Normal Values of Esophageal Distensibility and Distension-Induced Contractility Measured by Functional Luminal Imaging Probe Panometry.

BACKGROUND & AIMS: Functional luminal imaging probe (FLIP) panometry provides a comprehensive evaluation of esophageal functional at the time of endoscopy, including assessment of esophageal distensibility and distension-induced esophageal contractility. However, the few and inconsistent findings from healthy individuals pose challenges to the application of FLIP to research and clinical practice. We performed FLIP panometry in asymptomatic volunteers. METHODS: We performed a prospective study of 20 asymptomatic volunteers (ages, 23-44; 14 women) who were evaluated with 16-cm FLIP positioned across the esophagogastric junction (EGJ) and distal esophagus (and in 8 subjects also repositioned at the proximal esophagus) during sedated upper endoscopy. FLIP data were analyzed with a customized program that generated FLIP panometry plots and calculated the EGJ-distensibility index (DI) and distensibility plateaus (DP) of distal and proximal esophageal body. Distension-induced esophageal contractility was also assessed. RESULTS: The median EGJ-DI was 5.8 mm2/mm Hg (interquartile range [IQR], 4.9-6.7 mm2/mm Hg); all 20 subjects had an EGJ-DI greater than 2.8 mm2/mm Hg. The median DP values from all subjects tested were 20.2 mm (IQR, 19.8-20.8 mm) at the distal body, 21.1 mm (IQR, 20.3-22.9 mm) at the proximal body, and greater than 18 mm at both locations. Repetitive antegrade contractions (RACs) were observed in all 20 subjects; in 19 of 20 (95%) subjects, the RAC pattern persisted for 10 or more consecutive antegrade contractions. CONCLUSIONS: Normal parameters of FLIP panometry are EGJ-DI greater than 2.8 mm2/mm Hg, DP greater than 18 mm, and antegrade contractions that occur in a repetitive pattern (RACs)-these can be used as normal findings for esophageal distensibility and distension-induced contractility. These values can be used in comparative studies of esophageal diseases, such as achalasia and eosinophilic esophagitis, and will facilitate application of FLIP panometry to clinical practice.

Tissue-resident, extravascular Ly6c- monocytes are critical for inflammation in the synovium.

Monocytes are abundant immune cells that infiltrate inflamed organs. However, the majority of monocyte studies focus on circulating cells, rather than those in tissue. Here, we identify and characterize an intravascular synovial monocyte population resembling circulating non-classical monocytes and an extravascular tissue-resident monocyte-lineage cell (TR-MC) population distinct in surface marker and transcriptional profile from circulating monocytes, dendritic cells, and tissue macrophages that are conserved in rheumatoid arthritis (RA) patients. TR-MCs are independent of NR4A1 and CCR2, long lived, and embryonically derived. TR-MCs undergo increased proliferation and reverse diapedesis dependent on LFA1 in response to arthrogenic stimuli and are required for the development of RA-like disease. Moreover, pathways that are activated in TR-MCs at the peak of arthritis overlap with those that are downregulated in LFA1-/- TR-MCs. These findings show a facet of mononuclear cell biology that could be imperative to understanding tissue-resident myeloid cell function in RA.

Weighing the Association Between BMI Change and Suicide Mortality.

OBJECTIVE: Suicide rates continue to rise, necessitating the identification of risk factors. Obesity and suicide mortality rates have been examined, but associations among weight change, death by suicide, and depression among adults in the United States remain unclear. METHODS: Data from 387 people who died by suicide in 2000-2015 with a recorded body mass index (BMI) in the first and second 6 months preceding their death ("index date") were extracted from the Mental Health Research Network. Each person was matched with five people in a control group (comprising individuals who did not die by suicide) by age, sex, index year, and health care site (N=1,935). RESULTS: People who died by suicide were predominantly male (71%), White (69%), and middle aged (mean age=57 years) and had a depression diagnosis (55%) and chronic health issues (57%) (corresponding results for the control group: 71% male, 66% White, 14% with depression diagnosis, and 43% with chronic health issues; mean age=56 years). Change in BMI within the year before the index date statistically significantly differed between those who died by suicide (mean change=-0.72±2.42 kg/m2) and the control group (mean change=0.06±4.99 kg/m2) (p<0.001, Cohen's d=0.17). A one-unit BMI decrease was associated with increased risk for suicide after adjustment for demographic characteristics, mental disorders, and Charlson comorbidity score (adjusted odds ratio=1.11, 95% confidence interval=1.05-1.18, p<0.001). For those without depression, a BMI change was significantly associated with suicide (p<0.001). CONCLUSIONS: An increased suicide mortality rate was associated with weight loss in the year before a suicide after analyses accounted for general and mental health indicators.

