Simple Nutrient-Based Rules vs. a Nutritionally Rich Plant-Centered Diet in Prediction of Future Coronary Heart Disease and Stroke: Prospective Observational Study in the US

To better understand nutrition paradigm shift from nutrients to foods and dietary patterns, we compared associations of a nutrient-based blood cholesterol-lowering diet vs. a food-based plant-centered diet with risk of coronary heart disease (CHD) and stroke. Participants were 4701 adults aged 18–30 years and free of cardiovascular disease at baseline, followed for clinical events from 1985 and 86 to 2018. A plant-centered diet was represented by higher A Priori Diet Quality Score (APDQS). A blood cholesterol-lowering diet was represented by lower Keys Score. Proportional hazards regression was used to calculate hazard ratios (HR). Higher APDQS showed a nutrient-dense composition that is low in saturated fat but high in fiber, vitamins and minerals. Keys Score and APDQS changes were each inversely associated with concurrent plasma low-density lipoprotein cholesterol (LDL-C) change. Over follow-up, 116 CHD and 80 stroke events occurred. LDL-C predicted CHD, but not stroke. APDQS, but not Keys Score, predicted lower risk of CHD and of stroke. Adjusted HRs (95% CIs) for each 1-SD higher APDQS were 0.73 (0.55–0.96) for CHD and 0.70 (0.50–0.99) for stroke. Neither low dietary fat nor low dietary carbohydrate predicted these events. Our findings support the ongoing shift in diet messages for cardiovascular prevention.     

Exploring the gaps in the evidence‐based application of narrowband UVB for the treatment of vitiligo

While narrowband ultraviolet light B (NB‐UVB) has become integral to the treatment of diffuse vitiligo, evidence‐based guidelines have been lacking with regard to dosing and administration. This is largely the result of heterogeneous study designs, ambiguous methodologies, disparate dosing strategies, and the use of varied, and somewhat arbitrary, outcome measures. In the absence of prospective trials to address each of these concerns, the available literature regarding the application of NB‐UVB for vitiligo was reviewed and the authors now pose a set of questions to the phototherapy community in an attempt to highlight gaps within our understanding. We aim to stimulate discussion, elicit expert opinion, and identify areas for future research to move toward a unified and safe treatment guideline for patients afflicted by this disease.     

Validation of a real-time electrocardiographic monitor for detection of myocardial ischemia secondary to coronary artery disease

A new real-time electrocardiographic (ECG) monitor (QMED Monitor OneTM) was evaluated to assess its accuracy in detecting ischemic ST-segment changes in 43 patients (34 men, 9 women, mean age 56 +/- 11 years) during exercise stress testing. The output of QMED was compared with ST-segment measurements from a Marquette CASE-II computer (ECGM) using a bipolar lead CM5, defining a positive ECG as at least 1 mm of planar or downsloping ST depression. Results were concordant in 33 patients, 15 with both positive and 18 both negative responses, yielding an accuracy (expressed as sensitivity, specificity, positive and negative predictive accuracy) of 83%, 72%, 68% and 86%, respectively. Seven false-positive QMED episodes occurred: 4 due to excess baseline wander or noise in the control ECG, which may have been prevented by reapplication of electrodes, and all 7 episodes were correctly discounted by inspection of the sample ischemic ECG output, yielding an accuracy of 81%, 100%, 100% and 85%. Mean duration and maximal magnitude of ST depression in patients with a positive ECG response was 7.9 +/- 7 minutes and 1.7 +/- 0.6 mm for QMED and 8.9 +/- 7 minutes and 2.2 +/- 0.7 mm for ECGM. The 3 false-negative QMED events were relatively brief and mild ischemic episodes and slight differences in electrode placement between the 2 systems may account for this discrepancy in 2 of the patients. Real-time ST monitoring with QMED is sufficiently reliable for clinical use. Optimal specificity depends on the ability to inspect sample ECG traces to verify a stable baseline and confirm episodes of ischemic ST-segment shift.     

Development of a catadioptric endoscope objective with forward and side views

Autofluorescence endoscopy is a promising functional imaging technique to improve screening of pre-cancerous or early cancer lesions in the gastrointestinal (GI) tract. Tissue autofluorescence signal is weak compared to white light reflectance imaging. Conventional forward-viewing endoscopes are inefficient in the collection of light from objects of interest along on the GI luminal wall. A key component of a complete autofluorescence endoscope is the light collection module. In this paper, we report the design, optimization, prototype development, and testing of an endoscope objective that is capable of acquiring simultaneous forward and radial views. The radial-view optical design was optimized for a balance between image quality and light collection. Modulation transfer function (MTF), entrance pupil radius, manufacturability, and field-of-view were parameters used in the lens optimization. In comparison with the typical forward-viewing endoscopes, our nonsequential ray trace simulations suggest the proposed radial-view design is more practical in the light collection. To validate the proposed simulation methods, a 3:1 scaled-up prototype was fabricated. Contrast measurements were taken with the prototype, and then compared with the simulated MTF.     

