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Background IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. While studies have primarily focused on identifying risk factors for disease progression, very few data exist on the likelihood of achieving complete recovery from the disease. Methods We conducted a single-center retrospective study on all consecutive patients with biopsy-proven IgAN diagnosed between 1986 and 2018 in our pediatric center. Biopsies were classified according to the MEST-C Oxford classification score. “Complete clinical remission” was defined as the absence of proteinuria, hematuria, and hypertension in patients with normal kidney function who had been off therapy for more than 2 years. Results Overall, 153 patients with age at onset of 10.6 ± 4 years were enrolled in the study. Of these, 41 achieved “complete clinical remission.” The estimated probability of complete clinical remission at 10 years was 43% (95%CI 33–54). However, seven patients relapsed within 10 years. Multivariable analysis showed that higher age at onset (HR 0.89, 95%CI 0.80–0.98, p  = 0.017) and segmental glomerulosclerosis lesions (HR 0.28, 95%CI 0.10–0.79, p  = 0.017) decreased significantly the chances of achieving complete clinical remission. Immunosuppressive therapy was not significantly associated with clinical outcomes. Conclusions Approximately one-third of patients with pediatric-onset IgAN achieve prolonged remission, in particular, very young children at disease onset without sclerotic glomerular lesions. Longer term follow-up is needed to assess if these patients have achieved permanent remission. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information

Background The COVID-19 pandemic and associated public health measures have had a profound impact on health systems worldwide. The aim of this study was to assess quantitative and qualitative changes in Pediatric Emergency Department (PED) visits in Sardinia, Italy, during the early period of the COVID-19 pandemic. Methods We retrospectively investigated the number and characteristics of visits to two major Sardinian PEDs, in the periods January-June 2020 and January-June 2019. Results From January to June 2020, 8399 PED visits with 1160 hospital admissions (13.8% of PED visits) were registered, compared with 15,692 PED visits (Δ = -46.5%) and 1819 hospital admissions (11.6% of PED visits) occurring from January to June 2019. Comparing January-June 2020 with January-June 2019, we found differences in the percentage of visits for age groups, and significant changes in the proportion of triage codes, with a decrease in green codes (72.1% vs 74.2%, respectively) and an increase in white codes (19.0% vs 16.5%, respectively). Moreover, in the period January-June 2020, the frequency of skin disorders and acute respiratory disease significantly decreased, while the frequency of trauma, acute surgical disease, intoxication, and neuropsychiatric disease significantly increased. Conclusions After the beginning of the Italian lockdown, we observed a marked drop in the number of PED visits, an increase in hospital admission rate, and radical changes in the reason for visit.

Historically, the complement system (classical, lectin, alternative, and terminal pathways) is known to play a crucial role in the etiopathogenesis of many kidney diseases. Direct or indirect activation in these settings is revealed by consumption of complement proteins at the serum level and kidney tissue deposition seen by immunofluorescence and electron microscopy. The advent of eculizumab has shown that complement inhibitors may improve the natural history of certain kidney diseases. Since then, the number of available therapeutic molecules and experimental studies on complement inhibition has increased exponentially. In our narrative review, we give a summary of the main complement inhibitors that have completed phase II and phase III studies or are currently used in adult and pediatric nephrology. The relevant full-text works, abstracts, and ongoing trials (clinicaltrials.gov site) are discussed. Data and key clinical features are reported for eculizumab, ravulizumab, crovalimab, avacopan, danicopan, iptacopan, pegcetacoplan, and narsoplimab. Many of these molecules have been shown to be effective in reducing proteinuria and stabilizing kidney function in different complement-mediated kidney diseases. Thanks to their efficacy and target specificity, these novel drugs may radically improve the outcome of complement-mediated kidney diseases, contributing to an improvement in our understanding of their underlying pathophysiology.

