Nondiagnostic Fine Needle Aspiration of Thyroid Nodules: Review of Predisposing Factors.

OBJECTIVE: Fine needle aspiration (FNA) of thyroid nodules is the gold standard screening test for thyroid malignancy. Unfortunately, FNA may produce insufficient material for diagnosis. If nodules requiring FNA with a higher risk for nondiagnostic (ND) cytology could be identified pre-procedure, this might allow better patient guidance and potentially facilitate an altered approach to FNA. METHODS: The literature investigating risk factors for ND cytology was reviewed, including studies of patient factors, sonographic or nodule factors, and procedural factors. Twenty-five studies that included assessment of at least two potential factors in ND outcomes for initial FNA were identified. Individual factors were evaluated in terms of the general consensus of studies reporting either a positive significant association with ND cytology or no association. RESULTS: Most patient and nodule factors lack consensus as far as their association with ND cytology across these studies. Factors where there are some consensuses include practitioner experience, depth of nodule, and cystic content; however, hypervascularity of the nodule does not appear to have a consensus. CONCLUSION: A number of study design improvements suggested by this review could realistically be incorporated into higher powered future studies. Novel factors such as tissue composition anterior to the nodule or the age of the patient could also be investigated in future work. Operator experience is the most convincing procedural factor, and approaches to future studies of the FNA technique itself are proposed. That said, the factors with consensus among studies can be seen leading candidates for this future research, and the published studies illuminate a number of as yet unexplored factors that could in many cases be studied retrospectively.

Effects of High-protein and High-fiber Diets on Weight and Glucose Regulation in Spiny Mice (Acomys cahirinus).

Despite the long-term contributions of the spiny mouse (Acomys cahirinus) to research, basic knowledge of appropriate nutrition is lacking for this species. In the wild, spiny mice eat a high-fiber, high-protein food source. In the research setting, spiny mice are prone to obesity that can lead to diabetes mellitus. Common dietary modifications for weight control in humans with diabetes mellitus consist of increased fiber and protein. We hypothesized that increasing the dietary protein or fiber of spiny mice would reduce weight gain and improve their glycemic control, whereas the combination of protein and fiber in the diet would achieve optimal weight management and glycemic control without diet-related pathologic changes. We randomly assigned cages of young adult spiny mice (n = 34) to one of 4 diets: high protein (HP), high fiber (HF), a combination of both high protein and high fiber (HPF), or the base (control) diet (BD). Over the 8-wk study, spiny mice given HF diets maintained baseline weights despite the elevated dietary protein. None of the diets altered blood glucose levels; all diet groups maintained mean blood glucose levels within normal ranges. Spiny mice seem particularly sensitive to changes within their environment, as seen by increased food waste and transient elevated blood glucose levels when the spiny mice were transitioned to novel diets. The short-term elevations in protein and fiber that we tested were well tolerated by spiny mice. Although HF was effective in controlling weight, the ideal percentage of fiber still needs to be determined. The combination diet (HPF) maintained weight and body condition scores and showed a nonsignificant elevation of blood glucose that warrants a longer diet trial before our recommending this specific combination.

A digital health intervention to stabilize the 24-hour rhythm of sleep, meals, and physical activity for reducing depression among older bereaved spouses: Protocol for a randomized controlled trial.

BACKGROUND: Despite the high prevalence of depression and disruption to 24-h sleep-wake routines following the death of a spouse in late-life, no bereavement interventions have been developed to re-entrain a regular sleep-wake routine among older widow(er)s. We describe the rationale and methodology of the NIH-funded WELL Study (Widowed Elders' Lifestyle after Loss), a randomized controlled trial (RCT) comparing the efficacy of a digital health intervention (DHI) to enhanced usual care (EUC) arm for reducing depression symptoms in older spousally-bereaved adults. METHODS: We will randomize approximately 200 recently bereaved (<12 months) adults aged 60+ years to one of two 12-week interventions: digital monitoring of the timing and regularity of sleep, meals, and physical activity plus weekly motivational health coaching; or enhanced usual care consisting of weekly telephone calls and similar assessment schedules. Participants will complete self-report and clinical assessments at baseline, post-intervention, and 3-, 6-, and 12-months post-intervention, and objective actigraphic assessments of their 24-h rest-activity rhythm (RAR) at baseline and 1-, 2-, and 3-months during the intervention. The primary outcome is change in depression symptoms burden (using the Hamilton Rating Scale for Depression) from pre- to post-intervention and over 12 months of follow-up. DISCUSSION: WELL Study findings will inform the development of widely generalizable and scalable technology-based interventions to support bereaved spouses in community-based settings. Clinical http://Trials.gov Identifier: NCT04016896.

