Diehl, Nancy N.

ABSTRACTBackgroundVariants within the leucine‐rich repeat kinase 2 gene are recognized as the most frequent genetic cause of Parkinson's disease. Leucine‐rich repeat kinase 2 variation related to disease susceptibility displays many features that reflect the nature of complex, late‐onset sporadic disorders like Parkinson's disease.MethodsThe Genetic Epidemiology of Parkinson's Disease Consortium recently performed the largest genetic association study for variants in the leucine‐rich repeat kinase 2 gene across 23 different sites in 15 countries.ResultsHerein, we detail the allele frequencies for the novel risk factors (p.A419V and p.M1646T) and the protective haplotype (p.N551K‐R1398H‐K1423K) nominated in the original publication. Simple population allele frequencies not only can provide insight into the clinical relevance of specific variants but also can help genetically define patient groups.ConclusionsEstablishing individual patient‐based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies. © 2013 International Parkinson and Movement Disorder Society

Background. Previous reports have shown a positive association between serum calcium level and prostate cancer mortality. However, there is no data regarding whether higher serum calcium levels are associated with increased risk of biochemical recurrence (BCR) following salvage radiation therapy (SRT) for prostate cancer. Herein, we evaluate the association between pretreatment serum calcium levels and BCR in a cohort of men who underwent SRT. Methods. We evaluated 165 patients who underwent SRT at our institution. Median dose was 65.0 Gy (range: 54.0–72.4 Gy). We considered serum calcium as both a continuous variable and a 3-level categorical variable (low [≤9.0 mg/dL], moderate [>9.0 mg/dL and ≤9.35 mg/dL], and high [>9.35 mg/dL]) based on sample tertiles. Results. We observed no evidence of a linear association between serum calcium and BCR (relative risk (RR): 0.96, P=0.76). Compared to men with low calcium, there was no significantly increased risk of BCR for men with moderate (RR: 0.94, P=0.79) or high (RR: 1.08, P=0.76) serum calcium levels. Adjustment for clinical, pathological, and SRT characteristics in multivariable analyses did not alter these findings. Conclusion. Our results provide evidence that pretreatment serum calcium is unlikely to be a useful tool in predicting BCR risk following SRT.

Abstract Background: Preanesthesia medical examination is a common procedure performed before ophthalmic surgery. The frequency and characteristics of new medical issues and unstable medical conditions revealed by ophthalmic preanesthesia medical examination are unknown. We conducted a prospective observational study to estimate the proportion of patients with new medical issues and unstable medical conditions discovered during ophthalmic preanesthesia medical examination. Secondary aims were to characterize abnormal findings and assess surgical delay and adverse perioperative events, in relation to findings. Methods: Patients having preanesthesia medical examination, before ophthalmic surgery, were enrolled over a period of 2 years. A review was conducted of historical, physical examination, and test findings from the preanesthesia medical examination. Results: From review of medical records of 530 patients, 100 patients (19%; 95% CI, 16–23%) were reported by providers to have abnormal conditions requiring further medical evaluation. Of these, 12 (12%) had surgery delayed. Retrospective review of examination results identified an additional 114 patients with abnormal findings for a total of 214 (40%; 95% CI, 36–45%) patients. Among the 214 patients, primary findings were cardiovascular (139, 26%), endocrine (26, 5%), and renal (24, 5%). Complications occurred in 49 (9%; 95% CI, 7–12%) patients within 1 month of surgery. Conclusions: Ophthalmic preanesthesia medical examination frequently detects new medical issues or unstable existing conditions, which do not typically alter conduct of perioperative procedures or outcomes. However, these conditions are relevant to long-term patient health and should be conveyed to primary care physicians for further evaluation.

