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Objective: To measure the current state of organizational and well-being factors in otolaryngology residency programs and associate these perceptions with demographics, pursuit of subspecialty fellowships, and performance on the Otolaryngology Training Examination (OTE). Materials and Methods: Anonymous mail and online survey study of otolaryngology residents from the Southern, Mid-Atlantic, and East South-Central Regions of the United States. Summary of Results: A total of 46 otolaryngology residents across 14 residency training programs (22% resident response rate) completed our survey. Residents who scored above the 80th percentile on the OTE perceived greater organizational support (median = 3.84) than residents who scored below the 40th percentile (median = 3.31), U = 48.00, P = .047, η2 = 0.14. Residents interested in fellowship reported less burnout (median = 2.44) compared to those who did not plan to pursue fellowship (median = 3.56), U = 105.00, P = .010, η2 = 0.05. Residents pursuing fellowship also reported less work–life strain (median = 2.56) than those forgoing fellowship (median = 2.89), U = 126.00, P = .044, η2 = 0.10. Residents with children reported greater work–life strain (median = 3.11) compared to those without (median = 2.56), U = 60.50, P = .008, η2 = 0.15. Conclusion: For otolaryngology residents in this survey sample, the perception of organizational support and well-being may influence resident performance (on OTE examinations) and ultimate career goals (fellowship applications). Program directors and coordinators can use this information to strengthen the perceptions of organizational support as well as improve the clinical learning environment to optimize training conditions for their residents. Residency program directors can also use the identified study measures to assess resident perceptions of the clinical learning environment and well-being for annual evaluation and improvement purposes.

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Advanced stages of neuroblastoma, the most common extracranial malignant solid tumor of the central nervous system in infants and children, are refractive to therapy. Ectopic expression of melanoma differentiation associated gene-7/Interleukin-24 (mda-7/IL-24) promotes broad-spectrum antitumor activity in vitro, in vivo in pre-clinical animal models and in a Phase I clinical trial in patients with advanced cancers, without harming normal cells. mda-7/IL-24 exerts cancer-specific toxicity (apoptosis or toxic autophagy) by promoting ER stress and modulating multiple signal transduction pathways regulating cancer cell growth, invasion, metastasis, survival and angiogenesis. To enhance cancer-selective expression and targeted anti-cancer activity of mda-7/IL-24 we created a tropism-modified Cancer Terminator Virus (Ad.5/3-CTV), which selectively replicates in cancer cells producing robust expression of mda-7/IL-24. We now show that Ad.5/3-CTV induces profound neuroblastoma anti-proliferative activity and apoptosis in a caspase 3/9-independent manner both in vitro and in vivo in a tumor xenograft model. Ad.5/3-CTV promotes these effects through a unique pathway involving apoptosis inducing factor (AIF) translocation into the nucleus. Inhibiting AIF rescued neuroblastoma cells from Ad.5/3-CTV-induced cell death, whereas pan-caspase inhibition failed to promote survival. Ad.5/3-CTV infection of neuroblastoma cells increased ATM phosphorylation instigating nuclear translocation and increased γ–H2AX, triggering nuclear translocation and intensified expression of AIF. These results were validated further using two ATM small molecule inhibitors that attenuated PARP cleavage by inhibiting γ–H2AX, which in turn inhibited AIF changes in Ad.5/3-CTV-infected neuroblastoma cells. Taken together, we elucidate a novel pathway for mda-7/IL-24-induced caspase-independent apoptosis in neuroblastoma cells mediated through modulation of AIF, ATM and γ–H2AX.

Preoperative sarcopenia does not appear to affect length of stay but does portend worse long-term survival. This simple preoperative measurement may help vascular surgeons tailor repair thresholds and avoid nonbeneficial procedures.

