Impact of primary tumor resection in the management of metastatic well-differentiated neuroendocrine tumors of the small bowel and pancreas.

Patients with gastroenteropancreatic (GEP) neuroendocrine tumors (NET) often present with advanced disease. Primary tumor resection (PTR) in the setting of unresectable metastatic disease is controversial. Most studies evaluating the impact of PTR on overall survival (OS) have been performed using large population-based databases, with limited treatment related data. This study aims to determine whether PTR improves OS and progression-free survival (PFS) in patients with metastatic well-differentiated GEP-NET. This is a retrospective single-institution study of patients with metastatic well-differentiated GEP-NET between 1978 and 2021. The primary outcome was OS. The secondary outcome was PFS. Chi-squared tests and Cox regression were used to perform univariate and multivariate analyses (MVA). OS and PFS were estimated using the Kaplan-Meier method and log-rank test. Between 1978 and 2021, 505 patients presented with metastatic NET, 151 of whom had well-differentiated GEP-NET. PTR was performed in 31 PNET and 77 SBNET patients. PTR was associated with improved median OS for PNET (136 vs. 61 months, p = .003) and SBNET (not reached vs. 79 months, p<.001). On MVA, only higher grade (HR 3.70, 95%CI 1.49-9.17) and PTR (HR 0.21, 95%CI 0.08-0.53) influenced OS. PTR resulted in longer median PFS for patients with SBNET (46 vs. 28 months, p = .03) and a trend toward longer median PFS for patients with PNET (20 vs. 13 months, p = .07). In patients with metastatic well-differentiated GEP-NET, PTR is associated with improved OS and may be associated with improved PFS and should be considered in a multidisciplinary setting. Future prospective studies are needed to validate these findings.

Pregnancy Outcomes among Pregnant Persons after COVID-19 Vaccination: Assessing Vaccine Safety in Retrospective Cohort Analysis of U.S. National COVID Cohort Collaborative (N3C).

COVID-19 vaccines have been shown to be effective in preventing severe illness, including among pregnant persons. The vaccines appear to be safe in pregnancy, supporting a continuously favorable overall risk/benefit profile, though supportive data for the U.S. over different periods of variant predominance are lacking. We sought to analyze the association of adverse pregnancy outcomes with COVID-19 vaccinations in the pre-Delta, Delta, and Omicron SARS-CoV-2 variants' dominant periods (constituting 50% or more of each pregnancy) for pregnant persons in a large, nationally sampled electronic health record repository in the U.S. Our overall analysis included 311,057 pregnant persons from December 2020 to October 2023 at a time when there were approximately 3.6 million births per year. We compared rates of preterm births and stillbirths among pregnant persons who were vaccinated before or during pregnancy to persons vaccinated after pregnancy or those who were not vaccinated. We performed a multivariable Poisson regression with generalized estimated equations to address data site heterogeneity for preterm births and unadjusted exact models for stillbirths, stratified by the dominant variant period. We found lower rates of preterm birth in the majority of modeled periods (adjusted incidence rate ratio [aIRR] range: 0.42 to 0.85; p-value range: <0.001 to 0.06) and lower rates of stillbirth (IRR range: 0.53 to 1.82; p-value range: <0.001 to 0.976) in most periods among those who were vaccinated before or during pregnancy compared to those who were vaccinated after pregnancy or not vaccinated. We largely found no adverse associations between COVID-19 vaccination and preterm birth or stillbirth; these findings reinforce the safety of COVID-19 vaccination during pregnancy and bolster confidence for pregnant persons, providers, and policymakers in the importance of COVID-19 vaccination for this group despite the end of the public health emergency.

Maternal COVID-19 Vaccination and Prevention of Symptomatic Infection in Infants.

