Unusual Bronchopulmonary Foregut Malformation Associated with Pericardial Defect: Bronchogenic Cyst Communicating with Tubular Esophageal Duplication

We report a case of unusual bronchopulmonary foregut malformation composed of a mediastinal bronchogenic cyst with sequestrated lung tissue and communicating tubular esophageal duplication associated with complete pericardial defect. A 18-yr-old man, who had suffered from dry cough and mild dyspnea, was admitted because of an incidentally detected chest mass. A computed tomography scan demonstrated a cystic mass with an air fluid level connected with esophagus in the middle mediastinum. The surgically resected mass was a pleural invested accessory lobe of the lung (8.0×7.0×4.5 cm) connected with the esophageal wall by a tubular structure (3.0 cm in length and 2.0 cm in diameter). A complete left pericardial defect was also identified. Histologically, the cystic wall was composed of fibrovascular connective tissue with a smooth muscle layer, mixed seromucous glands and cartilage, and the inner surface of the cyst was lined by ciliated pseudostratified columnar epithelium. The inner surface of the tubular structure was lined by non-keratinizing or keratinizing squamous epithelium, and the wall contained submucosal mucous glands, muscularis mucosa, and duplicated muscularis propria. This case is important in understanding the embryological pathogenesis of the variable spectrum of the bronchopulmonary foregut malformation

Identifying and Characterizing a Chronic Cough Cohort Through Electronic Health Records

Background Chronic cough (CC) of 8 weeks or more affects about 10% of adults and may lead to expensive treatments and reduced quality of life. Incomplete diagnostic coding complicates identifying CC in electronic health records (EHRs). Natural language processing (NLP) of EHR text could improve detection. Research Question Can NLP be used to identify cough in EHRs, and to characterize adults and encounters with CC? Study Design and Methods A Midwestern EHR system identified patients aged 18 to 85 years during 2005 to 2015. NLP was used to evaluate text notes, except prescriptions and instructions, for mentions of cough. Two physicians and a biostatistician reviewed 12 sets of 50 encounters each, with iterative refinements, until the positive predictive value for cough encounters exceeded 90%. NLP, International Classification of Diseases, 10th revision, or medication was used to identify cough. Three encounters spanning 56 to 120 days defined CC. Descriptive statistics summarized patients and encounters, including referrals. Results Optimizing NLP required identifying and eliminating cough denials, instructions, and historical references. Of 235,457 cough encounters, 23% had a relevant diagnostic code or medication. Applying chronicity to cough encounters identified 23,371 patients (61% women) with CC. NLP alone identified 74% of these patients; diagnoses or medications alone identified 15%. The positive predictive value of NLP in the reviewed sample was 97%. Referrals for cough occurred for 3.0% of patients; pulmonary medicine was most common initially (64% of referrals). Limitations Some patients with diagnosis codes for cough, encounters at intervals greater than 4 months, or multiple acute cough episodes may have been misclassified. Interpretation NLP successfully identified a large cohort with CC. Most patients were identified through NLP alone, rather than diagnoses or medications. NLP improved detection of patients nearly sevenfold, addressing the gap in ability to identify and characterize CC disease burden. Nearly all cases appeared to be managed in primary care. Identifying these patients is important for characterizing treatment and unmet needs

Tumour brain: pre‐treatment cognitive and affective disorders caused by peripheral cancers

People that develop extracranial cancers often display co-morbid neurological disorders, such as anxiety, depression and cognitive impairment, even before commencement of chemotherapy. This suggests bidirectional crosstalk between non-CNS tumours and the brain, which can regulate peripheral tumour growth. However, the reciprocal neurological effects of tumour progression on brain homeostasis are not well understood. Here, we review brain regions involved in regulating peripheral tumour development and how they, in turn, are adversely affected by advancing tumour burden. Tumour-induced activation of the immune system, blood–brain barrier breakdown and chronic neuroinflammation can lead to circadian rhythm dysfunction, sleep disturbances, aberrant glucocorticoid production, decreased hippocampal neurogenesis and dysregulation of neural network activity, resulting in depression and memory impairments. Given that cancer-related cognitive impairment diminishes patient quality of life, reduces adherence to chemotherapy and worsens cancer prognosis, it is essential that more research is focused at understanding how peripheral tumours affect brain homeostasis

Cost of subcutaneous immunotherapy in a large insured population in the United States

