Faculty Bibliography

Limbic encephalitis presents as altered mood, memory loss and confusion. Clinical features may include psychiatric symptoms and seizures. In contrast to paraneoplastic disorders, non-paraneoplastic autoimmune encephalitis often responds to immunotherapy and sometimes with marked recovery. However, relapse can occur. An 82-year-old male presented with subacute episodes of memory loss over a few days. The patient was unable to recognize his own home and family members. Physical exam was unremarkable. Neuropsychological assessment revealed deficits in cognitive performance that could be consistent with moderate dementia or a more rapidly progressive encephalopathy. Agitated behavior and anxiety were also noted. Laboratory evaluation included hyponatremia, which was corrected with no symptom improvement. B12, TSH, and HIV were normal. CSF analysis revealed 10 WBCs/muL, Glucose-52 mg/dl, Protein-62 mg/dl and was negative for infectious, neoplastic causes, varicella, VDRL, viral cultures, NMDA receptor antibody, GAD 65 antibody and Anti-Hu antibody. Occult malignancy work up with CT scan of chest and abdomen and colonoscopy was normal. Serum for voltage-gated potassium channel antibodies was positive at 849 pmol/l (>88). EEG showed occasional focal left fronto-temporal slowing without epileptiform activity. MRI revealed focal enhancement of the medial left temporal lobe consistent with limbic encephalitis. The patient started high dose steroids with improvement in memory and complete resolution of focal abnormality within the left hippocampal/parahippocampal region suggestive of resolving encephalitis. At seven months after tapering steroids the patient presented with myoclonus and recurrent memory loss. MRI demonstrated recurrent encephalitis with gyral swelling and FLAIR hyperintensity in the left temporal lobe. The patient was restarted on high dose steroids with addition of Rituximab. This case illustrates that limbic encephalitis can present as a rapidly progressive dementia. Differential diagnosis should include more unusual forms of rapidly progressive dementia such as Jakob-Creutzfeldt disease if myoclonus is present, Lewy body dementia if waxing and waning memory, and Alzheimer's dementia with acute delirium if presenting over a period of months. In this patient, MRI changes were crucial to recognizing a potentially reversible limbic encephalitis. Early recognition and treatment may decrease relapse and reduce functional impairment

Parathyroid hormone (PTH) is a primary calcium regulatory hormone. Elevated serum PTH concentrations in primary and secondary hyperparathyroidism have been associated with bone disease, hypertension, and in some studies, cardiovascular mortality. Genetic causes of variation in circulating PTH concentrations are incompletely understood. We performed a genome-wide association study of serum PTH concentrations among 29,155 participants of European ancestry from 13 cohort studies (n=22,653 and n=6502 in discovery and replication analyses, respectively). We evaluated the association of single nucleotide polymorphisms (SNPs) with natural log-transformed PTH concentration adjusted for age, sex, season, study site, and principal components of ancestry. We discovered associations of SNPs from five independent regions with serum PTH concentration, including the strongest association with rs6127099 upstream of CYP24A1 (P=4.2 × 10^-53), a gene that encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-dihydroxyvitamin D. Each additional copy of the minor allele at this SNP associated with 7% higher serum PTH concentration. The other SNPs associated with serum PTH concentration included rs4074995 within RGS14 (P=6.6 × 10^-17), rs219779 adjacent to CLDN14 (P=3.5 × 10^-16), rs4443100 near RTDR1 (P=8.7 × 10^-9), and rs73186030 near CASR (P=4.8 × 10^-8). Of these five SNPs, rs6127099, rs4074995, and rs219779 replicated. Thus, common genetic variants located near genes involved in vitamin D metabolism and calcium and renal phosphate transport associated with differences in circulating PTH concentrations. Future studies could identify the causal variants at these loci, and the clinical and functional relevance of these variants should be pursued.

OBJECTIVES:This study sought to evaluate the association of physical activity with chronic myocardial damage, assessed by elevated high-sensitivity cardiac troponin T (hs-cTnT), in individuals with and without obesity. BACKGROUND:Physical activity is associated with reduced risk of heart failure (HF), particularly among obese people. The role of chronic myocardial damage in this association is uncertain. METHODS:. Physical activity was categorized per American Heart Association guidelines as recommended, intermediate, or poor. We evaluated cross-sectional associations of physical activity and obesity with elevated hs-cTnT (≥14 ng/l). In prospective analyses, we quantified the association of elevated hs-cTnT with HF risk within cross-categories of baseline physical activity and obesity. RESULTS:People with poor physical activity were more likely to have elevated hs-cTnT than those with recommended levels (odds ratio [OR]: 1.39; 95% confidence interval [CI]: 1.15 to 1.68). In cross-categories of physical activity and obesity, using the non-obese/recommended activity group as the reference, individuals with obesity and poor activity were most likely to have elevated hs-cTnT (OR: 2.46; 95% CI: 1.91 to 3.19), whereas the obese/recommended activity group had a weaker association (OR: 1.68; 95% CI: 1.28 to 2.21; p < 0.001 for interaction between physical activity and obesity). In prospective analyses, elevated hs-cTnT was strongly associated (p < 0.001) with incident HF in all obesity/physical activity cross-categories (p > 0.20 for interaction). CONCLUSIONS:Physical activity is inversely associated with chronic subclinical myocardial damage. Physical activity might lessen the association between obesity and subclinical myocardial damage, which could represent a mechanism by which physical activity reduces HF risk.

