Molecular Markers In The Diagnosis Of Thyroid Nodules.

An indeterminate thyroid nodule cytology result occurs about every sixth fine-needle aspiration. These indeterminate nodules harbor a 24% risk of malignancy (ROM); too high to ignore, but driving surgery where most nodules are benign. Molecular diagnostics have emerged to ideally avoid surgery when appropriate, and to trigger the correct therapeutic surgery when indicated, as opposed to an incomplete diagnostic surgery. No current molecular test offers both high sensitivity and high specificity. A molecular diagnostic test with high sensitivity (e.g. Afirma Gene Expression Classifier sensitivity 90%) offers a high Negative Predictive Value when the ROM is relatively low, such as < 30%. Only such tests can rule-out cancer. In this setting, a molecularly benign result suggests the same ROM as that of operated cytologically benign nodules (~6%). Thus, clinical observation can replace diagnostic surgery; increasing quality of life and decreasing medical costs. However, its low specificity cannot rule-in cancer as a suspicious result has a Positive Predictive Value (PPV) of ~40%, perhaps too low to routinely reflex to definitive cancer surgery. Conversely, high specificity tests (BRAF, RAS, PPAR/PAX-8, RET/PTC, PTEN) offer high PPV results, and only these tests can rule-in cancer. Here a positive molecular result warrants definitive therapeutic surgery. However, their low sensitivity cannot rule-out cancer and a negative molecular result cannot dissuade diagnostic surgery; limiting their cost-effectiveness. Whether or not there is a useful and cost-effective role to sequentially combine these approaches, or to modify existing approaches, is under investigation.5789-9

Development of a digital toolkit to improve quality of life of patients with systemic lupus erythematosus

OBJECTIVE: The purpose of this manuscript is to detail development and initial usability testing of an e-toolkit designed to provide skills and knowledge around self-management behaviors for individuals living with systemic lupus erythematosus. METHODS: Researchers worked with a steering committee of patients and providers to (1) develop a clickable prototype of an e-toolkit and (2) conduct alpha (individuals not affiliated with an academic clinic as patient or provider) and beta (individual patients with systemic lupus erythematosus as well as members of the clinic healthcare team and individuals who work in patient advocacy organizations) usability testing through semistructured interviews. RESULTS: During the review of the e-toolkit, the feedback provided by participants in both alpha and beta groups centered on two overarching themes: (1) improving user interface and materials and (2) integration of information and supports between toolkit and clinical personnel. CONCLUSION: Digital approaches that are tailored to individual symptom variation and integrated with a clinical system have the opportunity to enhance ongoing clinical care. These findings support movement toward integrated, team-based care models, tailored digital resources, and use of expanded virtual interaction options to ensure on-going engagement between healthcare providers and systemic lupus erythematosus patients

Preclinical evaluation of the simultaneous inhibition of MCL-1 and BCL-2 with the combination of S63845 and venetoclax in multiple myeloma

This work was supported by the Spanish ISCIII-FIS and FEDER Funds (PI 15/00067 and PI 15/02156) and the Regional Health Council of Castilla y León (GRS 1604/A/17). EMA was supported by a grant from the Regional Education Council of Castilla y León co-financed by the European Social Fund

Ovine pedomics : the first study of the ovine foot 16S rRNA-based microbiome

We report the first study of the bacterial microbiome of ovine interdigital skin based on 16S rRNA by pyrosequencing and conventional cloning with Sanger-sequencing. Three flocks were selected, one a flock with no signs of footrot or interdigital dermatitis, a second flock with interdigital dermatitis alone and a third flock with both interdigital dermatitis and footrot. The sheep were classified as having either healthy interdigital skin (H), interdigital dermatitis (ID) or virulent footrot (VFR). The ovine interdigital skin bacterial community varied significantly by flock and clinical condition. The diversity and richness of operational taxonomic units was greater in tissue from sheep with ID than H or VFR affected sheep. Actinobacteria, Bacteriodetes, Firmicutes and Proteobacteria were the most abundant phyla comprising 25 genera. Peptostreptococcus, Corynebacterium and Staphylococcus were associated with H, ID and VFR respectively. Sequences of Dichelobacter nodosus, the causal agent of ovine footrot, were not amplified due to mismatches in the 16S rRNA universal forward primer (27F). A specific real time PCR assay was used to demonstrate the presence of D. nodosus which was detected in all samples including the flock with no signs of ID or VFR. Sheep with ID had significantly higher numbers of D. nodosus (104-109 cells/g tissue) than those with H or VFR feet

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

A recipe for thriving in nursing homes: A meta-ethnography

Aim: To explore contributors for thriving in nursing homes by evaluating, analysing and synthesizing peer‐reviewed qualitative literature on the topic. Background: Thriving is a positive life‐world concept that has been explored by several qualitative studies; however, descriptions of thriving and contributors to thriving have not been compared or contrasted among different studies and contexts, nor have they been reviewed and synthesized. Design: Qualitative meta‐ethnography. Data sources: Four electronic databases were searched in October 2019, with sources published between 2000 and 2019 included. Review methods: Sources of peer‐reviewed literature that employed qualitative methods to explore thriving in nursing homes were evaluated. In total, 1,017 sources were screened at title‐level, 95 advanced to abstract‐level review and 11 were assessed at full‐text level. Each source was evaluated by two researchers independently in relation to methodological quality and relevance to the study aim. Themes pertaining to thriving in nursing homes were extracted, interpreted and synthesized. Results: In total, seven sources of peer‐reviewed literature were included. Two main themes illustrating the contributors to thriving were identified: ingredients for thriving (subthemes: personal contributors and social contributors) and environment for thriving (subthemes: spacial contributors and societal contributors). Conclusion:Contributors to thriving in nursing homes include personal attributes, relationships with others, the lived environment and societal structures. Thriving for older people could thereby be defined as a holistic concept denoting lived experiences of situated contentment. Future studies should explore different temporal facets of thriving in the nursing home setting. Impact: This meta‐synthesis proposes a ‘recipe’ for thriving as comprising the right ingredients and the right environment, determined by the preferred ‘taste’ of the individual person. The proposed definition and contributors illuminate thriving as a positive life‐world concept that is based on one's lived experiences and context