Impact of Cystic Fibrosis Transmembrane Conductance Regulator Modulators on Maternal Outcomes During and After Pregnancy.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are available to the majority of people with CF in the United States (US); little is known about pregnancy outcomes with modulator use. This retrospective study aims to determine the impact of CFTR modulators on maternal outcomes. RESEARCH QUESTION: Does pregnancy differentially impact outcomes in females with CF with and without CFTR modulators? STUDY DESIGN AND METHODS: We collected data on pregnancies from 2010-2021 from 11 US adult CF centers. We conducted multivariable longitudinal regression analysis to assess whether changes in percent predicted forced expiratory volume in 1 second (ppFEV1), body mass index (BMI), pulmonary exacerbations (PEx), and Pseudomonas aeruginosa prevalence differed from before, during, and after pregnancy by CFTR modulator use, while adjusting for confounders. We also describe infant outcomes based on maternal modulator use. RESULTS: Among 307 pregnancies, mean age at conception was 28.5 years (range: 17-42), pre-pregnancy ppFEV1 was 74.2 and BMI was 22.3 kg/m2. One hundred and fourteen pregnancies (37.1%) had CFTR modulator exposure during pregnancy (77 with highly effective modulator therapy [HEMT] and 37 with other modulators). The adjusted mean change in ppFEV1 from pre- to during pregnancy was -2.36 (95%CI: -3.56, -1.16) in the unexposed group and +2.60(95%CI: 0.23, 4.97) in the HEMT group, with no significant change from during to one-year post-pregnancy. There was an overall decline in ppFEV1 from pre- to post-pregnancy in the no modulator group (-2.56; 95%CI:-3.62, -1.49) that was not observed in the HEMT group (1.10; 95%CI: -1.13, 3.34). PEx decreased from pre- to post-pregnancy in the HEMT group and BMI increased from pre- to during pregnancy in all groups but without a significant change post-pregnancy. Missing infant outcome data precluded firm conclusions. INTERPRETATION: We observed superior pregnancy and post-pregnancy pulmonary outcomes in individuals who used HEMT, including a preservation of ppFEV1, compared with those unexposed to HEMT.

The contemporary management of perforated appendicitis in adults: To operate or wait?

Objectives: The optimal management of perforated appendicitis remains controversial. Many studies advocate for antibiotics and an interval appendectomy whereas others suggest that performing an appendectomy at the time of presentation decreases post-operative morbidity. Confounding this argument further are the patients who fail non-operative management and end up requiring surgery during their initial hospitalization. This study aims to determine if early operative intervention should be considered for perforated appendicitis. Methods: This was a retrospective review of all patients who underwent an appendectomy (both laparoscopic or open) for perforated appendicitis between 2015 and 2020 at our institution. Results: A total of 271 patients met inclusion criteria for this study. Of this group, 250 patients underwent an immediate appendectomy whereas the remaining 21 patients underwent a trial of non-operative management and eventually required an appendectomy during their initial admission. When comparing the immediate versus delayed operative groups, there were no differences in demographic data including age and gender, and no differences in various imaging findings including AAST Grade IV or V appendicitis. Operatively, patients in the delayed group had a longer operative time (83.1 ± 32.9 vs. 64.1 ± 26.2, p = 0.01), were more likely to require an open operation (23.8 % vs. 2.8 %, p < 0.0001), and were more likely to have a drain placed intra-operatively (42.9 % vs 14.4 %, p = 0.004). While there were no differences in 30-day readmission rates, patients in the delayed group had a significantly longer hospital length of stay than patients in the immediate group (9.4 ± 7.4 vs. 3.1 ± 3.3, p = 0.008). Conclusions: Patients undergoing an immediate appendectomy for perforated appendicitis can discharge from the hospital sooner and demonstrate no increase in post-operative morbidity suggesting that surgeons can initially manage this disease process in an operative fashion.

Association between unplanned pregnancies and maternal exacerbations in cystic fibrosis.

INTRODUCTION: Following availability of the highly effective cystic fibrosis (CF) transmembrane conductance regulator modulator, elexacaftor/tezacaftor/ivacaftor, there was a near doubling of pregnancies reported in the United States (US) in people with CF. We sought to determine health impacts of planned (PP) versus unplanned pregnancies (UP). METHODS: We collected retrospective pregnancy data from January 2010-December 2020 from 11 US CF centers. After adjusting for potential confounding effects, we conducted multivariable, multilevel longitudinal regression analysis using mixed effect modeling to assess whether changes in percent predicted forced expiratory volume in one second (ppFEV1), body mass index (BMI), and pulmonary exacerbations (PEx) 1-year-pre- to 1-year-post-pregnancy were associated with pregnancy planning. RESULTS: Our analysis included 163 people with 226 pregnancies; the cohort had a mean age at conception of 29.6 years, mean pre-pregnancy ppFEV1 of 75.4 and BMI of 22.5 kg/m2. PpFEV1 declined in both PP (adjusted decline of -2.5 (95% CI: -3.8, -1.2)) and UP (adjusted decline of -3.0 (95% CI: -4.6, -1.4)) groups, they did not differ from each other (p = 0.625). We observed a difference in change in the annual number of PEx pre- to post-pregnancy (PP: 0.8 (0.7, 1.1); UP: 1.3 (1.0, 1.7); interaction effect p = 0.029). In a subset of people with available infant data, infants resulting from UP had more preterm births, lower APGAR scores, and more intensive care unit stays. CONCLUSIONS: Following UP, there is an increased trajectory for PEx and potentially for infant complications compared to PP. Clinicians should consider increased surveillance in the setting of UP.