Association of Lipoprotein (a) with peri-coronary inflammation in persons with and without HIV infection.

BACKGROUND: Persons with HIV (PWH) have an increased risk of developing cardiovascular disease (CVD) compared to persons without HIV (PWoH). Lipoprotein a (Lp(a)) is a known atherosclerotic risk factor in PWoH, but there are no studies investigating Lp(a) and peri-coronary inflammation. OBJECTIVE: To investigate whether Lp(a) is associated with peri-coronary inflammation as assessed by the fat attenuation index (FAI) and activated monocytes and T lymphocytes in PWH and PWoH. METHODS: We measured plasma levels of Lp(a) at study entry in 58 PWH and 21 PWoH without CVD and who had FAI measurements. Associations of Lp(a) with FAI values of the right coronary artery (RCA) and left anterior descending artery (LAD) were evaluated using multivariable regression models adjusted for potential confounders. Correlations between Lp(a) levels and systemic inflammatory markers and immune cell subsets were examined. RESULTS: Lp(a) was associated with greater peri-coronary inflammation among PWH compared to PWoH (ß=1.73, P=0.019) in the RCA, in adjusted models. Significant correlations were observed with certain inflammatory markers (TNFR-I, b=0.295, P<0.001; TNFR-II, b=0.270, P=0.002; hs-CRP, b=0.195, P=0.028). Significant correlations were found between Lp(a) levels and several markers of monocyte activation: CD16 -CD163+ (b= -0.199, P=0.024), and CD16 -DR+ MFI (b= -0.179, P=0.042) and T cell subset CD38+CD4+ TEMRA (b= 0.177, P= 0.044). CONCLUSIONS: Lp(a) was associated with greater peri-coronary inflammation in the RCA in PWH compared to PWoH, as well as with select systemic inflammatory markers and specific subsets of immune cells in peripheral circulation.

A Multimodal Ayurveda and Mind-Body Therapeutic Intervention for Chronic Symptoms Attributed to a Postinfectious Syndrome: A Pilot Study.

Objective: Evaluate feasibility and impact of a multimodal integrative therapeutic intervention in patients presenting with chronic symptoms attributed to a postinfectious syndrome. Design: This was a prospective longitudinal single-center pilot study conducted from January 2019 to December 2020. Setting/Location: University of Maryland Lyme Program, Baltimore Maryland. Subjects: Persons presenting for Lyme evaluation for symptoms attributed to Lyme disease. Interventions: Participants attended two 1-h individual instructional sessions consisting of Ayurveda-based dietary intervention and breath-coordinated mind-body practice to be used for home practice. Outcome measures: Standard measures of impact were obtained at baseline, 1, 3, 6, and 12 months using the following validated survey instruments: Perceived Stress Scale (PSS), PROMIS Global Health v1.2 (GH), and PROMIS 29 v2.0 survey. Results: From 216 patients presenting for Lyme evaluation, 19 participants enrolled with 84% completing the study (N = 16). Baseline PROMIS GH scores consisting of general Physical Health (GPH) and general Mental Health (GMH) scores were lower in the study population than in the general U.S. population. PROMIS 29 scores were higher for fatigue, anxiety, and pain than those in the general U.S. population. Over 12-month period, improvement in both the GPH and GMH was 6.09 (confidence interval [95% CI] = 2.71-9.46; p < 0.001) and 4.65 (95% CI = 1.50-7.80; p = 0.004), respectively. PROMIS 29 scores showed the greatest improvement in fatigue at -7.91 (95% CI = -12.34 to -3.48; p < 0.001), pain interference -5.08 (95% CI = -9.20 to -0.96; p = 0.016), and ability to participate in social roles and activities 7.48 (95% CI = 3.21-11.75; p = 0.001) and least with depression -1.82 (95% CI = -4.74 to 1.10; p = 0.223). Employment status had significant effects on almost all outcome scores. Postinfectious state was associated with improvement in anxiety and PSS scores. Conclusions: A multimodal Ayurvedic and breath-coordinated mind-body therapeutic intervention is feasible and a potential nonpharmacologic therapeutic option for persons presenting with pain, stress, fatigue, physical dysfunction, and sleep disturbance attributed to a postinfectious syndrome. Further research is needed to determine efficacy in this population and in other groups with similar symptom complexes due to postinfectious syndromes.

The Effect of Soy and Whey Protein Supplementation on Glucose Homeostasis in Healthy Normal Weight Asian Indians.

