Exo-trig selenocyclization of secondary allylic carboxamides using Woollins' reagent: en route to 2,5-disubstituted selenazolines.

We report microwave-assisted selenation and exo-trig cyclization of secondary allylic carboxamides using Woollins' reagent, a serendipitous finding observed during an attempt to synthesize N-allylbenzoselenoamide compounds. This resulted in the first reported synthesis of 2-aryl-5-methyl selenazolines. Twenty-one diversified selenazolines and three late-stage-functionalized drug molecules were synthesized in 42-93% and 25-52% yield, respectively, and these were evaluated further for their anti-proliferative activity.

Detecting early physiologic changes through cardiac implantable electronic device data among patients with COVID-19.

Background: Cardiac implantable electronic devices (CIEDs) may enable early identification of COVID-19 to facilitate timelier intervention. Objective: To characterize early physiologic changes associated with the onset of acute COVID-19 infection, as well as during and after acute infection, among patients with CIEDs. Methods: CIED sensor data from March 2020 to February 2021 from 286 patients with a CIED were linked to clinical data from electronic health records. Three cohorts were created: known COVID-positive (n = 20), known COVID-negative (n = 166), and a COVID-untested control group (n = 100) included to account for testing bias. Associations between changes in CIED sensors from baseline (including HeartLogic index, a composite index predicting worsening heart failure) and COVID-19 status were evaluated using logistic regression models, Wilcoxon signed rank tests, and Mann-Whitney U tests. Results: Significant differences existed between the cohorts by race, ethnicity, CIED device type, and medical admissions. Several sensors changed earlier for COVID-positive vs COVID-negative patients: HeartLogic index (mean 16.4 vs 9.2 days [P = .08]), respiratory rate (mean 8.5 vs 3.9 days [P = .01], and activity (mean 8.2 vs 3.5 days [P = .008]). Respiratory rate during the 7 days before testing significantly predicted a positive vs negative COVID-19 test, adjusting for age, sex, race, and device type (odds ratio 2.31 [95% confidence interval 1.33-5.13]). Conclusion: Physiologic data from CIEDs could signal early signs of infection that precede clinical symptoms, which may be used to support early detection of infection to prevent decompensation in this at-risk population.

Multiple cArdiac seNsors for mAnaGEment of Heart Failure (MANAGE-HF) - Phase I Evaluation of the Integration and Safety of the HeartLogic Multisensor Algorithm in Patients With Heart Failure.

BACKGROUND: Patients with heart failure (HF) and reduced ejection fraction suffer from a relapsing and remitting disease course, where early treatment changes may improve outcomes. We assessed the clinical integration and safety of the HeartLogic multisensor index and alerts in HF care. METHODS: The Multiple cArdiac seNsors for mAnaGEment of Heart Failure (MANAGE-HF) study enrolled 200 patients with HF and reduced ejection fraction (<35%), New York Heart Association functional class II-III symptoms, implanted with a cardiac resynchronization therapy-defibrillator or and implantable cardioverter defibrillator, who had either a hospitalization for HF within 12 months or unscheduled visit for HF exacerbation within 90 days or an elevated natriuretic peptide concentration (brain natriuretic peptide [BNP] of ≥150 pg/mL or N-terminal pro-BNP [NT-proBNP] of ≥600 pg/mL). This phase included the development of an alert management guide and evaluated changes in medical treatment, natriuretic peptide levels, and safety. RESULTS: The mean age of participants was 67 years, 68% were men, 81% were White, and 61% had a HF hospitalization in prior 12 months. During follow-up, there were 585 alert cases with an average of 1.76 alert cases per patient-year. HF medications were augmented during 74% of the alert cases. HF treatment augmentation within 2 weeks from an initial alert was associated with more rapid recovery of the HeartLogic Index. Five serious adverse events (0.015 per patient-year) occurred in relation to alert-prompted medication change. NTproBNP levels decreased from median of 1316 pg/mL at baseline to 743 pg/mL at 12 months (P < .001). CONCLUSIONS: HeartLogic alert management was safely implemented in HF care and may optimize HF management. This phase supports further evaluation in larger studies. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03237858).

