Faculty Bibliography

In this study, we sought to determine the burden and characteristics of orgasmic dysfunction (OD) and concomitant erectile dysfunction (ED) in men with type 1 diabetes (T1D) enrolled in the Epidemiology of Diabetes Interventions and Complications (EDIC) study. In 2010, we assessed orgasmic and erectile function using the International Index of Erectile Function (IIEF). Sociodemographic, clinical, and diabetes characteristics were compared by OD status (OD only, OD and ED, no ED or OD). Age-adjusted associations between risk factors and OD status were examined. OD and ED information was available from 563 men. Eighty-three men (14.7%) reported OD of whom 21 reported OD only and 62 reported OD and ED. Age-adjusted odds ratios demonstrated that men who reported OD only had higher odds of depression, low sexual desire, and decreased alcohol use compared with men reporting no dysfunction. Men with OD concomitant with ED had greater odds of elevated hemoglobin A1C, peripheral and autonomic neuropathy, and nephropathy. Men reporting both dysfunctions were also more likely to report smoking, lower urinary tract symptoms, and had greater odds of androgen deficiency than men with no sexual dysfunction. Men with longstanding T1D suffer from an increased burden of OD. Psychogenic factors predominate in men reporting OD only while men who present with concomitant ED report increased burden of diabetes severity, characteristics previously observed with incident ED. ED may be the central impediment to sexual function in men with OD and ED. Longitudinal studies to characterize OD and ED experience over time are warranted.

PURPOSE/OBJECTIVE:To identify, appraise, and assess clinical practice guidelines informing patient counseling on female age-related fertility decline. METHODS:Searched electronic database records from January 1, 2006, to September 10, 2018, and professional society websites. The search terms included iterations of "guideline," "counseling," "preconception," "age-related fertility decline," and "reproductive life planning." English-language professional organization guidelines addressing patient counseling on age-specific reproductive health topics were included. Assessed the methodological quality of included guidelines using the AGREE II instrument. Guidelines were categorized as high quality or low quality based on AGREE II scores. Extracted age-specific reproductive health recommendations of high-quality guidelines. RESULTS:The search identified 2918 records. Nineteen records addressed counseling on age-related fertility decline; only 6 focused only on reproductive aging, with the remaining 13 covering related topics. Eleven met criteria for high quality. All high-quality guidelines had high "rigor of development" scores on AGREE II. Ten high-quality guidelines stated an age at which female fertility declines, ranging from 30 to "late 30s." One recommended a specific age at which patients should be counseled. Five of eleven high-quality guidelines did not discuss the obstetric and perinatal risks of advanced maternal age. CONCLUSIONS:Few high-quality guidelines address counseling on female age-related fertility decline, and existing guidance on reproductive aging counseling is inconsistent and incomplete. Greater rigor of development and incorporation of age-specific counseling recommendations into clinical practice guidelines could lead to improved patient anticipatory guidance and more informed reproductive choices.

BACKGROUND:Thirty years after the Mangled Extremity Severity Score (MESS) was developed, advances in vascular, trauma and orthopedic surgery have rendered the sensitivity of this score obsolete. A significant number of patients receive amputation during subsequent admissions, which are often missed in the analysis of amputation at the index admission. We aimed to identify risk factors for and predict amputation on initial admission or within 30 days of discharge (peritraumatic amputation or PTA). STUDY DESIGN/METHODS:The Nationwide Readmission Database for 2016 and 2017 was used in our analysis. Factors associated with PTA were identified. We used XGBoost, Random Forest, and Logistic Regression methods to develop a framework for machine learning (ML) based prediction models for PTA. RESULTS:We identified 1098 adult patients with traumatic lower extremity fracture and arterial injuries, 206 underwent amputation. 176 (85.4%) underwent amputation during the index admission and 30 (14.6%) underwent amputation within a 30-day readmission period. After identifying factors associated with PTA, we constructed machine learning models based on Random Forest, XGBoost, and Logistic Regression to predict PTA. We discovered that Logistic regression had the most robust predictive ability, with an accuracy of 0.88, sensitivity of 0.47, and specificity of 0.98. We then built on the Logistic Regression by the NearMiss algorithm, increasing sensitivity to 0.71, but decreasing accuracy to 0.74 and specificity to 0.75. CONCLUSIONS:ML-based prediction models combined with sampling algorithms (such as the NearMiss algorithm in this study), can help identify patients with traumatic arterial injuries at high risk for amputation and guide targeted intervention in the modern age of vascular surgery.

