We sought to characterize the incidence and risk factors associated with developing maternal morbidity following preterm prelabor rupture of membranes.Retrospective case-control study of patients with preterm prelabor rupture of membranes at a single institution from 2013 to 2019 admitted at ≥23 weeks gestational age. The primary outcome was a composite of maternal morbidity which included: death, sepsis, intensive care unit (ICU) admission, acute kidney injury, postpartum dilation and curettage, postpartum hysterectomy, venous thromboembolism, postpartum hemorrhage, postpartum wound complication, postpartum endometritis, pelvic abscess, postpartum pneumonia, readmission, and/or need for blood transfusion were compared with patients without above morbidities. Severe morbidity was defined as: death, ICU admission, venous thromboembolism, acute kidney injury, postpartum hysterectomy, sepsis, and/or transfusion >2 units. Demographics, antenatal, and delivery characteristics were compared between patients with and without maternal morbidity. Bivariate statistics and regression models were used to compare outcomes and calculate adjusted odd ratios.Of 361 included patients, 64 patients (17.7%) experienced maternal morbidity and nine (2.5%) had severe morbidity. Patients who experienced maternal morbidity were significantly (p < 0.05) more likely to be older, have private insurance, have BMI ≥40, have chorioamnionitis at delivery, and undergo cesarean or operative vaginal delivery when compared with patients who did not experience morbidity. After controlling for confounders, cesarean delivery (aOR 2.38, 95% CI[1.30,4.39]), body mass index ≥40 at admission (aOR 2.54, 95% CI[1.12,5.79]), private insurance (aOR 3.08, 95% CI[1.54,6.16]), and tobacco use (aOR 3.43, 95% CI[1.58,7.48]) were associated with increased odds of maternal morbidity.In this cohort, maternal morbidity occurred in 17.7% of patients with preterm prelabor rupture of membranes. Private insurance, body mass index ≥40, tobacco use, and cesarean delivery were associated with higher odds of morbidity. These data can be used in counseling and to advocate for smoking cessation.· 17.7% of patients with PPROM experienced maternal morbidity.. · BMI ≥40 was associated with higher odds of maternal morbidity.. · Tobacco use and cesarean delivery were associated with higher odds of maternal morbidity..
Abstract Progressive disease (PD) in patients with chronic lymphocytic leukemia (CLL) on ibrutinib often presents with acquired mutations in BTK and/or PLCG2. Reported variant allele frequencies (VAF) are often low, leading some to question the role of these mutations. Further, several co-existing mutations are often identified. Here we investigated the clonal composition of PD on single cell level, across time, and different anatomic compartments. 84 CLL patients (52 treatment-naïve; 32 relapsed/refractory) with either a TP53 aberration or age ≥65 years received single-agent ibrutinib 420 mg once daily until PD or limiting side effects on a phase 2 study (NCT01500733). The median progression-free survival was 86.6 months. 39 (46.4%) patients progressed, 31 with CLL (PD-CLL), and 8 with Richter’s transformation. Median time to PD-CLL was 57.2 months. In PD-CLL patients, peripheral blood (PB) was sent for genotyping of known hotspot mutations in BTK/PLCG2 (Neogenomics). We then designed digital droplet PCR probes to test for BTK C481S/R/Y and PLCG2 R665W/L845/S707F mutations in samples collected at baseline, during response to ibrutinib and at PD in 29 patients. 26 (89.7%) patients had detectable BTK/PLCG2 mutations (VAF range 0.04 - 0.96). 12 (41%) patients carried multiple BTK/PLCG2 mutations. In 11 evaluable cases single-cell DNA sequencing (Mission Bio) showed individual mutations present in separate cells consistent with branching evolution. Having confirmed oligoclonality, we calculated the cumulative cell fraction (cCF) of BTK/PLCG2 mutations in the 29 PD-CLL patients. 