Esophageal anatomy and physiology vary across spastic and non-spastic phenotypes of disorders of esophagogastric junction outflow.

BACKGROUND: Pathophysiologic mechanisms of disorders of esophagogastric junction (EGJ) outflow are poorly understood. We aimed to compare anatomic and physiologic characteristics among patients with disorders of EGJ outflow and normal motility. METHODS: We retrospectively evaluated adult patients with achalasia types 1, 2, 3, EGJ outflow obstruction (EGJOO) or normal motility on high-resolution manometry who underwent endoscopic ultrasound (EUS) from January 2019 to August 2022. Thickened circular muscle was defined as ≥1.6 mm. Characteristics from barium esophagram (BE) and functional lumen imaging probe (FLIP) were additionally assessed. KEY RESULTS: Of 71 patients (mean age 56.2 years; 49% male), there were 8 (11%) normal motility, 58 (82%) had achalasia (5 (7%) type 1, 32 (45%) classic type 2, 21 (30%) type 3 [including 12 type 2 with FEPs]), and 7 (7%) had EGJOO. A significantly greater proportion of type 3 achalasia had thickened distal circular muscle (76.2%) versus normal motility (0%; p < 0.001) or type 2 achalasia (25%; p < 0.001). Type 1 achalasia had significantly wider mean maximum esophageal diameter on BE (57.8 mm) compared to type 2 achalasia (32.8 mm), type 3 achalasia (23.4 mm), EGJOO (15.9 mm), and normal motility (13.5 mm). 100% type 3 achalasia versus 0% type 1 achalasia/normal motility had tertiary contractions on BE. Mean EGJ distensibility index on FLIP was lower for type 3 achalasia (1.2 mmHg/mm2 ) and EGJOO (1.2 mmHg/mm2 ) versus type 2 (2.3 mmHg/mm2 ) and type 1 achalasia (2.9 mmHg/mm2 ). CONCLUSIONS: Our findings suggest distinct pathologic pathways may exist: type 3 achalasia and EGJOO may represent a spastic outflow phenotype consisting of a thickened, spastic circular muscle, which is distinct from type 1 and 2 achalasia consisting of a thin caliber circular muscle layer with more prominent esophageal dilation.

Efficacy of beetroot juice on reducing blood pressure in hypertensive adults with autosomal dominant polycystic kidney disease (BEET-PKD): study protocol for a double-blind, randomised, placebo-controlled trial.

BACKGROUND: In autosomal dominant polycystic kidney disease (ADPKD) impaired nitric oxide (NO) synthesis, in part, contributes to early-onset hypertension. Beetroot juice (BRJ) reduces blood pressure (BP) by increasing NO-mediated vasodilation. The aim of this double-blind, randomised, placebo-controlled study is to test the hypothesis that BRJ reduces systolic and diastolic clinic BP in hypertensive adults with ADPKD. METHODS: Participants with ADPKD and treated hypertension (n = 60) will be randomly allocated (1:1) to receive a daily dose of either nitrate-replete (400 mg nitrate/day) or nitrate-deplete BRJ for 4 weeks. The co-primary outcomes are change in mean systolic and diastolic clinic BP before and after 4 weeks of treatment with daily BRJ. Secondary outcomes are changes in daily home BP, urinary albumin to creatinine ratio, serum and salivary nitrate/nitrite levels and serum asymmetric dimethylarginine levels before and after 4 weeks of BRJ. DISCUSSION: The effect of BRJ in ADPKD has not been previously tested. BRJ is an accessible, natural dietary supplement that, if effective, will provide a novel adjunctive approach for treating hypertension in ADPKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT05401409. Retrospectively registered on 27th May 2022.

Evaluating the impact of stay-at-home orders on the time to reach the peak burden of Covid-19 cases and deaths: does timing matter?

BACKGROUND: The economic, psychological, and social impact of pandemics and social distancing measures prompt the urgent need to determine the efficacy of non-pharmaceutical interventions (NPIs), especially those considered most stringent such as stay-at-home and self-isolation mandates. This study focuses specifically on the impact of stay-at-home orders, both nationally and internationally, on the control of COVID-19. METHODS: We conducted an observational analysis from April to May 2020 and included both countries and US states with known stay-at-home orders. Our primary exposure was the time between the date of the first reported case of COVID-19 to an implemented stay-at-home mandate for each region. Our primary outcomes were the time from the first reported case to the highest number of daily cases and daily deaths. We conducted linear regression analyses, controlling for the case rate of the outbreak in each respective region. RESULTS: For countries and US states, a longer period of time between the first reported case and stay-at-home mandates was associated with a longer time to reach both the peak daily case and death counts. The largest effect was among regions classified as the latest 10% to implement a mandate, which in the US, predicted an extra 35.3 days (95% CI: 18.2, 52.5) to the peak number of cases, and 38.3 days (95% CI: 23.6, 53.0) to the peak number of deaths. CONCLUSIONS: Our study supports the association between the timing of stay-at-home orders and the time to peak case and death counts for both countries and US states. Regions in which mandates were implemented late experienced a prolonged duration to reaching both peak daily case and death counts.

Hypertensive Disorders of Pregnancy and Risk of Future Cardiovascular Disease in Women.

