Sleep-disordered breathing in heart failure.

PURPOSE OF REVIEW: This review addresses the evolving intersection of sleep-disordered breathing (SDB) and heart failure, a topic of increasing clinical significance due to the high prevalence of SDB in heart failure patients and its impact on morbidity and mortality. It reflects recent advancements in diagnostic methodologies and therapeutic strategies. It emphasizes the need for heightened awareness among healthcare providers about the complex relationship between SDB and various forms of heart failure. RECENT FINDINGS: Recent studies underscore the high incidence of SDB in heart failure patients, varying with the cause of heart failure. Emerging diagnostic tools, including home sleep tests and advanced inpatient screening methods, have improved the early detection and accurate diagnosis of SDB. Novel treatment modalities, like hypoglossal and phrenic nerve stimulation, are promising, especially where conventional therapies are inadequate. The review also discusses the complexities of managing SDB in the context of different heart failure subtypes. SUMMARY: Findings from recent literature suggest that improved screening, diagnosis, and innovative treatment of SDB in heart failure patients can reduce morbidity, mortality, and healthcare costs. This review emphasizes the need for personalized treatment approaches tailored to individual patient profiles, highlighting the potential of new technologies and multidisciplinary strategies in clinical practice.

Ventricular assist devices and sleep-disordered breathing-A mechanical heart stimulating a sleepy brain.

Sleep-disordered breathing, including obstructive sleep apnea (OSA) and central sleep apnea (CSA), is common in severe heart failure (HF) patients. There is limited data on the effect of left ventricular assist devices (LVAD) on sleep apnea. We performed a retrospective review of 350 durable LVAD patients and found 5 with a history of pre- and post-LVAD sleep studies. All five patients had OSA, and three had concomitant CSA. We observed reduced apnea-hypopnea index following LVAD placement. This was due to a near abolishment of CSA in three mixed sleep apnea patients-as seen by a central apnea index improvement from an average of 25.9 ± 13.1 to 1.4 ± 2.5 events per hour (p = 0.063). LVAD placement was associated with an increase in thermodilution cardiac output from 2.7 ± 0.6 to 4.1 ± 1.1 L/min (p = 0.014). These findings support chemoreception physiology seen in patients with poor circulation and the effect of restoring this circulation with LVAD support.

Impact of Donor Hemodynamics on Recipient Survival in Heart Transplantation.

BACKGROUND: Heart transplantation is the gold-standard therapy for end-stage heart failure, but rates of donor-heart use remain low due to various factors that are often not evidence based. The impact of donor hemodynamics obtained via right-heart catheterization on recipient survival remains unclear. METHODS: The United Network for Organ Sharing registry was used to identify donors and recipients from September 1999-December 2019. Donor hemodynamics data were obtained and analyzed using univariate and multivariable logistical regression, with the primary endpoints being 1- and 5-year post-transplant survival. RESULTS: Of the 85,333 donors who consented to heart transplantation during the study period, 6573 (7.7%) underwent right-heart catheterization, of whom 5531 eventually underwent procurement and transplantation. Donors were more likely to undergo right-heart catheterization if they had high-risk criteria. Recipients who had donor hemodynamic assessment had 1- and 5-year survival rates similar to those without donor hemodynamic assessment (87% vs 86%, 1 year). Abnormal hemodynamics were common in donor hearts but did not impact recipient survival rates, even when risk-adjusted in multivariable analysis. CONCLUSIONS: Donors with abnormal hemodynamics may represent an opportunity to expand the pool of viable donor hearts.

Pulmonary Artery Wedge Pressure Respiratory Variation Increases With Sodium Nitroprusside Vasodilator Challenge.