BACKGROUND AND OBJECTIVES: Maternal vaccination may prevent infant coronavirus disease 2019 (COVID-19). We aimed to quantify protection against infection from maternally derived vaccine-induced antibodies in the first 6 months of an infant's life. METHODS: Infants born to mothers vaccinated during pregnancy with 2 or 3 doses of a messenger RNA COVID-19 vaccine (nonboosted or boosted, respectively) had full-length spike (Spike) immunoglobulin G (IgG), pseudovirus 614D, and live virus D614G, and omicron BA.1 and BA.5 neutralizing antibody (nAb) titers measured at delivery. Infant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was determined by verified maternal-report and laboratory confirmation through prospective follow-up to 6 months of age between December 2021 and July 2022. The risk reduction for infection by dose group and antibody titer level was estimated in separate models. RESULTS: Infants of boosted mothers (n = 204) had significantly higher Spike IgG, pseudovirus, and live nAb titers at delivery than infants of nonboosted mothers (n = 271), and were 56% less likely to acquire infection in the first 6 months (P = .03). Irrespective of boost, for each 10-fold increase in Spike IgG titer at delivery, the infant's risk of acquiring infection was reduced by 47% (95% confidence interval 8%-70%; P = .02). Similarly, a 10-fold increase in pseudovirus titers against Wuhan Spike, and live virus nAb titers against D614G, and omicron BA.1 and BA.5 at delivery were associated with a 30%, 46%, 56%, and 60% risk reduction, respectively. CONCLUSIONS: Higher transplacental binding and nAb titers substantially reduced the risk of SARS-CoV-2 infection in infants, and a booster dose amplified protection during a period of omicron predominance. Until infants are age-eligible for vaccination, maternal vaccination provides passive protection against symptomatic infection during early infancy.

The current state of pertussis vaccination in pregnancy around the world, with recommendations for improved care: Consensus statements from the Global Pertussis Initiative.

Bordetella pertussis, which causes a respiratory disease known as pertussis ("whooping cough") remains an important global challenge, with the incidence in pertussis cases increasing in recent years. Newborns and infants are at increased risk for severe morbidity and mortality from this bacterium. Vaccination in pregnancy has become an important strategy to both passively transfer immunity as well as prevent infection in pregnant persons, who are a major source of newborn infection, thus attempting to decrease the impact of this serious disease. It is considered safe for the pregnant person, the developing fetus, and the infant, and during the first 3 months of life it has been shown to be highly effective in preventing pertussis. There are a variety of strategies, recommendations, and adherence rates associated with pertussis vaccination in pregnancy around the world. We summarize the 2021 Global Pertussis Initiative Annual Meeting that reviewed the current global status of pertussis vaccination in pregnancy and remaining medical and scientific questions, with a focus on vaccination challenges and strategies for obstetric and gynecologic healthcare providers.

Using Oncolytic Virus to Retask CD19-Chimeric Antigen Receptor T Cells for Treatment of Pancreatic Cancer: Toward a Universal Chimeric Antigen Receptor T-Cell Strategy for Solid Tumor.

BACKGROUND: Chimeric antigen receptor (CAR) T cells targeting the B-cell antigen CD19 are standard therapy for relapsed or refractory B-cell lymphoma and leukemia. CAR T cell therapy in solid tumors is limited due to an immunosuppressive tumor microenvironment and a lack of tumor-restricted antigens. We recently engineered an oncolytic virus (CF33) with high solid tumor affinity and specificity to deliver a nonsignaling truncated CD19 antigen (CD19t), allowing targeting by CD19-CAR T cells. Here, we tested this combination against pancreatic cancer. STUDY DESIGN: We engineered CF33 to express a CD19t (CF33-CD19t) target. Flow cytometry and ELISA were performed to quantify CD19t expression, immune activation, and killing by virus and CD19-CAR T cells against various pancreatic tumor cells. Subcutaneous pancreatic human xenograft tumor models were treated with virus, CAR T cells, or virus+CAR T cells. RESULTS: In vitro, CF33-CD19t infection of tumor cells resulted in >90% CD19t cell-surface expression. Coculturing CD19-CAR T cells with infected cells resulted in interleukin-2 and interferon gamma secretion, upregulation of T-cell activation markers, and synergistic cell killing. Combination therapy of virus+CAR T cells caused significant tumor regression (day 13): control (n = 16, 485 ± 20 mm 3 ), virus alone (n = 20, 254 ± 23 mm 3 , p = 0.0001), CAR T cells alone (n = 18, 466 ± 25 mm 3 , p = NS), and virus+CAR T cells (n = 16, 128 ± 14 mm 3 , p < 0.0001 vs control; p = 0.0003 vs virus). CONCLUSIONS: Engineered CF33-CD19t effectively infects and expresses CD19t in pancreatic tumors, triggering cell killing and increased immunogenic response by CD19-CAR T cells. Notably, CF33-CD19t can turn cold immunologic tumors hot, enabling solid tumors to be targetable by agents designed against liquid tumor antigens.

