Publications

Objectives To evaluate serum-derived bovine immunoglobulin/protein isolate (SBI) for safety and impact on gastrointestinal (GI) symptoms in HIV patients with chronic idiopathic diarrhea. Methods A multi-center trial comprised of a double-blind, placebo (PBO)-controlled lead-in phase, (participants received PBO or SBI at 2.5 or 5.0 g BID for 4 weeks) followed by a 20-week, PBO-free phase (SBI at either 2.5 or 5.0 g BID). Participants included HIV-infected patients who were virologically suppressed with a history of chronic idiopathic diarrhea, defined as > 3 loose stools per day for ≥ 3 months without an identifiable cause. Safety was evaluated by monitoring adverse events (AEs) and clinical laboratory testing. Health status and changes in GI symptoms were assessed using validated questionnaires. Results SBI was well tolerated by the 103 participants with only 2 withdrawals due to AEs potentially associated with SBI. Mean number of daily unformed stools decreased from about 4 at baseline to less than 2 by week 4 for all study groups. Improvements in several other GI symptoms were also reported. Comparison of the PBO group to SBI groups showed no significant differences, although both SBI cohorts reported significantly improved health status scores. GI symptom improvements were maintained throughout the 20-week PBO-free phase. Conclusions Oral SBI is safe and well tolerated at the doses studied in HIV patients with chronic diarrhea. No conclusions could be drawn regarding impact on GI symptoms. Additional studies are ongoing to examine the biological and immunologic effects of SBI in virologically suppressed HIV-infected patients.

Importance

Coronary computed tomography angiography (CCTA) is a new approach for the diagnosis of anatomical coronary artery disease (CAD), but it is unclear how CCTA performs compared with the standard approach of functional stress testing.

Objective

To compare the clinical effectiveness of CCTA with that of functional stress testing for patients with suspected CAD.

Data Sources

A systematic literature search was conducted in PubMed and MEDLINE for English-language randomized clinical trials of CCTA published from January 1, 2000, to July 10, 2016.

Study Selection

Researchers selected randomized clinical trials that compared a primary strategy of CCTA with that of functional stress testing for patients with suspected CAD and reported data on patient clinical events and changes in therapy.

Data Extraction and Synthesis

Two reviewers independently extracted data from and assessed the quality of the trials. This analysis followed the PRISMA statement for reporting systematic reviews and meta-analyses and used the Cochrane Collaboration's tool for assessing risk of bias in randomized trials. The Mantel-Haenszel method was used to conduct the primary analysis. Summary relative risks were calculated with a random-effects model.

Main Outcomes and Measures

The outcomes of interest were all-cause mortality, cardiac hospitalization, myocardial infarction, invasive coronary angiography, coronary revascularization, new CAD diagnoses, and change in prescription for aspirin and statins.

Results

Thirteen trials were included, with 10 315 patients in the CCTA arm and 9777 patients in the functional stress testing arm who were followed up for a mean duration of 18 months. There were no statistically significant differences between CCTA and functional stress testing in death (1.0% vs 1.1%; risk ratio [RR], 0.93; 95% CI, 0.71-1.21) or cardiac hospitalization (2.7% vs 2.7%; RR, 0.98; 95% CI, 0.79-1.21), but CCTA was associated with a reduction in the incidence of myocardial infarction (0.7% vs 1.1%; RR, 0.71; 95% CI, 0.53-0.96). Patients undergoing CCTA were significantly more likely to undergo invasive coronary angiography (11.7% vs 9.1%; RR, 1.33; 95% CI, 1.12-1.59) and revascularization (7.2% vs 4.5%; RR, 1.86; 95% CI, 1.43-2.43). They were also more likely to receive a diagnosis of new CAD and to have initiated aspirin or statin therapy.

Conclusions and Relevance

Compared with functional stress testing, CCTA is associated with a reduced incidence of myocardial infarction but an increased incidence of invasive coronary angiography, revascularization, CAD diagnoses, and new prescriptions for aspirin and statins. Despite these differences, CCTA is not associated with a reduction in mortality or cardiac hospitalizations.

