BK polyomavirus infection in pediatric heart transplant recipients: a prospective study.

BKV infection and nephropathy complicate pediatric HTx, but the incidence and time course of the disease are unknown. We assessed the incidence of BKV infection and its association with kidney dysfunction in pediatric HTx recipients. A single center prospective study compared pediatric (<18 years) HTx recipients, with and without BKV infection, who received an allograft between September 2013 and December 2014. Screening of urine for BKV was performed prior to transplant, and at week 1, and at months 3, 6, 9, 12, and 15 months post-transplantation. Serum for BKV DNA was assayed if BK viruria was present. Statistics included Fisher's exact test and Student's t test. Twelve patients were enrolled. Two patients were removed per parent request. Two (20%) had BK viruria and one (10%) had BK viremia. No patients developed BKVN. BK viruria was present within 2 months following transplantation. There were no identifiable risk factors for BKV infection and no statistically significant difference in renal function between the groups; however, there was a trend toward worsening renal function in those with BKV infection. BKV infection can occur early following heart transplantation. Screening for BK viruria should be considered in HTx recipients.

Focal adhesion kinase modulates Cdc42 activity downstream of positive and negative axon guidance cues.

There is biochemical, imaging and functional evidence that Rho GTPase signaling is a crucial regulator of actin-based structures such as lamellipodia and filopodia. However, although Rho GTPases are believed to serve similar functions in growth cones, the spatiotemporal dynamics of Rho GTPase signaling has not been examined in living growth cones in response to known axon guidance cues. Here we provide the first measurements of Cdc42 activity in living growth cones acutely stimulated with both growth-promoting and growth-inhibiting axon-guidance cues. Interestingly, we find that both permissive and repulsive factors can work by modulating Cdc42 activity, but in opposite directions. We find that the growth-promoting factors laminin and BDNF activate Cdc42, whereas the inhibitor Slit2 reduces Cdc42 activity in growth cones. Remarkably, we find that regulation of focal adhesion kinase (FAK) activity is a common upstream modulator of Cdc42 by BDNF, laminin and Slit. These findings suggest that rapid modulation of Cdc42 signaling through FAK by receptor activation underlies changes in growth cone motility in response to permissive and repulsive guidance cues.

The Impact of Wearable Breast Pumps on Physicians' Breastfeeding Experience and Success.

Background: Physician mothers face many barriers in their ability to meet their lactation goals. This is often due to short maternity leaves and an often busy, inflexible work schedule at the time of return to work. We aimed to characterize the effect of using wireless, wearable breast pumps in the workplace and determine if these devices may help overcome barriers to breastfeeding success for physician mothers. Methods: A cross-sectional survey was distributed to female physicians and trainees identified through the group "Doctor Mothers Interested in Lactation Knowledge (Dr. MILK)" using an anonymous, Qualtrics® survey on the group's social media site. Participants were analyzed in two groups: those who had used wearable pumps versus those who had only used traditional breast pumps. Results: Of the 542 respondents analyzed, 321 (59%) had used a wearable pump in the workplace and 221 (41%) had only used a traditional electric breast pump. Those who had used a wearable pump reported statistically significant shorter lactation breaks (p < 0.00001) and were more likely to be able to provide breast milk to their infants for their entire intended duration (p = 0.005) compared to the traditional pump group. The ability to pump as often as needed while at work (p = 0.16) and the frequency of lactation breaks throughout the day (p = 0.223) were not significantly different when comparing the two groups. Conclusions: This study demonstrates a benefit to using wearable breast pumps for women physicians as they return to work after maternity leave. Utilization of these new wearable pumps correlates with shorter lactation breaks and the ability of physician mothers to provide breast milk to their infants for their intended duration.

The Role for Metyrosine in the Treatment of Patients With Pheochromocytoma and Paraganglioma.

