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Idiopathic nephrotic syndrome is the most frequent pediatric glomerular disease, affecting from 1.15 to 16.9 per 100,000 children per year globally. It is characterized by massive proteinuria, hypoalbuminemia, and/or concomitant edema. Approximately 85–90% of patients attain complete remission of proteinuria within 4–6 weeks of treatment with glucocorticoids, and therefore, have steroid-sensitive nephrotic syndrome (SSNS). Among those patients who are steroid sensitive, 70–80% will have at least one relapse during follow-up, and up to 50% of these patients will experience frequent relapses or become dependent on glucocorticoids to maintain remission. The dose and duration of steroid treatment to prolong time between relapses remains a subject of much debate, and patients continue to experience a high prevalence of steroid-related morbidity. Various steroid-sparing immunosuppressive drugs have been used in clinical practice; however, there is marked practice variation in the selection of these drugs and timing of their introduction during the course of the disease. Therefore, international evidence-based clinical practice recommendations (CPRs) are needed to guide clinical practice and reduce practice variation. The International Pediatric Nephrology Association (IPNA) convened a team of experts including pediatric nephrologists, an adult nephrologist, and a patient representative to develop comprehensive CPRs on the diagnosis and management of SSNS in children. After performing a systematic literature review on 12 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, recommendations were formulated and formally graded at several virtual consensus meetings. New definitions for treatment outcomes to help guide change of therapy and recommendations for important research questions are given.

Background Anabolic androgenic steroids (AAS) are testosterone derivatives used by athletes and recreational users to improve athletic performance and/or enhance appearance. Anabolic androgenic steroids use may have serious and potentially irreversible adverse effects on different organs and systems, including the reproductive system. Objective This systematic review and meta-analysis aimed to critically assess the impact of AAS use on the reproductive system of athletes and recreational users. Methods An electronic literature search was conducted using the databases MEDLINE, CENTRAL, and Google Scholar. Studies were included when the following criteria were fulfilled: participants were athletes or recreational users of any age, sex, level or type of sport; AAS use of any type, dose, form or duration; AAS effects on the reproductive system were assessed as stated by medical history, clinical examination, hormone and/or semen analysis. Random-effects meta-analysis was performed to assess the weighted mean difference (WMD) of serum gonadotropin (luteinizing hormone, follicle-stimulating hormone) and testosterone levels compared with baseline, during the period of AAS use, as well as following AAS discontinuation. Results Thirty-three studies (three randomized clinical trials, 11 cohort, 18 cross-sectional, and one non-randomized parallel clinical trial) were included in the systematic review (3879 participants; 1766 AAS users and 2113 non-AAS users). The majority of the participants were men; only six studies provided data for female athletes. A meta-analysis (11 studies) was conducted of studies evaluating serum gonadotropin and testosterone levels in male subjects: (1) prior to, and during AAS use (six studies, n  = 65 AAS users; seven studies, n  = 59, evaluating gonadotropin and testosterone levels respectively); (2) during AAS use and following AAS discontinuation (four studies, n  = 35; six studies, n  = 39, respectively); as well as (3) prior to AAS use and following AAS discontinuation (three studies, n  = 17; five studies, n  = 27, respectively). During AAS intake, significant reductions in luteinizing hormone [weighted mean difference (WMD) −3.37 IU/L, 95% confidence interval (CI) −5.05 to −1.70, p  < 0.001], follicle-stimulating hormone (WMD −1.73 IU/L, 95% CI −2.67 to −0.79, p  < 0.001), and endogenous testosterone levels (WMD −10.75 nmol/L, 95% CI −15.01 to −6.49, p  < 0.001) were reported. Following AAS discontinuation, serum gonadotropin levels gradually returned to baseline values within 13–24 weeks, whereas serum testosterone levels remained lower as compared with baseline (WMD −9.40 nmol/L, 95% CI −14.38 to −4.42, p  < 0.001). Serum testosterone levels remained reduced at 16 weeks following discontinuation of AAS. In addition, AAS abuse resulted in structural and functional sperm changes, a reduction in testicular volume, gynecomastia, as well as clitoromegaly, menstrual irregularities, and subfertility. Conclusion The majority of AAS users demonstrated hypogonadism with persistently low gonadotropin and testosterone levels, lasting for several weeks to months after AAS withdrawal. Anabolic androgenic steroid use results in profound and prolonged effects on the reproductive system of athletes and recreational users and potentially on fertility.