16 (55%) patients had cCF >0.5 (range 0.59-0.96), 10 patients (35%) had cCF < 0.5 (range 0.04-0.43) and 3 patients (10%) had no detectable mutations. BTK/PLCG2 mutations were detected in samples collected at median 21.6 months (range 0 - 75) prior to PD. In 11 cases, we tested lymph node (LN) biopsies at PD. In 6 cases with cCF <0.5 in PB, 4 corresponding LN samples had higher cCF (0.01/0.92; 0/0.85; 0.06/0.69; 0.46/0.99 for PB/LN, respectively). In 5 cases, PB contained 2-6 distinct subclones with cCF >0.5, in 3 cases the corresponding LN harbored fewer subclones than PB (6/3; 3/2; 3/0 for PB/LN, respectively). To characterize the genomic background of PD-CLL, we performed whole-exome sequencing of longitudinal samples from 26 patients. In addition to BTK/PLCG2, the most frequently mutated genes were TP53, SF3B1, NOTCH1, and POT1. Furthermore, copy number variations (CNA), such as del17p, del13q, del14q, del3p, and del8p, were common. In summary, in our cohort BTK/PLCG2 mutations were identified in 89.7% of PD-CLL patients. These mutations arise in oligoclonal populations with variable distribution across anatomical sites. In rare patients without BTK/PLCG2 mutations, the co-evolution of putative driver mutations and multiple CNAs generated genomic complexity reminiscent of lymphoma transformation. Citation Format: Chingiz Underbayev, Jonathan Chen, Hailey M. Harris, Lauren T. Vaughn, Andy Itsara, Adrian Wiestner. The genomic architecture of ibrutinib resistance in CLL: Oligoclonal progression with variable anatomical distribution [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5828.
Because of the coronavirus disease 2019 (COVID-19) pandemic, medical practices are adjusting care delivery to minimize exposure risk for patients and healthcare workers. Prenatal care presents an interesting challenge, as many visits must occur in person and should not be delayed. The severity of COVID-19 in pregnancy remains unclear; therefore, COVID-19–positive and quarantined COVID-19–exposed pregnant women need access to essential obstetrical care and evaluation to ensure disease stability. Although telehealth can be used to provide care and reduce exposure, there are circumstances when in-person visits are indicated.1Aziz A. Zork N. Aubey J.J. et al.Telehealth for high-risk pregnancies in the setting of the COVID-19 pandemic.Am J Perinatol. 2020; 37: 800-808Crossref PubMed Scopus (163) Google Scholar In some cases, pregnant women with COVID-19 have been unable to receive needed prenatal care because of insufficient infection control measures. Thus, the objective of this study is to demonstrate feasibility of a cohorted prenatal care model that isolates COVID-19–positive and quarantined COVID-19–exposed pregnant women in a separate clinic location to provide obstetrical care while minimizing exposure risk. We conducted an institutional review board–approved retrospective cohort study of gravid women from a single academic health system's obstetrics (OB) COVID-19 clinic. Women receiving prenatal care within a 3-hospital system with COVID-19 or at high risk based on the American College of Obstetricians and Gynecologists COVID-19 algorithm2American College of Obstetricians and GynecologistsCOVID-19 FAQs for obstetrician-gynecologists, obstetrics.https://www.acog.org/clinical-information/physician-faqs/covid-19-faqs-for-ob-gyns-obstetricsDate: 2020Google Scholar were eligible for care in the OB COVID-19 clinic. Nurses at each site providing obstetrical care were trained on following the algorithm, ordering testing, and scheduling. Clinic services offered in a location with car-side check-in and a separate entrance and bathrooms. The clinic was staffed by a consistent team with training in donning and doffing personal protective equipment (PPE) (2 medical assistants and 1 maternal-fetal