BACKGROUND: The physiologic factors leading to pulmonary arterial wedge pressure respiratory variation (PAWPvar) are underexplored. We hypothesized that PAWPvar is associated with baseline PAWP and would predict response to sodium nitroprusside (SNP). METHODS AND RESULTS: We performed a retrospective study of right heart catheterization studies in 51 subjects with SNP challenge at our institution from 2012 to 2019. PAWPvar was defined as expiratory minus inspiratory PAWP. Baseline %PAWPvar was inversely correlated with baseline PAWP (R = -0.5). SNP administration led to increased %PAWPvar (+27%, P < .01). Subjects with low baseline PAWPvar (less than the median) had an increase in PAWPvar with SNP (3 ± 4 mm Hg), whereas those with a high baseline PAWPvar (greater than the median) did not (-0.6 ± 4 mm Hg, P = .003). Those who had a greater than the median PAWPvar increase with SNP had greater cardiac output augmentation compared with those who had less than a median increase in PAWPvar (1.7 ± 1.5 L/min vs 0.9 ± 0.7 L/min, P = .02). An increasing PAWPvar after SNP was associated with significant discrepancy in the number of subjects achieving transplant-acceptable pulmonary vascular resistance (<2.5 Wood units) when calculated by expiratory versus mean PAWP (37 vs 27 subjects, 20% discrepancy rate). Subjects with a higher PAWPvar after SNP were more likely to demonstrate discrepant transplant-acceptable pulmonary vascular resistance calculations comparing expiratory versus mean PAWP than those with lower PAWPvar post-SNP (47% vs 13%, odds ratio 5.5, P = .03). CONCLUSIONS: Our findings indicate that PAWPvar is a meaningful physiologic parameter that is influenced by the compliance of the left heart/pulmonary vascular system and its relative preload and afterload states.

ASSOCIATION BETWEEN VISUAL FUNCTION AND SUBRETINAL DRUSENOID DEPOSITS IN NORMAL AND EARLY AGE-RELATED MACULAR DEGENERATION EYES.

PURPOSE: To examine the association between subretinal drusenoid deposits (SDDs) identified by multimodal retinal imaging and visual function in older eyes with normal macular health or in the earliest phases of age-related macular degeneration (AMD). METHODS: Age-related macular degeneration status for each eye was defined according to the Age-Related Eye Disease Study (AREDS) 9-step classification system (normal = Step 1, early AMD = Steps 2-4) based on color fundus photographs. Visual functions measured were best-corrected photopic visual acuity, contrast and light sensitivity, mesopic visual acuity, low-luminance deficit, and rod-mediated dark adaptation. Subretinal drusenoid deposits were identified through multimodal imaging (color fundus photographs, infrared reflectance and fundus autofluorescence images, and spectral domain optical coherence tomography). RESULTS: The sample included 1,202 eyes (958 eyes with normal health and 244 eyes with early AMD). In normal eyes, SDDs were not associated with any visual function evaluated. In eyes with early AMD, dark adaptation was markedly delayed in eyes with SDDs versus no SDD (a 4-minute delay on average), P = 0.0213. However, this association diminished after age adjustment, P = 0.2645. Other visual functions in early AMD eyes were not associated with SDDs. CONCLUSION: In a study specifically focused on eyes in normal macular health and in the earliest phases of AMD, early AMD eyes with SDDs have slower dark adaptation, largely attributable to the older ages of eyes with SDD; they did not exhibit deficits in other visual functions. Subretinal drusenoid deposits in older eyes in normal macular health are not associated with any visual functions evaluated.

Delayed Rod-Mediated Dark Adaptation Is a Functional Biomarker for Incident Early Age-Related Macular Degeneration.

