Adrenal suppression: A practical guide to the screening and management of this under-recognized complication of inhaled corticosteroid therapy

Inhaled corticosteroids (ICSs) are the most effective anti-inflammatory agents available for the treatment of asthma and represent the mainstay of therapy for most patients with the disease. Although these medications are considered safe at low-to-moderate doses, safety concerns with prolonged use of high ICS doses remain; among these concerns is the risk of adrenal suppression (AS). AS is a condition characterized by the inability to produce adequate amounts of the glucocorticoid, cortisol, which is critical during periods of physiological stress. It is a proven, yet under-recognized, complication of most forms of glucocorticoid therapy that can persist for up to 1 year after cessation of corticosteroid treatment. If left unnoticed, AS can lead to significant morbidity and even mortality. More than 60 recent cases of AS have been described in the literature and almost all cases have involved children being treated with ≥500 μg/day of fluticasone

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

patients?: Turkish Oncology Group Study

Purpose: The purpose of this study was to determine whether primary tumor localization may be a risk factor for relapse and survival in seminomatous germ cell tumors (GCT) patients.Methods: In our study, 612 seminomatous GCT patients diagnosed in 22 centers between 01.01.1989 and 03.02.2019 were retrospectively evaluated. Patient interview information, patient files and electronic system data were used for the study.Results: The primary tumor was localized in the right testis in 305 (49.9%) patients and in 307 (50.1%) in the left testis. Mean age of the patients was 36 years (range 16-85 +/- 10.4).The median follow-up period was 47 months (1-298). Recurrence was observed in 78 (127%) patients and 29 (4.7%) died during the follow-up period. Four-year overall survival (OS) was 95.4% and 4-year progression-free survival (PFS) was 84.5%. The relationship between localization and relapse was significant in 197 patients with stage 2 and stage 3 (p=0.003). In this patient group, 41 (20.8%) relapses were observed. Thirty (73.2%) of the relapses were in the right testis and 11 (26.8%) in the left testis.Four-year OS was 92.1% in patients with right tumor; and 98.7% in patients with left tumor (p=0.007). When 612 patients were evaluated with a mean follow-up of 4 years, there was a 6.6% survival advantage in patients with left testicular tumor and this difference was significant (p=0.007).Conclusion: Survival rates of patients with primary right testicular localization were worse compared with left testicular localization, and relapse rates were higher in stage 2 and 3 patients with right testicular localization.C1 [Yildiz, Birol; Erturk, Ismail; Acar, Ramazan; Karadurmus, Nuri] Hlth Sci Univ, Gulhane Training & Res Hosp, Dept Med Oncol, Ankara, Turkey.[Kucukarda, Ahmet; Gokyer, Ali] Trakya Univ, Fac Med, Dept Med Oncol, Edirne, Turkey.[Demiray, Atike Gokcen] Pamukkale Univ, Fac Med, Dept Med Oncol, Denizli, Turkey.[Paydas, Semra] Cukurova Univ, Fac Med, Dept Med Oncol, Adana, Turkey.[Aral, Ipek Pinar] Nevsehir State Hosp, Dept Radiat Oncol, Nevsehir, Turkey.[Gumusay, Ozge] Gazi Osman Pasa Univ, Fac Med, Dept Med Oncol, Tokat, Turkey.[Bilici, Ahmet] Medipol Univ, Fac Med, Dept Med Oncol, Istanbul, Turkey.[Akdeniz, Nadiye] Dicle Univ, Fac Med, Dept Med Oncol, Diyarbakir, Turkey.[Bahceci, Aykut] Gaziantep Dr Ersin ARSLAN Training & Res Hosp, Dept Med Oncol, Gaziantep, Turkey.[Demir, Hacer] Afyon Kocatepe Univ, Fac Med, Dept Med Oncol, Afyon, Turkey.[Esin, Ece] Bayindir Hosp, Dept Med Oncol, Ankara, Turkey.[Uyeturk, Ummugul] Abant Izzet Baysal Univ, Fac Med, Dept Med Oncol, Bolu, Turkey.[Okten, Ilker Nihat] Istanbul Medeniyet Univ, Gortepe Training & Res Hosp, Dept Med Oncol, Istanbul, Turkey.[Turk, H. Mehmet] BezmiAlem Vakif Univ, Dept Med Oncol, Istanbul, Turkey.[Topaloglu, Ulas Serkan] Kayseri City Hosp, Dept Internal Med, Kayseri, Turkey.[Basoglu, Tugba] Marmara Univ, Fac Med, Dept Med Oncol, Istanbul, Turkey.[Turhal, Nazim Serdar] Anadolu Med Ctr, Dept Med Oncol, Kocaeli, Turkey.[Cinkir, Havva Yesil] Gaziantep Univ, Dept Med Oncol, Fac Med, Gaziantep, Turkey.[Menekse, Serkan; Kut, Engin] Manisa City Hosp, Dept Med Oncol, Manisa, Turkey.[Cakmak, Yagmur] Kocaeli Univ, Fac Med, Dept Med Oncol, Kocaeli, Turkey.[Urun, Yuksel] Ankara Univ, Fac Med, Dept Med Oncol, Ankara, Turkey.[Dal, Pinar] Eskisehir City Hosp, Dept Med Oncol, Eskisehir, Turkey.[Sakalar, Teoman] Kahramanmaras City Hosp, Dept Med Oncol, Kahramanmaras, Turkey.[Aktepe, Oktay Halit] Hacettepe Univ, Fac Med, Dept Med Oncol, Ankara, Turkey

A dominant mutation in mec-7/β-tubulin affects axon development and regeneration in Caenorhabditis elegans neurons

Microtubules have been known for decades to be basic elements of the cytoskeleton. They form long, dynamic, rope-like structures within the cell that are essential for mitosis, maintenance of cell shape, and intracellular transport. More recently, in vitro studies have implicated microtubules as signaling molecules that, through changes in their stability, have the potential to trigger growth of axons and dendrites in developing neurons. In this study, we show that specific mutations in the Caenorhabditis elegans mec-7/βtubulin gene cause ectopic axon formation in mechanosensory neurons in vivo. In mec-7 mutants, the ALM mechanosensory neuron forms a long ectopic neurite that extends posteriorly, a phenotype that can be mimicked in wild-type worms with a microtubule-stabilizing drug (paclitaxel), and suppressed by mutations in unc-33/CRMP2 and the kinesin-related gene, vab-8. Our results also reveal that these ectopic neurites contain RAB-3, a marker for presynaptic loci, suggesting that they have axon-like properties. Interestingly, in contrast with the excessive axonal growth observed during development, mec-7 mutants are inhibited in axonal regrowth and remodeling following axonal injury. Together our results suggest that MEC-7/βtubulin integrity is necessary for the correct number of neurites a neuron generates in vivo and for the capacity of an axon to regenerate