Temporal Association of Atrial Fibrillation With Cardiac Implanted Electronic Device Detected Heart Failure Status.

OBJECTIVES: This study sought to investigate the temporal association between changes in physiologic heart failure (HF) sensors, atrial fibrillation (AF) progression, and clinical HF in patients with cardiac resynchronization therapy implantable defibrillators (CRT-D) designed to monitor AF and HF daily. BACKGROUND: AF is a common comorbidity in HF; however, it is unclear if HF triggers AF, or vice-versa. Current implantable cardiac devices have sensors capable of quantifying HF status, which permits a greater understanding of the impact of AF on HF status and may help guide treatment. METHODS: The MultiSENSE (Multisensor Chronic Evaluation in Ambulatory Heart Failure Patients) study collected multiple sensor data indicative of HF status in patients with CRT-D followed for up to 12 months. Patients were grouped according to their longest daily AF burden: 1) at least 24 hours of AF (HIGH AF); 2) between 6 minutes and 24 hours (MID AF); and 3) <6 minutes (NO AF). Sensor data were aligned to the first qualifying AF event or a randomly selected day for patients in the NO AF group. RESULTS: Among 869 patients with daily AF data available, 98 patients had HIGH AF, 141 patients MID AF, and 630 patients NO AF. At baseline, history of AF, N-terminal pro hormone B-type natriuretic peptide and device-measured S3 were associated with development of AF. HeartLogic index increased before AF onset (Δ HeartLogic = 9.83 ± 2.49; P < 0.001). Multivariable time-dependent Cox regression showed an increased risk for HF events following a 24-hour AF episode compared with no 24-hour AF (hazard ratio: 1.96; 95% confidence interval: 1.03-3.74). CONCLUSIONS: Device-measured HF indicators worsened before AF onset, whereas clinical HF deterioration only became apparent after AF occurred. Thus, the sensitivity of methods to ascertain AF and HF status appear to influence the direction of perceived causality. (Multisensor Chronic Evaluation in Ambulatory Heart Failure Patients [MultiSENSE]; NCT01128166).

Multiparameter diagnostic sensor measurements in heart failure patients presenting with SARS-CoV-2 infection.

AIMS: Implantable device-based sensor measurements including heart sounds, markers of ventilation, and thoracic impedance have been shown to predict heart failure (HF) hospitalizations. We sought to assess how these parameters changed prior to COVID-19 (Cov-19) and how these compared with those presenting with decompensated HF or pneumonia. METHODS AND RESULTS: This retrospective analysis explores patterns of changes in daily measurements by implantable sensors in 10 patients with Cov-19 and compares these findings with those observed prior to HF (n = 88) and pneumonia (n = 12) hospitalizations from the MultiSENSE, PREEMPT-HF, and MANAGE-HF trials. The earliest sensor changes prior to Cov-19 were observed in respiratory rate (6 days) and temperature (5 days). There was a three-fold to four-fold greater increase in respiratory rate, rapid shallow breathing index, and night heart rate compared with those presenting with HF or pneumonia. Furthermore, activity levels fell more in those presenting with Cov-19, a change that was often sustained for some time. In contrast, there were no significant changes in 1st or 3rd heart sound (S1 and S3 ) amplitude in those presenting with Cov-19 or pneumonia compared with the known changes that occur in HF decompensation. CONCLUSIONS: Multi-sensor device diagnostics may provide early detection of Cov-19, distinguishable from worsening HF by an extreme and fast rise in respiratory rate along with no changes in S3.

Small decreases in biventricular pacing percentages are associated with multiple metrics of worsening heart failure as measured from a cardiac resynchronization therapy defibrillator.

