Drug induced iatrogenic Cushing’s syndrome

Drug-induced (iatrogenic) Cushing's syndrome results from excessive or prolonged exposure to glucocorticoids, commonly prescribed for autoimmune, inflammatory, and hematological disorders due to their anti-inflammatory, immunosuppressive, and proapoptotic effects. Despite their therapeutic benefits, these medications can lead to a range of multisystemic symptoms mirroring those of endogenous Cushing’s syndrome. This review aims to elucidate the causes, clinical presentation, diagnosis, and management of iatrogenic Cushing's syndrome, emphasizing awareness of medications that can trigger its onset. The following review covers cortisol physiology, Cushing's syndrome etiology and subtypes, hypercortisolism complications and prognosis, and strategies for glucocorticoid withdrawal. This article synthesizes key findings and recommendations, highlighting challenges and controversies in the diagnosis and treatment of iatrogenic Cushing's syndrome

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

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

Summary 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 middleincome 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 lowincome 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 lowincome, 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

Identificação de agentes infecciosos pulmonares em autópsias de pacientes com a síndrome da imunodeficiência adquirida Identification of infectious agents in the lungs in autopsies of patients with acquired immunodeficiency syndrome

As afecções pulmonares são freqüentes em indivíduos infectados pelo vírus da imunodeficiência humana. Neste trabalho, procurou-se identificar através de histoquímica e imunohistoquímica, agentes infecciosos nos pulmões de indivíduos portadores da síndrome da imunodeficiência adquirida (SIDA), autopsiados entre março de 1990 e julho de 2000 na FMTM. Fragmentos de pulmão de 40 indivíduos com SIDA autopsiados foram analisados histologicamente. Foram identificados agentes infecciosos em 34 (85%) casos dos 40 analisados, sendo que bactérias foram encontradas em 22 (55%) casos. Entre os agentes fúngicos o Pneumocystis carinii foi encontrado em oito (19,1%) casos; Cryptococcus sp em quatro (9,5%), Histoplasma sp em dois (4,8%) e Candida sp em um (2,4%) caso. Detectou-se também associação entre Pneumocystis carinii, Citomegalovirus e Cryptococcus sp; CMV e Toxoplasma gondii. Em cinco casos, Candida sp, CMV e Pneumocystis carinii estiveram associados a bactérias. Entre as infecções não bacterianas, os fungos foram os agentes infecciosos mais isolados dos pulmões em autópsias de indivíduos com SIDA, sendo o Pneumocystis carinii o mais freqüente.<br>Lung diseases are frequently observed in individuals infected with HIV. The aim of this study was to identify infectious agents in the lungs in the autopsied individuals with AIDS performed between march 1990 and july 2000 at the school of medicine (Uberaba- Brazil), using histochemical and immunohistochemical techniques. Analysis was made on lungs obtained from 40 individuals with AIDS. Infectious agents were observed in 34 (85%) cases of the 40 analyzed. Regarding fungis, Pneumocystis carinii was found in 8 (19.1%)cases; Cryptococcus sp in 4 (9.5%)cases, Histoplasma sp in 2 (4.8%)cases and Candida sp in 1 (2.4%)case. Association of Pneumocystis carinii, Citomegalovirus and Cryptococcus sp, was observed in one case, and in another, the association of CMV, and Toxoplasma gondii. There were 5 cases with Candida sp, CMV and Pneumocystis carinii associated with bacteria. In conclusion, this study shows that following bacterial agents fungi were the second most common infectious agents in post mortem examination of the lungs from patients with AIDS, being Pneumocystis carinii the most prevalent

Desempenho de estratégias de aeração de milho armazenado: Fungos e condutividade elétrica Performance of aeration strategies for stored corn: Molds and electrical conductivity

