Infant Mortality Categorized by Birth Weight Percentiles for Deliveries Between 22 and 28 Weeks of Gestation.

OBJECTIVE: Our objective was to describe infant mortality within 1 year of life according to gestational age and birth weight percentile in infants delivered between 22 and 28 weeks of gestation. STUDY DESIGN: This study was a retrospective cohort study based on publicly available U.S. birth certificate data linked to infant death data between 2014 and 2020. Maternal-neonate pairs of singleton live births between 220/7 and 286/7 weeks' gestation (vaginal or cesarean) were evaluated. We excluded infants with major fetal anomalies, chromosomal disorders, and birth weight outliers. Our primary outcome was infant mortality within 1 year of life. Individuals were categorized into eight sex-specific birth weight percentiles categories: less than the 3rd, 3rd-less than the 10th, 10th-less than the 25th, 25th-to less than the 50th, 50th-less than the 75th, 75th-to less than the 90th, 90th-less than the 97th, and 97th or higher. RESULTS: Of 27,014,444 individuals with live births from January 2014 to December 2020, 151,677 individuals who gave birth at 22 to 28 weeks of gestation were included in the study population. The mortality rate ranged from 4.2% for the 50th-less than the 75th percentiles at 28 weeks to 80.3% for the 3rd-less than the 10th percentile at 22 weeks. Using the 50th-less than the 75th birth weight percentile at each gestational age as a reference group, birth weight less than the 50th percentile was associated with increased mortality at all gestational ages in a dose-dependent manner. From 22 to 25 weeks of gestation, higher birth weight percentiles were associated with lower mortality, while the 97th or higher birth weight percentile was associated with increased mortality compared with the 50th-less than the 75th birth weight percentile at 26 to 28 weeks of gestation. CONCLUSION: The lower birth weight percentiles were associated with higher mortality across all gestational ages, but the association between higher birth weight percentiles and infant mortality exhibited an opposite pattern at 22 to 25 weeks as compared to later gestational age. KEY POINTS: · Birth weight ≥97th percentile was associated with increased infant mortality at 26 to 28 weeks.. · Higher birth weight percentiles were associated with a lower risk of mortality at 22 to 25 weeks.. · Lower birth weight percentiles were associated with a higher risk of mortality at 22 to 28 weeks..

Neonatal and Maternal Outcomes at 22-28 Weeks of Gestation by Mode of Delivery.

OBJECTIVE: To compare neonatal and maternal outcomes after 22- to 28-week delivery between cesarean and vaginal delivery after stratification by gestational age and fetal presentation. METHODS: This study was a repeated cross-sectional analysis using U.S. birth certificate data linked to infant death data from 2017 to 2020. We limited analyses to women with singleton pregnancies who gave birth at 22-28 weeks of gestation and whose neonates were admitted to the intensive care unit. Our primary outcome was neonatal death within 28 days. We also examined infant mortality within 1 year and severe maternal morbidity (SMM; any transfusion, unplanned hysterectomy, and intensive care unit admission). Outcomes were compared between cesarean and vaginal delivery after stratification by gestational age and fetal presentation. Multivariable logistic regression was performed to calculate adjusted odds ratios (vaginal delivery as a referent), controlling for potential confounders. RESULTS: Of 69,672 individuals with eligible deliveries, 1,740 (2.5%) delivered at 22 weeks of gestation, 6,155 (8.8%) delivered at 23 weeks, 9,341 (13.4%) delivered at 24 weeks, 10,516 (15.1%) delivered at 25 weeks, 11,994 (17.2%) delivered at 26 weeks, 13,662 (19.6%) delivered at 27 weeks, and 16,264 (23.3%) delivered at 28 weeks. In cephalic fetuses, cesarean delivery compared with vaginal delivery was associated with neonatal death and infant mortality at 24 weeks of gestation and greater (not significant at 22-23 weeks) and SMM in all gestational age groups. In contrast, in noncephalic fetuses, cesarean delivery compared with vaginal delivery was associated with decreased odds of neonatal death and infant mortality in all gestational age groups. Sample size for SMM in noncephalic fetuses precluded multivariable modeling. CONCLUSION: Cesarean delivery in cephalic fetuses was associated with increased odds of adverse neonatal outcomes (24 weeks of gestation or greater) and SMM (all gestational age groups). Cesarean delivery was associated with decreased odds of neonatal death compared with vaginal delivery for noncephalic fetuses in all gestational age groups.

