Xu, Timothy T.

Purpose: The purpose of this study is to quantify cancer risk in patients with Fuchs endothelial corneal dystrophy (FECD). Methods: Using the 2014 to 2016 Medicare Limited 5% Data Sets—Carrier Line File, US Medicare fee-for-service beneficiaries (aged 65 years or older) with FECD and cancer were identified through International Classification of Diseases, ninth and 10th Revision diagnostic codes from January 1, 2014, to December 31, 2016. The main outcome measures were odds ratios (ORs) of cancer at various anatomic locations in patients with versus without FECD. Results: Of the 1,462,740 Medicare beneficiaries, 15,534 patients (1.1%) had an International Classification of Disease code for FECD. Compared with US Medicare beneficiaries without FECD, patients with FECD were at increased risk for the following malignancies: breast [OR: 1.32; 95% confidence interval (CI): 1.22–1.43; P < 0.001], cutaneous basal cell (OR: 1.42; 95% CI: 1.35–1.49; P < 0.001), cutaneous melanoma (OR: 1.20; 95% CI: 1.03–1.40; P = 0.02), cutaneous squamous cell (OR: 1.45; 95% CI: 1.38–1.53; P < 0.001), ovarian (OR: 1.84; 95% CI: 1.48–2.30; P < 0.001), and thyroid (OR: 1.32; 95% CI: 1.04–1.68; P = 0.02). By contrast, FECD cases were at lower odds of having lung (OR: 0.81; 95% CI: 0.71–0.93; P = 0.003) and prostate cancer diagnoses (OR: 0.88; 95% CI: 0.81–0.96; P = 0.002). Conclusions: Patients with FECD aged 65 years or older may be at increased risk for cancer at several anatomic locations. Follow-up studies are needed to further explore the association of FECD and malignancy, elucidate potential disease mechanisms, and identify genetic and/or environmental risk factors.

Purpose of review To review recent advancements in the genetic understanding, diagnosis, prognosis, and treatment of uveal melanoma (UM). Recent findings UM is a molecularly distinct melanocytic malignancy driven by mutations in GNAQ or GNA11, with mitogen-activated protein kinase pathway upregulation. Earlier diagnosis and treatment are important factors for improving life prognosis. These goals can be aided by more objective multimodal imaging risk factors for the prediction of malignant nevus transformation and novel treatment strategies such as customized radiation fields and nanoparticle therapy to reduce vision-threatening treatment side effects. The risk for metastatic disease can be reliably predicted through gene expression profiling or the Cancer Genome Atlas project classification, and combined use of clinical tumor features with molecular data allows for highly individualized patient prognosis. Patients with high-risk UM should be considered for clinical trials of adjuvant therapy to prevent metastatic disease. For patients with clinically evident metastasis, combination immunotherapy regimens, T cell-based therapies, and focal adhesion kinase inhibitors offer hope for improved clinical response rates. Summary Improved understanding of UM molecular pathogenesis and clinical trials of targeted therapy for prevention and treatment of metastatic disease may improve patient survival for this challenging disease.

Background The absence of appropriate and timely critical care in resource-limited countries like Vietnam contributes to poor outcomes and excessive mortality in the acutely ill, pediatric population. Often, tertiary care is limited to major urban centers and patients from remote locations face lengthy travel. How these distances impact care-seeking behavior of the patients’ caregiver, patient acuity on admission, and hospitalization outcome in critically ill children remains unknown. Methods We assessed 471 pediatric patients admitted to intensive care units (ICUs) from the emergency department in a pediatric referral center in Hanoi that serves northern Vietnam. Demographic information from caregivers and medical information was collected by trained staff on site and from the medical record. Patient outcome was followed for sixty days in the ICUs. We analyzed associations between patient admission acuity and outcome to socio-geographic and-demographic data using bivariate logistic regression and log-rank analyses. Results The median child’s age in our study was 1.8 months, with the majority under 1 year (83.3%). On admission to the ICU, 40.5% of patients required life-saving treatment. Within sixty days of admission, 73.3% of patients were discharged, 21.8% experienced extended admission and 3.08% expired in the ICU. Patient and caretaker’s distance from home residence to Vietnam National Children’s Hospital (VNCH) greater than 60 kilometers was significantly associated with a more severe patient acuity on ICU admission (Odds Ratio, OR=2.01, 95% Confidence Limit, CL=1.33, 3.06), an extended admission or expiration in the ICU (OR=1.94, 95% CL=1.15, 3.20), a lower family income (OR=3.74, 95% CL=2.46, 5.64), lack of caregiver college education (OR=3.73, 95% CL=2.34, 6.05), and greater referrals and days delayed seeking care. Conclusions These findings highlight numerous barriers facing acutely ill children and their caretakers, who must travel long distances to reach appropriate critical care at a tertiary referral hospital. Research into current protocols, skills, and staffing at lower facilities and public health education in these regions is needed to determine the best avenues for improvement of critical care services beyond tertiary centers.