PURPOSE OF REVIEW/OBJECTIVE:This article intends to review biomarkers derived from blood, urine, and tissue that can aid in the diagnosis of prostate cancer (PCa). RECENT FINDINGS/RESULTS:PCa screening requires tools that complement prostate-specific antigen (PSA) with a higher specificity for clinically significant disease. Novel blood biomarkers, such as the Prostate Health Index (phi) and 4Kscore, utilize isoforms of PSA to more accurately predict high-grade PCa than traditional tools such as PSA and the percentage free-to-total PSA. Several gene products associated with PCa can be detected in the urine through commercially available assays. PCa antigen 3 (PCA3), though approved for repeat biopsy decisions, appears inferior to other biomarkers such as phi for identifying aggressive disease. However, combinations of PCA3 with other urine assays have shown promising results. One tissue-based hypermethylation test, named ConfirmMDx, can also be used to determine the need for repeat biopsy in men with a prior negative biopsy. SUMMARY/CONCLUSIONS:Several biomarkers have been developed to aid in the screening and diagnosis of PCa. Such tests are often indicated in men with moderately elevated PSA or history of a prior negative biopsy. Their use facilitates reduction of unnecessary biopsies without sacrificing the early diagnosis of clinically significant PCa.

BACKGROUND:The 2020 American Heart Association Impact Goal aims to improve cardiovascular health of all Americans by 20% while reducing deaths from cardiovascular disease and stroke by 20%. A large step toward this goal would be to better understand and take advantage of the significant intersection between behavior and biology across the entire life-span. In the proposed FAMILIA studies, we aim to directly address this major knowledge and clinical health gap by implementing an integrated family-centric health promotion intervention and focusing on the intersection of environment and behavior, while understanding the genetic and biologic basis of cardiovascular disease. METHODS:We plan to recruit 600 preschool children and their 600 parents or caregivers from 12-15 Head Start schools in Harlem, NY, and perform a 2:1 (2 intervention/1 control) cluster randomization of the schools. The preschool children will receive our intensive 37-hour educational program as the intervention for 4 months. For the adults, those in the "intervention" group will be randomly assigned to 1 of 2 intervention programs: an "individual-focused" or "peer-to-peer based." The primary outcome in children will be a composite score of knowledge (K), attitudes (A), habits (H), related to body mass index Z score (B), exercise (E), and alimentation (A) (KAH-BEA), using questionnaires and anthropometric measurements. For adults, the primary outcome will be a composite score for behaviors/outcomes related to blood pressure, exercise, weight, alimentation (diet) and tobacco (smoking; Fuster-BEWAT score). Saliva will be collected from the children for SNP genotyping, and blood will be collected from adults for RNA sequencing to identify network models and predictors of primary prevention outcomes. CONCLUSION/CONCLUSIONS:The FAMILIA studies seek to demonstrate that targeting a younger age group (3-5 years) and using a family-based approach may be a critical strategy in promoting cardiovascular health across the life-span.

The number of new HIV infections continues to be on the rise in many high-income countries, most notably among men who have sex with men (MSM). Despite recent attention to the use of antiretroviral medications as pre-exposure prophylaxis (PrEP) among MSM, considerably less research has been devoted to examining the awareness and use of post-exposure prophylaxis (PEP). Based on a convenience sample of 179 self-reported HIV-uninfected MSM using a geosocial-networking smartphone application, this study is among the first to examine the awareness and use of PEP and their demographic and behavioral correlates among MSM in London. Most respondents (88.3%) had heard of PEP, where 27.4% reported having used it. In multivariable models, the disclosure of one's sexual orientation to their general practitioner (Prevalence ratio [PR]: 3.49; 95% confidence interval (CI): 1.14, 10.70; p = .029) and reporting one's HIV status as negative (rather than unknown) (PR: 11.49; 95% CI: 1.68, 76.92; p = .013) were associated with having heard of PEP; while the recent use of club drugs (PR: 3.02; 95% CI: 1.42, 6.43; p = .004) was associated with having ever used PEP. High awareness and use in this sample suggest that PEP is a valuable risk-reduction strategy that should be capitalized on, be it in addition to or in the absence of PrEP.