BACKGROUND: Lower BiVentricular (BiV) pacing percentages have been associated with significantly worse survival in patients with chronic heart failure (HF). However, the pathophysiology behind this observation has not been further delineated. This analysis evaluated whether small incremental decreases in BiV pacing percentages were associated with worse measures, related to HF physiology using individual sensor trends and the HeartLogic composite index. METHODS: Sensor data was obtained from 900 ambulatory HF patients with implanted CRT devices. The percent of cardiac cycles with BiV pacing was assessed for periods (median = 7.3 days) between data downloads (median = 55 periods/patient). RESULTS: The third heart sound (S3), respiration rate, RSBI, and night-time heart rate were significantly elevated with sub-optimal pacing (<98%), while the first heart sound (S1), thoracic impedance, and activity were significantly lower. All sensor changes were in the direction associated with worsening HF. While IN the HeartLogic alert state (threshold above an Index of 16) the odds of optimal BiV pacing (≥98%) were less than when OUT of the HeartLogic alert state for a given subject (OR: 0.655; 95% CI: 0.626-0.686; p < 0.0001). The percent BiV pacing was reduced and the HeartLogic Index was increased in the periods surrounding HFhospitalizations. CONCLUSION: Lower BiV pacing percent is associated with multiple sensor changes indicative of worsening HF, and patients in HeartLogic alert are more likely to have suboptimal BiV pacing. Collectively, these data provide strong evidence that even small decreases in BiV percent pacing can lead to worsening HF.

Physical Activity Patterns Among Patients with Intracardiac Remote Monitoring Devices Before, During, and After COVID-19-related Public Health Restrictions.

Nationwide public health restrictions due to the coronavirus disease 2019 (COVID-19) pandemic have disrupted people's routine physical activities, yet little objective information is available on the extent to which physical activity has changed among patients with pre-existing cardiac diseases. Using remote monitoring data of 9,924 patients with pacemakers and implantable cardiac defibrillators (ICDs) living in New York City and Minneapolis/Saint Paul, we assessed physical activity patterns among these patients in 2019 and 2020 from January through October. We found marked declines in physical activity among patients with implantable cardiac devices during COVID-19-related restrictions and the reduction was consistent across age and sex subgroups. Moreover, physical activity among these vulnerable patients did not return to pre-restrictions levels several months after COVID-19 restrictions were eased. Our findings highlight the need to consider the unintended consequences of mitigation strategies and develop approaches to encourage safe physical activity during the pandemic.

Trends in Thoracic Impedance and Arrhythmia Burden Among Patients with Implanted Cardiac Defibrillators During the COVID-19 Pandemic.

Hospitalizations for acute cardiac conditions have markedly declined during the coronavirus disease 2019 (COVID-19) pandemic, yet the cause of this decline is not clear. Using remote monitoring data of 4,029 patients with implantable cardiac defibrillators (ICDs) living in New York City and Minneapolis/Saint Paul, we assessed changes in markers of cardiac status among these patients and compared thoracic impedance and arrhythmia burden in 2019 and 2020 from January through August. We found no change in several key disease decompensation markers among patients with implanted ICD devices during the first phase of COVID-19 pandemic, suggesting that the decrease in cardiovascular hospitalizations in this period is not reflective of a true population-level improvement in cardiovascular health.

Field Assisted Reactive Gas Etching of Multiple Tips Observed using FIM.

A simple and cost effective method to fabricate multiple tungsten (W) single atom tips (SATs) from both poly and single crystalline wires is reported. Two or four tips attached to a holder are electrochemically etched together in NaOH solution followed by a controlled field assisted reactive gas etching in vacuum using nitrogen as an etching gas and helium as an imaging gas. A Common high voltage is applied simultaneously to all nanotips to shape the apexes towards single atoms. Single atom tips were achieved for both W(111) and W(110) while trimer tips were also achieved for W(111). This observation can lead to an important step towards realizing simplified etching processes of multiple tips which in turn can help to simultaneously fabricate numerous tips leading to mass fabrication and characterization.

Case Reports of Implantable Cardiac Device Physiologic Sensor Changes in Subjects with Coronavirus Disease-2019 Infection.

The severe acute respiratory syndrome novel coronavirus-2 pandemic has established a new set of challenges to health care delivery. Remotely monitored physiologic sensors on implantable cardiac devices can provide insight into the differential diagnosis of dyspnea in the heart failure population. We report on a unique pattern of sensor deviations that seem to occur specifically with severe acute respiratory syndrome novel coronavirus-2 infection.

Quantitative Multilayer Cu(410) Structure and Relaxation Determined by QLEED.