Intrahepatic cholestasis of pregnancy: a comparison of Society for Maternal-Fetal Medicine and the Royal College of Obstetricians and Gynaecologists' guidelines.

This study reviewed the literature regarding the diagnosis, antepartum surveillance, and timing of delivery of pregnancies complicated by intrahepatic cholestasis of pregnancy, comparing the guidelines published by the Society for Maternal-Fetal Medicine in February 2021 and those published by the Royal College of Obstetricians and Gynaecologists in the United Kingdom in June 2022. Several key differences exist in the clinical guidelines between the 2 organizations. With regard to the diagnosis of intrahepatic cholestasis of pregnancy, the Society for Maternal-Fetal Medicine considers any elevation in bile acids above the upper limit of normal in the setting of maternal pruritus diagnostic of intrahepatic cholestasis of pregnancy, whereas the Royal College of Obstetricians and Gynaecologists requires a pregnancy-specific elevated bile acid level of ≥19 mmol/L for diagnosis. Regarding the treatment of intrahepatic cholestasis of pregnancy, the Society for Maternal-Fetal Medicine recommends ursodeoxycholic acid as the first-line treatment of maternal symptoms. In contrast, the Royal College of Obstetricians and Gynaecologists specifically recommends against the routine use of ursodeoxycholic acid for intrahepatic cholestasis of pregnancy because of a lack of evidence regarding both maternal and fetal benefit. The Society for Maternal-Fetal Medicine recommends fetal surveillance at a gestational age when abnormal fetal testing would result in delivery being performed, whereas the Royal College of Obstetricians and Gynaecologists does not recommend any fetal testing beyond fetal kick count assessment. The Society for Maternal-Fetal Medicine recommends delivery at 36 to 39 weeks' gestation for intrahepatic cholestasis of pregnancy with bile acids <100 mmol/L and delivery at 36 weeks for bile acid levels >100 mmol/L. The Royal College of Obstetricians and Gynaecologists recommends serial assessment of bile acids with delivery timing stratified between 35- and 40-weeks' gestation according to bile acid levels.

Adherence to Recommendations from Comprehensive Geriatric Assessment of Older Individuals with HIV.

This retrospective cohort study sought to assess the effectiveness of comprehensive geriatric assessment (CGA) for older patients at an HIV clinic in a large US city. We systematically reviewed medical records of all patients who underwent CGA from June 2013 to July 2017. In addition, physicians and social workers completed an anonymous survey about the impact of CGA on their patients. For the 76 patients (median age 67.2; Q1, Q3 = 60.9, 72.6) seen by geriatricians at the clinic, there were 184 recommendations, 54 instances of counseling, and 11 direct actions. Overall adherence to recommendations was 32.8%, 34.9% for patient-directed, and 31.7% for provider-directed recommendations. No demographic or CGA variables were associated with adherence. Despite this lack of adherence, surveyed providers reported that they usually or always followed recommendations; the most frequently cited barrier to implementation was lack of feasibility. Further research will be needed to determine how CGA can improve outcomes for this population.

Clinical features and response to systemic therapy in a historical cohort of advanced or unresectable mucosal melanoma.