BackgroundThe best treatment for IgAN is still debated. The trials NEFIGAN and NEFIGARD have demonstrated that TRF-budesonide (Nefecon) efficiently and safely reduced proteinuria in adults, leading to FDA approval of Nefecon for adult IgAN. In pediatric IgAN, an etiological treatment does not yet exist, and the main therapies remain RAAS inhibitors and oral steroids. To our knowledge, this is one of the few pediatric reports of TRF-budesonide therapy.Case report—diagnosis/treatmentA 13-year-old boy underwent a kidney biopsy for recurrent macrohematuria and proteinuria, resulting in an IgAN diagnosis (MEST-C score M1-E1-S0-T0-C1). At admission, serum creatinine and UPCR were slightly increased. Three methylprednisolone pulses were performed, followed by prednisone and RAAS inhibitors therapy. However, after 10 months, macrohematuria became constant, and UPCR increased. A new kidney biopsy was performed, showing an increase in sclerotic lesions. Prednisone was discontinued, and a trial with IBD TRF-budesonide 9 mg/day started. One month later, macrohematuria episodes disappeared and UPCR decreased, with a stable kidney function. After 5 months, due to a reduction in morning cortisol levels and difficulty in drug provisioning, we started to wean TRF-budesonide by 3 mg every 3 months, with complete withdrawal after 1 year. During this period, episodes of macrohematuria dramatically decreased, and UPCR and kidney function were maintained stable.ConclusionOur case demonstrates that TRF-budesonide could be considered an effective second-line treatment in pediatric IgAN, particularly when a long course of steroids is necessary to control active inflammation. However, pediatric clinical trials to identify the correct dosage and tolerability of TRF-budesonide are urgently needed.

BackgroundRegional citrate anticoagulation (RCA) is the preferred modality of anticoagulation used in continuous kidney replacement therapy (CKRT) in adults and less extensively in children. Potential metabolic complications limit widespread use in infants, neonates, and in children with liver failure.MethodsWe report our experience with a simplified protocol in 50 critically ill children, infants, and neonates, some of them with liver failure, with commercially available solutions containing phosphorous and higher concentration of potassium and magnesium.ResultsRCA allowed attainment of a mean filter lifetime of 54.5 ± 18.2 h, 42.5% of circuits lasted more than 70 h, and scheduled change was the most frequent cause of CKRT interruption. Patient Ca++ and circuit Ca++ were maintained in the target range with mean values of 1.15 ± 0.13 mmol/l and 0.38 ± 0.07 mmol/l, respectively. No session had to be stopped because of metabolic complications. The most frequent complications were hyponatremia, hypomagnesemia, and metabolic acidosis mostly related to primary disease and critical illness. No session had to be stopped because of citrate accumulation (CA). Transitory CA occurred in 6 patients and was managed without requiring RCA interruption. No patients with liver failure presented CA episodes.ConclusionsIn our experience, RCA with commercially available solutions was easily applied and managed in critically ill children, even in patients with low weight or with liver failure. Solutions containing phosphate and higher concentrations of magnesium and potassium allowed reduction of metabolic derangement during CKRT. Prolonged filter life was ensured with no detrimental effects on patients and reduced staff workload.

Adrenaline, also known as epinephrine, is a hormone, neurotransmitter, and medication. It is the best established drug in neonatal resuscitation, but only weak evidence supports current recommendations for its use. Furthermore, the available evidence is partly based on extrapolations from adult studies, and this introduces further uncertainty, especially when considering the unique physiological characteristics of newly born infants. The timing, dose, and route of administration of adrenaline are still debated, even though this medication has been used in neonatal resuscitation for a long time. According to the most recent Neonatal Resuscitation Guidelines from the American Heart Association, adrenaline use is indicated when the heart rate remains < 60 beats per minute despite the establishment of adequate ventilation with 100% oxygen and chest compressions. The aforementioned guidelines recommend intravenous administration (via an umbilical venous catheter) of adrenaline at a dose of 0.01–0.03 mg/kg (1:10,000 concentration). Endotracheal administration of a higher dose (0.05–0.1 mg/kg) may be considered while venous access is being obtained, even if supportive data for endotracheal adrenaline are lacking. The safety and efficacy of intraosseous administration of adrenaline remain to be investigated. This article reviews the evidence on the circulatory effects and tolerability of adrenaline in the newborn, discusses literature data on adrenaline use in neonatal cardiopulmonary resuscitation, and describes international recommendations and outcome data regarding the use of this medication during neonatal resuscitation.