AbstractBackgroundRecent studies have demonstrated that cytomegalovirus (CMV) infection and disease are associated with increased risk of graft loss and death in high‐risk (donor CMV seropositive/recipient CMV seronegative) liver transplant recipients (LTR) despite effective antiviral chemoprophylaxis. Predictors of CMV infection and disease in this important population are incompletely defined.MethodsA retrospective cohort study of 227 high‐risk first LTR who received primary anti‐CMV chemoprophylaxis during the first 100 days after transplant was performed. A large number of patient, donor, operative, and post‐transplant potential risk factors were collected. Associations of potential risk factors for CMV infection or disease that occurred during the first year after transplant were assessed using Cox regression models. After Bonferroni adjustment for multiple testing, P‐values ≤0.00125 (associations with CMV infection) and ≤0.00122 (associations with CMV disease) were considered as statistically significant.ResultsCMV infection and disease occurred in 91 (40%) and 43 (19%) of LTR, respectively. In multivariable analysis, increased risk of CMV infection was observed for patients with lower model for end‐stage liver disease (MELD) score (P = 0.025), lower total bilirubin (P = 0.014), and longer operative time (P = 0.038), whereas increased risk of CMV disease was seen in patients with lower MELD score (P = 0.026), lower total bilirubin (P = 0.044), and lower international normalized ratio (P = 0.043). However, after adjustment for multiple testing, none of these findings approached statistical significance.ConclusionOur results suggest that interventions designed to prevent CMV infection and disease should be applied to all high‐risk LTR until more definitive predictors of these complications are identified.

BackgroundIschaemic stroke shares common traditional risk factors with coronary artery disease (CAD) and myocardial infarction (MI). This study evaluated whether genetic risk factors for CAD and MI also affect susceptibility to ischaemic stroke in Caucasians and African Americans.MethodsIncluded in the study were a Caucasian series (713 ischaemic stroke patients, 708 controls) and a small African American series (166 ischaemic stroke patients, 117 controls). Twenty single‐nucleotide polymorphisms (SNPs) previously shown to be associated with CAD or MI were genotyped and assessed for association with ischaemic stroke and ischaemic stroke subtypes using odds ratios (ORs) from multivariable logistic regression models.ResultsIn Caucasians, four SNPs on chromosome 9p21 were significantly associated with risk of cardioembolic stroke, the strongest of which was rs1333040 (OR 1.55, P = 0.0007); similar but weaker trends were observed for small vessel stroke, with no associations observed regarding large vessel stroke. Chromosome 9p21 SNPs were also associated with risk of ischaemic stroke in African Americans (rs1333040, OR 0.65, P = 0.023; rs1333042, OR 0.55, P = 0.070; rs2383207, OR 0.55, P = 0.070). The PSMA6 SNP rs1048990 on chromosome 14q13 was associated with overall ischaemic stroke in both Caucasians (OR 0.80, P = 0.036) and African Americans (OR 0.31, P = 0.020).ConclusionsOur results provide evidence that chromosome 9p21 variants are associated with cardioembolic ischaemic stroke in Caucasians and with overall ischaemic stroke in African Americans. The PSMA6 variant rs1048990 also appears to affect susceptibility to ischaemic stroke in both populations. These findings require validation, particularly the preliminary findings regarding African Americans given the small size of that series.

AbstractBackgroundCancer‐specific anxiety (CSA) can affect treatment decisions and is common in men following surgery for prostate cancer (PCa). We hypothesized that CSA is also associated with factors affecting quality of life. Herein, we examine the association of CSA with psychosocial factors and PCa aggressiveness in a cohort of men 1 year after prostatectomy for localized PCa.MethodsFrom our prospective PCa Registry, we identified 365 men who underwent prostatectomy for localized PCa who completed the Memorial Anxiety Scale for Prostate Cancer (MAX‐PC) and Expanded Prostate Cancer Index Composite at 1‐year follow‐up. We evaluated the association of scores on the MAX‐PC with demographics, clinicopathologic features, sexual function, and depression scores using Wilcoxon Rank Sum and Kendall's tau correlation tests.ResultsHigher scores on the MAX‐PC (i.e., higher anxiety) are associated with younger age (p < 0.01) and non‐Caucasian race (p < 0.01). Men with higher MAX‐PC scores also reported poor sexual satisfaction/function (p < 0.01) and increasing depressive symptoms (p < 0.01). Finally, although higher anxiety is associated with several pathologic features of aggressiveness (stage, positive margins, PSA at 1 year; all p‐values < 0.01), we noted several men with clinically indolent disease who reported significant anxiety.ConclusionsOur data suggest that higher levels of CSA are associated with poor sexual function and increased depressive symptoms 1 year after prostatectomy. Moreover, we noted demographic and pathologic features associated with higher CSA as well. If confirmed, our data support development of models to predict men at high risk of CSA following PCa surgery and targeted referral for additional counseling. Copyright © 2012 John Wiley & Sons, Ltd.