Industrially relevant catalytically active surfaces exhibit defects. These defects serve as active sites; expose incoming adsorbates to both high and low coordinated surface atoms; determine morphology, reactivity, energetics, and surface relaxation. These, in turn, affect crystal growth, oxidation, catalysis, and corrosion. Systematic experimental analyses of such surface defects pose challenges, esp., when they do not exhibit order. High Miller index surfaces can provide access to these features and information, albeit indirectly. Here, we show that with quantitative low-energy electron diffraction (QLEED) intensity analyses and density functional theory (DFT) calculations, we can visualize the local atomic configuration, the corresponding electron distribution, and local reactivity. The QLEED-determined Cu(410) structure (Pendry reliability factor RP ≃ 0.0797) exhibits alternating sequences of expansion (+) and contraction (-) (of the first 16 atomic interlayers) relative to the bulk-truncated interlayer spacing of ca. 0.437 Å. The corresponding electron distribution shows smoothening relative to the bulk-determined structure. These results should aid us to further gain an atomic-scale understanding of the nature of defects in materials.

Expert Coaching in Weight Loss: Retrospective Analysis.

BACKGROUND: Providing coaches as part of a weight management program is a common practice to increase participant engagement and weight loss success. Understanding coach and participant interactions and how these interactions impact weight loss success needs to be further explored for coaching best practices. OBJECTIVE: The purpose of this study was to analyze the coach and participant interaction in a 6-month weight loss intervention administered by Retrofit, a personalized weight management and Web-based disease prevention solution. The study specifically examined the association between different methods of coach-participant interaction and weight loss and tried to understand the level of coaching impact on weight loss outcome. METHODS: A retrospective analysis was performed using 1432 participants enrolled from 2011 to 2016 in the Retrofit weight loss program. Participants were males and females aged 18 years or older with a baseline body mass index of ≥25 kg/m², who also provided at least one weight measurement beyond baseline. First, a detailed analysis of different coach-participant interaction was performed using both intent-to-treat and completer populations. Next, a multiple regression analysis was performed using all measures associated with coach-participant interactions involving expert coaching sessions, live weekly expert-led Web-based classes, and electronic messaging and feedback. Finally, 3 significant predictors (P<.001) were analyzed in depth to reveal the impact on weight loss outcome. RESULTS: Participants in the Retrofit weight loss program lost a mean 5.14% (SE 0.14) of their baseline weight, with 44% (SE 0.01) of participants losing at least 5% of their baseline weight. Multiple regression model (R2=.158, P<.001) identified the following top 3 measures as significant predictors of weight loss at 6 months: expert coaching session attendance (P<.001), live weekly Web-based class attendance (P<.001), and food log feedback days per week (P<.001). Attending 80% of expert coaching sessions, attending 60% of live weekly Web-based classes, and receiving a minimum of 1 food log feedback day per week were associated with clinically significant weight loss. CONCLUSIONS: Participant's one-on-one expert coaching session attendance, live weekly expert-led interactive Web-based class attendance, and the number of food log feedback days per week from expert coach were significant predictors of weight loss in a 6-month intervention.

What Matters in Weight Loss? An In-Depth Analysis of Self-Monitoring.

