Loneliness Among Medical Students, Physician Trainees and Faculty Physicians.

OBJECTIVE: Aims of this study were to explore 1) how often medical students, residents, fellows, and faculty physicians who completed a suicide screening questionnaire at a large US academic medical center endorsed intense loneliness and 2) the relationships of loneliness with other negative mental health states. METHODS: Between May 2009 and September 2001, all medical students, residents, fellows, and faculty physicians were invited to complete an anonymous online questionnaire as part of a screening program to identify and engage individuals in distress with mental health support. The questionnaire assessed intense loneliness, other affective states known to be associated with suicide risk, burnout, depressive symptoms, and suicidal thoughts and behaviors. Chi-square tests, independent sample t-tests, ANOVA, and correlation analysis were used to examine relationships between loneliness and these other signals of suicide risk. RESULTS: The response rate was ~ 20%. Overall, 364 of 2016 respondents (18.1%) endorsed intense. loneliness "a lot" or "most" of the time. This included 134/641 (20.9%) medical students, 170/703 (24.2%) residents and fellows and 60/664 (9.4%) faculty physicians. A greater odds of endorsing intense loneliness was seen in those under age 40 (OR = 0.35, p < 0.001), women (OR = 1.30, p = 0.030), and non-Whites (OR = 1.70, p < 0.001); and in those with burnout (OR = 3.14, p < 0.001), depression (OR = 12.34, p < 0.001), other intense affective states (OR = 4.34-8.34, p < 0.05), and suicidal ideation (OR = 3.47-13.00, p < 0.001). CONCLUSION: Interventions to mitigate loneliness in healthcare trainees and professionals may help decrease burnout, depression, and other suicide risk factors. A limitation of the study was the use of a single item to assess loneliness.

Association of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and De Ritis ratio with mortality in renal cell carcinoma: A multicenter analysis.

Background: Several markers of inflammation have been associated with oncologic outcomes. Prognostic markers are not well-defined for renal cell carcinoma (RCC). We sought to investigate the association of preoperative neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and De Ritis ratio with mortality in RCC. Methods: Multi-center retrospective analysis of patients undergoing surgery for RCC. Primary outcome of interest was all-cause mortality (ACM). Secondary outcomes were non-cancer mortality (NCM) and cancer-specific mortality (CSM). Elevated NLR was defined as ≥2.27, elevated PLR as ≥165, and elevated De Ritis ratio as ≥ 2.72. Multivariable cox regression analysis (MVA) was conducted to elucidate risk factors for primary and secondary outcomes, and Kaplan-Meier analysis (KMA) was used to evaluate survival outcomes comparing elevated and non-elevated NLR, PLR, and De Ritis ratio. Results: 2656 patients were analyzed (874 patients had elevated NLR; 480 patients had elevated PLR and 932 patients had elevated De Ritis). Elevated NLR was a significant predictor of ACM (HR 1.32, 95% CI: 1.07-1.64, p=0.003) and NCM (HR 1.79, 95% CI: 1.30-2.46, p<0.001) in MVA. Elevated De Ritis was a significant predictor of ACM (HR 2.04, 95% CI: 1.65-2.52), NCM (HR 1.84, 95% CI: 1.33-2.55, p<0.001), and CSM (HR 1.97, 95% CI:1.48-2.63, p<0.001). KMA revealed significant difference in 5-year overall survival (OS) (48% vs. 68%, p<0.001), non-cancer survival (NCS) (69% vs. 87%, p<0.001), and cancer-specific survival (CSS) (60% vs. 73%, p<0.001) for elevated versus non-elevated NLR. For PLR, there was a difference in 5-year OS (51% vs. 61%, p<0.001) and CSS (60% vs. 73%, p<0.001) with KMA. Conclusions: Elevated NLR was independently associated with worse ACM and NCM, while elevated De Ritis was predictive for CSM in addition to ACM and NCM. These differences may be useful in refining risk stratification with respect to cancer-related and non-cancer mortality in RCC patients and deserve further investigation.

Comparison of renal functional outcomes of active surveillance and partial nephrectomy in the management of oncocytoma.