PURPOSE: To examine whether slowed rod-mediated dark adaptation (DA) in adults with normal macular health at baseline is associated with the incidence of age-related macular degeneration (AMD) 3 years later. DESIGN: Prospective cohort. PARTICIPANTS: Adults aged ≥60 years were recruited from primary care ophthalmology clinics. Both eyes were required to be step 1 (normal) on the Age-Related Eye Disease Study 9-step AMD classification system based on color fundus photographs graded by experienced and masked evaluators. METHODS: Rod-mediated DA was assessed at baseline in 1 eye after a photobleach using a computerized dark adaptometer with targets centered at 5° on the inferior vertical meridian. Speed of DA was characterized by the rod-intercept value, with abnormal DA defined as rod-intercept ≥12.3 minutes. Demographic characteristics, best-corrected visual acuity, and smoking status were also assessed. Log-binomial regression was used to calculate unadjusted and adjusted risk ratios (RRs) and associated 95% confidence intervals (CIs) for the association between baseline DA and incident AMD. MAIN OUTCOME MEASURES: Presence of AMD at the 3-year follow-up visit for the eye tested for DA at baseline. RESULTS: Both baseline and follow-up visits were completed by 325 persons (mean age, 67.8 years). At baseline, 263 participants had normal DA with mean rod-intercept of 9.1 (standard deviation [SD], 1.5), and 62 participants had abnormal DA with mean rod-intercept of 15.1 (SD, 4.0). After adjustment for age and smoking, those with abnormal DA in the tested eye at baseline were approximately 2 times more likely to have AMD in that eye (RR, 1.92; 95% CI, 1.03-3.62) by the time of the follow-up visit, compared with those who had normal DA at baseline. CONCLUSIONS: Delayed rod-mediated DA in older adults with normal macular health is associated with incident early AMD 3 years later, and thus is a functional biomarker for early disease. The biological relevance of this test is high, because it assesses translocation of vitamin A derivatives across the retinal pigment epithelium and Bruch's membrane, 2 tissues with prominent age- and AMD-related pathology.

Dark adaptation in relation to choroidal thickness in healthy young subjects: a cross-sectional, observational study.

BACKGROUND: Dark adaptation is an energy-requiring process in the outer retina nourished by the profusely perfused choroid. We hypothesized that variations in choroidal thickness might affect the rate of dark adaptation. METHOD: Cross-sectional, observational study of 42 healthy university students (mean age 25 ± 2.0 years, 29 % men) who were examined using an abbreviated automated dark adaptometry protocol with a 2° diameter stimulus centered 5° above the point of fixation. The early, linear part of the rod-mediated dark adaptation curve was analyzed to extract the time required to reach a sensitivity of 5.0 × 10(-3) cd/m2 (time to rod intercept) and the slope (rod adaptation rate). The choroid was imaged using enhanced-depth imaging spectral-domain optical coherence tomography (EDI-OCT). RESULTS: The time to the rod intercept was 7.3 ± 0.94 (range 5.1 - 10.2) min. Choroidal thickness 2.5° above the fovea was 348 ± 104 (range 153-534) µm. There was no significant correlation between any of the two measures of rod-mediated dark adaptation and choroidal thickness (time to rod intercept versus choroidal thickness 0.072 (CI95 -0.23 to 0.38) min/100 µm, P = 0.64, adjusted for age and sex). There was no association between the time-to-rod-intercept or the dark adaptation rate and axial length, refraction, gender or age. CONCLUSION: Choroidal thickness, refraction and ocular axial length had no detectable effect on rod-mediated dark adaptation in healthy young subjects. Our results do not support that variations in dark adaptation can be attributed to variations in choroidal thickness.

Multimodal characterization of proliferative diabetic retinopathy reveals alterations in outer retinal function and structure.