Milk and legumes are good source of protein foods used to sustain muscle mass, but their effects on postprandial glucose homeostasis and energy metabolism may be different. This is relevant, for example, in the dietetic response to obesity or diabetes, where the intake of high-quality protein is often increased significantly. The objective of this study was to characterize the acute effect of whey and soy protein (15% vs. 30%) on glucose homeostasis, energy metabolism, and satiety. Healthy, normal body mass index (BMI) Indian adult males aged 20-35 years (n = 15) received 4 test meals (2 proteins (soy vs. whey) and 2 doses (15% vs. 30% protein: energy ratio)). Blood samples were collected serially after the meal to calculate the incremental area under the curve for plasma glucose and insulin. Energy expenditure and substrate oxidation were measured after the meal. Satiety was measured with a visual analogue scale. The insulin response, represented by the incremental area under the curve, was significantly higher for the 30% whey compared to the 30% soy protein meal (p < 0.01) but was not significantly different between the 15% protein doses. There were no differences in the plasma glucose response across protein sources or doses. The mean peak fat and carbohydrate oxidation, satiety, and energy expenditure did not differ between the protein sources and doses. In conclusion, at higher doses, whey protein has a greater insulinogenic response, compared to soy protein, and exhibits a dose-response effect. However, at lower doses, whey and soy protein elicit similar insulinogenic responses, making them equally effective protein sources in relation to glucose homoeostasis.

Predictors of Nonadherence Among Patients With Infectious Complications of Substance Use Who Are Discharged on Parenteral Antimicrobial Therapy.

Background: The management of invasive infections related to substance use disorder (SUD) needing parenteral antimicrobial therapy is challenging and may have poor treatment outcomes including nonadherence and lack of completion of parenteral antimicrobial therapy. Methods: In this retrospective cohort of 201 patients with invasive infections related to SUD, we looked at frequency and determinants of unfavorable outcomes including nonadherence. Results: Seventy-nine percent of patients with SUD-related infection completed parenteral antibiotic therapy in skilled nursing facilities. A total of 21.5% of patient episodes had documentation of nonadherence. Nonadherence was higher in patients with active injection drug use (IDU) (28.5% versus 15% in non IDU; adjusted odds ratio [OR] 2.36; 95% confidence interval [CI], 1.1-5.5; P = .024), patients with active SUD in the prior year (24.5% vs 11%, P = .047), patients with use of more than 1 illicit substance (30.3% vs 17%, P = .031), as well as in people experiencing homelessness (32.8% vs 15.7% in stably housed, P = .005). In a multivariate model, nonadherence was significantly associated with IDU (OR, 2.38; 95% CI, 1.03-5.5) and homelessness (OR, 2.25; 95% CI, 1.01-4.8) Medication for opioid use disorder was prescribed at discharge in 68% of overall cohort and was not associated with improved outcomes for any of the above groups. Conclusions: Nonadherence to parenteral antimicrobial therapy is high in the most vulnerable patients with unstable high-risk SUD and adverse social determinants of health.

Documentation quality of patient-directed discharge and early warning interactions in an adult inpatient service.

Documentation quality of patient-physician discussion, assessment, and intervention at the time of patient-directed discharges (elopement and 'against medical advice' discharges) is found to be poor in available studies and, importantly, may be a proxy for quality of care delivered. Less is known about the patient-physician interactions and documentation at the time a patient vocalizes the desire to leave early ('early warning interaction') prior to a patient-directed discharge. This was a cohort study comprising a retrospective chart review of patients leaving 'against medical advice' from an inpatient internal medicine-infectious disease service at a tertiary medical center from 01 July 2020 to 24 September 2021. Documentation quality was assessed using 11 extractable factors detailing patient-physician conversation elements from the assess, investigate, mitigate, explain, and document framework, plus related interventions pertinent to patient safety and care optimization. Descriptive statistics were mainly utilized with inferential statistics and regression models as appropriate. Fifty-two patients left against medical advice and 49 eloped; 11% had an early warning interaction. Aggregate documentation quality scores at early warning interaction (13%), 'against medical advice' discharge (42%), and at elopement (31%) were low. Half of the suggested documentation elements were recorded in no patients. The overall documentation quality was poor, suggesting the need for further training and interventions to facilitate more thorough documentation.

Hepatitis C cure and medications for opioid use disorder improve health-related quality of life in patients with opioid use disorder actively engaged in substance use.