C3 glomerulopathy is an ultra-rare, severe form of glomerulonephritis caused by overactivation of the alternative complement pathway. We aimed to assess efficacy and safety of iptacopan (LNP023), an oral, proximal complement inhibitor that targets factor B to selectively inhibit the alternative pathway of the complement cascade. APPEAR-C3G was a multicentre, randomised, double-blind, placebo-controlled, phase 3 study of iptacopan versus placebo (both in addition to supportive care [renin–angiotensin–aldosterone system (RAAS) inhibitors] and immunosuppression). Adult participants (aged 18–60 years) with biopsy-confirmed C3 glomerulopathy were enrolled from 35 hospitals or medical centres in 18 countries. Inclusion criteria included reduced serum C3 concentration (ie, <77 mg/dL [defined as <0·85 × lower limit of the central laboratory normal range]) at screening, urine protein–creatinine ratio (UPCR) of 1·0 g/g or higher at day –75 and day –15 before randomisation, estimated glomerular filtration rate (eGFR) of 30 mL/min per 1·73 m2 or higher at screening and day –15, and vaccination against Neisseria meningitidis and Streptococcus pneumoniae. All eligible participants were randomised 1:1 via interactive response technology to either the iptacopan or the placebo group, stratified by treatment with corticosteroids, mycophenolic acid, or both (yes or no). During the 6-month double-blind period, participants orally received either iptacopan 200 mg twice daily or placebo; this was followed by a 6-month open-label period in which all participants received iptacopan 200 mg twice daily. The primary endpoint was relative reduction in proteinuria (measured by log-transformed ratio to baseline in UPCR sampled from a 24-h urine collection) at 6 months. The primary analyses were done in the full analysis set (ie, all participants to whom study treatment was assigned by randomisation); all participants who received at least one dose of study treatment were included in the safety analysis. This trial was registered with ClinicalTrials.gov (NCT04817618) and the adult cohort has been completed. Between July 28, 2021, and Feb 15, 2023, 132 participants were screened, of whom 58 did not complete the screening period and 74 (64% male; 69% White) were randomised 1:1 to receive either iptacopan (n=38) or placebo (n=36). One participant in the placebo group discontinued treatment during the open-label period. The 24-h UPCR percentage change relative to baseline at 6 months was –30·2% (95% CI –42·8 to –14·8) in the iptacopan group and 7·6% (–11·9 to 31·3) in the placebo group. In the iptacopan group, the geometric mean of 24-h UPCR was 3·33 g/g (95% CI 2·79 to 3·97) at baseline and 2·17 g/g (1·62 to 2·91) at 6 months; in the placebo group, this was 2·58 g/g (2·18 to 3·05) at baseline and 2·80 g/g (2·37 to 3·30) at 6 months. The primary endpoint was met with a relative reduction in 24-h UPCR at 6 months for iptacopan versus placebo of 35·1% (13·8 to 51·1; p=0·0014). 30 (79%) of 38 participants in the iptacopan group had treatment-emergent adverse events, compared with 24 (67%) of 36 participants in the placebo group; most of these were of mild or moderate severity. There were no deaths, no treatment discontinuations due to treatment-emergent adverse events, and no meningococcal infections. Serious adverse events were reported in three (8%) participants in the iptacopan group and one (3%) participant in the placebo group. Iptacopan showed a statistically significant, clinically meaningful proteinuria reduction in addition to RAAS inhibitors and immunosuppression at 6 months. Iptacopan was well tolerated with an acceptable safety profile in patients with C3 glomerulopathy. Novartis Pharma.

