Citations

Abstract Rationale Chronic obstructive pulmonary disease (COPD) is a well-established independent risk factor for lung cancer; however, the literature on the association between asthma and lung cancer is mixed. Whether asthma–COPD overlap (ACO) is associated with lung cancer has not been studied. Objectives We aimed to compare lung cancer risk among patients with ACO versus COPD and other conditions associated with airway obstruction. Methods We studied 13,939 smokers from the National Lung Cancer Screening Trial who had baseline spirometry and used spirometric indices and history of childhood asthma to categorize participants into five specific airway disease subgroups. We used Poisson regression to compare unadjusted and adjusted lung cancer risk. Results The incidence rate of lung cancer per 1,000 person-years was as follows: ACO, 13.2 (95% confidence interval [CI], 8.1–21.5); COPD, 11.7 (95% CI, 10.5–13.1); asthmatic smokers, 1.8 (95% CI, 0.6–5.4); Global Initiative for Chronic Obstructive Lung Disease–Unclassified, 7.7 (95% CI, 6.4–9.2); and normal spirometry smokers, 4.1 (95% CI, 3.5–4.8). Patients with ACO had increased adjusted risk of lung cancer compared with patients with asthma (incidence rate ratio [IRR], 4.5; 95% CI, 1.3–15.8) and normal spirometry smokers (IRR, 2.3; 95% CI, 1.3–4.2) in models adjusting for other risk factors. Adjusted lung cancer incidence in patients with ACO and COPD were not found to be different (IRR, 1.2; 95% CI, 0.7–2.1). Conclusions The risk of lung cancer among patients with ACO is similar to those with COPD and higher than other groups of smokers. These results provide further evidence that COPD, with or without a history of childhood asthma, is an independent risk factor for lung cancer.

Objectives We evaluated the outcomes of metastatic pancreatic cancer (MPC) patients who underwent liver metastases (LMs)–directed ablative radiotherapy (RT) and sought to characterize patients with more favorable prognosis. Methods A retrospective analysis of 76 MPC patients who underwent ablative RT (median dose, 50 Gy) to LM at 3 academic centers between 2008 and 2018 was performed. Endpoints were local control (LC), progression-free survival, and overall survival (OS) since RT. Results Median follow-up was 10.9 months. Liver metastases were metachronous in 68%. Before RT, LM was responsive/stable on chemotherapy (CTX) in 36% whereas progressive in 43%. Median carbohydrate antigen 19-9 (CA 19-9) at RT was 334 U/mL. After RT, 32% had ≥6 months of CTX break. Twelve-month outcomes were: LC, 66%; progression-free survival, 7%; and OS, 38%. On multivariable analysis, Eastern Cooperative Oncology Group 2–3 (hazard ratio [HR], 13.49; P < 0.01), progressive LM on CTX (HR, 3.26; P < 0.01), and higher CA 19-9 (log 10 scale; HR, 1.39; P < 0.01) at RT predicted worse OS. Conclusions Ablative RT to LM in setting of MPC may offer LC of systemic disease and thus quality time off CTX. Selected patients with good performance status, stable/responsive LM on CTX, and lower CA 19-9 have more favorable prognosis.

Abstract Context Nutritional rickets results from the interaction of low vitamin D status and limited calcium intake. Serum alkaline phosphatase (AP) activity is a biomarker of impaired mineralization in rickets. Objective To assess the performance of serum AP activity in identifying nutritional rickets in calcium-deprived Nigerian children. Methods We reanalyzed data from a case-control study of children with active rickets and matched control subjects without rickets, using a multivariate logistic regression to assess the odds of rickets associated with AP activity, adjusting for age, sex, and weight-for-age z-score. Results A total of 122 children with rickets and 119 controls were included. Rachitic children had a mean (±SD) age of 54 ± 29 months, and 55 (45.1%) were male. Cases and controls had low dietary calcium intakes (216 ± 87 and 214 ± 96 mg/day, respectively). Serum AP activity levels in cases and controls were 812 ± 415 and 245 ± 78 U/L, respectively (P &lt; 0.001). AP was negatively associated with 25-hydroxyvitamin D values (r = −0.34; P &lt; 0.001). In the adjusted model, the odds ratio (95% CI) receiver operating characteristic curve was 0.978. AP &gt; 350 U/L identified nutritional rickets in Nigerian children with sensitivity 0.93, specificity 0.92, positive likelihood ratio 11.3, and negative likelihood ratio 0.07. Conclusion An AP &gt; 350 U/L effectively discriminated between Nigerian children with and without nutritional rickets. AP is a low-cost biochemical test that could be used to screen for nutritional rickets, but cutoff values require validation in other populations, and laboratory values need to be standardized for widespread population studies.