Upfront DPYD Genotyping and Toxicity Associated with Fluoropyrimidine-Based Concurrent Chemoradiotherapy for Oropharyngeal Carcinomas: A Work in Progress

Simple SummaryThe combination of carboplatin and 5-fluorouracil (5-FU) is effective when used concurrently with radiotherapy for locoregionally advanced oropharyngeal carcinomas. DPYD polymorphisms can be associated with an increased risk of severe toxicity to fluoropyrimidines. Upfront screening for the DPYD*2A allele has been available in the province of Québec, Canada, since March 2017. This study aimed to determine the effect of upfront genotyping on the incidence of grade ≥3 toxicities. We included 181 patients in the analysis. Extended screening for three supplemental at-risk DPYD variants was also retrospectively performed in August 2019. The DPYD*2A, c.2846A>T and c.1236G>A polymorphisms were associated with an increased risk of grade ≥3 toxicity to 5-FU. Upfront DPYD genotyping can thus identify patients in whom 5-FU-related toxicity should be avoided.AbstractBackground: 5-FU-based chemoradiotherapy (CRT) could be associated with severe treatment-related toxicities in patients harboring at-risk DPYD polymorphisms. Methods: The studied population included consecutive patients with locoregionally advanced oropharyngeal carcinoma treated with carboplatin and 5-FU-based CRT one year before and after the implementation of upfront DPYD*2A genotyping. We aimed to determine the effect of DPYD genotyping on grade ≥3 toxicities. Results: 181 patients were analyzed (87 patients before and 94 patients following DPYD*2A screening). Of the patients, 91% (n = 86) were prospectively genotyped for the DPYD*2A allele. Of those screened, 2% (n = 2/87) demonstrated a heterozygous DPYD*2A mutation. Extended genotyping of DPYD*2A-negative patients later allowed for the retrospective identification of six additional patients with alternative DPYD variants (two c.2846A>T and four c.1236G>A mutations). Grade ≥3 toxicities occurred in 71% of the patients before DPYD*2A screening versus 62% following upfront genotyping (p = 0.18). When retrospectively analyzing additional non-DPYD*2A variants, the relative risks for mucositis (RR 2.36 [1.39–2.13], p = 0.0063), dysphagia (RR 2.89 [1.20–5.11], p = 0.019), and aspiration pneumonia (RR 13 [2.42–61.5)], p = 0.00065) were all significantly increased. Conclusion: The DPYD*2A, c.2846A>T, and c.1236G>A polymorphisms are associated with an increased risk of grade ≥3 toxicity to 5-FU. Upfront DPYD genotyping can identify patients in whom 5-FU-related toxicity should be avoided.     

Primary amenorrhea secondary to imperforate hymen

Hymen imperforation is uncommon. Symptoms include primary amenorrhea, cyclical lower abdominal pain, and rarely a pelvic mass syndrome. Delayed discovery may lead to endometriosis and infertility. Pelvic ultrasound and nuclear magnetic resonance detect associated genito‐urinary malformations. Hymenectomy is the standard surgical treatment.     

How good is endoscopic ultrasound for TNM staging of gastric cancers？ A meta-analysis and systematic review

AIM： To evaluate the accuracy of endoscopic ultrasound （EUS） for staging of gastric cancers.
METHODS： Only EUS studies confirmed by surgery were selected. Only studies from which a 2×2 table could be constructed for true positive, false negative, false positive and true negative values were included. Articles were searched in Medline, Pubmed, Ovid journals, Cumulative index for nursing ＆ allied health literature, International pharmaceutical abstracts, old Medline, Medline nonindexed citations, and Cochrane control trial registry. Two reviewers independently searched and extracted data. The differences were resolved by mutual agreement. 2×2 tables were constructed with the data extracted from each study. Meta-analysis for the accuracy of EUS was analyzed by calculating pooled estimates of sensitivity, specificity, likelihood ratios, and diagnostic odds ratio. Pooling was conducted by both the Mantel-Haenszel method （fixed effects model） and DerSimonian Laird method （random effects model）. The heterogeneity of studies was tested using Cochran＇s Q test based upon inverse variance weights.
RESULTS： Initial search identified 1620 reference articles and of these, 376 relevant articles were selected and reviewed. Twenty-two studies （n = 1896） which met the inclusion criteria were included in this analysis. Pooled sensitivity of T1 was 88.1% （95% CI： 84.5-91.1） and T2 was 82.3% （95% CI： 78.2-86.0）. For T3, pooled sensitivity was 89.7% （95% CI： 87.1-92.0）. T4 had a pooled sensitivity of 99.2% （95% CI： 97.1-99.9）. For nodal staging, the pooled sensitivity for N1 was 58.2% （95% CI： 53.5-62.8） and N2 was 64.9% （95% CI： 60.8-68.8）. Pooled sensitivity to diagnose distant metastasis was 73.2% （95% CI： 63.2-81.7）. The P for chi-squared heterogeneity for all the pooled accuracy estimates was 〉0. 10.
CONCLUSION： EUS results are more accurate with advanced disease than early disease. If EUS diagnoses advanced disease, such as T4 disease, the patient is