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BACKGROUND: Adrenal insufficiency is usually diagnosed in children who will need lifelong hydrocortisone therapy. However, medicines for pediatrics, in terms of dosage and acceptability, are currently unavailable. RESEARCH DESIGN AND METHODS: Semi-solid extrusion (SSE) 3D printing (3DP) was utilized for manufacturing of personalized and chewable hydrocortisone formulations (printlets) for an upcoming clinical study in children at Vall d'Hebron University Hospital in Barcelona, Spain. The 3DP process was validated using a specific software for dynamic dose modulation. RESULTS: The printlets contained doses ranging from 1 to 6 mg hydrocortisone in three different flavor and color combinations to aid adherence among the pediatric patients. The pharma-ink (mixture of drugs and excipients) was assessed for its rheological behavior to ensure reproducibility of printlets through repeated printing cycles. The printlets showed immediate hydrocortisone release and were stable for 1 month of storage, adequate for prescribing instructions during the clinical trial. CONCLUSIONS: The results confirm the suitability and safety of the developed printlets for use in the clinical trial. The required technical information from The Spanish Medicines Agency for this clinical trial application was compiled to serve as guidelines for healthcare professionals seeking to apply for and conduct clinical trials on 3DP oral dosage forms.

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Urinary tract infections (UTIs) associated with indwelling urinary catheterization (IUC) in premature newborns (PNBs) pose a significant challenge in neonatal intensive care units (NICUs) due to the vulnerability of this population to infections and the necessity of invasive procedures. While bacterial UTIs have historically been predominant, there is a rising incidence of fungal pathogens, particularly non-albicans Candida strains like Candida glabrata and Candida tropicalis, attributed to broad-spectrum antibiotic use. Diagnosis of fungal UTIs in a PNB relies on culturing Candida spp. from properly collected urine samples, particularly critical in very low birth weight (VLBW) PNBs because of the risk of invasive candidiasis and associated complications. We present a case of an extremely premature newborn (EPNB) successfully treated for a UTI caused by C. glabrata with micafungin. Our case exhibits micafungin as a potentially safe and effective alternative for treating C. glabrata UTIs in neonates.

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OBJECTIVES: Mastitis is mainly caused by Gram-positive bacteria and usually involves treatment with beta-lactam antibiotics and clindamycin. Oxazolidinones show good results in the treatment of skin and soft tissue infections (SSTIs) due to its pharmacokinetic characteristics. We aimed to describe clinical characteristics and outcomes of patients who received oxazolidinones for the treatment of SSTIs of the mammary tissue. METHODS: Retrospective single-centre study of patients with a diagnosis of breast infection who received treatment with oxazolidinones as initial or salvage therapy between September 2016 and November 2022. Patients were identified through the pharmacy database. The primary outcome was clinical cure. RESULTS: Twenty-nine patients received oxazolidinones: 27 received linezolid and 2 tedizolid. Median age was 41 years (IQR 31.0-56.5) and 28 patients were female. Ten patients (35%) had a history of breast cancer, while three (10%) had an immunosuppressive condition. Microbiological isolation was obtained in 24 individuals (83%). Predominant isolations were methicillin-resistant Staphylococcus aureus (8, 28%) and methicillin-susceptible S. aureus (7, 24%). Twenty-four patients (83%) received oxazolidinones as a salvage therapy, with a median duration of 14 days (IQR 10-17). Clinical cure was achieved in 24 patients (83%), while 4 relapsed after a median of 15 days (IQR 4-34). One was lost to follow-up. Three patients (10%) were taking selective serotonin reuptake inhibitors, and one of them concurrently received linezolid for 4 days with no adverse events recorded. Cytopenia during treatment was observed in 2/12 individuals. Oxazolidinones allowed hospital discharge in 11/13 hospitalized patients. CONCLUSIONS: Oxazolidinones could be considered as an alternative for treating breast infections.

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Background: Nephrotoxicity is the most frequent serious adverse effect associated with amphotericin B deoxycholate treatment, for this reason, in recent years it has been relegated from routine clinical practice and replaced by the new liposomal formulations that have less nephrotoxicity. Nevertheless, dyselectrolytemia are a frequent adverse effect of the use of liposomal amphotericin B that usually are resolved with the withdrawal of the drug. Case presentation: We present a preterm neonate of 25 weeks gestation, with preserved renal function and most electrolytes within normal limits for gestational age except for mild hyponatremia in the first month of life. Due to an infection of the central nervous system and growth of Candida albicans, he required treatment with endovenous liposomal amphotericin B as well as intrathecal amphotericin B deoxycholate showing severe hydroelectrolyte disturbances and clinical worsening compatible with possible tubulopathy showing hypokalemia and severe hyponatremia a few days after starting treatment that persisted over time even after withdrawal of both drugs. Subsequently to the main alterations described, hypomagnesemia, hypophosphatemia, glycosuria and tubular proteinuria were also observed. Calcium levels remained stable after amphotericin B administration and did not require supplementation. In preterm or low birth weight newborns who present unjustified, severe and difficult to correct hydroelectrolyte disturbances despite the usual treatment, a possible tubulopathy should be considered, whether hereditary, primary or secondary to toxins or drugs. What Is New and Conclusion: We present the first case reported in a neonate in whom dyselectrolithemia has been maintained over time after withdrawal of liposomal amphotericin B.