Current and Future Challenges in the Delivery of Mental Healthcare during COVID-19.

The USA is in the midst of the COVID-19 pandemic. We assess the impact of COVID-19 on psychiatric symptoms in healthcare workers, those with psychiatric comorbidities, and the general population. We highlight the challenges ahead and discuss the increased relevance of telepsychiatry. We analyzed all available literature available as of March 25, 2020, on PubMed, Ovid Medline, and PsychInfo. We utilized the MeSH term "covid AND (psychiatry OR mental health)" and included all articles. Duplicates were removed resulting in 32 articles, of which 19 are cited. Four additional references are included to examine suicide data. During the review process, an additional 7 articles were identified which are also included. Frontline healthcare workers are currently experiencing increased psychiatric symptoms and this is more severe in females and nurses. Non-frontline healthcare workers, as well as the general population, are experiencing vicarious traumatization. People with psychiatric comorbidities, and the general population, face increased psychiatric symptom burden. Migrant workers, the elderly, children, and the homeless may be disproportionately impacted. Suicide rates may be impacted. The COVID-19 pandemic has resulted in a severe disruption to the delivery of mental healthcare. Psychiatric facilities are facing unprecedented disruptions in care provision as they struggle to manage an infected population with comorbid psychiatric symptoms. Telepsychiatry is a flawed but reasonable solution to increase the availability of mental healthcare during COVID-19.

The Impact of Socioeconomic Status, Race/Ethnicity, and Patient Perceptions on Medication Adherence in Depression Treatment.

OBJECTIVE: Nonadherence to pharmacotherapy for psychiatric conditions is associated with poor outcomes, including increased risk of relapse, increased health care costs, and reduced quality of life. The objective of this study was to investigate the strength of association between socioeconomic factors, race/ethnicity, and patient perceptions with medication adherence in individuals with depression. METHODS: Baseline surveys were sent out in 2012 to 4,216 adult patients within a large health system who presented with a clinical diagnosis of major depressive disorder (ICD-9), recorded at least twice in the electronic medical record in the year 2011. A total of 1,573 patients responded to the baseline survey. Of those, 1,209 patients who completed the survey and had used antidepressants in the last 12 months were recruited for the study. Perception of medication risk was assessed using the Beliefs About Medicines Questionnaire, and adherence to medications was assessed using the Morisky Medication Adherence Scale. Logistic regression was used to investigate the relationship between perception of medicine risk and treatment adherence. RESULTS: For non-Hispanic white individuals, medication adherence was higher among those who were least concerned about the risk of medications (64%; 95% CI, 58-70) compared to those who were most concerned (34%; 95% CI, 26-43). In the logistic regression model, less concern about medications and their side effects was associated with higher medication adherence (odds ratio = 2.6; 95% CI, 1.77-3.84; P < .0001). This association remained significant after adjustment for age, race, education level, and extramedical use of other medications or substances. Moreover, patients with older age and lower education level as well as those who were non-Hispanic white and had no extramedical use of other medications/substances were more likely to be adherent to medications. CONCLUSIONS: This study contributes quantitative data on factors that impact treatment adherence. Identifying patients at increased risk of nonadherence, having discussions with patients early in the treatment process to understand their concerns regarding treatment options, being sensitive to cultural beliefs, and patiently proceeding with the decision-making process could help ensure better outcomes.

Complementary therapies for patients with systemic sclerosis.