PURPOSE: To compare functional outcomes of partial nephrectomy (PN) and active surveillance (AS) in oncocytoma. METHODS: Multicenter retrospective analysis of patients with oncocytoma managed with PN or AS (biopsy-confirmed). Primary outcome development of de novo chronic kidney disease (CKD) (eGFR < 60 mL/min/1.73m2). Cox regression Multivariable analysis (MVA) was carried out for predictors of de novo CKD. Linear regression was carried out for factors associated with increasing deltaGFR. Kaplan-Meier Analysis (KMA) was performed to analyze 5-year CKD-free survival. RESULTS: 295 patients were analyzed (224 PN/71 AS, median follow-up 37.4 months). No differences were noted for clinical tumor size (AS 2.6 vs. PN 2.9 cm, p = 0.108), and baseline eGFR (AS 79.6 vs. PN 77, p = 0.9670). Median change in tumor diameter for AS was 0.42 cm. Compared to PN, AS had deltaGFR (-15.3 vs. -6.4 mL/min/1.73m2, p < 0.001) and de novo CKD (28.2% vs. 12.1%, p = 0.002). AS patients who developed CKD had higher RENAL score (p = 0.005) and lower baseline eGFR (73 vs. 91.2 mL/min/1.73m2, p < 0.001) than AS patients who did not. MVA demonstrated increasing age (OR = 1.03, p = 0.025), tumor size (HR = 1.26, p = 0.032) and AS (HR = 4.91, p < 0.001) to be predictive for de novo CKD. Linear regression demonstrated AS was associated with larger decrease in deltaGFR (B = -0.219, p < 0.001). KMA revealed 5-year CKD survival was higher in PN (87%) vs. AS (62%, p < 0.001). CONCLUSION: AS was associated with greater functional decline than PN in oncocytoma. PN may be considered to optimalize renal functional preservation in select circumstances. Further investigation into mechanisms of functional decline in oncocytoma is requisite.

Elevated preoperative C-reactive protein is associated with renal functional decline and non-cancer mortality in surgically treated renal cell carcinoma: analysis from the INternational Marker Consortium for Renal Cancer (INMARC).

OBJECTIVE: To investigate association of preoperative C-reactive protein (CRP) and non-cancer mortality (NCM) in a cohort of patients undergoing surgery for localised renal cell carcinoma (RCC). PATIENTS AND METHODS: Retrospective multicentre analysis of patients surgically treated for clinical Stage 1-2 RCC from 2006 to 2017, excluding all cases of cancer-specific mortality. Descriptive analyses were obtained between the pre-treatment normal-CRP (≤5 mg/L) and elevated-CRP (>5 mg/L) groups. The primary outcome was NCM. The secondary outcomes included progression to de novo chronic kidney disease Stages 3-4 (estimated glomerular filtration rate [eGFR] of <60, <45, and <30 mL/min/1.73 m2 ). Multivariable analyses (MVA) were performed to assess for risk factors associated with functional decline and NCM, and Kaplan-Meier analysis was used to obtain survival estimates for outcomes. RESULTS: A total of 1987 patients who underwent radical or partial nephrectomy were analysed (normal-CRP group, n = 963; elevated-CRP group, n = 1024). Groups were similar in age (59 vs 60 years, P = 0.079). An elevated CRP was more frequent in males (36.8% vs 27.8%, P < 0.001), African-Americans (22.6% vs 2.9%, P < 0.001), and in those with a higher median body mass index (30 vs 25 kg/m2 , P < 0.001) and larger median tumour size (4.5 vs 3.3 cm, P < 0.001). On MVA, an elevated CRP was independently associated with development of de novo eGFR of <60 mL/min/1.73 m2 (hazard ratio [HR] 1.32, P = 0.015), <45 mL/min/1.73 m2 (HR 1.41, P = 0.023) and <30 mL/min/1.73 m2 (odds ratio 2.23, P < 0.001). The MVA for factors associated with NCM demonstrated increasing age (HR 1.06, P < 0.001), preoperative elevated CRP (HR 2.18, P < 0.001) and an eGFR of <45 mL/min/1.73 m2 (HR 1.16; P = 0.021) as independent risk factors. Kaplan-Meier analysis revealed significantly higher 5-year NCM in the elevated-CRP group vs the normal-CRP group (98% vs 80%, P < 0.001). CONCLUSIONS: Pre-treatment elevated CRP was independently associated with both progressive renal functional decline and NCM in patients undergoing surgery for Stage 1-2 RCC. Patients with elevated CRP and Stage 1 and 2 RCC may be considered as having indication for nephron-sparing strategies, which may be prioritised if oncologically appropriate.

OCT Angiography to Predict Geographic Atrophy Progression using Choriocapillaris Flow Void as a Biomarker.