BACKGROUND: This study aims to determine whether Hepatitis C (HCV) treatment improves health-related quality of life (HRQL) in patients with opioid use disorder (OUD) actively engaged in substance use, and which variables are associated with improving HRQL in patients with OUD during HCV treatment. METHODS: Data are from a prospective, open-label, observational study of 198 patients with OUD or opioid misuse within 1 year of study enrollment who received HCV treatment with the primary endpoint of Sustained Virologic Response (SVR). HRQL was assessed using the Hepatitis C Virus Patient Reported Outcomes (HCV-PRO) survey, with higher scores denoting better HRQL. HCV-PRO surveys were conducted at Day 0, Week 12, and Week 24. A mixed-effects model investigated which variables were associated with changing HCV-PRO scores from Day 0 to Week 24. RESULTS: Patients had a median age of 57 and were predominantly male (68.2%) and Black (83.3%). Most reported daily-or-more drug use (58.6%) and injection drug use (IDU) (75.8%). Mean HCV-PRO scores at Day 0 and Week 24 were 64.0 and 72.9, respectively. HCV-PRO scores at Week 24 improved compared with scores at Day 0 (8.7; p<0.001). Achieving SVR (10.4; p<0.001) and receiving medications for OUD (MOUD) at Week 24 (9.5; p<0.001) were associated with improving HCV-PRO scores. HCV-PRO scores increased at Week 24 for patients who experienced no decline in IDU frequency (8.1; p<0.001) or had a UDS positive for opioids (8.0; p<0.001) or cocaine (7.5; p=0.003) at Week 24. CONCLUSION: Patients with OUD actively engaged in substance use experience improvement in HRQL from HCV cure unaffected by ongoing substance use. Interventions to promote HCV cure and MOUD engagement could improve HRQL for patients with OUD.

Cancer in patients with and without HIV infection in the national cancer registry of Rwanda.

OBJECTIVE: As antiretroviral therapy (ART) has been widely scaled up in Rwanda, life expectancies among people with HIV (PWH) have increased. With increasing viral suppression, AIDS-defining cancers (ADCs) typically decrease; however, as the PWH population ages, non-AIDS-defining cancers (NADCs) will be expected to increase. The aim of this study was to compare cancer diagnoses between PWH and patients without HIV in Rwanda and to describe the changes in the number and types of cancer over time. DESIGN: Retrospective cohort study. METHODS: Rwanda National Cancer Registry (RNCR) recorded the HIV status, primary site, and morphological description for cancer diagnoses from 2007 to 2018. Descriptive analyses were carried out by cancer group (HIV+ and HIV-). A portion of patients whose HIV status was unknown (63%) were excluded from the present analysis. RESULTS: Among the 20 258 cases registered in the Registry, there were 1048 PWH and 6359 HIV- individuals. The proportion of ADCs were significantly higher in the PWH group compared to those without HIV ( P  < 0.001). Among PWH, there was a longitudinal increase in NADCs and a decrease in ADCs ( P  < 0.001) over time. Among the ADCs in the PWH group, there was a significant decline in Kaposi sarcoma cases over time. CONCLUSIONS: The study demonstrates a decreasing frequency of ADCs driven by declines in Kaposi sarcoma diagnoses and an increased frequency of NADCs among PWH in Rwanda over time. These findings support a need for focusing early detection and management efforts on NADCs, as they begin to play a larger role in the disease processes that affect the aging PWH population.

Predictors of in-hospital mortality in a cohort of people living with HIV (PLHIV) admitted to an academic medical intensive care unit from 2009 to 2014: A retrospective cohort study.

Outcomes for critically ill people living with human immunodeficiency virus (PLHIV) have changed with the use of antiretroviral therapy (ART). To identify these outcomes and correlates of mortality in a contemporary critically ill cohort in an urban academic medical center in Baltimore, a city with a high burden of HIV, we conducted a retrospective cohort study of individuals admitted to a medical intensive care unit (MICU) at a tertiary care center between 2009 and 2014. PLHIV who were at least 18 years of age with an index MICU admission of ≥24 hours during the 5-year study period were included in this analysis. Data were obtained for participants from the time of MICU admission until hospital discharge and up to 180 days after MICU admission. Logistic regression was used to identify independent predictors of hospital mortality. Between June 2009 and June 2014, 318 PLHIV admitted to the MICU met inclusion criteria. Eighty-six percent of the patients were non-Hispanic Blacks. Poorly controlled HIV was very common with 70.2% of patients having a CD4 cell count <200 cells/mm3 within 3 months prior to admission and only 34% of patients having an undetectable HIV viral load. Hospital mortality for the cohort was 17%. In a univariate model, mortality did not differ by demographic variables, CD4 cell count, HIV viral load, or ART use. Regression analysis adjusted by relevant covariates revealed that MICU patients admitted from the hospital ward were 6.4 times more likely to die in hospital than those admitted from emergency department. Other positive predictors were a diagnosis of end-stage liver disease, cardiac arrest, ventilator-dependent respiratory failure, vasopressor requirement, non-Hodgkin lymphoma, and symptomatic cytomegalovirus disease. In conclusion, in this critically ill cohort with HIV infection, most predictors of mortality were not directly related to HIV and were similar to those for the general population.

