Reported Adverse Events in a Multicenter Cohort of Patients Ages 6-18 Years with Cystic Fibrosis and at Least one F508del Allele Receiving Elexacaftor/Tezacaftor/Ivacaftor.

OBJECTIVE: To describe reported adverse events (AEs) associated with elexacaftor/tezacaftor/ivacaftor (ETI) in a pediatric sample with cystic fibrosis (CF) aged 6-18 years, with at least one F508del variant, followed at multiple Italian CF centers. STUDY DESIGN: This was a retrospective, multicenter, observational study. All children receiving ETI therapy from October 2019 to December 2023 were included. We assessed the prevalence and type of any reported potential drug-related AEs, regardless of discontinuation necessity. Persistent AEs were defined as those continuing at the end of the observation period. RESULTS: Among 608 patients on ETI, 109 (17.9%) reported at least one AE. The majority (N=85, 77.9%) were temporary, with a median duration of 11 days (range 1-441 days). Only 7 (1.1%) patients permanently discontinued treatment, suggesting good overall safety of ETI. The most common AEs leading to discontinuation were transaminase elevations (temporary 14.1%, persistent 25.9%) and urticaria (temporary 41.2%, persistent 7.4%). Creatinine phosphokinase elevation was uncommon. No significant differences in AEs were observed based on sex, age groups (6-11 vs. 12-18 years), or genotype. Pre-existing CF-related liver disease was associated with an increased risk of transaminase elevations. We identified significant variability in the percentage of reported AEs (ANOVA p-value 0·026). CONCLUSIONS: This real-world study highlights significant variability in reported AEs. Our findings suggest that ETI is a safe and well-tolerated therapy in children and adolescents with CF. However, further long-term safety and effectiveness investigations are warranted.

Trypanosoma cruzi: chemotherapeutic effects of clomipramine in mice infected with an isolate obtained from an endemic area.

The susceptibility of Trypanosoma cruzi strains to nifurtimox and benznidazole has been investigated and resistant strains have been described. Some tricyclic drugs are lethal for trypomastigote and epimastigote forms of T. cruzi (Tulahuen strain) and prevent the disease in mice. We investigated whether clomipramine, a tricyclic antidepressant drug with anti-trypanothione reductase and anti-calmodulin effects, could be effective in treating Albino Swiss mice infected with trypomastigotes of a new T. cruzi isolate from a chronic patient from an endemic area of Argentina in two different treatment schedules. Both treatment schedules were effective in reducing electrocardiographic changes and preventing myocardial structural damage. The cardiac beta-receptors low affinity was compensated for by an increment in their density. This probably maintained cardiac function since 70% of the mice survived for more than 2 years even though anti-cruzipain titers remained high. These results demonstrate that clomipramine, clinically used as a neuroleptic, could be a promising trypanocidal agent for the treatment of Chagas' disease.

The intermittent ductus revisited: echocardiographic evidence and successful coil occlusion: a case report and review of literature.

Intermittent occurrence of a large ductal shunt by physical examination and Doppler echocardiography is reported. Cineangiography confirmed a tubular ductus arteriosus with an angulated, narrow, pulmonary end. Presumably this angulation intermittently caused functional closure of the ductus. Trans-arterial delivery of coils resulted in complete occlusion.

The disappearing pulmonary artery band.

A child is presented who had pulmonary artery bands that eroded or cut-through to the point where congestive heart failure and pulmonary arterial hypertension recurred. A summary of previously reported cases of band erosion or cut-through is presented, noting that many of these children died. Pulmonary artery banding is now mainly used in infants with complex defects where mortality of early repair is prohibitive or where the Fontan procedure is the only "repair" possible. To obtain good results, a normal pulmonary vascular resistance is preferred; therefore, it is important that the pulmonary artery band is truly protective over the period of time needed. The occurrence of pulmonary vascular disease can cause a decrease in left-to-right shunting and allow a child to clinically improve, thus duplicating the response to a successful banding. If noninvasive evaluation cannot provide clear-cut proof that the band is protective, then measurement of pulmonary artery pressure and flow must be done.

Congenital fistulous tract between aorta and right atrium presenting as heart failure in a newborn.

A newborn with a fistulous communication between the right coronary sinus and right atrium had congestive heart failure on the first day of life. Medical management was unsuccessful and operative repair was performed using bypass surgery at 5 days of age. Echocardiographic evaluation preoperatively diagnosed the defect correctly and postoperatively confirmed a complete repair. Since aneurysms and/or fistulae can occur in other sinuses after an initial repair of the presenting lesion, the infant will continue to be followed with periodic echocardiographic and clinical evaluations.

Digoxin toxicity in a premature infant: treatment with Fab fragments of digoxin-specific antibodies.

The first use of Fab fragments to treat digoxin toxicity in a premature infant with renal failure, 18 h after the onset of severe arrhythmias, is reported with dramatic results. The development of digoxin toxicity in the context of accepted therapeutic dosing to treat heart failure due to a cerebral arteriovenous malformation is discussed.

[Non fermentative gram negative bacilli isolated in a hospital laboratory]. / Bacilos gramnegativos no fermentadores (BGNNF) aislados en un laboratorio hospitalario.

OBJECTIVE: To report a prospective study on non fermentative gramnegative bacilli, excluded Pseudomonas aeruginosa, isolated at Dr. Julio C. Perrando Hospital in Resistencia (Argentina). The goal of this study was to know their frequency and antimicrobial susceptibility. MATERIAL AND METHODS: For bacterial identifications we used biochemical tests. RESULTS: The greatest percentages of non fermentative gramnegative bacilli isolates were found in blood samples (25%), respiratory secretions and urine (23.9%). Acinetobacter baumannii (34.7%), Pseudomonas fluorescens/Pseudomonas putida (15.2%), Stenotrophomonas maltophilia (9.7%) and Burkholderia cepacia (8.7%) were the non fermentative gramnegative bacilli species most commonly isolated. Distribution of microorganism strains according to samples and area is also assessed. Antimicrobial sensitivity of most commonly isolated non fermentative gramnegative bacilli strain analyzed. CONCLUSIONS: We concluded that non fermentative gramnegative bacilli are most frequently present in hospitalized that in outpatients and antibacterial therapy must be provided according to bacteriological information.