Purpose: To investigate the relationship between choriocapillaris (CC) flow void (FV) percentage and geographic atrophy (GA) growth rate, and study how variations in FV percentage surrounding GA predict regional GA growth. Methods: This prospective, longitudinal study enrolled subjects with GA secondary to nonexudative age-related macular degeneration. Optical coherence tomography angiography imaged the CC and FV percentage was evaluated using a validated algorithm. GA growth rate was measured as the difference in the square root of GA area divided by the months between baseline and follow-up imaging. Results: Twelve eyes from 7 subjects with a mean age of 80 ± 5 years (range 74-86) were studied once at baseline and 7 to 16 months later. GA expansion rate was positively correlated with increased CC FV percentage (Spearman rank correlation coefficient r = 0.69 [P = 0.038] and 0.76 [P = 0.013]) within the 6 x 6 mm scanned macular region and the 2° margin surrounding each GA lesion, respectively. Regions with CC FV at baseline located within 480 µm from the GA margin showed 33% greater chance of becoming atrophic compared with regions within 480 µm from the GA margin that did not show CC FV at baseline. Conclusions: GA expansion rate and CC FV density throughout the macular region and surrounding the GA margin were significantly correlated. The regional magnitude of FV immediately surrounding GA was associated with GA growth into that region. Translational Relevance: CC FV analysis may facilitate prediction of GA growth over time for patients with advanced nonneovascular age-related macular degeneration.

Quantifying choriocapillaris hypoperfusion in patients with choroidal neovascularization using swept-source OCT angiography.

PURPOSE: To compare choriocapillaris flow voids (FV) in patients with neovascular age-related macular degeneration (AMD) with age-matched normal controls using swept-source optical coherence tomography angiography (SS-OCTA). PATIENTS AND METHODS: Eleven eyes of 11 subjects with neovascular AMD and 11 eyes of 11 age-similar normal subjects were imaged using SS-OCTA with a 6x6mm scanning pattern. Choriocapillaris FV, defined as a percentage of regions determined to have flow deficits divided by the total scanned region, was measured using a one standard deviation thresholding algorithm developed from a database of age-similar normal subjects. RESULTS: Choriocapillaris FV was more extensive in patients with choroidal neovascularization (CNV) compared to age-similar normal subjects (FV: 20.56±4.95, 95% CI: 17.64-23.49 vs FV: 10.95±2.08, 95% CI: 9.73-12.18, respectively; P=0.0001). FV within a two-degree margin surrounding CNV in wet AMD subjects (FV: 35.04±9.34; 95% CI: 29.52-40.56) was increased compared to normal subjects (P<0.001). FV of the region outside the two-degree margin surrounding CNV (FV: 19.61±6.08, 95% CI: 16.02-23.20) was increased compared to age-similar controls (P=0.0002). In neovascular AMD eyes, FV was greater within two degrees of the margin of CNV than in the remainder of the macula (margin: 35.04±9.34; outside: 19.61±6.08; P=0.002), and CNV lesion area was positively correlated with FV (correlation coefficient =0.84; 95% CI: 0.49-0.96; P=0.001). CONCLUSION: Choriocapillaris flow deficits were significantly greater in wet AMD subjects than age-similar normal subjects, suggesting that choroidal hypo-perfusion likely plays a role in the pathogenesis of neovascular AMD. Recognition of choriocapillaris flow deficits in patients with AMD may facilitate earlier diagnosis and identify alternative therapeutic targets for this multifactorial disease.

Quantifying Choriocapillaris Flow Voids in Patients With Geographic Atrophy Using Swept-Source OCT Angiography.

BACKGROUND AND OBJECTIVE: To compare choriocapillaris (CC) flow voids (FVs) throughout the macula in patients with age-related macular degeneration (AMD) and geographic atrophy (GA) to age-similar controls using swept-source optical coherence tomography angiography (SS-OCTA). PATIENTS AND METHODS: In this cross-sectional study, 12 subjects with GA secondary to nonexudative AMD and 12 age-similar controls participated. SS-OCTA was performed using a 6 mm × 6 mm scanning pattern. CC FVs were calculated using a one-standard deviation thresholding method developed from a normal database. RESULTS: CC FVs were significantly increased in patients with GA compared with age-similar controls (P < .001). FVs within 2° of GA were significantly increased compared with the area outside 2° (P < .001). FVs beyond 2° of GA were significantly increased compared with age-similar controls (P < .001). CONCLUSIONS: FV analysis of in vivo CC images revealed diffuse CC perfusion deficits throughout the macular region in subjects with GA secondary to nonexudative AMD. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e229-e235.].