This work presents PUCHEROS+, a high-resolution echelle spectrograph designed and built in the Centro de Astro-Ingenieria UC (AIUC), and recently installed in the ESO1.52m at La Silla observatory. Spectrographs are widely used instruments in as- tronomy, that work with the principle of dispersion of the light as a way of obtaining information from it, for example, measuring the wavelength shift due to Doppler effect in the spectra of a star (radial velocity), it is posible to detect exoplanets orbiting it.PUCHEROS+ is an enhanced version of PUCHEROS, the first high-resolution low cost echelle spectrograph developed by the AIUC. Due to its limitations, the instrument is focused on teaching and also research of bright objects. In this new version, and through an opportune investment, improvements were made in the scientific detector and objective; in the calibration system; in the acquisition/guiding system; and in thermal stability, adding two temperature control systems for fine and coarse control. The instrument has reached the performance of spectral resolution of 18000, sampling of 3 pixels, limiting magnitude of about 12 in V Band, spectral range from 400nm to 680nm. Also, thanks to the improvements mentioned and suitable environmental conditions that the telescope provides, the instrument reached a precision on radial velocities of 50 ~ 100m/s, with strong opportunities to keep improving in this matter. This way the instrument proved to be an effective scientific tool in the framework of the PLATOSpec project.In this work, the instrument and all its related engineering systems will be described in detail, focusing on its improvements with its predecessor. Finally the results of measure- ments of radial velocity are presented, with an analysis about precision.

We present PUCHEROS +, a new spectrograph developed as an enhanced version of PUCHEROS (Pontificia Universidad Catolica High Echelle Resolution Optical Spectrograph), which was the first high-resolution spectrograph built at the Pontificia Universidad Catolica de Chile (UC). With respect to its predecessor, PUCHEROS + includes a substantial number of improvements, mainly: a new scientific detector, improved objective optics, calibration system, guiding, active thermal control, and remote observing mode. These upgrades convert our early prototype into a much more powerful instrument for science. With a spectral resolution of R = 18000, a spectral range between 400 and 730 nm and an instrument efficiency of about 30 per cent, PUCHEROS + was tested at the ESO (European Southern Observatory) 1.52-m telescope where it has reached a limiting magnitude of about 12 in V band and radial velocity precision of about 30 m/s. The instrument was conceived as a pathfinder for the high-resolution echelle spectrograph PLATOSpec and at the same time, it demonstrates that a compact, relatively low-cost spectrograph can be efficiently employed for long-term monitoring campaigns and as support facility for space missions, in particular if operated remotely at relatively small- or medium-sized telescopes.

We report the discovery and characterisation of three transiting warm Jupiters: TIC 147027702b, TIC 245076932b and TIC 87422071b. These systems were initially identified as transiting candidates using light curves generated from the full-frame images of the TESS mission. We confirmed the planetary nature of these objects with ground-based spectroscopic follow-up observations using FEROS and the new PLATOSpec spectrograph attached to the ESO 1.52 m telescope at the La Silla Observatory, and with ground-based photometric observations of the Observatoire Moana, Las Cumbres Observatory Global Telescope and ASTEP. From a global fit to the photometry and radial velocities, we determine that the planet TIC 147027702b has a low-eccentric orbit (\\(e = 0.13 \\pm 0.05\\)) with a period of 44.4 days and has a mass of \\(1.09^{+0.07}_{-0.13}\\) M\\(_J\\) and a radius of \\(0.98 \\pm 0.06\\) R\\(_J\\). TIC 245076932b has a moderately low mass of \\(0.51 \\pm 0.05\\) M\\(_J\\), a radius of \\(0.97 \\pm 0.05\\) R\\(_J\\), and an eccentric orbit (\\(e = 0.43 \\pm 0.02\\)) with a period of 21.6 days. TIC 87422071b has a mass of \\(1.29 \\pm 0.10\\) M\\(_J\\), a radius of \\(0.97 \\pm 0.08\\) R\\(_J\\), and has a slightly eccentric orbit (\\(e = 0.12 \\pm 0.07\\)) with a period of 11.3 days. These well-characterised warm Jupiters expand the currently limited sample of similar gas giants and provide valuable benchmarks for testing models of giant-planet formation, migration, and tidal evolution.