PCOM Library / Hot Topics in Research / Archive for "Internal Medicine"

Category: Internal Medicine

Hot Topics: Exercise in Older Adults Boosts Memory

Jackie Werner Geriatrics, Hot Topics in Research, Memory Impairment

Semantic Memory Activation After Acute Exercise in Healthy Older Adults

Won J, Alfini AJ, Weiss LR, et al. Semantic memory activation after acute exercise in healthy older adults. Journal of the International Neuropsychological Society: 1-12. https://doi.org/10.1017/S1355617719000171.

Objectives: A growing body of research suggests that regular participation in long-term exercise is associated with enhanced cognitive function. However, less is known about the beneficial effects of acute exercise on semantic memory. This study investigated brain activation during a semantic memory task after a single session of exercise in healthy older adults using functional magnetic resonance imaging (fMRI). Methods: Using a within-subjects counterbalanced design, 26 participants (ages, 55–85 years) underwent two experimental visits on separate days. During each visit, participants engaged in 30 min of rest or stationary cycling exercise immediately before performing a Famous and Non-Famous name discrimination task during fMRI scanning. Results: Acute exercise was associated with significantly greater semantic memory activation (Famous>Non-Famous) in the middle frontal, inferior temporal, middle temporal, and fusiform gyri. A planned comparison additionally showed significantly greater activation in the bilateral hippocampus after exercise compared to rest. These effects were confined to correct trials, and as expected, there were no differences between conditions in response time or accuracy. Conclusions: Greater brain activation following a single session of exercise suggests that exercise may increase neural processes underlying semantic memory activation in healthy older adults. These effects were localized to the known semantic memory network, and thus do not appear to reflect a general or widespread increase in brain blood flow. Coupled with our prior exercise training effects on semantic memory-related activation, these data suggest the acute increase in neural activation after exercise may provide a stimulus for adaptation over repeated exercise sessions.

Hot Topics: Steroid Implant Restores Sight

Jackie Werner Hot Topics in Research, Oncology, Surgery

Outcomes Associated With Sustained-Release Intraocular Fluocinolone Implants in a Case of Melanoma-Associated Retinopathy Treated Without Systemic Immunosuppression

Karatsai E, Robson AG, Taylor SRJ. Outcomes associated with sustained-release intraocular fluocinolone implants in a case of melanoma-associated retinopathy treated without systemic immunosuppression. 2019. https://doi.org/10.1001/jamaophthalmol.2019.0284.

Importance  Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome in which antiretinal antibodies crossreact with retinal ON-bipolar cells, resulting in night blindness and progressive visual field loss. Current therapeutic options include cytoreductive surgery in combination with immunoglobulin, corticosteroids, or plasmapheresis, but their effectiveness is limited and may be contraindicated, given the possible protective role of circulating autoantibodies against metastatic spread. We report 3-year follow-up of the first case (to our knowledge) of MAR treated with intravitreal long-acting steroid implants.

Objective  To report on a patient with MAR who was treated with intravitreal fluocinolone acetonide implants in the absence of systemic immunosuppression.

Design, Setting, and Participants  This is a 3-year follow-up of a 73-year-old woman with a history of surgical excision of a malignant melanoma of the left pinna who presented with visual symptoms of shimmering and nyctalopia. Fundus examination, fundus autofluorescence, and optical coherence tomography were normal, with no evidence of cystoid macular edema. Automated perimetry showed a reduction in visual field and full-field electroretinography (ERG) demonstrated findings consistent with generalized ON-bipolar cell dysfunction, typical of MAR. The patient was treated with bilateral fluocinolone acetonide intravitreal implants.

Main Outcomes and Measures  Visual acuity, visual field, and electroretinography testing for 3 years after treatment.

Results  Visual fields improved in this 73-year-old patient from 20/30 (Snellen measured as 6/9) OD and 20/16 (6/5) OS at baseline to 20/20 OU within 1 week of treatment. Detailed electroretinography monitoring indicated characteristic abnormalities that partly resolved after treatment, consistent with improved inner retinal ON-bipolar cell function. Bilateral cataracts developed approximately 2 years after injection; cataract surgery was performed uneventfully. At 3 years posttreatment, the patient remained visually stable and in systemic disease remission, with best-corrected visual acuity remaining at 20/20 OU.

