Esophageal disease and loss to follow-up are common among patients who experience non-endoscopic resolution of food impaction.

Many patients who experience esophageal food impaction (EFI) will have non-endoscopic resolution (NER) of their EFI, but this population is poorly defined. The purpose of this study is to describe the outcomes of patients with NER of EFI. A retrospective chart review from 2007 to 2017 was performed at a single tertiary care center. There were 593 patients who presented to the emergency department with EFI, defined as recent soft food ingestion and inability to tolerate oral secretions. Adequate follow-up was defined as a gastroenterology clinic visit or EGD within 6 months of EFI. Out of these, 149 patients (25.1%) had NER of their EFI. Patients with NER were less likely to have adequate follow-up than those with ER (45.0% vs. 59.5%, P = 0.003). Of those without established esophageal disease and NER, 92.5% had significant esophageal pathology on endoscopy, including stricture (34.0%), features of eosinophilic esophagitis (30.2%), and esophagitis (22.6%). Recurrent EFI occurred at a similar rate between patients with NER and ER (9.4% vs. 14.6%, P = 0.14). Patients with established esophageal disease (odds ratio [OR]: 1.51, P = 0.04) and recommendation to follow-up at time of EFI (OR: 6.06, P < 0.001) were most likely to follow up after EFI. Approximately, a quarter of patients with EFI will experience NER of their EFI. Virtually, all patients (92.5%) were found to have esophageal disease warranting longitudinal care. Importantly, follow-up rates are significantly lower in those with NER than their counterparts requiring EGD. Our study highlights the need to develop standardized protocols that improve follow-up for patients after NER of EFI.

Empiric proton pump inhibitor therapy after esophageal food impaction may mask eosinophilic esophagitis diagnosis at follow-up.

Esophageal food impaction (EFI) is often the first presentation for patients with eosinophilic esophagitis (EoE); however, there is significant heterogeneity in the management of EFI. We aimed to study the impact of EFI management, particularly post-EFI medication prescriptions on EoE diagnosis, follow-up, and recurrence in patients with endoscopic features of EoE. In our retrospective study, adults presenting between 2007 and 2017 with EFI requiring endoscopic dis-impaction with endoscopic features of EoE (furrows, rings, and/or exudates) were included. We examined the impact of demographics and EFI management on EoE diagnosis, follow-up (esophagogastroduodenoscopy [EGD] or clinic visit within 6 months), and recurrence. We identified 164 cases of EFI due to suspected EoE. Biopsy was performed in 68 patients (41.5%), and 144 patients (87.8%) were placed on proton pump inhibitor (PPI) and/or swallow corticosteroids after EFI, including 88.5% of those not biopsied. PPI use at time of biopsy was negatively associated with EoE diagnosis (odds ratio: 0.39, confidence interval: 0.17-0.85). Sixty-one (37.4%) patients were lost to follow-up at 6 months. Recurrent EFI at 1 year occurred in 3.7% of patients. Medications, most commonly PPI, are frequently prescribed after EFI when the endoscopic features of EoE are present, which may mask the diagnosis of EoE on follow-up EGD. We estimated that for every five patients biopsied on PPI, one case of EoE is masked. As recurrent EFI within 1 year is uncommon, empiric therapy should be avoided until diagnostic biopsies are obtained. Further efforts to reduce loss to follow-up after EFI are also needed.

Hedgehog signaling reprograms hair follicle niche fibroblasts to a hyper-activated state.