Chimeric Antigen Receptor-T Cell and Oncolytic Viral Therapies for Gastric Cancer and Peritoneal Carcinomatosis of Gastric Origin: Path to Improving Combination Strategies.

Precision immune oncology capitalizes on identifying and targeting tumor-specific antigens to enhance anti-tumor immunity and improve the treatment outcomes of solid tumors. Gastric cancer (GC) is a molecularly heterogeneous disease where monoclonal antibodies against human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor (VEGF), and programmed cell death 1 (PD-1) combined with systemic chemotherapy have improved survival in patients with unresectable or metastatic GC. However, intratumoral molecular heterogeneity, variable molecular target expression, and loss of target expression have limited antibody use and the durability of response. Often immunogenically "cold" and diffusely spread throughout the peritoneum, GC peritoneal carcinomatosis (PC) is a particularly challenging, treatment-refractory entity for current systemic strategies. More adaptable immunotherapeutic approaches, such as oncolytic viruses (OVs) and chimeric antigen receptor (CAR) T cells, have emerged as promising GC and GCPC treatments that circumvent these challenges. In this study, we provide an up-to-date review of the pre-clinical and clinical efficacy of CAR T cell therapy for key primary antigen targets and provide a translational overview of the types, modifications, and mechanisms for OVs used against GC and GCPC. Finally, we present a novel, summary-based discussion on the potential synergistic interplay between OVs and CAR T cells to treat GCPC.

Who is pregnant? Defining real-world data-based pregnancy episodes in the National COVID Cohort Collaborative (N3C).

Objectives: To define pregnancy episodes and estimate gestational age within electronic health record (EHR) data from the National COVID Cohort Collaborative (N3C). Materials and Methods: We developed a comprehensive approach, named Hierarchy and rule-based pregnancy episode Inference integrated with Pregnancy Progression Signatures (HIPPS), and applied it to EHR data in the N3C (January 1, 2018-April 7, 2022). HIPPS combines: (1) an extension of a previously published pregnancy episode algorithm, (2) a novel algorithm to detect gestational age-specific signatures of a progressing pregnancy for further episode support, and (3) pregnancy start date inference. Clinicians performed validation of HIPPS on a subset of episodes. We then generated pregnancy cohorts based on gestational age precision and pregnancy outcomes for assessment of accuracy and comparison of COVID-19 and other characteristics. Results: We identified 628 165 pregnant persons with 816 471 pregnancy episodes, of which 52.3% were live births, 24.4% were other outcomes (stillbirth, ectopic pregnancy, abortions), and 23.3% had unknown outcomes. Clinician validation agreed 98.8% with HIPPS-identified episodes. We were able to estimate start dates within 1 week of precision for 475 433 (58.2%) episodes. 62 540 (7.7%) episodes had incident COVID-19 during pregnancy. Discussion: HIPPS provides measures of support for pregnancy-related variables such as gestational age and pregnancy outcomes based on N3C data. Gestational age precision allows researchers to find time to events with reasonable confidence. Conclusion: We have developed a novel and robust approach for inferring pregnancy episodes and gestational age that addresses data inconsistency and missingness in EHR data.

COVID-19 booster vaccination during pregnancy enhances maternal binding and neutralizing antibody responses and transplacental antibody transfer to the newborn.