BACKGROUND:Studies suggest that migraine is often underdiagnosed and inadequately treated in the primary care setting, despite many patients relying on their primary care provider (PCP) to manage their migraine. Many women consider their women's healthcare provider to be their PCP, yet very little is known about migraine knowledge and practice patterns in the women's healthcare setting. OBJECTIVE:The objective of this study was to assess women's healthcare providers' knowledge and needs regarding migraine diagnosis and treatment. METHODS:The comprehensive survey assessing migraine knowledge originally developed for PCPs was used in this study, with the addition of a section regarding the use of hormonal medications in patients impacted by migraine. Surveys were distributed online, and primarily descriptive analyses were performed. RESULTS:The online survey was completed by 115 women's healthcare providers (response rate 28.6%; 115/402), who estimated that they serve as PCPs for approximately one-third of their patients. Results suggest that women's healthcare providers generally recognize the prevalence of migraine, but experience some knowledge gaps regarding migraine management. Despite 82.6% (95/115) of survey respondents feeling very comfortable or somewhat comfortable with diagnosing migraine, only 57.9% (66/114) reported routinely asking patients about headaches during annual visits. Very few were familiar with the American Academy of Neurology guidelines on preventative treatment (6.3%; 7/111) and the Choosing Wisely Campaign recommendations on migraine treatment (17.3%; 19/110), and many prescribed medications known to contribute to medication overuse headache. In addition, only 24.3% (28/115) would order imaging for a new type of headache, 35.7% (41/115) for worsening headache, and 47.8% (55/115) for headache with neurologic symptoms; respondents cited greater tendency with sending patients to an emergency department for the same symptoms. Respondents had limited knowledge of evidence-based, non-pharmacological treatments for migraine (i.e., biofeedback or cognitive behavioral therapy), with nearly none placing referrals for these services. Most providers were comfortable prescribing hormonal contraception (mainly progesterone only) to women with migraine without aura (80.9%; 89/110) and with aura (72.5%; 79/109), and followed American College of Obstetricians and Gynecologists (ACOG) guidelines to limit combination hormonal contraception for patients with aura. When queried, 6.3% or less (5/79) of providers would prescribe estrogen-containing contraception for women with migraine with aura. Only 37.3% (41/110) of respondents reported having headache/migraine education. Providers indicated interest in education pertaining to migraine prevention and treatment (96.3%; 105/109), migraine-associated disability (74.3%; 81/109), and diagnostic testing (59.6%; 65/109). CONCLUSION/CONCLUSIONS:Women's healthcare providers appear to have several knowledge gaps regarding the management of migraine in their patients. These providers would likely benefit from access to a headache-specific educational curriculum to improve provider performance and patient outcomes.

BACKGROUND:Coronavirus disease 2019 (COVID-19) predisposes to arterial and venous thromboembolic complications. We describe the clinical presentation, management, and outcomes of acute arterial ischemia and concomitant infection at the epicenter of cases in the United States. METHODS:Patients with confirmed COVID-19 infection between March 1, 2020 and May 15, 2020 with an acute arterial thromboembolic event were reviewed. Data collected included demographics, anatomical location of the thromboembolism, treatments, and outcomes. RESULTS:Over the 11-week period, Northwell Health System cared for 12,630 hospitalized patients with COVID-19. A total of 49 patients with arterial thromboembolism and confirmed COVID-19 were identified. Median age was 67 years (58-75) and 37 (76%) were male. The most common preexisting conditions were hypertension (53%) and diabetes (35%). Median D-dimer level was 2673 ng/mL (723-7139). The distribution of thromboembolic events included upper 7 (14%) and lower 35 (71%) extremity ischemia, bowel ischemia 2 (4%), and cerebral ischemia 5 (10%). Six patients (12%) had thrombus in multiple locations. Concomitant deep vein thrombosis was found in 8 patients (16%). Twenty-two (45%) patients presented with signs of acute arterial ischemia and were subsequently diagnosed with COVID-19. The remaining 27 (55%) developed ischemia during hospitalization. Revascularization was performed in 13 (27%) patients, primary amputation in 5 (10%), administration of systemic tissue plasminogen activator in 3 (6%), and 28 (57%) were treated with systemic anticoagulation only. The rate of limb loss was 18%. Twenty-one patients (46%) died in the hospital. Twenty-five (51%) were successfully discharged and 3 patients are still in the hospital. CONCLUSIONS:While the mechanism of thromboembolic events in patients with COVID-19 remains unclear, the occurrence of such complication is associated with acute arterial ischemia which results in a high limb loss and mortality.