Conclusions and Relevance  We report what is, to our knowledge, the first case of MAR treated with intravitreal slow-release corticosteroid implants, which shows improvements in visual symptoms, visual fields, and retinal function. Sustained-release intraocular steroid implants may offer an effective and safe alternative to systemic immunosuppression in MAR, although results from 1 case should be generalized with abundant caution.

Hot Topics: Algorithm Predicts Irregular Heartbeats

Jackie Werner Cardiology, Hot Topics in Research

A New Prediction Model for Ventricular Arrhythmias in Arrhythmogenic Right Ventricular Cardiomyopathy

Bhonsale A, Murray B, Tichnell C, et al. A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy. . 2019. https://doi.org/10.1093/eurheartj/ehz103.

Aims: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients.

Methods and Results: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44–9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73–0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92–0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.6% reduction of ICD placements with the same proportion of protected patients (P < 0.001).

Conclusion: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).

Hot Topics: Online Intervention May Decrease HIV Risk

Jackie Werner Hot Topics in Research, Infectious Disease, Psychology and Psychiatry

Acceptability and Preliminary Efficacy of an Online HIV Prevention Intervention for Single Young Men Who Have Sex with Men Seeking Partners Online: The myDEx Project

Bauermeister JA, Tingler RC, Demers M, et al. Acceptability and preliminary efficacy of an online HIV prevention intervention for single young men who have sex with men seeking partners online: The myDEx project. AIDS and Behavior. 2019. https://doi.org/10.1007/s10461-019-02426-7.

Prevention of new cases of HIV among young gay, bisexual and other men who have sex with men (YGBMSM; ages 18–24) remains a priority. We developed and pilot tested an online intervention (myDEx) using a pilot randomized trial design with 180 online-recruited single YGBMSM who reported recent unprotected anal intercourse, self-reporting as HIV negative or status-unaware, and who met sexual partners through online dating applications. myDEx participants reported higher overall satisfaction (d = 0.46) and willingness to recommend the intervention to friends (d = 0.48) than controls. myDEx participants were less likely to report foregoing condoms to achieve an emotional connection with a partner (d =0 .43), and more likely to report greater emotional regulation during their partner-seeking behaviors (d = 0.44). myDEx participants reported fewer partners with whom they had condomless receptive anal sex (d = 0.48). Our pilot results demonstrate the potential of the myDEx intervention, suggesting that a larger efficacy trial may be warranted in the future.

Hot Topics: Routine Data Can Quickly Detect Sepsis in Newborns

Jackie Werner Critical Care, Hot Topics in Research, Pediatrics

Machine learning models for early sepsis recognition in the neonatal intensive care unit using readily available electronic health record data

Masino AJ, Harris MC, Forsyth D, et al. Machine learning models for early sepsis recognition in the neonatal intensive care unit using readily available electronic health record data. PLOS ONE. 2019;14(2):e0212665. https://doi.org/10.1371/journal.pone.0212665.

Background

Rapid antibiotic administration is known to improve sepsis outcomes, however early diagnosis remains challenging due to complex presentation. Our objective was to develop a model using readily available electronic health record (EHR) data capable of recognizing infant sepsis at least 4 hours prior to clinical recognition.

Methods and findings

We performed a retrospective case control study of infants hospitalized ≥48 hours in the Neonatal Intensive Care Unit (NICU) at the Children’s Hospital of Philadelphia between September 2014 and November 2017 who received at least one sepsis evaluation before 12 months of age. We considered two evaluation outcomes as cases: culture positive–positive blood culture for a known pathogen (110 evaluations); and clinically positive–negative cultures but antibiotics administered for ≥120 hours (265 evaluations). Case data was taken from the 44-hour window ending 4 hours prior to evaluation. We randomly sampled 1,100 44-hour windows of control data from all times ≥10 days removed from any evaluation. Model inputs consisted of up to 36 features derived from routine EHR data. Using 10-fold nested cross-validation, 8 machine learning models were trained to classify inputs as sepsis positive or negative. When tasked with discriminating culture positive cases from controls, 6 models achieved a mean area under the receiver operating characteristic (AUC) between 0.80–0.82 with no significant differences between them. Including both culture and clinically positive cases, the same 6 models achieved an AUC between 0.85–0.87, again with no significant differences.

Conclusions

Machine learning models can identify infants with sepsis in the NICU hours prior to clinical recognition. Learning curves indicate model improvement may be achieved with additional training examples. Additional input features may also improve performance. Further research is warranted to assess potential performance improvements and clinical efficacy in a prospective trial.