Objetivou-se, com o presente trabalho, avaliar e comparar o desempenho de três estratégias de aeração de milho armazenado quanto à ocorrência de fungos e à condutividade elétrica dos grãos. As estratégias avaliadas foram: aeração contínua; aeração noturna e aeração em condições de umidade de equilíbrio entre os grãos e o ar ambiente. Realizaram-se dois ensaios de aeração com grãos de milho secos (11% b.u.) e úmidos (17% b.u.). Amostras de grãos foram retiradas durante os ensaios para contagem de fungos e medida da condutividade elétrica dos grãos. Grãos armazenados úmidos apresentaram maior ocorrência de fungos do que grãos armazenados secos. Observou-se que o Fusarium spp. apresentou contagens mais elevadas, o Penicillium spp. manifestou desenvolvimento e o Aspergillus spp. ocorreu com menor frequência. As estratégias de aeração empregadas não interferiram na condutividade elétrica dos grãos de milho armazenados, visto que não houve diferença significativa dos valores de condutividade elétrica entre os grãos submetidos a aeração e os grãos armazenados sem aeração.<br>The aim of this study was to evaluate and to compare the performance of three aeration strategies for stored corn as for occurrence of molds and electrical conductivity of grain: continuous aeration; night aeration and aeration under equilibrium moisture content conditions between the grains and the ambient air. Two tests of aeration with dry corn grain (11% w.b.) and wet corn (17% w.b.) were done. Grain samples were taken during testing for counting of molds and measuring of electrical conductivity of grains. Wet corn stored had increased incidence of molds more than dry corn stored. It was observed that the Fusarium spp. showed higher scores, Penicillium spp. showed development and Aspergillus spp. occurred with lesser frequency. Aeration strategies employed did not affect the electrical conductivity of corn stored because there was no significant difference in electrical conductivity values between the aerated grain and non-aerated grains

Very high energy gamma-ray observation of the peculiar transient event Swift J1644+57 with the MAGIC telescopes and AGILE

Context. On March 28, 2011, the BAT instrument on board the Swift satellite detected a new transient event that in the very beginning was classified as a gamma ray burst (GRB). However, the unusual X-ray flaring activity observed from a few hours up to days after the onset of the event made a different nature seem to be more likely. The long-lasting activity in the X-ray band, followed by a delayed brightening of the source in infrared and radio activity, suggested that it is better interpreted as a tidal disruption event that triggered a dormant black hole in the nucleus of the host galaxy and generated an outflowing jet of relativistic matter. Aims. Detecting a very high energy emission component from such a peculiar object would be enable us to constrain the dynamic of the emission processes and the jet model by providing information on the Doppler factor of the relativistic ejecta. Methods. The MAGIC telescopes observed the peculiar source Swift J1644+57 during the flaring phase, searching for gamma-ray emission at very-high energy (VHE, E > 100 GeV), starting observations nearly 2.5 days after the trigger time. MAGIC collected a total of 28 h of data during 12 nights. The source was observed in wobble mode during dark time at a mean zenith angle of 35 degrees. Data were reduced using a new image-cleaning algorithm, the so-called sum-cleaning, which guarantees a better noise suppression and a lower energy threshold than the standard analysis procedure. Results. No clear evidence for emission above the energy threshold of 100 GeV was found. MAGIC observations permit one to constrain the emission from the source down to 100 GeV, which favors models that explain the observed lower energy variable emission. Data analysis of simultaneous observations from AGILE, Fermi and VERITAS also provide negative detection, which additionally constrain the self-Compton emission component

Dornase alfa improves the health-related quality of life among Brazilian patients with cystic fibrosis - A one-year prospective study