PURPOSE: To identify changes in retinal function and structure in persons with proliferative diabetic retinopathy (PDR), including the effects of panretinal photocoagulation (PRP). DESIGN: Cross-sectional study. PARTICIPANTS: Thirty adults who underwent PRP for PDR, 15 adults with untreated PDR, and 15 age-matched controls. METHODS: Contrast sensitivity, frequency doubling perimetry (FDP), Humphrey visual fields, photostress recovery, and dark adaptation were assessed. Fundus photography and macular spectral-domain optical coherence tomography (SD OCT) were performed. To quantify retinal layer thicknesses, SD OCT scans were segmented semiautomatically. MAIN OUTCOME MEASURES: Visual function measures were compared among patients with PDR and PRP, untreated patients with PDR, and controls. Mean retinal layer thicknesses were compared between groups. Correlation analyses were performed to evaluate associations between visual function measures and retinal layer thicknesses. RESULTS: A significant reduction of FDP mean deviation (MD) was exhibited in PRP-treated patients with PDR (MD ± standard deviation, -8.20±5.76 dB; P < 0.0001) and untreated patients (-5.48±4.48 dB; P < 0.0001) relative to controls (1.07±2.50 dB). Reduced log contrast sensitivity compared with controls (1.80±0.14) also was observed in both PRP-treated patients (1.42±0.17; P < 0.0001) and untreated patients (1.56±0.20; P = 0.001) with PDR. Compared with controls, patients treated with PRP demonstrated increased photostress recovery time (151.02±104.43 vs. 70.64±47.14 seconds; P = 0.001) and dark adaptation speed (12.80±5.15 vs. 9.74±2.56 minutes; P = 0.022). Patients who underwent PRP had diffusely thickened nerve fiber layers (P = 0.024) and diffusely thinned retinal pigment epithelium (RPE) layers (P = 0.009) versus controls. Untreated patients with PDR also had diffusely thinned RPE layers (P = 0.031) compared with controls. CONCLUSIONS: Patients with untreated PDR exhibited inner retinal dysfunction, as evidenced by reduced contrast sensitivity and FDP performance, accompanied by alterations in inner and outer retinal structure. Patients who underwent PRP had more profound changes in outer retinal structure and function. Distinguishing the effects of PDR and PRP may guide the development of restorative vision therapies for patients with advanced diabetic retinopathy.

Twelve-month natural history of dark adaptation in patients with AMD.

PURPOSE: A sensitive endpoint is required for clinical trials evaluating preventative therapies for early age-related macular degeneration (AMD). Dark adaptation (DA) is a sensitive marker of AMD and has been proposed as a potential endpoint. This study evaluated whether significant changes in DA speed could be detected in participants with early to intermediate AMD at 12 months following baseline DA measurement. METHODS: Dark adaptation, visual acuity (VA), and fundus photography were obtained at baseline and at 6 and 12 months in 26 subjects with AMD and in 6 subjects with normal retinal health. Disease severity was assessed by the Nine-Step Age-Related Eye Disease Study AMD severity scale. RESULTS: At 12 months, significant progression of DA impairment occurred in 5 of 26 (19%) participants with AMD. None of the participants with AMD exhibited a significant worsening of fundus grade or decrease of acuity related to disease progression. The normal group exhibited stable DA and VA during the observation period. CONCLUSIONS: Significant worsening of DA was observed in 19% of subjects with AMD in 12 months of observation, despite stable VA and fundus appearance. This study suggests that DA may be a suitable functional endpoint for early clinical studies evaluating novel treatments for early to intermediate AMD.

Right Ventricular Contractility and Pulmonary Arterial Coupling After Less Invasive Left Ventricular Assist Device Implantation.

Right ventricular failure contributes significantly to morbidity and mortality after left ventricular assist device implantation. Recent data suggest a less invasive strategy (LIS) via thoracotomy may be associated with less right ventricular failure than conventional median sternotomy (CMS). However, the impact of these approaches on load-independent right ventricular (RV) contractility and RV-pulmonary arterial (RV-PA) coupling remains uncertain. We hypothesized that the LIS approach would be associated with preserved RV contractility and improved RV-PA coupling compared with CMS. We performed a retrospective study of patients who underwent durable, centrifugal left ventricular assist device implantation and had paired hemodynamic assessments before and after implantation. RV contractility (end-systolic elastance [Ees]), RV afterload (pulmonary effective arterial elastance [Ea]), and RV-PA coupling (Ees/Ea) were determined using digitized RV pressure waveforms. Forty-two CMS and 21 LIS patients were identified. Preimplant measures of Ees, Ea, and Ees/Ea were similar between groups. After implantation, Ees declined significantly in the CMS group (0.60-0.40, p = 0.008) but not in the LIS group (0.67-0.58, p = 0.28). Coupling (Ees/Ea) was unchanged in CMS group (0.54-0.59, p = 0.80) but improved significantly in the LIS group (0.58-0.71, p = 0.008). LIS implantation techniques may better preserve RV contractility and improve RV-PA coupling compared with CMS.

Milk of Calcium Causing a Case of Calcific Pericardial Effusion.