Although the gold standard of monitoring kidney transplant function relies on glomerular filtration rate (GFR), little is known about GFR trajectories after transplantation, their determinants, and their association with outcomes. To evaluate these parameters we examined kidney transplant recipients receiving care at 15 academic centers. Patients underwent prospective monitoring of estimated GFR (eGFR) measurements, with assessment of clinical, functional, histological and immunological parameters. Additional validation took place in seven randomized controlled trials that included a total of 14,132 patients with 403,497 eGFR measurements. After a median follow-up of 6.5 years, 1,688 patients developed end-stage kidney disease. Using unsupervised latent class mixed models, we identified eight distinct eGFR trajectories. Multinomial regression models identified seven significant determinants of eGFR trajectories including donor age, eGFR, proteinuria, and several significant histological features: graft scarring, graft interstitial inflammation and tubulitis, microcirculation inflammation, and circulating anti-HLA donor specific antibodies. The eGFR trajectories were associated with progression to end stage kidney disease. These trajectories, their determinants and respective associations with end stage kidney disease were similar across cohorts, as well as in diverse clinical scenarios, therapeutic eras and in the seven randomized control trials. Thus, our results provide the basis for a trajectory-based assessment of kidney transplant patients for risk stratification and monitoring.

BACKGROUND:Oldest-old patients (≥85 years) constitute half the acute myocardial infarction hospitalizations among older adults and more commonly have atypical presentation, under-treatment and functional impairments. Yet this group has not been well characterized. OBJECTIVES/OBJECTIVE:We characterized differences in presentation, functional impairments, treatments, health status, and mortality among middle-old (75-84 years) and oldest-old patients with myocardial infarction. METHODS:We analyzed data from the ComprehenSIVe Evaluation of Risk Factors in Older Patients with AMI (SILVER-AMI) study that enrolled 3041 patients ≥75 years of age from 94 hospitals across the US between 2013-2016. We performed Cox proportional hazards regression to examine the association between the oldest-old (n=831) and middle-old (n=2210) age categories with post-discharge 6-month case fatality rate adjusting for socio-demographic and clinical variables, and mobility impairment. RESULTS:The oldest-old were less likely to present with chest pain (52.7% vs. 57.7%) as their primary symptom or to receive coronary revascularization (58.1% vs. 71.8) (p<0.01 for both). The oldest-old were more likely to have functional impairments and had higher 6-month mortality compared with the middle-old patients (HR 1.78, 95% CI 1.39-2.28). This association was substantially attenuated after adjusting for mobility impairment (HR 1.29, 95% CI 0.99-1.68). CONCLUSIONS:There is considerable heterogeneity in presentation, treatment and outcomes among older patients with myocardial infarction. Mobility impairment, a marker for frailty, modifies the association between advanced age and treatments as well as outcomes.

We used plasma neuronal extracellular vesicles to examine how neuronal insulin signaling proteins relate cross-sectionally to brain structure in nondemented older adults with varying levels of cortical amyloid. Extracellular vesicles enriched for neuronal origin by anti-L1CAM immunoabsorption were isolated from plasma of Atherosclerosis Risk in Communities-Positron Emission Tomography study participants (n = 88; mean age: 77 years [standard deviation: 6]). Neuronal extracellular vesicle levels of phosphorylated insulin signaling cascade proteins were quantified. Brain volume and white matter hyperintensity (WMH) volume were assessed using 3T magnetic resonance imaging. After adjusting for demographic variables and extracellular vesicle marker Alix, higher levels of a neuronal insulin signaling composite measure were associated with lower WMH and greater temporal lobe volume. Secondary analyses found the levels of downstream protein kinases involved in cell survival (p70S6K) and tau phosphorylation/neuroinflammation (GSK-3β) to be most strongly associated with WMH and temporal lobe volume, respectively. Associations between neuronal insulin signaling and lower WMH volume were attenuated in participants with elevated cortical amyloid. These results suggest that enhanced neuronal proximal insulin signaling is associated with preserved brain structure in nondemented older adults.

Dipeptidyl peptidase-4 (DPP-4) inhibitors increase endogenous glucagon-like peptide-1 (GLP-1). We hypothesized that genetic variation in the gene encoding the GLP-1 receptor (GLP1R) could affect the metabolic response to DPP-4 inhibition. To evaluate the relationship between the GLP1R rs6923761 variant (G-to-A nucleic acid substitution) and metabolic responses, we performed mixed meal studies in individuals with type 2 diabetes mellitus and hypertension after 7-day treatment with placebo and the DPP-4 inhibitor sitagliptin. This analysis is a substudy of NCT02130687. The genotype frequency was 13:12:7 GG:GA:AA among individuals of European ancestry. Postprandial glucose excursion was significantly decreased in individuals carrying the rs6923761 variant (GA or AA) as compared with GG individuals during both placebo (P = 0.001) and sitagliptin treatment (P = 0.045), while intact GLP-1 levels were similar among the genotype groups. In contrast, sitagliptin lowered postprandial glucose to a greater degree in GG as compared with GA/AA individuals (P = 0.035). The relationship between GLP1R rs6923761 genotype and therapies that modulate GLP-1 signalling merits study in large populations.