The immune response to COVID-19 booster vaccinations during pregnancy for mothers and their newborns and the functional response of vaccine-induced antibodies against Omicron variants are not well characterized. We conducted a prospective, multicenter cohort study of participants vaccinated during pregnancy with primary or booster mRNA COVID-19 vaccines from July 2021 to January 2022 at 9 academic sites. We determined SARS-CoV-2 binding and live virus and pseudovirus neutralizing antibody (nAb) titers pre- and post-vaccination, and at delivery for both maternal and infant participants. Immune responses to ancestral and Omicron BA.1 SARS-CoV-2 strains were compared between primary and booster vaccine recipients in maternal sera at delivery and in cord blood, after adjusting for days since last vaccination. A total of 240 participants received either Pfizer or Moderna mRNA vaccine during pregnancy (primary 2-dose series: 167; booster dose: 73). Booster vaccination resulted in significantly higher binding and nAb titers, including to the Omicron BA.1 variant, in maternal serum at delivery and in cord blood compared to a primary 2-dose series (range 0.44-0.88 log10 higher, p < 0.0001 for all comparisons). Live virus nAb to Omicron BA.1 were present at delivery in 9 % (GMT ID50 12.7) of Pfizer and 22 % (GMT ID50 14.7) of Moderna primary series recipients, and in 73 % (GMT ID50 60.2) of mRNA boosted participants (p < 0.0001), although titers were significantly lower than to the D614G strain. Transplacental antibody transfer was efficient for all regimens with median transfer ratio range: 1.55-1.77 for IgG, 1.00-1.78 for live virus nAb and 1.79-2.36 for pseudovirus nAb. COVID-19 mRNA vaccination during pregnancy elicited robust immune responses in mothers and efficient transplacental antibody transfer to the newborn. A booster dose during pregnancy significantly increased maternal and cord blood binding and neutralizing antibody levels, including against Omicron BA.1. Findings support the use of a booster dose of COVID-19 vaccine during pregnancy.

Attitudes Toward COVID-19 Vaccination Among Pregnant Persons in Urban Hospital-Affiliated Practices: Exploring Themes in Vaccine Hesitancy.

OBJECTIVE: To explore beliefs and attitudes toward the COVID-19 vaccine among vaccinated and unvaccinated pregnant persons in order to identify reasons for both vaccine hesitancy and vaccine uptake. METHODS: From June-August 2021, we conducted a qualitative study consisting of semi-structured interviews with pregnant persons (n = 30). Participants were recruited from university-owned obstetric practices during prenatal and ultrasound appointments. Interviews were audio recorded and transcribed; transcripts were coded and analyzed to identify themes and subthemes. RESULTS: Of the participants, one-third (n = 10) had received the COVID-19 vaccine, while two-thirds (n = 20) were unvaccinated. Primary themes for unvaccinated participants were concern about the paucity of research on the vaccine in pregnancy and potential impact of the vaccine on both fetal development and maternal health. For vaccinated participants, main themes included potential maternal and fetal protection from COVID-19 and anticipated health complications from contracting COVID-19 as their motivations to get vaccinated. While most participants cited healthcare providers as the most trusted source of vaccine information, a majority reported that the internet was their primary source of vaccine information. Many participants wanted to learn more about the COVID-19 vaccine from their obstetric providers, and notably, most vaccinated participants reported the importance of their obstetrician in their vaccine decision-making process. CONCLUSIONS: COVID-19 vaccine hesitancy is prevalent among pregnant persons, with concerns for vaccine safety for their fetus, as well as for themselves, being common. Obstetric providers must therefore be prepared to address common concerns with patients during prenatal appointments, taking the time to actively recommend vaccination.

Contemporary Cancer Program Practice Profile Report Compliance Rates for Gastric Cancer: A National Cancer Database Analysis.

BACKGROUND: The Commission on Cancer (CoC) established quality measures to be reported in National Cancer Database (NCDB) Quality Reporting Tools. Compliance is provided to accredited cancer programs as Cancer Program Practice Profile Reports (CP3R). At the time of this study, the quality metric for gastric cancer (GC) was removal and pathologic examination of 15 regional lymph nodes for resected GC (G15RLN). OBJECTIVE: This study evaluates national trends in quality metric compliance for GC based on CoC CP3R. METHODS: The National Cancer Database (NCDB) was queried from 2004-2017 to identify patients with stage I-III GC who met criteria for inclusion. National trends in compliance were compared. Overall survival (OS) was compared stage for stage. RESULTS: Overall, 42 997 patients with GC qualified. In 2017, 64.5% of patients met compliance with G15RLN compared to 31.4% in 2004. When comparing academic and non-academic institutions, compliance was met 67.0% vs 60.0% of the time in 2017 (P < .01) and 36% vs 30.6% of the time in 2004 (P < .01). On multivariate logistic regression, patients receiving care at academic institutions (OR 1.5, 95% CI 1.4-1.5) and who underwent surgery at institutions in the >75th percentile for case volume (OR 1.5, 95% CI 1.4-1.6) had higher odds of compliance. When stratified by stage, median OS was better across all stages when compliance was met. CONCLUSION: Compliance rates with GC quality measures have improved over time. Compliance with the G15RLN metric is associated with improved OS, stage for stage. Continued efforts to improve compliance rates across all institutions are critical.