A 60-year-old man presented with heart failure symptoms and was found to have a calcified pericardial effusion consistent with "milk of calcium" and constrictive physiology. The patient received a pericardiectomy and has had favorable outcomes at his 1-year follow-up. There are minimal reports of calcific pericardial effusion with constrictive pathology.

Cardio-Obstetric Shock: Mechanical Circulatory Support as a Bridge to Pregnancy Viability.

Cardiogenic shock in pregnancy is rare but is associated with significant morbidity and mortality. Timely recognition with multidisciplinary management is necessary for optimal maternal and fetal outcomes. Here we present a case of cardiogenic shock in the antepartum period managed with mechanical circulatory support as a bridge to pregnancy viability.

Cardiac output assessment methods in left ventricular assist device patients: A problem of heteroscedasticity.

Equipoise remains about how best to measure cardiac output (CO) in patients with left ventricular assist devices (LVAD). In this study, direct Fick CO was compared with thermodilution (TD) and indirect Fick (iFick) CO in 61 LVAD patients. TD and LaFarge iFick showed moderate correlation with direct Fick (R2 = 0.49 and R2 = 0.38, p < 0.001 for both), while Dehmer and Bergstra iFick showed poor correlation with direct Fick (R2 = 0.29 and R2 = 0.31, p < 0.001 for both). Absolute bias between all CO estimation techniques and direct Fick CO was lowest for TD compared to iFick methods but significant for all methods. All methods tended to overestimate CO compared to direct Fick, with greatest overestimation present in those with the lowest measured direct Fick CO. Bias and frequency of significant discrepancy were least using TD and Lafarge iFick CO estimation methods in this study, with TD CO demonstrating modestly better correlation and less heteroscedasticity compared to Lafarge.

Hemodynamic and Clinical Determinants of Left Atrial Enlargement in Liver Transplant Candidates.

New-onset heart failure is a frequent complication after orthotopic liver transplantation (OLT). Left atrial enlargement (LAE) may be a sign of occult left heart disease. Our primary objective was to determine invasive hemodynamic and clinical predictors of LAE and then investigate its effect on post-transplant outcomes. Of 609 subjects who received OLT between January 1, 2010, and October 1, 2018, 145 who underwent preoperative right-sided cardiac catheterization and transthoracic echocardiography were included. Seventy-eight subjects (54%) had pretransplant LAE. Those with LAE had significantly lower systemic vascular resistance with higher cardiac and stroke volume index (61.0 vs 51.7 ml/m2; p <0.001), but there was no difference in pulmonary artery wedge pressure. There was a linear relation between left atrial volume index and stroke volume index (R2 = 0.490, p<0.001), but not pulmonary artery wedge pressure. The presence of severe LAE was associated with a reduced likelihood (hazard ratio = 0.26, p = 0.033) of reaching the composite end point of new-onset systolic heart failure, heart failure hospitalization, or heart failure death within 12 months post-transplant. There was also a significant reduction in LAE after transplantation (p = 0.013). In conclusion, LAE was common in OLT recipients and was more closely associated with stroke volume than left heart filling pressures. The presence of LAE was associated with a reduced likelihood of reaching composite outcomes and tended to regress after transplant.

Hemodynamic reserve predicts early right heart failure after LVAD implantation.