The therapeutic potential of donor-derived mesenchymal stromal cells (MSCs) has been investigated in diverse diseases 1 , including steroid-resistant acute graft versus host disease (SR-aGvHD) 2 . However, conventional manufacturing approaches are hampered by challenges with scalability and interdonor variability, and clinical trials have shown inconsistent outcomes 3 , 4 . Induced pluripotent stem cells (iPSCs) have the potential to overcome these challenges, due to their capacity for multilineage differentiation and indefinite proliferation 5 , 6 . Nonetheless, human clinical trials of iPSC-derived cells have not previously been completed. CYP-001 (iPSC-derived MSCs) is produced using an optimized, good manufacturing practice (GMP)-compliant manufacturing process. We conducted a phase 1, open-label clinical trial (no. NCT02923375) in subjects with SR-aGvHD. Sixteen subjects were screened and sequentially assigned to cohort A or cohort B ( n  = 8 per group). One subject in cohort B withdrew before receiving CYP-001 and was excluded from analysis. All other subjects received intravenous infusions of CYP-001 on days 0 and 7, at a dose level of either 1 × 10 6 cells per kg body weight, to a maximum of 1 × 10 8 cells per infusion (cohort A), or 2 × 10 6 cells per kg body weight, to a maximum dose of 2 × 10 8 cells per infusion (cohort B). The primary objective was to assess the safety and tolerability of CYP-001, while the secondary objectives were to evaluate efficacy based on the proportion of participants who showed a complete response (CR), overall response (OR) and overall survival (OS) by days 28/100. CYP-001 was safe and well tolerated. No serious adverse events were assessed as related to CYP-001. OR, CR and OS rates by day 100 were 86.7, 53.3 and 86.7%, respectively. The therapeutic application of iPSC-derived MSCs may now be explored in diverse inflammatory and immune-mediated diseases. A GMP-compliant process for generating human iPSC-derived mesenchymal stromal cells tested in a phase 1 trial is safe and well tolerated in subjects with acute steroid-resistant graft versus host disease.

Background Immune checkpoint inhibitors (ICIs) have revolutionized cancer care with incredible reductions in mortality. One of the most devastating complications of treatment is ICI-related pneumonitis (ICI-p). Despite this, little is known regarding risk factors for severe pneumonitis and treatment effectiveness of various therapeutic options for steroid-refractory disease. To address this, we conducted a retrospective study on patients with cancer who developed ICI-p. Methods We examined consecutive patients who received ICIs and developed ICI-p. Risk factors of interest for severe disease and steroid-refractory ICI-p, including pre-treatment pulmonary function tests (PFTs) and chest imaging, were compared between patients with severe (grades 3-5) and mild (grades 1-2) pneumonitis. The clinical and treatment courses for patients with steroid-refractory ICI-p were recorded. Results A total of 132 patients developed ICI-p, with 60 patients having mild and 72 with severe disease. We found that lower forced vital capacity percent predicted (66.24 vs 85.05, P = .05), lower total lung capacity percent predicted (85.23 vs 99.71, P = .13), and specific radiographic patterns on pre-treatment chest imaging were predictors of severe disease. Initial corticosteroid dose of less than 1 milligram per kilogram prednisone equivalent (P = .14) was correlated with partially steroid-responsive or steroid-refractory ICI-p. Ten patients had steroid refractory ICI-p, and those who received IVIG alone as the immune suppressant beyond corticosteroids had improved survival (P = 05). Conclusions We are the first to identify pre-treatment PFTs and chest imaging abnormalities as risk factors for severe ICI-p. We also found that lower corticosteroid doses were associated with partially steroid-responsive and steroid-refractory ICI-p. Larger, prospective studies are needed to validate our results. Little is known about risk factors for severe pneumonitis and the treatment effectiveness of various therapeutic options for steroid-refractory disease. This retrospective study focused on cancer patients who developed immune checkpoint inhibitor treatment-related pneumonitis.

Despite recent advances in the perinatal management of neonatal respiratory distress syndrome (RDS), controversies still exist. We report updated recommendations of a European Panel of expert neonatologists who developed consensus guidelines after critical examination of the most up-to-date evidence in 2007 and 2010. This second update of the guidelines is based upon published evidence up to the end of 2012. Strong evidence exists for the role of antenatal steroids in RDS prevention, but it is still not clear if the benefit of repeated courses on respiratory outcomes outweighs the risk of adverse outcomes in the short and long term. Many practices involved in preterm neonatal stabilization at birth are not evidence based, including oxygen administration and positive pressure lung inflation, and they may at times be harmful. Surfactant replacement therapy is crucial in the management of RDS but the best preparation, optimal dose and timing of administration at different gestations is not completely clear. In addition, use of very early continuous positive airway pressure (CPAP) has altered the indications for prophylactic surfactant administration. Respiratory support in the form of mechanical ventilation may be lifesaving but can cause lung injury, and protocols should be directed at avoiding mechanical ventilation where possible by using non-invasive respiratory support such as CPAP. For babies with RDS to have best outcomes, it is essential that they have optimal supportive care, including maintenance of normal body temperature, proper fluid management, good nutritional support, appropriate management of the ductus arteriosus and support of the circulation to maintain adequate tissue perfusion.