Recurrence risk and risk factors for monozygotic twin and triplet birth in over 65,000 single-embryo transfers.

PURPOSE: To determine the recurrence risk and risk factors for monozygotic splitting after elective single-embryo transfers (eSET). METHODS: A retrospective cohort study was performed investigating 65,664 eSET cycles that resulted in a clinical pregnancy as reported in the Society for Assisted Reproductive Technology (SART) Clinical Outcomes Reporting System (CORS) between 2004 and 2017. Monozygosity was defined as more than one fetal heart tone by the first-trimester ultrasound and concordant sex at live birth. The primary outcome was recurrence risk, with recurrence defined as one patient having two or more cycles of eSET resulting in monozygotic multiples. The secondary objective was to identify factors associated with smonozygotic splitting, using a multivariable logistic regression model and a stepwise purposeful model selection. RESULTS: There were 1355 (2.05%) pregnancies that resulted in two or more fetal heart tones after SET, including 840 monozygotic twins and triplets at birth. Recurrence occurred in two cases-0.0001% of patients with multiple eSET cycles. One case resulted from embryos created from a single cohort with intracytoplasmic sperm injection (ICSI), assisted hatching (AH), and blastocyst transfers. The second case resulted from donor egg embryos with ICSI and blastocyst transfers. Risk factors associated with monozygotic live birth were blastocyst transfer (OR 1.23, 95% CI 1.04-1.47, P = 0.0176) and AH (OR 1.23, 95% CI 1.05-1.44, P = 0.0081). CONCLUSION: Recurrence of monozygotic live births in eSET was very rare. Blastocyst transfer and AH were confirmed to be risk factors for monozygotic live births, while ICSI, PGT, and FET do not appear to be associated.

Maternal Vaccination and Vaccine Hesitancy.

The American College of Obstetrics and Gynecology recommends influenza vaccine annually, Tdap with each pregnancy, and COVID-19 vaccine for those not previously vaccinated or who are due for boosters. The influenza and COVID-19 vaccines are safe during pregnancy and are effective in reducing morbidity in both the pregnant person and infant. The Tdap vaccine is given primarily to protect the newborn from pertussis through transplacental antibody transfer. Methods to enhance vaccination rates include stocking and giving vaccines in the obstetric office, recommending eligible vaccines at each visit, and focusing on the health of the infant in conversations with patients.

The Geographical Correlation Between Historical Preterm Birth Disparities and COVID-19 Burden.

Similar to obstetric outcomes, rates of SARS-CoV-2 (COVID-19) infection are not homogeneously distributed among populations; risk factors accumulate in discrete locations. This study aimed to investigate the geographical correlation between pre-COVID-19 regional preterm birth (PTB) disparities and subsequent COVID-19 disease burden. We performed a retrospective, ecological cohort study of an upstate New York birth certificate database from 2004 to 2018, merged with publicly available community resource data. COVID-19 rates from 2020 were used to allocate ZIP codes to "low-," "moderate-," and "high-prevalence" groups, defined by median COVID-19 diagnosis rates. COVID-19 cohorts were associated with poverty and educational attainment data from the US Census Bureau. The dataset was analyzed for the primary outcome of PTB using ANOVA. GIS mapping visualized PTB rates and COVID-19 disease rates by ZIP code. Within 38 ZIP codes, 123,909 births were included. The median COVID-19 infection rate was 616.5 (per 100 K). PTB (all) and COVID-19 were positively correlated, with high- prevalence COVID-19 ZIP codes also being the areas with the highest prevalence of PTB (F = 11.06, P = .0002); significance was also reached for PTB < 28 weeks (F = 15.87, P < .0001) and periviable birth (F = 16.28, P < .0001). Odds of PTB < 28 weeks were significantly higher in the "high-prevalence" COVID-19 cohort compared to the "low-prevalence" COVID 19 cohort (OR 3.27 (95% CI 2.42-4.42)). COVID-19 prevalence was directly associated with number of individuals below poverty level and indirectly associated with median household income and educational attainment. GIS mapping demonstrated ZIP code clustering in the urban center with the highest rates of PTB < 28 weeks overlapping with high COVID-19 disease burden. Historical disparities in social determinants of health, exemplified by PTB outcomes, map community distribution of COVID-19 disease burden. These data should inspire socioeconomic policies supporting economic vibrancy to promote optimal health outcomes across all communities.