During agonist stimulation of airway smooth muscle (ASM), agonists such as ACh induce a transient increase in cytosolic Ca2+ concentration ([Ca2+]cyt), which leads to a contractile response [excitation-contraction (E-C) coupling]. Previously, the sensitivity of the contractile response of ASM to elevated [Ca2+]cyt (Ca2+ sensitivity) was assessed as the ratio of maximum force to maximum [Ca2+]cyt. However, this static assessment of Ca2+ sensitivity overlooks the dynamic nature of E-C coupling in ASM. In this study, we simultaneously measured [Ca2+]cyt and isometric force responses to three concentrations of ACh (1, 2.6, and 10 μM). Both maximum [Ca2+]cyt and maximum force responses were ACh concentration dependent, but force increased disproportionately, thereby increasing static Ca2+ sensitivity. The dynamic properties of E-C coupling were assessed in several ways. The temporal delay between the onset of ACh-induced [Ca2+]cyt and onset force responses was not affected by ACh concentration. The rates of rise of the ACh-induced [Ca2+]cyt and force responses increased with increasing ACh concentration. The integral of the phase-loop plot of [Ca2+]cyt and force from onset to steady state also increased with increasing ACh concentration, whereas the rate of relaxation remained unchanged. Although these results suggest an ACh concentration-dependent increase in the rate of cross-bridge recruitment and in the rate of rise of [Ca2+]cyt, the extent of regulatory myosin light-chain (rMLC20) phosphorylation was not dependent on ACh concentration. We conclude that the dynamic properties of [Ca2+]cyt and force responses in ASM are dependent on ACh concentration but reflect more than changes in the extent of rMLC20 phosphorylation.

AbstractHidradenoma papilliferum (HP) is a benign adnexal neoplasm of the vulva that typically presents as a unilateral, flesh‐colored papule in the labium majus in middle‐aged Caucasian women. It is considered to be a close counterpart of the intraductal papilloma of the breast. Malignant transformation is rare with few reports in the literature. We present a case of vulvar mammary‐type apocrine hidradenocarcinoma arising in an HP.

Background. Remote simulation training provides a unique opportunity to captivate providers despite language, distance, and cultural barriers. Previously we developed a novel electronic decision support and rounding tool, the Checklist for Early Recognition and Treatment of Acute Illness in Pediatrics (CERTAINp). This study was conducted to determine the feasibility and impact of remote simulation training of international PICU providers using CERTAINp. Methods. We conducted train-the-trainer sessions in 7 hospitals based in 5 countries (China, Congo, Croatia, India, and Turkey) between 11/2015 and 11/2016. Providers first took part in a base line simulation session to assess their clinical performance. They had structured hands-on training using CERTAINp, which was done remotely using video conference with recording capabilities. Performance in PICU “admission” and “rounding” scenarios was assessed by their adherence to standard of care guidelines using CERTAINp. After this training, the providers were re-evaluated for performance using a validated instrument by 2 independent trained reviewers. Results. A total of 7 hospitals completed both baseline and post simulation sessions. We observed improved critical task (total 14) completion in the admission scenarios where pre training task completion was 8.2 ± 2.6, while after remote training was 11.2 ± 1.8, P = .01. In rounding scenarios, compliance to standard of care guidelines improved overall from 45% to 95% ( P < .01). Conclusion. We observed an improvement in compliance for measures determined as best practice guidelines in simulation rounding and overall improvement in critical tasks for simulated admission cases after remote training.

Human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) diagnostic testing algorithms recommended by the Centers for Disease Control involve up to three tests and rely mostly on detection of viral antigen and host antibody responses. HIV-1 p24 antigen/HIV-1/HIV-2 antibody-reactive specimens are confirmed with an immunochromatographic HIV-1/HIV-2 antibody differentiation assay, and negative or indeterminate results from the differentiation assay are resolved by an HIV-1-specific nucleic acid amplification test (NAT).