Cardiovascular disease continues to be the leading cause of mortality in women globally. In addition to traditional risk factors, some sex-specific conditions increase the burden of cardiovascular disease in women. With this literature review, we aimed to review evidence on associations between hypertensive disorders of pregnancy and risk of cardiovascular disease in later life. After a database search and application of inclusion and exclusion criteria, 11 studies were included in the review. Our findings suggest that a history of preeclampsia, gestational hypertension, or elevated systolic blood pressure alone during pregnancy is consistently associated with increased risk of developing and dying from myocardial infarction, heart failure, hypertension, and/or stroke in later life. Nurses and other health care providers should be aware of the cardiovascular risk associated with hypertensive disorders of pregnancy and engage women at risk in discussions about health promotion strategies and interventions to address modifiable cardiovascular disease risk factors.

Epithelial Recurrent Erosion Dystrophy Secondary to COL17A1 c.3156C>T Mutation in a Non-white Family.

PURPOSE: To report the identification of the collagen, type XVII, alpha 1 (COL17A1) c.3156C>T mutation associated with epithelial recurrent erosion dystrophy (ERED) in a Thai family. METHODS: Slit-lamp examination was performed to determine the affected status of each member of a Thai family, with multiple members demonstrating scattered Bowman layer opacities. After genomic deoxyribonucleic acid (DNA) was isolated from saliva, polymerase chain reaction (PCR) amplification and Sanger sequencing were performed to screen COL17A1 and exons 4 and 12 of the transforming growth factor ß-induced gene. RESULTS: The 67-year-old proband and her 4 siblings were examined by slit-lamp biomicroscopy, which identified bilateral subepithelial opacities in the proband and in one of the 4 siblings. In both the proband and the affected sister, screening of the COL17A1 gene identified a heterozygous c.3156C>T synonymous mutation that has been previously demonstrated to introduce a cryptic splice donor site, likely leading to aberrant splicing of COL17A1. This mutation was not identified in the unaffected siblings, and no mutations were identified in exons 4 and 12 of the transforming growth factor ß-induced gene in any of the screened family members. CONCLUSIONS: ERED associated with a COL17A1 mutation has been previously reported in only 6 families, all white. Identification of the c.3156C>T mutation, previously identified in 5 of these 6 families, in the Thai family we report indicates conservation of the genetic basis of ERED across different races and underscores the importance of ophthalmologists around the globe being familiar with ERED, which has only recently become a recognized corneal dystrophy.

Sensitivity and specificity of Urdu version of the PHQ-9 to screen depression in patients with coronary artery disease.

BACKGROUND: The Patient Health Questionnaire (PHQ-9) possesses many characteristics of a good screening tool and has the capacity to be used for screening depression in patients with coronary artery disease (CAD). AIM: To examine the psychometric properties and criterion validity of the PHQ-9 to screen and detect depression in patients with CAD in Pakistan. DESIGN: In this validation study, 150 patients with CAD completed the Urdu version of the PHQ-9. The major depressive episode module of the Mini International Neuropsychiatric Interview (MINI) was used as the gold standard. RESULTS: The Urdu version of the PHQ-9 revealed a good internal consistency with Cronbach's alpha of 0.83. Optimal sensitivity (76%) and specificity (76%) were achieved using the cut-off score of PHQ-9 ≥6, with area under the ROC curve of 0.86. CONCLUSION: The Urdu version of the PHQ-9 has acceptable psychometric properties to screen and detect major depression in patients with CAD.

CTG18.1 Expansion in TCF4 Increases Likelihood of Transplantation in Fuchs Corneal Dystrophy.

PURPOSE: Fuchs dystrophy is the leading indication of corneal transplantation in the United States. A CTG18.1 trinucleotide repeat in TCF4 correlates with increased severity in Fuchs dystrophy; however, quantitative estimates of increased transplantation risk, including effects of age and sex, are unclear. METHODS: In a tertiary institution clinical practice, 574 participants were enrolled in a longitudinal study of Fuchs dystrophy after slit-lamp biomicroscopy confirmed significant central guttae and/or corneal transplantation in both eyes. We documented clinical history, examination findings, and demographic information. We acquired blood samples, extracted DNA, and sequenced the CTG18.1 trinucleotide repeat in TCF4. In this retrospective case-control study, the number of participants with triplet expansion, defined as greater than 40 CTG repeats, and transplantation status were assessed. Kaplan-Meier estimates of timing and transplantation events were produced. The Cox proportional hazard regression model was used to assess the relationship between age, sex, triplet expansion, and surgery. RESULTS: A total of 106 participants (18.5%) previously underwent corneal transplantation in at least 1 eye at the time of initial evaluation. A higher proportion of individuals harboring allele expansion had undergone transplantation (78/357, 21.8%) compared with those without the expanded allele (28/217, 12.9%), a significant association (P = 0.007). The log-rank test demonstrates a significant difference in survival function over time (P = 0.027), with a hazard ratio of 1.64 (95% confidence interval, 1.05-2.55). CONCLUSIONS: Expansion of the TCF4 CTG trinucleotide repeat was associated with 1.64 times higher likelihood of corneal transplantation at a given age in patients with Fuchs dystrophy.