Background: Health-related quality of life (HRQOL) measurements provide valuable information about the psychological and social impact of treatment on patients with cystic fibrosis (CF). This study evaluated the HRQOL of Brazilian patients with CF and assessed the changes in HRQOL domains over 1 year after dornase alfa (Pulmozyme) introduction. Patients and Methods: One hundred fifty-six stable patients with CF and 89 caregivers answered the Portuguese-validated version of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at baseline (T 0), and at 3 (T 1), 6 (T 2), 9 (T 3), and 12 (T 4) months of follow-up. Eighteen patientswere excluded because they did not fulfill the inclusion criteria. The patients were analyzed in two groups: those aged 6-11 years and those aged 14 years and older. ANOVA for observed repeated results and the last observation carried forward (LOCF) method for missing data were used for the statistical analysis. Results: After 1 year of follow-up, there was significant improvement in respiratory symptoms (T 4-T 0=8.1; 95% confidence interval (95% CI)=[2.1;14.0]; effect size (ES)=0.35; P<0.001), Emotional Functioning (T 4-T 0=5.6; 95% CI=[1.1;10.1]; ES=0.31; P<0.05), Social Functioning (T 4-T 0=6.0; 95% CI=[1.3;11.7]; ES=0.31; P<0.05), Body Image (T 4-T 0=11.9; 95% CI=[4.1;19.7]; ES=0.42; P<0.05), and Treatment Burden (T 4-T 0=5.3; 95% CI=[0.3;10.3]; ES=0.24; P<0.05) domains in the younger group. A significant improvement in Role Functioning (T 4-T 0=6.1; 95% CI=[1.1;11.1]; ES=0.40; P<0.05), Body Image (T 4-T 0=12.6; 95% CI=[3.5;21.7]; ES=0.46; P<0.05), and Weight (T 4-T 0=11.7; 95% CI=[1.8;21.6]; ES=0.40; P<0.05) was obtained in the older group. The caregivers' CFQ-R showed improvements in the Digestive Symptoms (T 4-T 0=5.5; 95% CI=[1.5;9.4]; ES=0.30; P<0.05), Respiratory Symptoms (T 4-T 0=7.6; 95% CI=[3.9;11.4]; ES=0.48; P<0.05), and Weight (T 4-T 0=10.1; 95% CI=[1.6;18.6]; ES=0.26; P<0.05) domains. Conclusion: The introduction of dornase alfa improved the HRQL of the patients with CF during the first year of treatment. © 2010 Wiley-Liss, Inc

Criteria and definitions for the radiological and clinical diagnosis of bronchiectasis in adults for use in clinical trials: international consensus recommendations

Bronchiectasis refers to both a clinical disease and a radiological appearance that has multiple causes and can be associated with a range of conditions. Disease heterogeneity and the absence of standardised definitions have hampered clinical trials of treatments for bronchiectasis and are important challenges in clinical practice. In view of the need for new therapies for non-cystic fibrosis bronchiectasis to reduce the disease burden, we established an international taskforce of experts to develop recommendations and definitions for clinically significant bronchiectasis in adults to facilitate the standardisation of terminology for clinical trials. Systematic reviews were used to inform discussions, and Delphi processes were used to achieve expert consensus. We prioritised criteria for the radiological diagnosis of bronchiectasis and suggest recommendations on the use and central reading of chest CT scans to confirm the presence of bronchiectasis for clinical trials. Furthermore, we developed a set of consensus statements concerning the definitions of clinical bronchiectasis and its specific signs and symptoms, as well as definitions for chronic bacterial infection and sustained culture conversion. The diagnosis of clinically significant bronchiectasis requires both clinical and radiological criteria, and these expert recommendations and proposals should help to optimise patient recruitment into clinical trials and allow reliable comparisons of treatment effects among different interventions for bronchiectasis. Our consensus proposals should also provide a framework for future research to further refine definitions and establish definitive guidance on the diagnosis of bronchiectasis

Criteria and definitions for the radiological and clinical diagnosis of bronchiectasis in adults for use in clinical trials:international consensus recommendations

Bronchiectasis refers to both a clinical disease and a radiological appearance that has multiple causes and can be associated with a range of conditions. Disease heterogeneity and the absence of standardised definitions have hampered clinical trials of treatments for bronchiectasis and are important challenges in clinical practice. In view of the need for new therapies for non-cystic fibrosis bronchiectasis to reduce the disease burden, we established an international taskforce of experts to develop recommendations and definitions for clinically significant bronchiectasis in adults to facilitate the standardisation of terminology for clinical trials. Systematic reviews were used to inform discussions, and Delphi processes were used to achieve expert consensus. We prioritised criteria for the radiological diagnosis of bronchiectasis and suggest recommendations on the use and central reading of chest CT scans to confirm the presence of bronchiectasis for clinical trials. Furthermore, we developed a set of consensus statements concerning the definitions of clinical bronchiectasis and its specific signs and symptoms, as well as definitions for chronic bacterial infection and sustained culture conversion. The diagnosis of clinically significant bronchiectasis requires both clinical and radiological criteria, and these expert recommendations and proposals should help to optimise patient recruitment into clinical trials and allow reliable comparisons of treatment effects among different interventions for bronchiectasis. Our consensus proposals should also provide a framework for future research to further refine definitions and establish definitive guidance on the diagnosis of bronchiectasis