BACKGROUND: Early right heart failure (RHF) remains a major source of morbidity and mortality after left ventricular assist device (LVAD) implantation, yet efforts to predict early RHF have proven only modestly successful. Pharmacologic unloading of the left ventricle may be a risk stratification approach allowing for assessment of right ventricular and hemodynamic reserve. METHODS: We performed a multicenter, retrospective analysis of patients who had undergone continuous-flow LVAD implantation from October 2011 to April 2020. Only those who underwent vasodilator testing with nitroprusside during their preimplant right heart catheterization were included (n = 70). Multivariable logistic regression was used to determine independent predictors of early RHF as defined by Mechanical Circulatory Support-Academic Research Consortium. RESULTS: Twenty-seven patients experienced post-LVAD early RHF (39%). Baseline clinical characteristics were similar between patients with and without RHF. Patients without RHF, however, achieved higher peak stroke volume index (SVI) (30.1 ± 8.8 vs 21.7 ± 7.4 mL/m2; p < 0.001; AUC: 0.78; optimal cut-point: 22.1 mL/m2) during nitroprusside administration. Multivariable analysis revealed that peak SVI was significantly associated with early RHF, demonstrating a 16% increase in risk of early RHF per 1 ml/m2 decrease in SVI. A follow up cohort of 10 consecutive patients from July 2020 to October 2021 resulted in all patients being categorized appropriately in regards to early RHF versus no RHF according to peak SVI. CONCLUSION: Peak SVI with nitroprusside administration was independently associated with post-LVAD early RHF while resting hemodynamics were not. Vasodilator testing may prove to be a strong risk stratification tool when assessing LVAD candidacy though additional prospective validation is needed.

Acute Hemodynamic Effects of Cardiac Resynchronization Therapy Versus Alternative Pacing Strategies in Patients With Left Ventricular Assist Devices.

Background The hemodynamic effects of cardiac resynchronization therapy in patients with left ventricular assist devices (LVADs) are uncharacterized. We aimed to quantify the hemodynamic effects of different ventricular pacing configurations in patients with LVADs, focusing on short-term changes in load-independent right ventricular (RV) contractility. Methods and Results Patients with LVADs underwent right heart catheterization during spontaneous respiration without sedation and with pressures recorded at end expiration. Right heart catheterization was performed at different pacemaker configurations (biventricular pacing, left ventricular pacing, RV pacing, and unpaced conduction) in a randomly generated sequence with >3 minutes between configuration change and hemodynamic assessment. The right heart catheterization operator was blinded to the sequence. RV maximal change in pressure over time normalized to instantaneous pressure was calculated from digitized hemodynamic waveforms, consistent with a previously validated protocol. Fifteen patients with LVADs who were in sinus rhythm were included. Load-independent RV contractility, as assessed by RV maximal change in pressure over time normalized to instantaneous pressure, was higher in biventricular pacing compared with unpaced conduction (15.7±7.6 versus 11.0±4.0 s-1; P=0.003). Thermodilution cardiac output was higher in biventricular pacing compared with unpaced conduction (4.48±0.7 versus 4.38±0.8 L/min; P=0.05). There were no significant differences in heart rate, ventricular filling pressures, or atrioventricular valvular regurgitation across all pacing configurations. Conclusions Biventricular pacing acutely improves load-independent RV contractility in patients with LVADs. Even in these patients with mechanical left ventricular unloading via LVAD who were relative pacing nonresponders (required LVAD support despite cardiac resynchronization therapy), biventricular pacing was acutely beneficial to RV contractility.

Dark adaptation during transient hyperglycemia in type 2 diabetes.

It was the purpose of the present study to examine dark adaptation in subjects with type 2 diabetes during transient hyperglycemia. Twenty-four subjects with type 2 diabetes and minimal diabetic retinopathy were randomized to undergo an oral glucose tolerance test (OGTT) or to remain fasting. Dark adaptometry was measured in one eye, chosen at random, using a computer-controlled dark adaptometer. Dark adaptation and capillary blood glucose were measured at baseline and 80 minutes into the OGTT/fasting test. Blood glucose remained stable throughout the examination in the 12 fasting subjects, whereas glycemia increased in the 12 OGTT subjects, from 8.6±2.1 at baseline to 21.1±3.6 mM after 80 min. In the OGTT group, four out of seven subjects with delayed dark adaptation at baseline reached normal values during hyperglycemia. All examined aspects of rod adaptation were accelerated by hyperglycemia (time to rod-cone break -26%; time to rod intercept -16%, rod sensitivity recovery slope (log units/min) +35%), whereas no measurable change in cone adaptation was seen. The results are consistent with rod adaptation being limited by glycemia and with rod adaptation being delayed in subjects with diabetes compared with healthy subjects, the delay being reversible in response to hyperglycemia.

Visual dysfunction associated with diabetic retinopathy.