CONTEXT: Treatment of pheochromocytoma and paraganglioma (PPGL) requires preintervention titration of alpha- and beta-adrenergic blockade, but patients may still be at risk for complications from catecholamine excess. Metyrosine decreases catecholamine production, making it an attractive therapeutic adjunct for select patients. EVIDENCE ACQUISITION: A systematic literature review was performed (Ovid Medline and Scopus databases) on December 17, 2019, including studies with humans and original data. Studies with 10 or more patients on metyrosine for PPGL were included. Studies were screened for overlapping populations, and the most comprehensive study was included. The references of included studies were reviewed for additional data. Patient data from our institution between 2000 and 2015 were also reviewed. EVIDENCE SYNTHESIS: Metyrosine is well tolerated when used for a short course and can improve intraoperative outcomes in PPGL. Metyrosine should be considered when a difficult PPGL resection is expected (eg, pericardiac paraganglioma, abdominal paraganglioma with great vessel involvement), a large release of catecholamines is anticipated (eg, ablative therapy, chemotherapy), or when standard alpha- and beta-adrenergic blockade are not tolerated or cannot adequately control hypertension. Side effects are generally mild and self-limited, with sedation in a majority of patients. Extrapyramidal side effects are rare but can limit use of metyrosine. Because of its expense and limited availability, metyrosine use should be carefully planned and timed in relation to surgery. CONCLUSIONS: Metyrosine is a safe addition to traditional alpha- and beta-adrenergic blockade and should be considered in those patients with PPGL at high risk for acute release of catecholamines.

Cardiac Involvement in Facioscapulohumeral Muscular Dystrophy (FSHD).

Background: Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies and predominantly affects facial and shoulder girdle muscles. Previous case reports and cohort studies identified minor cardiac abnormalities in FSHD patients, but their nature and frequency remain incompletely characterized. Methods: We reviewed cardiac, neurological and genetic findings of 104 patients with genetically confirmed FSHD. Results: The most common conduction abnormality was complete (7%) or incomplete (5%) right bundle branch block (RBBB). Bifascicular block, left anterior fascicular block, complete atrioventricular block, and 2:1 atrioventricular block each occurred in 1% of patients. Atrial fibrillation or flutter were seen in 5% of patients. Eight percent of patients had heart failure with reduced ejection fraction and 25% had valvular disease. The latter included aortic stenosis in 6% (severe in 4% and moderate in 2%) and moderate aortic regurgitation in 8%. Mitral valve prolapse (MVP) was present in 9% of patients without significant mitral regurgitation. There were no significant associations between structural or conduction abnormalities and age, degree of muscle weakness, or size of the 4q deletion. Conclusions: Both structural and conduction abnormalities can occur in FSHD. The most common abnormalities are benign (RBBB and MVP), but more significant cardiac involvement was also observed. The presence of cardiac abnormalities cannot be predicted from the severity of the neurological phenotype, nor from the genotype.

Long, abundantly expressed non-coding transcripts are altered in cancer.

Recent studies with tiling arrays have revealed more genomic transcription than previously anticipated. Whole new groups of non-coding transcripts (NCTs) have been detected. Some of these NCTs, including miRNAs, can regulate gene expression. To date, most known NCTs studied have been relatively short, but several important regulatory NCTs, including XIST, MALAT-1, BC1 and BC200, are considerably larger in length and represent a novel class of long, non-coding RNA species. Whole-genome tiling arrays were utilized to identify novel long NCTs across the entire human genome. Our results have identified a new group of long (>400 nt), abundantly expressed NCTs and have found that a subset of these are also highly evolutionarily conserved. In this report, we have begun to characterize 15 long, conserved NCTs. Quantitative real-time RT-PCR was used to analyze their expression in different normal human tissue and also in breast and ovarian cancers. We found altered expression of many of these NCTs in both cancer types. In addition, several of these NCTs have consistent mutations when sequences of normal samples were compared with a panel of cancer-derived cell lines. One NCT was found to be consistently mutated in a panel of endometrial cancers compared with matched normal blood. These NCTs were among the most abundantly expressed transcripts detected. There are probably many long, conserved NCTs, albeit with lower levels of expression. Although the function of these NCTs is currently unknown, our study indicates that they may play an important function in both normal cells and in cancer development.

Relationship Between Anemia and Sudden Cardiac Death in Patients With Severe Aortic Stenosis.