The single greatest challenge to an HIV cure is the persistence of latently infected cells containing inducible, replication-competent proviral genomes, which constitute only a small fraction of total or infected cells in the body. Although resting CD4 T cells in the blood are a well-known source of viral rebound, more than 90% of the body's lymphocytes reside elsewhere. Many are in gut tissue, where HIV DNA levels per million CD4 T cells are considerably higher than in the blood. Despite the significant contribution of gut tissue to viral replication and persistence, little is known about the cell types that support persistence of HIV in the gut; importantly, T cells in the gut have phenotypic, functional, and survival properties that are distinct from T cells in other tissues. The mechanisms by which latency is established and maintained will likely depend on the location and cytokine milieu surrounding the latently infected cells in each compartment. Therefore, successful HIV cure strategies require identification and characterization of the exact cell types that support viral persistence, particularly in the gut. In this review, we describe the seeding of the latent HIV reservoir in the gut mucosa; highlight the evidence for compartmentalization and depletion of T cells; summarize the immunologic consequences of HIV infection within the gut milieu; propose how the damaged gut environment may promote the latent HIV reservoir; and explore several immune cell targets in the gut and their place on the path toward HIV cure.

In the United States, little is known about interventions that rely on mobile phones and/or text messaging to improve engagement in HIV care for vulnerable populations. Domestic studies using these technologies as part of the National Institute on Drug Abuse "Seek, Test, Treat, Retain" research initiative were queried regarding intervention components, implementation issues, participant characteristics, and descriptive statistics of mobile phone service delivery. Across five studies with 1,135 predominantly male, minority participants, implementation challenges occurred in three categories: (1) service interruptions; (2) billing/overage issues, and; (3) the participant user experience. Response rules for automated text messages frequently frustrated participants. The inability to reload minutes/texting capacity remotely was a significant barrier to intervention delivery. No study encountered confidentiality breaches. Service interruption was common, even if studies provided mobile phones and plans. Future studies should attend to the type of mobile phone and service, the participant user experience, and human subjects concerns.

Variants of the APOL1 gene, found primarily in individuals of African descent, are associated with various forms of kidney disease and kidney disease progression. Recent studies evaluating the association of APOL1 with cardiovascular disease have yielded conflicting results, and the potential role in cardiovascular disease remains unclear. In this review, we summarize the observational studies linking the APOL1 risk variants with chronic kidney and cardiovascular disease among persons of African descent.

RATIONALE

Minority drug-resistant Mycobacterium tuberculosis subpopulations can be associated with phenotypic resistance but are poorly detected by Sanger sequencing or commercial molecular diagnostic assays.

OBJECTIVES

To determine the role of targeted next-generation sequencing in resolving these minor variant subpopulations.

METHODS

We used single molecule overlapping reads (SMOR), a targeted next-generation sequencing approach that dramatically reduces sequencing error, to analyze primary cultured isolates phenotypically resistant to rifampin, fluoroquinolones, or aminoglycosides, but for which Sanger sequencing found no resistance-associated variants (RAVs) within respective resistance-determining regions (study group). Isolates also underwent single-colony selection on antibiotic-containing agar, blinded to sequencing results. As a positive control, isolates with multiple colocalizing chromatogram peaks were also analyzed (control group).

MEASUREMENTS AND MAIN RESULTS

Among 61 primary culture isolates (25 study group and 36 control group), SMOR described 66 (49%) and 45 (33%) of 135 total heteroresistant RAVs at frequencies less than 5% and less than 1% of the total mycobacterial population, respectively. In the study group, SMOR detected minor resistant variant subpopulations in 80% (n = 20/25) of isolates with no Sanger-identified RAVs (median subpopulation size, 1.0%; interquartile range, 0.2-3.9%). Single-colony selection on drug-containing media corroborated SMOR results for 90% (n = 18/20) of RAV-containing specimens, and the absence of RAVs in 60% (n = 3/5) of isolates. Overall, Sanger sequencing was concordant with SMOR for 77% (n = 53/69) of macroheteroresistant (5-95% total population), but only 5% of microheteroresistant (<5%) subpopulations (n = 3/66) across both groups.

CONCLUSIONS

Cryptic minor variant mycobacterial subpopulations exist below the resolving capability of current drug susceptibility testing methodologies, and may explain an important proportion of false-negative resistance determinations.

INTRODUCTION

Bismuth salts have been used to treat gastroenterological disorders and are readily available over-the-counter and via the internet. Even though generally considered safe, bismuth compounds can cause a syndrome of subacute, progressive encephalopathy when taken in large quantities.

CASE REPORT

We present the case of woman who developed progressive encephalopathy, aphasia, myoclonus, and gait instability after chronically ingesting large amounts of bismuth subgallate purchased from a major online marketing website to control symptoms of irritable bowel syndrome. After extensive neurological work-up, elevated bismuth levels in her blood, urine, and cerebrospinal fluid confirmed the diagnosis of bismuth-related neurotoxicity. She improved slowly following cessation of exposure.

CONCLUSION

This case highlights bismuth subgallate as a neurotoxic bismuth formulation and reminds providers of the potential for safety misconceptions of positively reviewed online supplements.