A Novel Scoring System for Humane Endpoints in Mice with Cecal Ligation and Puncture-Induced Sepsis.

Animal-based research is essential to the study of sepsis pathophysiology, diagnostics, and therapeutics. However, animal models of sepsis are often associated with high mortality because of the difficulty in predicting imminent death based on premortem assessment of the animals. The use of validated visual scoring would allow researchers to systematically identify humane endpoints but visual approaches require high interobserver agreement for accurate results. The objective of this study was to establish a scoring system for mice undergoing cecal ligation and puncture (CLP)-induced sepsis based on 3 visual parameters: respiratory status, activity and response to stimulus (ASR), and eye appearance, with scores ranging from 0 to 3. In the first study, we evaluated interobserver agreement. Veterinary and investigative staff assessed 283 mice with CLP and had substantial to near-perfect agreement for all 3 parameters as evaluated using weighted Cohen κ statistic. The second study assessed the ability of the scoring system and temperature to predict death. The scoring system and subcutaneous transpond- ers were used to monitor C57BL/6J mice (n = 80, male and female) until death or for 7 days after CLP. Results showed that the scoring system discriminates between surviving (n = 26) and nonsurviving (n = 54) septic mice. The scoring system was accurate in predicting death, with an AUC of 0.8997. The sensitivity and specificity of the ASR parameter were 96% and 92%, respectively, and for the eye parameter were 94% and 73%. A sum of the ASR and eye scores that was 5 or more was also predictive of death. Temperature was a quantitative predictor, with sensitivity and specificity of 93% and 92%, respectively. This scoring system refines the CLP model by allowing identification of humane endpoints and avoidance of spontaneous death.

Outcomes of Early Versus Late Tracheostomy in Patients With COVID-19: A Multinational Cohort Study.

Timing of tracheostomy in patients with COVID-19 has attracted substantial attention. Initial guidelines recommended delaying or avoiding tracheostomy due to the potential for particle aerosolization and theoretical risk to providers. However, early tracheostomy could improve patient outcomes and alleviate resource shortages. This study compares outcomes in a diverse population of hospitalized COVID-19 patients who underwent tracheostomy either "early" (within 14 d of intubation) or "late" (more than 14 d after intubation). DESIGN: International multi-institute retrospective cohort study. SETTING: Thirteen hospitals in Bolivia, Brazil, Spain, and the United States. PATIENTS: Hospitalized patients with COVID-19 undergoing early or late tracheostomy between March 1, 2020, and March 31, 2021. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: A total of 549 patients from 13 hospitals in four countries were included in the final analysis. Multivariable regression analysis showed that early tracheostomy was associated with a 12-day decrease in time on mechanical ventilation (95% CI, -16 to -8; p < 0.001). Further, ICU and hospital lengths of stay in patients undergoing early tracheostomy were 15 days (95% CI, -23 to -9 d; p < 0.001) and 22 days (95% CI, -31 to -12 d) shorter, respectively. In contrast, early tracheostomy patients experienced lower risk-adjusted survival at 30-day post-admission (hazard ratio, 3.0; 95% CI, 1.8-5.2). Differences in 90-day post-admission survival were not identified. CONCLUSIONS: COVID-19 patients undergoing tracheostomy within 14 days of intubation have reduced ventilator dependence as well as reduced lengths of stay. However, early tracheostomy patients experienced lower 30-day survival. Future efforts should identify patients most likely to benefit from early tracheostomy while accounting for location-specific capacity.