Diabetes and undernutrition are common risk factors for tB, associated with poor treatment outcomes and exacerbated by tB. We aimed to assess non-communicable multimorbidity (co-occurrence of two or more medical conditions) in filipino tB outpatients, focusing on malnutrition and diabetes. in a crosssectional study, 637 adults (70% male) from clinics in urban Metro Manila (N = 338) and rural Negros occidental (n = 299) were enrolled. Diabetes was defined as HbA1c of ≥6.5% and/or current diabetes medication. Study-specific HIV screening was conducted. The prevalence of diabetes was 9.2% (54/589, 95%CI: 7.0-11.8%) with 52% newly diagnosed. Moderate/severe undernutrition (body mass index (BMi) <17 kg/ 2) was 20.5% (130/634, 95%CI: 17.4-23.9%). Forty percent of participants had at least one co-morbidity (diabetes, moderate/severe undernutrition or moderate/severe anaemia (haemoglobin <11 g/dL)). HIV infection (24.4%, 74/303) was not associated with other co-morbidities (but high refusal in rural clinics). central obesity assessed by waist-to-hip ratio was more strongly associated with diabetes (Adjusted odds Ratio (AoR) = 6.16, 95%CI: 3.15-12.0) than BMI. Undernutrition was less common in men (AoR = 0.44, 95%CI: 0.28-0.70), and associated with previous history of TB (AoR = 1.97, 95%CI: 1.28-3.04) and recent reduced food intake. The prevalence of multimorbidity was high demonstrating a significant unmet need. HIV was not a risk factor for increased non-communicable multimorbidity.

Of these patients, 21 (88%) had repair because of size criteria, and 15 (63%) had an aneurysm related complication that warranted surgery. Sixtythree aneurysms (72%) did not require an intervention during our study window. The mean initial diameter at diagnosis was 16.9 mm (15.8, 18.1). Forty-eight (55%) aneurysms developed thrombus within the PAA. The mean ankle-brachial index of the evaluated extremity at diagnosis was 1.0 (0.941, 1.053). Univariate analysis identified initial diameter (14.7 vs 19.2 mm; P ¼ .02), atrial fibrillation (16.0% vs 53.8%, P ¼ .042), and the presence of thrombus (33.3% vs 66.7%, P # .001) as predictors of diameter expansion greater than the mean. Using multivariate analysis of the univariate factors determined that only initial diameter (OR, 5.53; P ¼ .007) and the presence or development of thrombus (OR, 4.00; P ¼ .08,) maintained significance.Conclusions: Although the majority of patient comorbidities and risk factors provided no predictive value concerning the expansion rate of PAAs, several identified a significant difference. Patients presenting with an aneurysm at or greater than 20 mm, significant thrombus, or atrial fibrillation may need to be observed using more frequent scanning intervals than those without these risk factors. Further studies are required to validate these predictive PAA growth factors.

BackgroundThe contribution of hepcidin as a regulator of iron metabolism & erythropoiesis on the severity of anemia in sickle cell disease (SCD) remains poorly characterized, especially in Sub-Saharan African populations. The aims of the study were to determine if hepcidin is associated with severity of steady-state anemia in SCD and to investigate factors associated with hepcidin and anemia in SCD.MethodsArchived samples from 199 Tanzanian children, 56% boys aged 3–18 with laboratory-confirmed SCD were analysed based on recorded averaged steady-state hemoglobin (ASSH) quartiles (lowest vs. highest). Univariable and multivariable logistic regression was used to assess associations with ASSH quartiles.FindingsIn univariable analysis, hepcidin <5·5 ng/mL was associated with increased odds of being in the lowest ASSH quartile (OR 2·20; 95%CI 1·2–3·93) but which was limited to girls (OR 4·85, 95%CI 1·79–13·09, p = .046 for interaction). In multivariable analyses including either reticulocyte percentage or erythropoietin, lower hepcidin remained significantly associated with lowest ASSH quartile, although the hepcidin-sex interaction no longer reached statistical significance. No associations with ASSH quartile were observed for markers of inflammation, hemolysis or potential iron markers except for microcytosis, associated with higher ASSH, but which was confounded by reticulocyte percentage and alpha-thalassaemia status.InterpretationHepcidin is lower in more severely anaemic children with SCD independent of inflammation or markers of erythropoiesis.FundingFunding sources include The Wellcome Trust (080025, 095009, 094780 & 070114), MRC-UK (MC-A760-5QX00), NIHR Oxford Biomedical Research Centre, and the Bill and Melinda Gates Foundation (“Hepcidin and Iron in Global Health”, OPP1055865).