Patients with systemic sclerosis often seek information regarding complementary and nutrition-based therapy. Some study results have shown that vitamins D and E, probiotics, turmeric, l-arginine, essential fatty acids, broccoli, biofeedback, and acupuncture may be beneficial in systemic sclerosis care. However, large randomized clinical trials have not been conducted. This review summarizes current data regarding various complementary therapies in systemic sclerosis and concludes with recommendations.

Diffuse cardiac fibrosis quantification in early systemic sclerosis by magnetic resonance imaging and correlation with skin fibrosis.

PURPOSE: To evaluate the utility of cardiac magnetic resonance (CMR) T1 mapping in early systemic sclerosis (SSc) and its association with skin score. METHODS: Twenty-four consecutive patients with early SSc referred for cardiovascular evaluation and 12 controls without SSc were evaluated. All patients underwent cine, T1 mapping, and late gadolinium enhanced (LGE) CMR imaging. T1 mapping indices were compared between SSc patients and controls (extracellular volume fraction [ECV], gadolinium partition coefficient [λ], pre-contrast T1, and post-contrast T1). The association between T1 mapping parameters and the modified Rodnan skin score (mRSS) was determined. RESULTS: There were no significant differences in cardiac structure/function between SSc patients and controls on cine imaging, and 8/24 (33%) SSc patients had evidence of LGE (i.e., focal myocardial fibrosis). Of the T1 mapping parameters (indices indicative of diffuse myocardial fibrosis), ECV differentiated SSc patients from controls the best, followed by λ, even when the eight SSc patients with LGE were excluded. ECV had a sensitivity and specificity of 75% and 75% for diffuse myocardial fibrosis (optimal abnormal cut-off value of >27% [area under ROC curve=0.85]). In the 16 patients without evidence of LGE, each of the 4 CMR T1 mapping parameters (ECV, λ, Pre-T1 and Post-T1) correlated with mRSS (R=0.51-0.65, P=0.007-0.043), indicating a correlation between SSc cardiac and skin fibrosis. CONCLUSIONS: The four T1 mapping indices are significantly correlated with mRSS in patients with early SSc. Quantification of diffuse myocardial fibrosis using ECV should be considered as a marker for cardiac involvement in SSc clinical studies.

Transcriptional Profiling of Synovial Macrophages Using Minimally Invasive Ultrasound-Guided Synovial Biopsies in Rheumatoid Arthritis.

OBJECTIVE: Currently, there are no reliable biomarkers for predicting therapeutic response in patients with rheumatoid arthritis (RA). The synovium may unlock critical information for determining efficacy, since a reduction in the numbers of sublining synovial macrophages remains the most reproducible biomarker. Thus, a clinically actionable method for the collection of synovial tissue, which can be analyzed using high-throughput strategies, must become a reality. This study was undertaken to assess the feasibility of utilizing synovial biopsies as a precision medicine-based approach for patients with RA. METHODS: Rheumatologists at 6 US academic sites were trained in minimally invasive ultrasound-guided synovial tissue biopsy. Biopsy specimens obtained from patients with RA and synovial tissue from patients with osteoarthritis (OA) were subjected to histologic analysis, fluorescence-activated cell sorting, and RNA sequencing (RNA-seq). An optimized protocol for digesting synovial tissue was developed to generate high-quality RNA-seq libraries from isolated macrophage populations. Associations were determined between macrophage transcriptional profiles and clinical parameters in RA patients. RESULTS: Patients with RA reported minimal adverse effects in response to synovial biopsy. Comparable RNA quality was observed from synovial tissue and isolated macrophages between patients with RA and patients with OA. Whole tissue samples from patients with RA demonstrated a high degree of transcriptional heterogeneity. In contrast, the transcriptional profile of isolated RA synovial macrophages highlighted different subpopulations of patients and identified 6 novel transcriptional modules that were associated with disease activity and therapy. CONCLUSION: Performance of synovial tissue biopsies by rheumatologists in the US is feasible and generates high-quality samples for research. Through the use of cutting-edge technologies to analyze synovial biopsy specimens in conjunction with corresponding clinical information, a precision medicine-based approach for patients with RA is attainable.