Aortic stenosis (AS) is associated with significant morbidity and mortality, including sudden cardiac death (SCD). Anemia is a known risk factor for mortality in patients with AS. We sought to understand the prognostic implications between anemia and SCD in severe AS. The Mayo Clinic AS database includes 8,357 adults with severe AS (mean gradient ≥40 mm Hg, aortic valve area ≤1 cm2, or peak aortic jet velocity ≥4 m/s) enrolled between January 1, 1995 and April 30, 2015. Survival and cause of death were ascertained from the National Death Index and SCD from medical records. We excluded patients with multiple valvular abnormalities, leaving 7,292 subjects. The median (interquartile range, [IQR]) age was 76 (68, 82) years with 56% male, and median (IQR) hemoglobin level was 12.9 (11.6, 14.1) g/dl. The frequency of anemia (hemoglobin <13.0g/dl for men, <12.0 g/dL for women) was 40%. During median (IQR) follow up of 4.4 (1.8, 8.1) years, 4,056 died (10-year survival 38%) including 225 with SCD (10-year cumulative incidence 5%). In a multivariate model including age, sex, body-mass index, hypertension, diabetes mellitus, myocardial infarction, estimated glomerular filtration rate, and time dependent aortic valve replacement, anemia was associated with increased all-cause mortality (hazard ratios 1.75, 95%CI 1.64, 1.87; p < 0.001) and increased SCD mortality (hazard ratios 1.42, 95%CI 1.07, 1.86; p = 0.01). In conclusions, anemia is a frequent finding in patients with severe AS and independently associated with increased all-cause mortality and SCD. Anemia may be a useful prognostic marker and a modifiable therapeutic target in managing patients with severe AS.

Development and evaluation of a service-learning model for preclinical student education in cardiovascular disease prevention.

BACKGROUND: Cardiovascular diseases are the leading cause of preventable morbidity and mortality in the USA. Medical schools must prepare trainees to address prevention, including improving ability in counseling patients to modify lifestyle risk factors. Most medical students do not receive significant training or clinical experience in preventive medicine until the clinical years of medical school. To enhance student education in disease prevention and lifestyle counseling, and simultaneously target cardiovascular disease prevention in high-risk Chicago neighborhoods, the Northwestern University Feinberg School of Medicine and Chicago Department of Public Health with support from the GE Foundation, developed the Keep Your Heart Healthy program. METHODS: Medical students participated in intensive faculty-led training. They subsequently screened local residents to identify and counsel for cardiovascular disease risk factors. Fifty-one predominantly preclinical medical students screened residents of the Humboldt Park and North Lawndale neighborhoods in Chicago, IL, at 31 screening events from August to December 2013. Fifty students (98% response rate) completed a survey assessing the educational value of various program components following the pilot. RESULTS: Of all respondents, 92% of students reported improved knowledge of cardiovascular disease prevention and 94% reported improved knowledge of vulnerable populations and health equity. The majority (88%) reported that their participation supplemented material they learned in the classroom. Eighty-six percent of students reported that their encounters with community participants were of educational value. Integration of this program into the medical school curriculum was supported by 68% of students. CONCLUSION: Keep Your Heart Healthy educates primarily preclinical medical students in cardiovascular disease prevention and prepares them to apply this knowledge for patient counseling. Results from student surveys demonstrate that this service-learning initiative enhances medical student knowledge in cardiovascular disease prevention, supplements classroom material, and provides students a valuable opportunity to apply interviewing and counseling skills in a real patient encounter.

Prevalence of BK polyomavirus infection and association with renal dysfunction in pediatric heart transplant recipients.

BACKGROUND: BK polyomavirus (BKV) infection and nephropathy complicate renal allografts; however, their effect in the native kidneys of pediatric heart transplant (HTx) recipients is unknown. We assessed the prevalence of BKV infection and its association with kidney dysfunction in survivors of pediatric HTx. METHODS: A single-center retrospective study compared pediatric (aged <18 years ) HTx recipients, with and without BKV (controls), who received an allograft from May 1989 to July 2013. Screening of urine for BKV was performed in patients with chronic kidney disease (CKD) stage ≥2 since 2006, and since April 2012 in all HTx recipients at least at an annual evaluation. Serum for BKV DNA was assayed if BK viruria was present. Data collected included recipient and donor demographics, the immunosuppressive regimen, and history of Epstein-Bar virus (EBV) and cytomegalovirus infection. Statistics included Fisher's exact test, chi-square test, Student's t-test, and multivariate logistic regression. RESULTS: Of 98 eligible recipients, 83 (85%) were screened: 28 (34%) had BK viruria, and 7 had BK viremia. One viremic patient had biopsy-proven BKV nephropathy that progressed to end-stage renal disease. Risk factors for BK viruria were (1) longer duration since HTx (6.02 vs 2.95 years; p = 0.01), (2) worsening estimated glomerular filtration rate (71.3 vs 86.3 ml/min/1.73 m(2), p = 0.03), (3) history of EBV infection (p = 0.0002), and (4) use of sirolimus (p = 0.0003). After multivariate logistic-regression, only history of EBV infection remained associated with BKV infection (p = 0.015). CONCLUSIONS: BKV may lead to BK viremia and BK nephropathy in pediatric HTx patients. Routine screening for BK viruria should be considered.