Hot Topics: Parkinson Cases Point to Pandemic

Jackie Werner Hot Topics in Research, Neurology

The Emerging Evidence of the Parkinson Pandemic

Dorsey ER, Sherer T, Okun MS, Bloem BR. The emerging evidence of the parkinson pandemic. Journal of Parkinson’s Disease. 2018;8(s1):S8. http://dx.doi.org/10.3233/JPD-181474.

Neurological disorders are now the leading source of disability globally, and the fastest growing neurological disorder in the world is Parkinson disease. From 1990 to 2015, the number of people with Parkinson disease doubled to over 6 million. Driven principally by aging, this number is projected to double again to over 12 million by 2040. Additional factors, including increasing longevity, declining smoking rates, and increasing industrialization, could raise the burden to over 17 million. For most of human history, Parkinson has been a rare disorder. However, demography and the by-products of industrialization have now created a Parkinson pandemic that will require heightened activism, focused planning, and novel approaches.

Hot Topics: Flu Vaccine Antibodies Inhibit Two Viral Proteins

Jackie Werner Hot Topics in Research, Infectious Disease

Neuraminidase inhibition contributes to influenza A virus neutralization by anti-hemagglutinin stem antibodies

Kosik I, Angeletti D, Gibbs JS, et al. Neuraminidase inhibition contributes to influenza A virus neutralization by anti-hemagglutinin stem antibodies. J Exp Med. 2019. dx.doi.org/10.1084/jem.20181624.

Broadly neutralizing antibodies (Abs) that bind the influenza virus hemagglutinin (HA) stem may enable universal influenza vaccination. Here, we show that anti-stem Abs sterically inhibit viral neuraminidase (NA) activity against large substrates, with activity inversely proportional to the length of the fibrous NA stalk that supports the enzymatic domain. By modulating NA stalk length in recombinant IAVs, we show that anti-stem Abs inhibit virus release from infected cells by blocking NA, accounting for their in vitro neutralization activity. NA inhibition contributes to anti-stem Ab protection in influenza-infected mice, likely due at least in part to NA-mediated inhibition of FcγR-dependent activation of innate immune cells by Ab bound to virions. Food and Drug Administration–approved NA inhibitors enhance anti-stem–based Fc-dependent immune cell activation, raising the possibility of therapeutic synergy between NA inhibitors and anti-stem mAb treatment in humans.

Hot Topics: New Therapy Enhances Peanut Allergy Tolerance

Jackie Werner Hot Topics in Research, Internal Medicine

AR101 Oral Immunotherapy for Peanut Allergy

PALISADE Group of Clinical Investigators, Vickery BP, Vereda A, et al. AR101 oral immunotherapy for peanut allergy. N Engl J Med. 2018;379(21):1991-2001. http://dx.doi.org/10.1056/NEJMoa1812856

BACKGROUND
Peanut allergy, for which there are no approved treatment options, affects patients who are at risk for unpredictable and occasionally life-threatening allergic reactions.

METHODS
In a phase 3 trial, we screened participants 4 to 55 years of age with peanut allergy for allergic dose-limiting symptoms at a challenge dose of 100 mg or less of peanut protein (approximately one third of a peanut kernel) in a double-blind, placebo-controlled food challenge. Participants with an allergic response were randomly assigned, in a 3:1 ratio, to receive AR101 (a peanut-derived investigational biologic oral immunotherapy drug) or placebo in an escalating-dose program. Participants who completed the regimen (i.e., received 300 mg per day of the maintenance regimen for approximately 24 weeks) underwent a double-blind, placebo-controlled food challenge at trial exit. The primary efficacy end point was the proportion of participants 4 to 17 years of age who could ingest a challenge dose of 600 mg or more, without dose-limiting symptoms.

RESULTS
Of the 551 participants who received AR101 or placebo, 496 were 4 to 17 years of age; of these, 250 of 372 participants (67.2%) who received active treatment, as compared with 5 of 124 participants (4.0%) who received placebo, were able to ingest a dose of 600 mg or more of peanut protein, without dose-limiting symptoms, at the exit food challenge (difference, 63.2 percentage points; 95% confidence interval, 53.0 to 73.3; P<0.001). During the exit food challenge, the maximum severity of symptoms was moderate in 25% of the participants in the active-drug group and 59% of those in the placebo group and severe in 5% and 11%, respectively. Adverse events during the intervention period affected more than 95% of the participants 4 to 17 years of age. A total of 34.7% of the participants in the active-drug group had mild events, as compared with 50.0% of those in the placebo group; 59.7% and 44.4% of the participants, respectively, had events that were graded as moderate, and 4.3% and 0.8%, respectively, had events that were graded as severe. Efficacy was not shown in the participants 18 years of age or older.