Hyperthermic intraperitoneal chemotherapy for gastric cancer: a narrative review.

BACKGROUND AND OBJECTIVE: Gastric cancer (GC) is the 5th most common malignancy globally, and although there have been modest gains in improving survival rates, it remains a leading cause of death. A component contributing to the poor survival rates includes advanced disease stage at presentation. Approximately 30-40% of GC patients present with metastases at diagnosis, with poorer outcomes when peritoneal metastases are present. However, recent studies have demonstrated potential utility of hyperthermic intraperitoneal chemotherapy (HIPEC) for GC with peritoneal carcinomatosis (GCPC) and for prevention of peritoneal carcinomatosis in high-risk patients. HIPEC for GC is highly debated. It is currently not recommended as part of standard of care for GC. The objective of this study is to discuss the various factors influencing the success of HIPEC, current intraperitoneal (IP) chemotherapy treatment regimens, timing of HIPEC administration, major randomized controlled trials (RCTs) and non-RCTs (NRCTs), and meta-analyses in GC patients. METHODS: A review of the Library of Congress, the Cochrane Review, Google Scholar, PubMed, and ClinicalTrials.gov was performed. All articles and trials with available data in English with full text were considered. Necessary keywords used to search included "gastric cancer" and/or "HIPEC". Included articles were independently reviewed by authors. KEY CONTENT AND FINDINGS: Optimal HIPEC administration timing is unclear, but many utilize it in a neoadjuvant or prophylactic setting. Signet ring pathology and epithelial mesenchymal transition (EMT) cell histologic subtypes may have more aggressive pathology, limiting HIPEC success rates. Patients who receive complete cytoreduction and have low peritoneal carcinomatosis index (PCI) burden have been shown to have improved median overall survival (OS) after HIPEC. The data suggests in GCPC, HIPEC can modestly improve recurrence-free and OS. The data regarding benefits of prophylactic HIPEC in advanced GC (AGC) remains mixed. CONCLUSIONS: HIPEC for GC is controversial. Much of the literature is exploratory in nature or difficult to compare, as many outcomes are novel/not cross validated against substantial preceding data, with highly variable patient populations and study designs. However, in certain clinical scenarios in high volume centers, some patients with non-metastatic or low burden disease who undergo prophylactic or intraoperative HIPEC may benefit with improved overall and recurrence free survival (RFS).

Who is pregnant? defining real-world data-based pregnancy episodes in the National COVID Cohort Collaborative (N3C).

Objective: To define pregnancy episodes and estimate gestational aging within electronic health record (EHR) data from the National COVID Cohort Collaborative (N3C). Materials and Methods: We developed a comprehensive approach, named H ierarchy and rule-based pregnancy episode I nference integrated with P regnancy P rogression S ignatures (HIPPS) and applied it to EHR data in the N3C from 1 January 2018 to 7 April 2022. HIPPS combines: 1) an extension of a previously published pregnancy episode algorithm, 2) a novel algorithm to detect gestational aging-specific signatures of a progressing pregnancy for further episode support, and 3) pregnancy start date inference. Clinicians performed validation of HIPPS on a subset of episodes. We then generated three types of pregnancy cohorts based on the level of precision for gestational aging and pregnancy outcomes for comparison of COVID-19 and other characteristics. Results: We identified 628,165 pregnant persons with 816,471 pregnancy episodes, of which 52.3% were live births, 24.4% were other outcomes (stillbirth, ectopic pregnancy, spontaneous abortions), and 23.3% had unknown outcomes. We were able to estimate start dates within one week of precision for 431,173 (52.8%) episodes. 66,019 (8.1%) episodes had incident COVID-19 during pregnancy. Across varying COVID-19 cohorts, patient characteristics were generally similar though pregnancy outcomes differed. Discussion: HIPPS provides support for pregnancy-related variables based on EHR data for researchers to define pregnancy cohorts. Our approach performed well based on clinician validation. Conclusion: We have developed a novel and robust approach for inferring pregnancy episodes and gestational aging that addresses data inconsistency and missingness in EHR data.

Obstetric Provider Attitudes and Office Practices for Maternal Influenza and Tdap Vaccination.

