of the WHO (World Health Organization) Blue Book Classification of breast tumors with alternative terminology of tall cell variant of papillary breast carcinoma and solid papillary carcinoma with reversed polarity. Here, we report an additional case of this rare tumor in a 71-year-old woman, and the problems correlating with its diagnosis.     

Dual Targeting of Oncogenic Activation and Inflammatory Signaling Increases Therapeutic Efficacy in Myeloproliferative Neoplasms

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The iMPROVE Study; Design,Dietary Patterns,and Development of a Lifestyle Index in Overweight and Obese Greek Adults

Background: Dietary and lifestyle habits constitute a significant contributing factor in the formation of anthropometric and biochemical characteristics of overweight and obese populations. The iMPROVE study recruited overweight and obese Greek adults and investigated the effect of gene–diet interactions on weight management when adhering to a six-month, randomized nutritional trial including two hypocaloric diets of different macronutrient content. The present paper displays the design of the intervention and the baseline findings of the participants’ dietary habits and their baseline anthropometric and biochemical characteristics. Methods: Baseline available data for 202 participants were analyzed and patterns were extracted via principal component analysis (PCA) on 69-item Food-Frequency Questionnaires (FFQ). Relationships with indices at baseline were investigated by multivariate linear regressions. A Lifestyle Index of five variables was further constructed. Results: PCA provided 5 dietary patterns. The “Mixed” pattern displayed positive associations with logBMI and logVisceral fat, whereas the “Traditional, vegetarian-alike” pattern was nominally, negatively associated with body and visceral fat, but positively associated with HDL levels. The Lifestyle Index displayed protective effects in the formation of logBMI and logGlucose levels. Conclusions: Dietary patterns and a Lifestyle Index in overweight and obese, Greek adults highlighted associations between diet, lifestyle, and anthropometric and biochemical indices.     

Association of NEDD4L ubiquitin ligase with essential hypertension

NEDD4L is a ubiquitin ligase that controls cell surface expression of kidney epithelial Na+ channels by ubiquitin-mediated endocytosis and lysosome targeting. Thus, it is a significant determinant of Na+ reabsorption in the distal nephron. The NEDD4L gene is located on human chromosome 18q21 within several blood pressure quantitative trait loci, including those for familial orthostatic hypotension, essential hypertension, pulse pressure, and systolic blood pressure response to postural challenge. Because of the importance of NEDD4L to Na+ balance, many of these studies have proposed that mutations in NEDD4L may be responsible for these blood pressure phenotypes. To test this hypothesis, we fine-mapped the NEDD4L region in 2 families with orthostatic hypotension, which we previously reported to be linked to human chromosome 18q21 but failed to implicate NEDD4L in these families. We also typed multiple NEDD4L single-nucleotide polymorphisms (SNPs) in a collection of US whites, Greek whites, and African-Americans individuals with essential hypertension. A significant association between several SNPs and hypertension was observed in all 3 populations. One of the SNPs associated in African Americans is known to result in premature truncation of the NEDD4L protein. Thus, genetic variation in NEDD4L may play a role in the development or progression of some forms of abnormal blood pressure.     

Evaluation of the “AMR Direct Flow Chip Kit” DNA microarray for detecting antimicrobial resistance genes directly from rectal and nasopharyngeal clinical samples upon ICU admission

IntroductionPrompt detection of antibiotic resistance genes in healthcare institutions is of utmost importance in tackling the spread of multi-drug resistant micro-organisms. We evaluated the Antimicrobial Resistance (AMR) Direct Flow Chip Kit versus phenotypic screening assays for rectal and nasopharyngeal specimens upon ICU admission.MethodsA total of 184 dual specimens (92 rectal and 92 nasopharyngeal swabs) from 92 patients were collected from 11/2017 to 8/2018. All swabs were subjected to both AMR and phenotypic tests according to their origin. The degree of agreement of the two methods was assessed by the kappa coefficient.ResultsThe kappa coefficient showed perfect agreement for MRSA, ESBLs, oxacillinases and vancomycin resistance genes (1.000, p < 0.01) and very good agreement for mecA-positive CoNS, KPC-carbapenemases and metallo-beta-lactamases (0.870, p < 0.01; 0.864, p < 0.01; and 0.912, p < 0.01, respectively).ConclusionThe AMR Direct Flow Chip Kit is a useful alternative to phenotypic testing for rapid detection of resistance markers.     

Pharmacologic treatment options for advanced epithelial skin cancer

Introduction: Epithelial skin cancers (ESCs), namely basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), are considered common skin malignancies, with rising incidence rates over the past few decades. A subgroup of patients with ESC present with advanced and ‘difficult’-to-treat tumours, including locally advanced and metastatic tumours. Currently, there is no widely accepted staging system for locally advanced ESCs, while metastatic BCCs and SCCs share a staging system. Therefore, selecting an appropriate therapeutic regimen for these patients may be difficult.

Areas covered: The purpose of this review is to highlight the pharmacologic treatment options for advanced ESCs. These include ‘conventional’ chemotherapeutic regimens such as 5-fluorouracil, cisplatin, vincristine, bleomycin and doxorubicin and newer, more ‘targeted’ therapies.

Expert opinion: Vismodegib, a Hedgehog (Hh) inhibitor, was recently approved for the treatment of advanced BCC showing a good efficacy rate and a relatively well-tolerated safety profile in clinical studies. In addition, a number of hedgehog inhibitors are now in Phase I and II trials of advanced BCC demonstrating encouraging results. Phase II studies with epithelial growth factor receptor inhibitors, such as cetuximab, gefitinib, panitimumab and erlotinib have been conducted in patients with advanced SCCs, used either as monotherapy or in combination with chemotherapy. However, there is still much knowledge to be gained about the treatment efficacies, optimal treatment durations, mechanisms of drug tolerance, adverse events and the ways in which these therapies influence patient outcomes and quality of life.     

Candida Infective Endocarditis: an Observational Cohort Study with a Focus on Therapy

Candida infective endocarditis is a rare disease with a high mortality rate. Our understanding of this infection is derived from case series, case reports, and small prospective cohorts. The purpose of this study was to evaluate the clinical features and use of different antifungal treatment regimens for Candida infective endocarditis. This prospective cohort study was based on 70 cases of Candida infective endocarditis from the International Collaboration on Endocarditis (ICE)-Prospective Cohort Study and ICE-Plus databases collected between 2000 and 2010. The majority of infections were acquired nosocomially (67%). Congestive heart failure (24%), prosthetic heart valve (46%), and previous infective endocarditis (26%) were common comorbidities. Overall mortality was high, with 36% mortality in the hospital and 59% at 1 year. On univariate analysis, older age, heart failure at baseline, persistent candidemia, nosocomial acquisition, heart failure as a complication, and intracardiac abscess were associated with higher mortality. Mortality was not affected by use of surgical therapy or choice of antifungal agent. A subgroup analysis was performed on 33 patients for whom specific antifungal therapy information was available. In this subgroup, 11 patients received amphotericin B-based therapy and 14 received echinocandin-based therapy. Despite a higher percentage of older patients and nosocomial infection in the echinocandin group, mortality rates were similar between the two groups. In conclusion, Candida infective endocarditis is associated with a high mortality rate that was not impacted by choice of antifungal therapy or by adjunctive surgical intervention. Additionally, echinocandin therapy was as effective as amphotericin B-based therapy in the small subgroup analysis.