BACKGROUND: Using technology to self-monitor body weight, dietary intake, and physical activity is a common practice used by consumers and health companies to increase awareness of current and desired behaviors in weight loss. Understanding how to best use the information gathered by these relatively new methods needs to be further explored. OBJECTIVE: The purpose of this study was to analyze the contribution of self-monitoring to weight loss in participants in a 6-month commercial weight-loss intervention administered by Retrofit and to specifically identify the significant contributors to weight loss that are associated with behavior and outcomes. METHODS: A retrospective analysis was performed using 2113 participants enrolled from 2011 to 2015 in a Retrofit weight-loss program. Participants were males and females aged 18 years or older with a starting body mass index of ≥25 kg/m2, who also provided a weight measurement at the sixth month of the program. Multiple regression analysis was performed using all measures of self-monitoring behaviors involving weight measurements, dietary intake, and physical activity to predict weight loss at 6 months. Each significant predictor was analyzed in depth to reveal the impact on outcome. RESULTS: Participants in the Retrofit Program lost a mean -5.58% (SE 0.12) of their baseline weight with 51.87% (1096/2113) of participants losing at least 5% of their baseline weight. Multiple regression model (R2=.197, P<0.001) identified the following measures as significant predictors of weight loss at 6 months: number of weigh-ins per week (P<.001), number of steps per day (P=.02), highly active minutes per week (P<.001), number of food log days per week (P<.001), and the percentage of weeks with five or more food logs (P<.001). Weighing in at least three times per week, having a minimum of 60 highly active minutes per week, food logging at least three days per week, and having 64% (16.6/26) or more weeks with at least five food logs were associated with clinically significant weight loss for both male and female participants. CONCLUSIONS: The self-monitoring behaviors of self-weigh-in, daily steps, high-intensity activity, and persistent food logging were significant predictors of weight loss during a 6-month intervention.

Retrofit Weight-Loss Outcomes at 6, 12, and 24 Months and Characteristics of 12-Month High Performers: A Retrospective Analysis.

BACKGROUND: Obesity is the leading cause of preventable death costing the health care system billions of dollars. Combining self-monitoring technology with personalized behavior change strategies results in clinically significant weight loss. However, there is a lack of real-world outcomes in commercial weight-loss program research. OBJECTIVE: Retrofit is a personalized weight management and disease-prevention solution. This study aimed to report Retrofit's weight-loss outcomes at 6, 12, and 24 months and characterize behaviors, age, and sex of high-performing participants who achieved weight loss of 10% or greater at 12 months. METHODS: A retrospective analysis was performed from 2011 to 2014 using 2720 participants enrolled in a Retrofit weight-loss program. Participants had a starting body mass index (BMI) of >25 kg/m² and were at least 18 years of age. Weight measurements were assessed at 6, 12, and 24 months in the program to evaluate change in body weight, BMI, and percentage of participants who achieved 5% or greater weight loss. A secondary analysis characterized high-performing participants who lost ≥10% of their starting weight (n=238). Characterized behaviors were evaluated, including self-monitoring through weigh-ins, number of days wearing an activity tracker, daily step count average, and engagement through coaching conversations via Web-based messages, and number of coaching sessions attended. RESULTS: Average weight loss at 6 months was -5.55% for male and -4.86% for female participants. Male and female participants had an average weight loss of -6.28% and -5.37% at 12 months, respectively. Average weight loss at 24 months was -5.03% and -3.15% for males and females, respectively. Behaviors of high-performing participants were assessed at 12 months. Number of weigh-ins were greater in high-performing male (197.3 times vs 165.4 times, P=.001) and female participants (222 times vs 167 times, P<.001) compared with remaining participants. Total activity tracker days and average steps per day were greater in high-performing females (304.7 vs 266.6 days, P<.001; 8380.9 vs 7059.7 steps, P<.001, respectively) and males (297.1 vs 255.3 days, P<.001; 9099.3 vs 8251.4 steps, P=.008, respectively). High-performing female participants had significantly more coaching conversations via Web-based messages than remaining female participants (341.4 vs 301.1, P=.03), as well as more days with at least one such electronic message (118 vs 108 days, P=.03). High-performing male participants displayed similar behavior. CONCLUSIONS: Participants on the Retrofit program lost an average of -5.21% at 6 months, -5.83% at 12 months, and -4.09% at 24 months. High-performing participants show greater adherence to self-monitoring behaviors of weighing in, number of days wearing an activity tracker, and average number of steps per day. Female high performers have higher coaching engagement through conversation days and total number of coaching conversations.

Using Capsule Endoscopy at an Academic Teaching Hospital in West Virginia: A Descriptive Analysis of our 7 year Experience and Determination of Diagnostic Yield for Obscure Gastrointestinal Bleeding.