medicine specialist). In addition, 1 staff member was designated as PPE observer and escort. Home pulse oximeters were distributed when indicated. Following resolution of COVID-19 quarantine, patients resumed care with their primary obstetrical practice. Demographic data, pregnancy complications, and outcomes were abstracted. Data were analyzed using descriptive statistics. Between March 18, 2020, and July 30, 2020, 85 women were seen in the OB COVID-19 clinic, of whom 63 had COVID-19. A total of 46 patients had known exposures: 25 (54%) were family-related, 20 (43%) were work-related, and 1 (3%) were travel-related. Another 27 women had unknown exposure. Of those with known exposure etiology, those with family-related (80%) and work-related (75%) exposures were most likely to receive positive test results. Latinx women were more likely to have COVID-19 than other racial and ethnic groups (P<.01) (Table). Among the 63 COVID-19–positive women, 6 (9.5%) were asymptomatic, 49 (77.8%) had mild disease, 6 (9.5%) had moderate disease, and 2 (3.2%) had severe disease. Only 7 patients required hospitalization. The length of stay ranged from 1 to 6 days; 3 patients received remdesivir, and none received corticosteroids. No patients developed fetal growth restriction, and 28 (44%) of the women have delivered (Table). Three healthcare workers developed COVID-19 infection.TableCharacteristics of patients managed by OB COVID-19 clinicCharacteristicsTotal populationOverall, n (%)n=85COVID-19 diagnosisCOVID-19–negative, n (%) n=22COVID-19–positive, n (%) n=63P valueMaternal age, y, median (IQR)29 (25, 33)31 (26, 35)29 (25, 33).30Race and ethnicity<.01 White12 (12.5)8 (38.1)4 (6.5) Black17 (20.5)7 (33.3)10 (16.1) Latinx49 (59.0)3 (14.3)46 (74.2) Asian5 (6.0)3 (14.3)2 (3.2)BMI, kg/m2, median (IQR)30.6 (26.7–35.8)27.5 (26–31.8)31.2 (27.2–36.3).14Multiparous61 (71.8)14 (63.6)47 (74.6).41Chronic hypertension7 (8.2)3 (13.6)4 (6.4).37Type 2 diabetes3 (3.5)2 (9.1)1 (1.6).16Gestational age at OB COVID-19 clinic visit, wk, median (IQR)29.6 (20.3–36.1)30.4 (24.1–36.0)28.7 (18.6–36.1).64Presented with fevers32 (37.7)3 (13.6)29 (46.0).01Presented with cough48 (56.5)10 (45.5)38 (60.3).32Presented with dyspnea27 (31.8)6 (27.3)21 (33.3).38Visit reason.13 COVID-19 symptoms37 (43.5)13 (59.1)24 (38.1) Routine OB care48 (56.5)9 (40.9)39 (60.9)Delivered41 (48.2)13 (59.1)28 (44.4)Mode of delivery (n=41).44 Vaginal28 (68.3)7 (53.9)21 (75) Planned cesarean9 (22.0)4 (30.8)5 (17.9) Unplanned cesarean4 (9.7)2 (15.3)2 (7.1)BMI, body mass index; COVID-19, coronavirus disease 2019; IQR, interquartile range; OB, obstetrics.Dotters-Katz. Specialized prenatal care delivery for coronavirus disease 2019–exposed or –infected pregnant women. Am J Obstet Gynecol 2021. Open table in a new tab BMI, body mass index; COVID-19, coronavirus disease 2019; IQR, interquartile range; OB, obstetrics. Dotters-Katz. Specialized prenatal care delivery for coronavirus disease 2019–exposed or –infected pregnant women. Am J Obstet Gynecol 2021. Cohorted obstetrical care during the COVID-19 pandemic allows an algorithm-driven method of providing prenatal care for COVID-19–positive and quarantined COVID-19–exposed pregnant women while minimizing exposures in clinics providing routine prenatal care.3American College of Obstetricians and GynecologistsOutpatient assessment and management for pregnant women With suspected or confirmed novel coronavirus (COVID-19).https://www.acog.org/-/media/project/acog/acogorg/files/pdfs/clinical-guidance/practice-advisory/covid-19-algorithm.pdfDate: 2020Google Scholar The clinic serves as a resource for a 3-hospital health system for pregnancy-related COVID-19 queries. This approach optimizes resource allocation across the health system, develops experts in donning and doffing PPE, and ensures that patients with COVID-19 in pregnancy receive consistent assessment and care recommendations.