Assessment of coronary inflammation in antiretroviral treated people with HIV infection and active HIV/hepatitis C virus co-infection.

OBJECTIVE: People with HIV (PWH) and co-infected with hepatitis C virus (PWH + HCV) have increased risk of cardiovascular disease (CVD). Peri-coronary inflammation, measured by fat attenuation index (FAI) on coronary computed tomography angiography (CCTA), independently predicts cardiovascular risk in the general population but has not been studied in the PWH + HCV population. We tested whether peri-coronary inflammation is increased in PWH or PWH + HCV, and whether inflammation changes over time. DESIGN: Cross-sectional analysis to determine FAI differences among groups. Longitudinal analysis in PWH to assess changes in inflammation over time. METHODS: Age-matched and sex-matched seropositive groups (PWH and PWH + HCV) virologically suppressed on antiretroviral therapy, HCV viremic, and without prior CVD and matched controls underwent CCTA. Peri-coronary FAI was measured around the proximal right coronary artery (RCA) and left anterior descending artery (LAD). Follow-up CCTA was performed in 22 PWH after 20.6-27.4 months. RESULTS: A total of 101 participants (48 women) were studied (60 PWH, 19 PWH + HCV and 22 controls). In adjusted analyses, peri-coronary FAI did not differ between seropositive groups and controls. Low attenuation coronary plaque was significantly less common in seropositive groups compared with controls (LAD, P = 0.035; and RCA, P = 0.017, respectively). Peri-coronary FAI values significantly progressed between baseline and follow-up in PWH (RCA: P = 0.001, LAD: P = <0.001). CONCLUSION: PWH and PWH + HCV without history of CVD do not have significantly worse peri-coronary inflammation, assessed by FAI, compared with matched controls. However, peri-coronary inflammation in mono-infected PWH significantly increased over approximately 22 months. FAI measures may be an important imaging biomarker for tracking asymptomatic CVD progression in PWH.

Prognostic determinants of locally advanced buccal mucosa cancer: Do we need to relook the current staging criteria?

OBJECTIVES: Current guidelines advocate non-surgical treatment for T4b buccal mucosa carcinoma with surgery preferred in other stages. We investigated oncologic outcomes of this cohort in comparison with T4a cohort, treated by similar multi-modality approach of primary surgery followed by adjuvant treatment and identified prognostic determinants of survival. MATERIALS AND METHODS: Oncologic outcome of prospectively accrued 282 patients with cT4a and cT4b buccal mucosa squamous cell carcinoma were evaluated for overall survival (OS) and disease free survival (DFS) at 2 years of the whole cohort and for the subgroups of T4a and T4b patients. Multivariate Cox proportional hazards regression analysis was performed to identify prognostic determinants. RESULTS: Of 277 eligible patients treated and followed for a median period of 21 months, the OS was comparable between T4a and T4b as 64% vs 58%, (p = 0.354). The DFS between the two subgroups was 64% vs 61%, (p = 0.316). Although there was 47% pathologic down staging from the clinical stage, there was no significant difference in oncologic outcome between pT4a and pT4b (OS, 57% vs 58% for T4a and T4b, p = 0.687; DFS, 58% vs 60% for T4a and T4b, p = 0.776). On multivariate analysis, extra capsular spread (p = 0.042), lateral pterygoid muscle involvement (p = 0.035) and defaulting adjuvant treatment (p < 0.001) were independent predictors of outcome for the T4b cohort when other factors were controlled. CONCLUSIONS: Primary surgery followed by adjuvant chemo-radiotherapy offers comparable results in selected T4b gingiva and buccal mucosal cancer, suggesting the need to relook the staging criteria for oral cavity cancer.