<p><b>Objective:</b> Allergic rhinitis (AR) affects up to 40% of the United States population, with approximately $11 billion annual medical costs. Allergy immunotherapy is the best option for long-term symptomatic relief, but treatment compliance can be low. The objective was to describe subcutaneous immunotherapy (SCIT)-related costs for patients overall and those with inconsistent treatment.</p> <p><b>Methods:</b> This study observed commercial and Medicare Advantage with Part D health plan enrollees. Included subjects had claims with AR diagnostic codes during 1 January 2011–31 December 2015 and ≥1 SCIT claim during 1 January 2013–31 December 2015 (index date = first SCIT claim date). A control sample was chosen randomly at a 1:3 ratio of SCIT to controls. Inconsistent use was defined as a ≥90 day gap after ≥1 SCIT. Patient characteristics were compared between SCIT patients and controls. Costs were calculated for all SCIT patients and the inconsistent subgroup.</p> <p><b>Results:</b> Compared with controls (<i>n</i> = 394,479), SCIT (<i>n</i> = 131,493) patients were younger (39.3 vs. 41.4 years), more likely female (56.4$205,741,125 (18% was for inconsistent subgroup) and patient-paid costs were $47,560,450 (15$0.48 plan-paid and $0.11 patient-paid, with$0.09 plan-paid and $0.02 patient-paid for inconsistent use.</p> <p><b>Conclusions:</b> This study showed 15% of patients may have costly inconsistent SCIT treatment. Greater understanding is needed regarding the reasons for inconsistent use of subcutaneous allergy immunotherapy.</p

Resource use and costs in high-risk symptomatic peripheral artery disease patients with diabetes and prior acute coronary syndrome: a retrospective analysis

<p><b>Objectives</b>: As the prevalence of peripheral artery disease (PAD) increases there is growing concern about the associated healthcare burden. This burden has not been well-characterized in high-risk patients with concurrent diabetes and/or acute coronary syndrome (ACS). The objective of this analysis was to assess comorbidities, medication use, outcomes, services and costs for 3 high-risk symptomatic PAD groups.</p> <p><b>Methods</b>: This retrospective longitudinal analysis used the MarketScan Commercial Claims and Encounters Database (2005-2013). The 3 high-risk symptomatic PAD groups were (1) symptomatic PAD with/without diabetes, (2) symptomatic PAD with/without prior ACS, and (3) symptomatic PAD with/without diabetes and prior ACS. The study time frame was a period of 1-year before the earliest date of a symptomatic PAD record and 3 years post.</p> <p><b>Results</b>: In all, 16,663 symptomatic PAD patients were identified across the three risk groups. Mean age ranged from 66.4-67.4 years; the majority (55.0%-63.3%) were men. At 3 years post index, patients with symptomatic PAD and a risk factor had significantly higher use of beta-blockers, ACE inhibitors and statins (<i>P</i><0.0007), and higher rates of all-cause and symptomatic PAD-related medical services, diagnoses and procedures (<i>P</i><0.05). Clopidogrel and statins were used by ≤41.2% and ≤66.7% of symptomatic PAD patients without risk, respectively, and ≤68.9% and ≤80.2% of patients with risks. All cause and symptomatic PAD-related treatment costs (<i>P</i><0.0001) were higher for symptomatic PAD patients with risks versus patients without risks where annualized all-cause cost differences ranged from $7,482 to$13,504 and annualized PAD-related cost differences ranged from $605 to$1,997.</p> <p><b>Conclusions</b>: Symptomatic PAD patients with diabetes and/or prior ACS have significantly higher medical resource use and costs compared to symptomatic PAD patients without these risk factors. The utilization rate of secondary prevention therapies is suboptimal; therefore, greater effort must be made to increase utilization and optimize treatment to minimize the impact of symptomatic PAD.</p

Innate mechanism of mucosal barrier erosion in the pathogenesis of acquired colitis

Summary: The colonic mucosal barrier protects against infection, inflammation, and tissue ulceration. Composed primarily of Mucin-2, proteolytic erosion of this barrier is an invariant feature of colitis; however, the molecular mechanisms are not well understood. We have applied a recurrent food poisoning model of acquired inflammatory bowel disease using Salmonella enterica Typhimurium to investigate mucosal barrier erosion. Our findings reveal an innate Toll-like receptor 4-dependent mechanism activated by previous infection that induces Neu3 neuraminidase among colonic epithelial cells concurrent with increased Cathepsin-G protease secretion by Paneth cells. These anatomically separated host responses merge with the desialylation of nascent colonic Mucin-2 by Neu3 rendering the mucosal barrier susceptible to increased proteolytic breakdown by Cathepsin-G. Depletion of Cathepsin-G or Neu3 function using pharmacological inhibitors or genetic-null alleles protected against Mucin-2 proteolysis and barrier erosion and reduced the frequency and severity of colitis, revealing approaches to preserve and potentially restore the mucosal barrier