CONCLUSIONS
In this phase 3 trial of oral immunotherapy in children and adolescents who were highly allergic to peanut, treatment with AR101 resulted in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo.

Hot Topics: YouTube Misinforms About Prostate Cancer

Jackie Werner Hot Topics in Research, Oncology

Dissemination of Misinformative and Biased Information about Prostate Cancer on YouTube

Loeb S, Sengupta S, Butaney M, et al. Dissemination of misinformative and biased information about prostate cancer on YouTube. Eur Urolhttps://doi.org/10.1016/j.eururo.2018.10.056.

YouTube is a social media platform with more than 1 billion users and >600 000 videos about prostate cancer. Two small studies examined the quality of prostate cancer videos on YouTube, but did not use validated instruments, examine user interactions, or characterize the spread of misinformation. We performed the largest, most comprehensive examination of prostate cancer information on YouTube to date, including the first 150 videos on screening and treatment. We used the validated DISCERN quality criteria for consumer health information and the Patient Education Materials Assessment Tool, and compared results for user engagement. The videos in our sample had up to 1.3 million views (average 45 223) and the overall quality of information was moderate. More videos described benefits (75%) than harms (53%), and only 50% promoted shared decision-making as recommended in current guidelines. Only 54% of the videos defined medical terms and few provided summaries or references. There was a significant negative correlation between scientific quality and viewer engagement (views/month p = 0.004; thumbs up/views p = 0.015). The comments section underneath some videos contained advertising and peer-to-peer medical advice. A total of 115 videos (77%) contained potentially misinformative and/or biased content within the video or comments section, with a total reach of >6 million viewers.

Patient summary
Many popular YouTube videos about prostate cancer contained biased or poor-quality information. A greater number of views and thumbs up on YouTube does not mean that the information is trustworthy.

Hot Topics: Botox May Help Aftermath of Cardiac Surgery

Jackie Werner Cardiology, Hot Topics in Research, Surgery

Long-term suppression of atrial fibrillation by botulinum toxin injection into epicardial fat pads in patients undergoing cardiac surgery: Three-year follow-up of a randomized study

Romanov A, Pokushalov E, Ponomarev D, et al. Long-term suppression of atrial fibrillation by botulinum toxin injection into epicardial fat pads in patients undergoing cardiac surgery: Three-year follow-up of a randomized study. Heart Rhythm. 2018. http://dx.doi.org/10.1016/j.hrthm.2018.08.019

Background
Botulinum toxin (BTX) injections into epicardial fat pads in patients undergoing coronary artery bypass grafting (CABG) has resulted in suppression of atrial fibrillation (AF) during the early postoperative period through 1-year of follow-up in a pilot program.

Objective
The purpose of this study was to report 3-year AF patterns by the use of implantable cardiac monitors (ICMs).

Methods
Sixty patients with a history of paroxysmal AF and indications for CABG were randomized 1:1 to either BTX or placebo injections into 4 posterior epicardial fat pads. All patients received an ICM with regular follow-up for 3 years after surgery. The primary end point of the extended follow-up period was incidence of any atrial tachyarrhythmia after 30 days of procedure until 36 months on no antiarrhythmic drugs. The secondary end points included clinical events and AF burden.

Results
At the end of 36 months, the incidence of any atrial tachyarrhythmia was 23.3% in the BTX group vs 50% in the placebo group (hazard ratio 0.36; 95% confidence interval 0.14–0.88; P = .02). AF burden at 12, 24, and 36 months was significantly lower in the BTX group than in the placebo group: 0.22% vs 1.88% ( P = .003), 1.6% vs 9.5% ( P < .001), and 1.3% vs 6.9% ( P = .007), respectively. In the BTX group, 2 patients (7%) were hospitalized during follow-up compared with 10 (33%) in the placebo group ( P = .02).

Conclusion
Injection of BTX into epicardial fat pads in patients undergoing CABG resulted in a sustained and substantial reduction in atrial tachyarrhythmia incidence and burden during 3-year follow-up, accompanied by reduction in hospitalizations.