There are very few data available regarding the pattern of first metastases in resected mucosal melanomas (MMs) as well as the response of advanced MM to cytotoxic therapy. A retrospective, single-institution cohort was assembled of all patients with advanced/unresectable MM between 1995 and 2012 who had received systemic therapy with available imaging (N=81). Responses to first-line and second-line systemic therapy were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The relationship between response, overall survival, and clinical covariates was investigated using Cox proportional hazards regression. Primary sites included anorectal (N=31, 38%), vulvovaginal (N=28, 35%), head and neck (N=21, 26%), and gallbladder (N=1, 1%) mucosa. Seven percent of patients had their first relapse in the brain. Cytotoxic therapy represented 82 and 51% of first-line and second-line regimens. The best response achieved in the first-line setting was similar for single-agent [10%; 95% confidence interval (CI): 1-32%] and combination alkylator therapy (8%; 95% CI: 2-21%). Median overall survival from first-line treatment was 10.3 months (95% CI: 8.7-13.9 months). Patients with elevated lactic dehydrogenase [hazard ratio (HR): 1.87, 95% CI: 1.10-3.19, P=0.020] and Eastern Cooperative Oncology Group performance status 1-2 (HR: 1.69, 95% CI: 1.05-2.72, P=0.030) had a higher risk of death, whereas patients with 12-week objective responses had a lower risk of death (HR: 0.12, 95% CI: 0.04-0.41, P<0.001). Cytotoxic systemic therapy has modest activity in advanced/unresectable MM, belying its adjuvant benefit. Patients whose tumors have an objective response to therapy have a lower probability of death. Brain imaging should be considered in routine surveillance.

Cixutumumab and temsirolimus for patients with bone and soft-tissue sarcoma: a multicentre, open-label, phase 2 trial.

BACKGROUND: Preclinical studies have shown synergistic antitumour activity by inhibition of insulin-like growth factor-1 receptor (IGF-1R) and mTOR. The expression of IGF-1R seems to be crucial for this effect. We investigated the safety and efficacy of the combination of the IGF-1R antibody cixutumumab and the mTOR inhibitor temsirolimus in patients with chemotherapy-refractory bone and soft-tissue sarcomas according to IGF-1R expression by immunohistochemistry. METHODS: We undertook a multicentre, open-label, phase 2 study in 19 cancer centres in the USA. Patients aged at least 16 years with a histologically confirmed diagnosis of bone or soft-tissue sarcoma were allocated on the basis of IGF-1R expression by immunohistochemistry to one of three treatment groups: IGF-1R-positive soft-tissue sarcoma (group A), IGF-1R-positive bone sarcomas (group B), or IGF-1R-negative bone and soft-tissue sarcoma (group C). Patients received weekly treatment with cixutumumab (6 mg/kg, intravenous) and temsirolimus (25 mg, intravenous flat dose) in 6-week cycles. A Simon optimal two-stage design was used for every arm. The primary endpoint was progression-free survival (PFS) at 12 weeks by intention-to-treat analysis in the first 54 patients assigned to every treatment arm. Although patients still remain on treatment, this trial has completed enrolment and this represents the final analysis. This study is registered with ClinicalTrials.gov, number NCT01016015. FINDINGS: Between Nov 18, 2009, and April 11, 2012, 388 patients were screened for IGF-1R expression and 54 were assigned to each arm. 17 of 54 patients in the IGF-1R-positive soft-tissue sarcoma group (31%; one-sided 95% CI lower bound 21%; two-sided 90% CI 21-43), 19 of 54 in IGF-1R-positive bone sarcoma group (35%; one-sided 95% CI lower bound 24%; two-sided 90% CI 24-47), and 21 of 54 in the IGF-1R-negative group (39%, one-sided 95% CI lower bound 28%; two-sided 90% CI 28-51) were progression free at 12 weeks. On April 6, 2011, the protocol was amended to include three additional patients in the IGF-1R-positive soft-tissue sarcoma group (total of 57 patients) and nine more in the IGF-1R-negative group (total of 63 patients). There were 2546 adverse events reported during the study, 214 (8%) of which were grade 3-4. The most common grade 3-4 toxicities in the 174 treated patients were anaemia in 16 (9%) patients, hyperglycaemia in 18 (10%), hypophosphataemia in 16 (9%), lymphopenia in 25 (14%), oral mucositis in 19 (11%), and thrombocytopenia in 19 (11%). INTERPRETATION: The combination of cixutumumab and temsirolimus shows clinical activity in patients with sarcoma and forms a basis for future trials. However, IGF-1R expression by immunohistochemistry is not predictive of clinical outcome after treatment with this combination. FUNDING: National Cancer Institute and CycleforSurvival Fund, Memorial Sloan-Kettering Cancer Center.