Serodiscussion-the mutual discussion of HIV statuses between sexual partners-can be viewed as an essential prerequisite for risk-reduction behaviors among men who have sex with men (MSM). The current study aimed to assess the prevalence of serodiscussion with one's most recent sexual partner and its association with sexual behaviors with these partners. Broadcast advertisements were placed on a geosocial-networking smartphone application, encouraging users to complete an online survey. A total of 200 MSM completed the survey. Serodiscussion occurred in 43.5% of dyads, and it was most common in dyads where both partners were reported to be HIV positive, chi2(5) = 60.3, P < .001. Serodiscussion was associated with engagement in both condomless insertive, chi2(1) = 3.847, P = .046, and receptive anal intercourse, chi2(1) = 6.5, P = .011. However, there were no significant differences in how recently a respondent was tested for HIV, representing potentially high-risk scenarios.

OBJECTIVE: To determine whether patient-specific 3D printed renal tumor models change pre-operative planning decisions made by urological surgeons in preparation for complex renal mass surgical procedures. MATERIALS AND METHODS: From our ongoing IRB approved study on renal neoplasms, ten renal mass cases were retrospectively selected based on Nephrometry Score greater than 5 (range 6-10). A 3D post-contrast fat-suppressed gradient-echo T1-weighted sequence was used to generate 3D printed models. The cases were evaluated by three experienced urologic oncology surgeons in a randomized fashion using (1) imaging data on PACS alone and (2) 3D printed model in addition to the imaging data. A questionnaire regarding surgical approach and planning was administered. The presumed pre-operative approaches with and without the model were compared. Any change between the presumed approaches and the actual surgical intervention was recorded. RESULTS: There was a change in planned approach with the 3D printed model for all ten cases with the largest impact seen regarding decisions on transperitoneal or retroperitoneal approach and clamping, with changes seen in 30%-50% of cases. Mean parenchymal volume loss for the operated kidney was 21.4%. Volume losses >20% were associated with increased ischemia times and surgeons tended to report a different approach with the use of the 3D model compared to that with imaging alone in these cases. The 3D printed models helped increase confidence regarding the chosen operative procedure in all cases. CONCLUSIONS: Pre-operative physical 3D models created from MRI data may influence surgical planning for complex kidney cancer.

BACKGROUND: The statistical association between increased exposure to air pollution and increased risk of morbidity and mortality is well established. However, documentation of the health benefits of lowering air pollution levels, which would support the biological plausibility of those past statistical associations, are not as well developed. A better understanding of the aftereffects of interventions to reduce air pollution is needed in order to: 1) better document the benefits of lowered air pollution; and, 2) identify the types of reductions that most effectively provide health benefits. METHODS: This study analyzes daily health and pollution data from three major cities in Israel that have undergone pollution control interventions to reduce sulfur emissions from combustion sources. In this work, the hypothesis tested is that transitions to cleaner fuels are accompanied by a decreased risk of daily cardiovascular and respiratory mortalities. Interrupted time series regression models are applied in order to test whether the cleaner air interventions are associated with a statistically significant reduction in mortality. RESULTS: In the multi-city meta-analysis we found statistically significant reductions of 13.3% [CI -21.9%, -3.8%] in cardiovascular mortality, and a borderline significant (p=0.06) reduction of 19.0% [CI -35.1%, 1.1%] in total mortality. CONCLUSIONS: Overall, new experiential evidence is provided consistent with human health benefits being associated with interventions to reduce air pollution. The methods employed also provide an approach that may be applied elsewhere in the future to better document and optimize the health benefits of clean air interventions.

In a longitudinal population-based study of 2,905 children, we investigated if infants' neuromotor development was associated with autistic traits in childhood. Overall motor development and muscle tone were examined by trained research assistants with an adapted version of Touwen's Neurodevelopmental Examination between ages 2 and 5 months. Tone was assessed in several positions and items were scored as normal, low, or high tone. Parents rated their children's autistic traits with the Social Responsiveness Scale (SRS) and the Pervasive Developmental Problems (PDP) subscale of the Child Behavior Checklist at 6 years. We defined clinical PDP if scores were >98th percentile of the norm population. Diagnosis of autism spectrum disorder (ASD) was clinically confirmed in 30 children. We observed a modest association between overall neuromotor development in infants and autistic traits. Low muscle tone in infancy predicted autistic traits measured by SRS (adjusted beta = 0.05, 95% CI for B: 0.00-0.02, P = 0.01), and PDP (adjusted beta = 0.08, 95% CI for B: 0.04-0.10, P < 0.001). Similar results emerged for the association of low muscle tone and clinical PDP (adjusted OR = 1.36, 95% CI: 1.08-1.72, P = 0.01) at age 6 years. Results remained unchanged if adjusted for child intelligence. There was no association between high muscle tone and SRS or PDP. Exclusion of children with ASD diagnosis did not change the association. This large study showed a prospective association of infant muscle tone with autistic traits in childhood. Our findings suggest that early detection of low muscle tone might be a gateway to improve early diagnosis of ASD. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.