Background: The aim of our study was to describe, analyze, and evaluate results of wireless capsule endoscopy (CE) as an imaging modality for various indications. Methods: We conducted a retrospective chart review study of all CE studies performed between January 1, 2007 and June 30, 2014 at Marshall University. The study included 272 patients between the ages of 21-85 years old. Results: The most common finding in our study was a normal study (57.7%) followed by small bowel erosions (14.3%), neoplasms (11.4%), Arteriovenous malformations (10.7%), inflammatory bowel disease (2.6%), and nonspecific findings (3.3%). Discussion: 90/209 patients who had indications for IDA, melena, or heme-positive stools demonstrated positive findings by CE; our diagnostic yield for obscure GI bleeding was therefore 43.1%.

MELD-Na as a prognostic indicator of 30- and 90-day mortality in patients with end-stage liver disease after creation of transjugular intrahepatic portosystemic shunt.

Previous studies have shown that the Model for End-Stage Liver Disease (MELD) score is superior to other liver disease scoring systems to establish optimal candidates for transjugular intrahepatic portosystemic shunt (TIPS) procedure and liver transplantation. Our aim was to compare MELD-Na score with MELD score as a predictor of 30-day as well as 90-day mortality for individuals with end-stage liver disease (ESLD) after creation of TIPS. We performed a chart review on cirrhotic patients who underwent TIPS procedure and documented presence and severity of ascites and hepatic encephalopathy, patient laboratory values, and results from TIPS procedures. We compared continuous variables by Student's t-test for independent samples and categorical variables by χ-test(s). In non-normal distributions, a nonparametric test was used. We performed a logistic regression to determine the effects of several variables and analyzed variable predictors of likelihood of death within 30 and 90 days of TIPS procedure. Of the six predictor variables, only MELD-Na score was a statistically significant predictor of 30- and 90-day mortality following TIPS procedure for ESLD (P=0.028). For each one point increase in MELD-Na score, the odds of death increased by 1.15 times [95% confidence interval (1.02-1.30), P=0.28]. Since hyponatremia may be associated with poor prognostic features of overall health, its incorporation into the MELD scoring system to predict mortality in ESLD after creation of TIPS serves a useful purpose. Our single-center experience suggests that the MELD-Na score is the most effective predictor of survival after TIPS creation.

Acute cardiomyopathy and multiorgan failure in a patient with pheochromocytoma and neurofibromatosis type 1.

Pheochromocytomas are catecholamine secreting tumours of the adrenal gland, discovered in 0.1% of patients with hypertension. Our case highlights an atypical presentation of pheochromocytoma in a patient with Neurofibromatosis type 1 who developed cardiogenic shock with multi-organ failure. The patient demonstrated reversible dilated cardiomyopathy during her hospital stay, and her blood pressure fluctuated widely. Discovery of right adrenal mass followed by biochemical testing facilitated the diagnosis. Judicious medical management led to an uneventful surgical removal of the tumour followed by marked stabilization of her blood pressure. We discuss the characteristics of pheochromocytoma associated with Neurofibromatosis type 1 via reversible cardiac dysfunction.

Screening diabetic and hypertensive patients for ocular pathology using telemedicine technology in rural West Virginia: a retrospective chart review.

PURPOSE: There is a disparity between the number of people who need healthcare and availability of medical services in rural areas. This paper describes the experience of using telemedicine technologies for ophthalmologic evaluation in diabetic and hypertensive patients presenting to a community health center in rural West Virginia. METHODS: A registered nurse at a community health center in McDowell County, WV was trained to use a retinal camera to capture high-resolution digital images of the retina. Patients with diabetes or hypertension were screened during their routine primary care visits. Retinal photos were transmitted to an ophthalmologist for review and reports from the screenings were returned with instruction for follow-up care or specialist referral when indicated. FINDINGS: A retrospective chart review of 643 patients with diabetes or hypertension who were screened for ocular problems from October 2003 to December 2009 was completed. 44.8% of patients who were screened in the primary care center were identified as having 1 of 34 types of eye pathology that were previously unknown, of which 33% of patients were recommended to seek prompt attention by a retina consultant or glaucoma specialist for suspected ocular pathology. CONCLUSIONS: Our review demonstrates the actual benefits of telemedicine in the effective screening of diabetic and hypertensive patients for eye pathology, and our experience suggests that using distance medicine and telemedicine technologies is valuable for screening rural populations.