Doctors are reaching for drugs that dampen the immune response — but these also undermine the body’s own fight against the coronavirus. How does the coronavirus kill? Uncertainty is hampering doctors’ ability to choose treatments. A medical worker looks at monitors showing lung CT scans

Athletes and bodybuilders have recognized for several decades that the use of anabolic steroids can promote muscle growth and strength but it is only relatively recently that these agents are being revisited for clinical purposes. Anabolic steroids are being considered for the treatment of cachexia associated with chronic disease states, and to address loss of muscle mass in the elderly, but nevertheless their efficacy still needs to be demonstrated in terms of improved physical function and quality of life. In sport, these agents are performance enhancers, this being particularly apparent in women, although there is a high risk of virilization despite the favourable myotrophic–androgenic dissociation that many xenobiotic steroids confer. Modulation of androgen receptor expression appears to be key to partial dissociation, with consideration of both intracellular steroid metabolism and the topology of the bound androgen receptor interacting with co‐activators. An anticatabolic effect, by interfering with glucocorticoid receptor expression, remains an attractive hypothesis. Behavioural changes by non‐genomic and genomic pathways probably help motivate training. Anabolic steroids continue to be the most common adverse finding in sport and, although apparently rare, designer steroids have been synthesized in an attempt to circumvent the dope test. Doping with anabolic steroids can result in damage to health, as recorded meticulously in the former German Democratic Republic. Even so, it is important not to exaggerate the medical risks associated with their administration for sporting or bodybuilding purposes but to emphasize to users that an attitude of personal invulnerability to their adverse effects is certainly misguided. British Journal of Pharmacology (2008) 154, 502–521; doi:fn1

Aims: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection has been rapidly emerging as a life-threatening nosocomial disease in many countries. However, studies on the corresponding risk factors of CRKP infection showed inconsistent results. To resolve these inconsistencies, we conducted a meta-analysis of previous studies on the potential risk factors of CRKP infection. The results of this study could be used to develop CRKP infection prevention strategies. Methods: Relevant works were systematically searched from five electronic databases up to September 2016. Z -test was used to determine the significance of the pooled odds ratios (ORs). ORs and 95% confidence intervals were utilized to compare the risk factors of CRKP infection. Results: Sixteen studies that involved 3,627 participants were included in the meta-analysis. We identified the following risk factors that were associated with CRKP infection: (1) longer length of hospital stay (LOS) (OR = 12.92), (2) admission to intensive care unit (ICU) (OR = 2.48), (3) prior hospitalization (OR = 1.85), (4) longer days of ICU stay (OR = 4.58), (5) transplant recipient (OR = 2.01), (6) steroid use (OR = 1.43), (7) central venous catheter use (OR = 2.30), (8) mechanical ventilation (OR = 2.54), (9) presence of tracheostomy (OR = 3.63), (10) parenteral nutrition (OR = 2.38), (11) previous antibiotic use (OR = 3.31), and (12) exposure to carbapenems (OR = 4.01), (13) aminoglycosides (OR = 2.05), (14) glycopeptides (OR = 2.40), (15) quinolones (OR = 2.28), and (16) anti-pseudomonal penicillins (OR = 2.67). Conclusions: Sixteen risk factors including longer LOS, admission to ICU, previous antibiotic use, and exposure to carbapenems were associated with the development of CRKP infection. Identification of modifiable risk factors could play an important role in the prevention of CRKP infection.

Supraphysiological doses of anabolic–androgenic steroids (AAS) is popular among recreational weightlifters and bodybuilders due to the performance-enhancing properties but is also associated with adverse cardiovascular effects. The knowledge about how AAS affect the vasculature is limited, although results from previous studies suggest alterations in vasoreactivity and morphology. In the present study we investigate the association between long-term use of AAS and vascular function. Hundred and twenty-three males were included in the study, 56 of them current AAS users and 67 weightlifting controls. Vascular function was evaluated by carotid artery reactivity and flow-mediated dilation. AAS users had significantly reduced carotid artery reactivity ( p  < 0.001) and flow-mediated dilation ( p  < 0.001) compared to weightlifting controls. Results from the present study indicate that long-term use of AAS affect the cardiovascular system negatively, measured as reduced carotid artery reactivity and flow-mediated dilation. These findings could partly explain sudden cardiovascular events among young long-term users of AAS.