Abstract Context: Surveillance of patients with differentiated thyroid cancer (DTC) is achieved using serum thyroglobulin (Tg), neck ultrasonography (US), and recombinant human TSH (rhTSH)-stimulated Tg (Tg-stim). Objective: Our primary aim was to assess the utility of rhTSH Tg-stim in patients with suppressed Tg (Tg-supp) below 0.1 ng/ml using a sensitive assay. Our secondary aims were to assess the utility of US and to summarize the profile of subsequent Tg-supp measures. Design: This is a retrospective study conducted at two sites of an academic institution. Patients: A total of 163 patients status after thyroidectomy and radioactive iodine treatment who had Tg-supp below 0.1 ng/ml and rhTSH Tg-stim within 60 d of each other were included. Results: After rhTSH stimulation, Tg remained below 0.1 ng/ml in 94 (58%) and increased to 0.1–0.5 in 56 (34%), more than 0.5–2.0 in nine (6%), and above 2.0 ng/ml in four (2%) patients. Serial Tg-supp levels were obtained in 138 patients followed over a median of 3.6 yr. Neck US were performed on 153 patients; suspicious exams had fine-needle aspiration (FNA). All positive FNA were identified around the time of the initial rhTSH test. Six of seven recurrences were detected by US (Tg-stim &gt;2.0 ng/ml in one, 0.8 in one and ≤0.5 in four). One stage IV patient had undetectable Tg-stim. Conclusion: In patients with DTC whose T4-suppressed serum Tg is below 0.1 ng/ml, long-term monitoring with annual Tg-supp and periodic neck US are adequate to detect recurrences. In our experience, rhTSH testing does not change management and is not needed in this group of patients.

Background: Prior reports on metabolic derangements observed in distance running frequently have small sample sizes, lack prerace laboratory measures, and report sodium as the sole measure. Hypothesis: Metabolic abnormalities—hyponatremia, hypokalemia, renal dysfunction, hemoconcentration—are frequent after completing a full or half marathon. Clinically significant changes occur in these laboratory values after race completion. Study Design: Observational, cross-sectional study. Methods: Consenting marathon and half marathon racers completed a survey as well as finger stick blood sampling on race day of the National Marathon to Fight Breast Cancer (Jacksonville, Florida, February 2008). Parallel blood measures were obtained before and after race completion (prerace, n = 161; postrace, n = 195). Results: The prevalence of prerace and postrace hyponatremia was 8 of 161 (5.0%) and 16 of 195 (8.2%), respectively. Hypokalemia was not present prerace but was present in 1 runner postrace (1 of 195). Renal dysfunction occurred prerace in 14 of 161 (8.7%) and postrace in 83 of 195 (42.6%). Among those with postrace renal dysfunction, 45.8% (38 of 83) were classified as moderate or severe. Hemoconcentration was present in 2 of 161 (1.2%) prerace and 6 of 195 (3.1%) postrace. The mean changes in laboratory values were (postrace minus prerace): sodium, 1.6 mmol/L; potassium, −0.2 mmol/L; blood urea nitrogen, 2.8 mg/dL; creatinine, 0.2 mg/dL; and hemoglobin, 0.3 g/dL for 149 pairs (except blood urea nitrogen, n = 147 pairs). Changes were significant for all comparisons ( P < 0.01) except potassium ( P = 0.08) and hemoglobin ( P = 0.01). Conclusions: Metabolic abnormalities are common among endurance racers, and they may be present prerace, including hyponatremia. The clinical significance of these findings is unknown. Clinical relevance: It is unclear which runners are at risk for developing clinically important metabolic derangements. Participating in prolonged endurance exercise appears to be safe in the majority of racers.