Hair follicle stem cells are regulated by dermal papilla fibroblasts, their principal signaling niche. Overactivation of Hedgehog signaling in the niche dramatically accelerates hair growth and induces follicle multiplication in mice. On single-cell RNA sequencing, dermal papilla fibroblasts increase heterogeneity to include new Wnt5ahigh states. Transcriptionally, mutant fibroblasts activate regulatory networks for Gli1, Alx3, Ebf1, Hoxc8, Sox18, and Zfp239. These networks jointly upregulate secreted factors for multiple hair morphogenesis and hair-growth-related pathways. Among these is non-conventional TGF-ß ligand Scube3. We show that in normal mouse skin, Scube3 is expressed only in dermal papillae of growing, but not in resting follicles. SCUBE3 protein microinjection is sufficient to induce new hair growth, and pharmacological TGF-ß inhibition rescues mutant hair hyper-activation phenotype. Moreover, dermal-papilla-enriched expression of SCUBE3 and its growth-activating effect are partially conserved in human scalp hair follicles. Thus, Hedgehog regulates mesenchymal niche function in the hair follicle via SCUBE3/TGF-ß mechanism.

Optimal experimental design for mathematical models of haematopoiesis.

The haematopoietic system has a highly regulated and complex structure in which cells are organized to successfully create and maintain new blood cells. It is known that feedback regulation is crucial to tightly control this system, but the specific mechanisms by which control is exerted are not completely understood. In this work, we aim to uncover the underlying mechanisms in haematopoiesis by conducting perturbation experiments, where animal subjects are exposed to an external agent in order to observe the system response and evolution. We have developed a novel Bayesian hierarchical framework for optimal design of perturbation experiments and proper analysis of the data collected. We use a deterministic model that accounts for feedback and feedforward regulation on cell division rates and self-renewal probabilities. A significant obstacle is that the experimental data are not longitudinal, rather each data point corresponds to a different animal. We overcome this difficulty by modelling the unobserved cellular levels as latent variables. We then use principles of Bayesian experimental design to optimally distribute time points at which the haematopoietic cells are quantified. We evaluate our approach using synthetic and real experimental data and show that an optimal design can lead to better estimates of model parameters.

Patients presenting to a Men's Health clinic are at higher risk for depression, insomnia, and sleep apnea.

Depression and sleep problems are highly prevalent disorders that are often comorbid with other medical disorders. We evaluated the prevalence and associations of these conditions in patients presenting to a Men's Health clinic. In this retrospective study, 124 patients presenting to a Men's Health clinic completed three urological questionnaires (International Index of Erectile Function [IIEF-5], International Prostate Symptom Score [IPSS], and Androgen Deficiency in Aging Males [ADAM]); and four non-urological questionnaires (Patient Health Questionnaire for depression [PHQ-9], STOP-BANG Sleep Apnea [OSA STOP-BANG], Insomnia Severity Index [ISI], and Epworth Sleepiness Scale [ESS]). Questionnaire results were evaluated in conjunction with patient clinical history and associated laboratory values via univariate and multivariate analysis. The mean age of the study participants was 54.1 years (SD 16). Comorbidities included hypertension (22.5%), vascular disease (15%), and diabetes mellitus (13.3%). Body Mass Index (BMI) was >25 in 77.3%. IIEF-5 scores were moderate-severe in 47.9%, ADAM questionnaire was positive in 79%, and IPSS scores were moderate-severe in 42.9% of patients. PHQ-9 demonstrated mild-severe depression in 38.6%, STOP-BANG showed intermediate-high risk for sleep apnea in 55.2%, ISI indicated moderate-severe insomnia in 18.1%, and ESS revealed mild-severe sleepiness in 16.6% of participants. On univariate analysis, BMI was associated with scores on the PHQ-9 (p = 0.035), STOP-BANG (p < 0.001), and ESS (p < 0.006). On multivariate analysis, positive ADAM questionnaire was associated with STOP-BANG (OR 3.29, 95% CI: 1.012-10.69), and IPSS with PHQ-9 (OR 4.64, 95% CI: 1.40-15.43) and ISI (OR 3.27, 95% CI: 1.06-10.1). Overall, patients presenting to a Men's Health Clinic were found to have high prevalence rates for risk of depression, insomnia and sleep apnea. Risks were elevated in older subjects, and those with increased BMI, hypogonadism, and lower urinary tract symptoms. Appropriate screening and referral to appropriate specialists are encouraged.