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Introducción: La nutrición parenteral agresiva con aportes energéticos y proteicos altos se utiliza para mejorar el crecimiento y el neurodesarrollo en recién nacidos prematuros de muy bajo peso. No obstante, hallazgos recientes sugieren que su uso puede ocasionar alteraciones electrolíticas. El objetivo del estudio era comparar la prevalencia de hipercalcemia, hipofosfatemia e hipopotasemia en dos grupos de recién nacidos prematuros que recibieron nutrición parenteral con distintos aportes de aminoácidos y analizar variables perinatales y nutricionales asociadas a la ocurrencia de alteraciones electrolíticas. Métodos: Estudio retrospectivo observacional, con comparación de dos grupos de recién nacidos prematuros con peso < 1.500 g y edad gestacional < 33 semanas, que recibían nutrición parenteral. Uno de los grupos recibió < 3 g/kg/d de aminoácidos, mientras que el otro recibió ≥ 3 g/kg/d. Se analizó la prevalencia de distintas alteraciones electrolíticas y su asociación con la nutrición parenteral agresiva, con ajustes para posibles factores de confusión. Resultados: El análisis incluyó 114 recién nacidos: 60 que recibieron < 3 g/kg/d de aminoácidos (bajo aporte) y 54 que recibieron ≥ 3 g/kg/d (alto aporte). La prevalencia de alteraciones electrolíticas fue similar en ambos grupos. La prevalencia de hipercalcemia fue de 1,67% en el grupo de bajo aporte y 1,85% en el grupo de alto aporte (p > 0,99). Los respectivos valores para las otras alteraciones fueron 11,7 vs. 9,3% en el caso de la hipofosfatemia grave y 15,0 vs. 11,1% en el caso de la hipopotasemia (p > 0,99). Se observó que una relación calcio:fósforo superior a 1,05 mostraba un efecto protector frente a la hipofosfatemia (p = 0,007). Conclusiones: No se observó asociación entre la hipercalcemia, hipofosfatemia o la hipopotasemia y el aporte de aminoácidos mediante nutrición parenteral en la población de recién nacidos prematuros con altos aportes de aminoácidos. (AU)

Introduction: Aggressive parenteral nutrition with delivery of high amino acid and energy doses is used to improve growth and neurodevelopmental outcomes in very low birth weight (VLBW) preterm infants. Recent findings, however, suggest that this approach may cause electrolyte imbalances. The aim of our study was to compare the prevalence of hypercalcaemia, hypophosphataemia, and hypokalaemia in 2 groups of preterm infants that received parenteral nutrition with different amounts of amino acids and to analyse perinatal and nutritional variables associated with the development of electrolyte imbalances. Methods: We conducted a retrospective observational study comparing 2 groups of preterm infants born before 33 weeks’ gestation with birth weights of less than 1,500 g managed with parenteral nutrition. One of the groups received less than 3 g/kg/day of amino acids and the other received 3 g/kg/day of amino acids or more. We analysed the prevalence of electrolyte imbalances and possible associations with aggressive parenteral nutrition, adjusting for potential confounders. Results: We studied 114 infants: 60 given less than 3 g/kg/day of amino acids (low-intake group) and 54 given at least 3 g/kg/day (high-intake group). The prevalence of electrolyte imbalances was similar in both groups. The prevalence of hypercalcaemia was 1.67% in the low-intake group and 1.85% in the high-intake group (p > .99), the prevalence of severe hypophosphataemia 11.7 vs. 9.3%, and the prevalence of hypokalaemia 15.0 vs. 11.1% (p > .99). A calcium to phosphorus ratio greater than 1.05 had a protective effect against hypophosphataemia (p = .007). Conclusions: We did not find any association between hypercalcemia, hypophosphatemia, and hypokalemia and amino acid intake by PN in the population of premature infants with quite high amino acid intake values. (AU)