Diabetic retinopathy is a leading cause of blindness and is commonly viewed as a vascular complication of diabetes mellitus. However, diabetes mellitus causes visual dysfunction before the onset of clinically visible microvascular changes associated with diabetic retinopathy. Thus, viewing diabetic retinopathy more generally as a neurovascular disease may lead to an improved understanding of the mechanisms responsible for vision loss. This article reviews the impact of diabetes mellitus on inner and outer retinal visual and electrophysiologic function and advocates for a multimodal approach to the study of diabetic retinopathy.

US residency training before and after the 1997 Balanced Budget Act.

CONTEXT: Graduate medical education (GME) determines the size and characteristics of the future workforce. The 1997 Balanced Budget Act (BBA) limited Medicare funding for additional trainees in GME. There has been concern that because Medicare is the primary source of GME funding, the BBA would discourage growth in GME. OBJECTIVE: To examine the number of residents in training before and after the BBA, as well as more recent changes in GME by specialty, sex, and type and location of education. DESIGN: Descriptive study using the American Medical Association/Association of American Medical Colleges National GME Census on physicians in Accreditation Council for Graduate Medical Education (ACGME)-accredited programs to examine changes in the number and characteristics of residents before and after the BBA. MAIN OUTCOME MEASURES: Differences in the number of physicians in ACGME-accredited training programs overall, by specialty, and by location and type of education. RESULTS: The number of residents and fellows changed little between academic year (AY) 1997 (n = 98,143) and AY 2002 (n = 98,258) but increased to 106,012 in AY 2007, a net increase of 7869 (8.0%) over the decade. The annual number of new entrants into GME increased by 7.6%, primarily because of increasing international medical graduates (IMGs). United States medical school graduates (MDs) comprised 44.0% of the overall growth from 2002 to 2007, followed by IMGs (39.2%) and osteopathic school graduates (18.8%). United States MD growth largely resulted from selection of specialties with longer training periods. From 2002 to 2007, US MDs training in primary care specialties decreased by 2641, while IMGs increased by 3286. However, increasing subspecialization rates led to fewer physicians entering generalist careers. CONCLUSION: After the 1997 BBA, there appears to have been a temporary halt in the growth of physicians training in ACGME programs; however, the number increased from 2002 to 2007.

Disorganization of Retinal Inner Layers (DRIL) and Neuroretinal Dysfunction in Early Diabetic Retinopathy.

Purpose: To elucidate the relationship between disorganization of retinal inner layers (DRILs) and retinal function in diabetic patients without diabetic retinopathy (DR) and with nonproliferative DR, but without diabetic macular edema (DME). Methods: Fifty-seven participants with diabetes mellitus (DM) and 18 healthy controls underwent comprehensive ophthalmic examination, fundus photography, and spectral-domain optical coherence tomography. Scans of the fovea were evaluated for the presence of DRIL. Retinal function was evaluated using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity, the quick contrast sensitivity function (qCSF) on the AST Sentio Platform, short-wavelength automated perimetry (SWAP), standard automated perimetry (SAP), and frequency doubling perimetry (FDP). ANOVA and Kruskal-Wallis were used to compare retinal function in subjects with and without DRIL. Tukey-Kramer test and Wilcoxon were used for post hoc analysis. Results: DRIL was identified in 9 of 57 diabetic subjects. DRIL subjects had higher body mass index and longer diabetes duration compared to diabetic subjects without DRIL (P = 0.03 and P = 0.009, respectively). Subjects with DRIL had reduced ETDRS visual acuity (P = 0.003), contrast sensitivity function (P = 0.0003), and SAP performance (PSD, P < 0.0001) compared to controls and diabetic subjects without DRIL. Structural analysis revealed inner retinal thinning, and some outer retinal thinning, associated with DRIL. Conclusions: Diabetic subjects with DRIL have reduced retinal function compared to those without DRIL, and defective retinal lamination may be an early cellular consequence of diabetes responsible for this in some patients. Following further longitudinal studies, DRIL may be a readily available and reliable structural biomarker for reduced retinal function in early diabetic neuroretinal disease.