Background: Although maternal vaccination with influenza and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines improve health outcomes for pregnant individuals and infants, maternal vaccination rates are low. This study assessed obstetric providers' attitudes and practices related to influenza and Tdap vaccination in four large health systems in New York (NY) and California (CA). Methods: We conducted a cross-sectional survey of all obstetric providers within four health systems (two in NY, two in CA) to evaluate provider attitudes and office systems used for Tdap and influenza vaccination. The survey assessed perceptions of influenza and Tdap vaccination based on the Health Belief Model, and assessed office systems (reminders, prompts, standing orders, and patient education) and communication with pregnant patients related to influenza and Tdap vaccines. Results: We had 112 responses (52% response rate) for analyses. Respondents strongly supported vaccination during pregnancy but viewed influenza disease as less of a concern for newborns than for pregnant individuals (40% vs. 67% considered influenza disease to be very significant, p < 0.001). Only 84% agreed that giving influenza vaccine in the first trimester is very safe. Patient vaccine refusal was the most commonly named barrier for both influenza and Tdap vaccination. Providers frequently used office system prompts, but did not frequently use standing orders, patient educational materials, vaccine champions, and feedback on vaccination rates. Conclusions: While most providers consider influenza and Tdap vaccination important during pregnancy, there is room for improvement in focusing on the importance of maternal vaccination to the health of the infant, and increasing the use of office systems to improve vaccination during pregnancy.

COVID-19 booster vaccination during pregnancy enhances maternal binding and neutralizing antibody responses and transplacental antibody transfer to the newborn (DMID 21-0004).

Importance: COVID-19 vaccination is recommended during pregnancy for the protection of the mother. Little is known about the immune response to booster vaccinations during pregnancy. Objective: To measure immune responses to COVID-19 primary and booster mRNA vaccination during pregnancy and transplacental antibody transfer to the newborn. Design: Prospective cohort study of pregnant participants enrolled from July 2021 to January 2022, with follow up through and up to 12 months after delivery. Setting: Multicenter study conducted at 9 academic sites. Participants: Pregnant participants who received COVID-19 vaccination during pregnancy and their newborns. Exposures: Primary or booster COVID-19 mRNA vaccination during pregnancy. Main Outcomes and Measures: SARS-CoV-2 binding and neutralizing antibody (nAb) titers after primary or booster COVID-19 mRNA vaccination during pregnancy and antibody transfer to the newborn. Immune responses were compared between primary and booster vaccine recipients in maternal sera at delivery and in cord blood, after adjusting for days since last vaccination. Results: In this interim analysis, 167 participants received a primary 2-dose series and 73 received a booster dose of mRNA vaccine during pregnancy. Booster vaccination resulted in significantly higher binding and nAb titers, including to the Omicron BA.1 variant, in maternal serum at delivery and cord blood compared to a primary 2-dose series (range 0.55 to 0.88 log 10 higher, p<0.0001 for all comparisons). Although levels were significantly lower than to the prototypical D614G variant, nAb to Omicron were present at delivery in 9% (GMT ID50 12.7) of Pfizer and 22% (GMT ID50 14.7) of Moderna recipients, and in 73% (GMT ID50 60.2) of boosted participants (p<0.0001). Transplacental antibody transfer was efficient regardless of vaccination regimen (median transfer ratio range: 1.55-1.77 for binding IgG and 1.00-1.78 for nAb). Conclusions and Relevance: COVID-19 mRNA vaccination during pregnancy elicited robust immune responses in mothers and efficient transplacental antibody transfer to the newborn. A booster dose during pregnancy significantly increased maternal and cord blood antibody levels, including against Omicron.Findings support continued use of COVID-19 vaccines during pregnancy, including booster doses. Trial Registration: clinical trials.gov; Registration Number: NCT05031468 ; https://clinicaltrials.gov/ct2/show/NCT05031468. Key Points: Question: What is the immune response after COVID-19 booster vaccination during pregnancy and how does receipt of a booster dose impact transplacental antibody transfer to the newborn?Findings: Receipt of COVID-19 mRNA vaccines during pregnancy elicited robust binding and neutralizing antibody responses in the mother and in the newborn. Booster vaccination during pregnancy elicited significantly higher antibody levels in mothers at delivery and cord blood than 2-dose vaccination, including against the Omicron BA.1 variant.Meaning: COVID-19 vaccines, especially booster doses, should continue to be strongly recommended during pregnancy.