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INTRODUCTION: Aggressive parenteral nutrition with delivery of high amino acid and energy doses is used to improve growth and neurodevelopmental outcomes in very low birth weight (VLBW) preterm infants. Recent findings, however, suggest that this approach may cause electrolyte imbalances. The aim of our study was to compare the prevalence of hypercalcaemia, hypophosphataemia, and hypokalaemia in 2 groups of preterm infants that received parenteral nutrition with different amounts of amino acids and to analyse perinatal and nutritional variables associated with the development of electrolyte imbalances. METHODS: We conducted a retrospective observational study comparing 2 groups of preterm infants born before 33 weeks' gestation with birth weights of less than 1500 g managed with parenteral nutrition. One of the groups received less than 3 g/kg/day of amino acids and the other received 3 g/kg//day of amino acids or more. We analysed the prevalence of electrolyte imbalances and possible associations with aggressive parenteral nutrition, adjusting for potential confounders. RESULTS: We studied 114 infants: 60 given less than 3 g/kg/day of amino acids (low-intake group) and 54 given at least 3 g/kg/day (high-intake group). The prevalence of electrolyte imbalances was similar in both groups. The prevalence of hypercalcaemia was 1.67% in the low-intake group and 1.85% in the high-intake group (P > .99), the prevalence of severe hypophosphataemia 11.7% vs 9.3%, and the prevalence of hypokalaemia 15.0% vs 11.1% (P > .99). A calcium to phosphorus ratio greater than 1.05 had a protective effect against hypophosphataemia (P = .007). CONCLUSIONS: We did not find an association between hypercalcaemia, hypophosphataemia, and hypokalaemia and the amino acid dose delivered by PN in the high-intake group of preterm infants.

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WHAT IS KNOWN AND OBJECTIVE: Tocilizumab is an IL-6 receptor inhibitor agent which has been proposed as a candidate to stop the inflammatory phase of infection by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, safety data of tocilizumab in pregnant women and their newborn are scarce. We aimed to describe maternal and neonatal safety outcomes associated with tocilizumab treatment in pregnant women with severe COVID-19. METHODS: This is a retrospective study of severe COVID-19 pregnant women, treated with tocilizumab in two Spanish hospitals between 1 March and 31 April 2020. Demographics, medical history, clinical and radiologic findings, treatment information and laboratory data of mothers and their newborns were collected from electronic medical records. RESULTS AND DISCUSSION: A total of 12 pregnant women were identified to have received tocilizumab during pregnancy in the two hospitals. Median gestational age at admission was 27.7 weeks (interquartile range, 18.0-36.4). Most of them received lopinavir/ritonavir, azithromycin and hydroxychloroquine, two patients received corticosteroids and one received interferon beta 1B. All 12 pregnancies resulted in live births. Somatometric values were normal for all newborns, and evolution at 14 and 28 days was favourable for all of them. Hepatotoxicity was observed in 2 patients, which improved or resolved at discharge. Cytomegalovirus reactivation was detected in another patient who had also received corticosteroids for 15 days, causing a congenital infection in her newborn. Both hepatotoxicity and viral reactivation adverse events were classified as possibly related to tocilizumab administration according to Naranjo's causality algorithm. WHAT IS NEW AND CONCLUSIONS: It does not appear that tocilizumab has detrimental effects for the mother and newborn. Close monitoring of infections should be considered, especially if other immunosuppressive agents are used.

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BACKGROUND: The epidemiological and clinical characteristics of solid organ transplant (SOT) patients during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic remains unclear. We conducted a matched retrospective cohort study to compare clinical outcomes among SOT recipients with the general population and to assess immunosuppression management. METHODS: Adult SOT recipients with laboratory polymerase chain reaction-confirmed SARS-CoV-2 infection admitted to a tertiary-care hospital in Barcelona, Spain, from March 11 to April 25, 2020, were matched to controls (1:4) on the basis of sex, age, and age-adjusted Charlson's Index. Patients were followed for up to 28 days from admission or until censored. Primary endpoint was mortality at 28 days. Secondary endpoints included admission to the intensive care unit and secondary complications. Drug-drug interactions (DDI) between immunosuppressants and coronavirus disease 2019 (COVID-19) management medication were collected. RESULTS: Forty-six transplant recipients and 166 control patients were included. Mean (SD) age of transplant recipients and controls was 62.7 (12.6) and 66.0 (12.7) years, 33 (71.7%) and 122 (73.5%) were male, and median (interquartile range) Charlson's Index was 5 (3-7) and 4 (2-7), respectively. Mortality was 37.0% in SOT recipients and 22.9% in controls (P = 0.51). Thirty-three (71.7%) patients underwent transitory discontinuation of immunosuppressants due to potential or confirmed DDI. CONCLUSIONS: In conclusion, hospitalized SOT recipients with COVID-19 had a trend toward higher mortality compared with controls, although it was not statistically significant, and a notable propensity for DDI.

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