Clinical features and treatment status of adult myasthenia gravis in Japan

Objective Myasthenia gravis (MG) is classified as early-onset MG (EOMG; age at onset ?49 years), late-onset MG (LOMG; age at onset ?50 years) or thymoma-associated MG (TAMG) (E-L-T classification). To clarify the characteristics of each group in the E-L-T classification in Japan, we carried out multicenter analyses of MG. Methods A total of 640 adult patients from 11 MG centers participated in the study. Age at onset, sex, clinical symptoms, frequency of crisis, thymic pathology, positivity of autoantibodies against acetylcholine receptor (AChR) and muscle-specific receptor tyrosine kinase (MuSK), selected treatment, Cushingoid appearance and post-intervention status were evaluated in each group. Results EOMG, LOMG and TAMG accounted for 44%, 33%, and 23% of the patients, respectively. Females predominated in the EOMG group (77%), whereas there was no sex difference in the LOMG group. The frequency of ocular MG was the highest in the LOMG group (EOMG 15%, LOMG 38%, TAMG 12%). Bulbar symptoms and crisis were most frequent in the TAMG group. Anti-AChR antibody was always positive in patients with TAMG (EOMG 70%, LOMG 78%, TAMG 99%), whereas anti-MuSK antibody was never positive in TAMG patients, and more frequently detected in EOMG patients than in LOMG patients. Thymectomy was carried out in 51% of EOMG patients, 26% of LOMG patients and 97% of TAMG patients. Immunotherapy was carried out most aggressively in TAMG patients, and least aggressively in LOMG patients. Minimal manifestations or better with prednisolone ?5 mg were achieved only in one-third of EOMG and TAMG patients. Conclusion Thymoma-associated MG required the most aggressive immunotherapy, followed by early-onset MG

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

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

The Detection of Gravitational Waves

The detection of gravitational waves is challenging researchers since half a century. The relative precision required, $10^{-21}$, is difficult to imagine, this is $10^{-5}$ the diameter of a proton over several km, using masses of tens of kg, or picometers over millions of km. A theoretical description of gravitational radiation and of its effects on matter, all consequence of the General theory of Relativity, is given. Then the astrophysical phenomena that are candidates for gravitational wave emission are discussed, considering also amplitudes and rates. The binary neutron star system PSR1913+16, which provided in 1975 the first evidence for energy loss by gravitational radiation, is briefly discussed. Then comes a description of the experimental developments, starting with ground based interferometers, their working principles and their most important sources of noise. The Earth wide network that is being built describes how these instruments will be used in the observation era. Several other detection techniques, space interferometry, pulsar timing arrays and resonant detectors, covering different bands of the gravitational wave frequency spectrum complete these lectures

Oleoresins from Capsicum spp.: Extraction Methods and Bioactivity

Capsicum spp. fruit is one of the most produced vegetables around the world, and it is consumed both as fresh vegetable and as a spice like a food additive for their characteristic red color and, in many cases, its pungency. In addition to its economic importance, the bioactivity of some important compounds such as capsaicinoids and carotenoids has promoted its research. The use of Capsicum oleoresins has been increased due to its advantages comparing with the traditional dry spice. These include obtaining higher quality products with the desired content of bioactive and flavored substances. The wide diversity of extraction methods including water extraction, organic solvent extraction, microwave-assisted extraction, and ultrasound assisted extraction as well as supercritical fluid extraction among others are discussed in the present review. Moreover, pretreatments such as chemical treatments, osmotic dehydration, sun and oven drying, and freeze-drying commonly used before the extraction are also presented. Due to its importance, Capsicum oleoresins produced with “green” solvents and the improvement of fractional extraction techniques that allow to obtain separately the various bioactive fractions will continue under research for further development