Outcomes and quality of life in immediate one-stage versus two-stage breast reconstructions without an acellular dermal matrix: 17- years of experience.

BACKGROUND: Advantages of one-stage implant-based reconstructions include expedited surgery and recovery. This study aimed to investigate clinical and patient-reported outcomes in one-stage implant-based breast reconstructions without acellular dermal matrix (ADM). METHODS: A prospectively collected database from 2002 to 2018 was retrospectively reviewed. One-stage and two-stage groups were compared for demographics, implant properties, early complications (hematoma, seroma, poor wound healing, implant removal), late complications (skin necrosis, capsular contracture, implant exposure, implant rupture), revision procedures, and Breast-Q questionnaire outcomes. RESULTS: A total of 223 patients, 187 one-stage (84%) and 36 two-stage (16%) patients were recruited. At a mean follow-up of 124.9 and 92.5 months, respectively (p < .01), there were no differences in early (p = .85) or late (p = .23) complications or revision procedures (p = .12). Eighty patients (36%) returned the Breast-Q questionnaire (60 one-stage, 20 two-stage patients). There were no statistical differences in patient reported outcomes in breast well-being (p = .07), psychosocial well-being (p = .84), or sexual well-being (p = .78). CONCLUSIONS: One-stage implant-based breast reconstruction without an ADM is a viable reconstruction providing comparable outcomes to two-stage procedures, with the benefit of minimal complications, a shorter reconstructive journey, and satisfactory quality of life.

Malnourishment-Associated Acetaminophen Toxicity in Pregnancy.

BACKGROUND: Although acetaminophen is commonly used in pregnancy, it can deplete glutathione concentrations and cause accumulation of 5-oxoproline, with subsequent metabolic acidosis. CASE: A malnourished 25-year-old woman, G2P1001, with chronic acetaminophen use presented with abdominal pain and high anion gap metabolic acidosis. After ruling out other potential causes, her urine 5-oxoproline level was found to be elevated. She received N-acetylcysteine, with resolution of the acidosis. CONCLUSION: Those who care for pregnant patients should remain alert to 5-oxoprolinemia as a cause of metabolic acidosis during pregnancy. Care must be taken when using acetaminophen in states of malnutrition. N-acetylcysteine seems to be an effective antidote.

Comparisons Between Normal Body Mass Index and Overweight Patients Who Underwent Unilateral Microsurgical Breast Reconstructions.

BACKGROUND: This study compared the outcomes of unilateral microsurgical breast reconstructions using abdomen-based flaps between normal body mass index (BMI; 18.5 < BMI < 24.9 kg/m2) and overweight (25 < BMI < 29.9 kg/m2) patients. METHODS: Between March 2000 and December 2015, patients who underwent unilateral breast reconstructions using abdomen-based flaps were retrospectively evaluated. Outcomes variables evaluated included the flap-used weight, flap-used/flap-harvested percentage, flap-used/specimen percentage, complication rates, revision procedures, and quality of life using the Breast-Q questionnaires. RESULTS: A total of 415 patients with a mean age of 45.3 ± 8.2 years underwent 418 abdomen-based flaps. The overall success rate was 98.8%, with 99.1% and 97.9% of patients included in the normal BMI and overweight groups, respectively (p = 0.36). The mean flap-used weight and flap-used/flap-harvested values of 461 ± 132.1 g and 82.2 ± 11.6%, respectively, in the normal BMI group were statistically different from values of 610 ± 148.9 g and 71.4 ± 14.1% in the overweight group (both p < 0.01). The mean flap-used/specimen percentage was 118.5 ± 32.9 and 111.7 ± 36.6 in the normal BMI and overweight groups, respectively (p = 0.26). At a mean follow-up of 135 ± 55.4 months, there were no statistical differences between the two groups in terms of total complication rates (25.7% vs. 29.2%; p = 0.30), revision times (36.1% vs. 36.5%; p = 0.91) and all four domains (all p > 0.05) of the Breast-Q. CONCLUSIONS: Patients with a normal BMI required a smaller flap-used weight but higher flap-used/flap-harvested percentage for unilateral microsurgical breast reconstructions that could be performed with a high success rate and comparable complication and revision rates.