Second primary malignancies in women with breast cancer.

BACKGROUND: Increased screening and treatment advancements have resulted in improved survival rates in women with breast cancer (BC). However, recent data suggests these women have elevated risk of developing a second primary malignancy (SPM) compared to the general population. Limited data exists on factors associated with BC patients developing a SPM. METHOD: A retrospective review of a prospective single institution database (1990-2016) identified 782 patients with a history of BC. One hundred and ninety-four BC patients developed a SPM. Clinicopathologic and treatment characteristics were analyzed. RESULTS: Of the 194 patients (24.8%) who developed a SPM, 56 (28.9%) BC patients were <50 years old (range: 24-87 years). Two-thirds (64.9%) had at least one first or second degree relative with a malignancy (no relatives-35.1%; ≥1 relative-62.9%). Most patients had invasive ductal carcinoma (n = 117, 60.3%) or ductal carcinoma in situ (n = 39, 20.1%). Twenty-two patients (11.3%) had pathogenic genetic mutations. Mean time to developing a SPM was 8.9 years (range: 4 months-50 years). Eighty (47.6%) patients received chemotherapy with 91 (54.5%) completing radiation. The most common SPMs were breast (22%), melanoma (17.8%), gynecologic (14.1%), colorectal (12.6%), hematologic (8.9%), and sarcoma (6.5%). Most breast tumors were estrogen receptor (ER) (n = 99, 78.0%) or progesterone receptor (PR) positive (n = 87, 73.1%) but not HER2-neu positive (n = 13, 14.0%). CONCLUSION: Most BC patients who developed a SPM had ER/PR positive tumors and a family history of malignancy, with most <50 years old. Although chemotherapy and radiation increase cancer risk, there were an equal number of patients with SPMs who did or did not receive either treatment. Most SPMs were breast, soft tissue, gynecologic, hematologic, or colorectal. BC patients should be followed closely given an elevated propensity for developing SPMs.

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.

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.

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.

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.

An old disease on the rise: new approaches to syphilis in pregnancy.

PURPOSE OF REVIEW: Maternal and congenital syphilis infection is on the rise in the United States and worldwide. Without adequate testing or provider recognition of infection, treatment can be neglected resulting in significant perinatal morbidity and mortality. This review article discusses the epidemiology of T. pallidum, describes novel diagnostic tests, and considers the need to expand therapeutic options. RECENT FINDINGS: A new chemiluminescence immunoassay for use in the reverse-sequence algorithm is more sensitive and specific in pregnant women than previously noted and is helpful for identifying pregnant women at highest risk for neonatal congenital syphilis. Point-of-care testing may be used to detect early syphilitic disease and provide same-day testing and treatment. Randomized control trials of oral cefixime for treatment of syphilis are paving the way for potential use in pregnant women. Penicillin skin testing, challenge, and desensitization in pregnancy can be done safely. SUMMARY: Congenital syphilis is a preventable disease and treatable infection in the modern world, but we are still met with challenges in its eradication. We should proceed with advancing efficient laboratory testing, expanding medical therapy, and implementing public health measures to curb the rise of the disease.

Long-term outcome of lower extremity lymphedema treated with vascularized lymph node flap transfer with or without venous complications.

BACKGROUND: Vascularized submental lymph node (VSLN) transfer is an emerging approach for extremity lymphedema. This study investigated the long-term outcome and venous complications of VSLN for unilateral lower extremity lymphedema. METHODS: Between 2010 and 2018, patients who underwent VSLN for unilateral lower extremity lymphedema were retrospectively evaluated. Patient demographics, operative records, complications, circumferential improvement, and episodes of cellulitis were analyzed. Further comparisons were performed between different types, numbers, and techniques of venous anastomoses. RESULTS: A total of 75 VSLNs in 70 patients survived, giving a 100% success rate. Six flaps (8%) had venous complications (VC group) and 69 flaps (92%) did not (No-VC group). There were no statistical differences in types, numbers, and techniques of anastomoses between two groups (P = .65, 1, and .56, respectively). At a mean follow-up of 32.0 ± 23.0 months, mean circumferential improvement and episodes of cellulitis between two groups did not statistically differ significantly (P = .31 and .09, respectively). CONCLUSIONS: VSLN is an effective treatment for lower extremity lymphedema. The types, numbers of veins, and techniques of venous anastomoses did not statistically affect the venous complication rates. Functional outcomes of the VSLNs were not compromised if venous complications were salvaged promptly.

Lymphedema microsurgery reduces the rate of implant removal for patients who have pre-existing lymphedema and total knee arthroplasty for knee osteoarthritis.

INTRODUCTION: Patients with pre-existing lymphedema who undergo total knee arthroplasty (TKA) for osteoarthritis (OA) are at high risk for periprosthetic joint infection. This complication usually requires removal of the implant. This study aimed to investigate whether surgical treatment of lymphedema reduces the rate of prosthesis removal in such patients. MATERIALS AND METHODS: We retrospectively reviewed our prospective database of patient information collected between January 2009 and December 2018. A total of 348 cases of lower extremity lymphedema were reviewed, and those who underwent total knee TKA for OA of the knee were included. Patient demographics, clinical data, lymphedema surgical history, and TKA surgical history including any episodes of removal were collected and analyzed. RESULTS: There were nine of 15 lymphedema patients with knee OA who subsequently underwent TKA. The mean patient age was 70.4 ± 7.1 years. A total of 18 TKAs were performed in nine patients. The knee prosthesis removal rate was 66.7% (12/18). The prosthesis removal rate was 40% (2/5) in patients who underwent lymphedema microsurgery vs 76.9% (10/13) for those who did not (P = .03). CONCLUSIONS: Pre-existing lymphedema is associated with a high rate of knee prosthesis removal. Lymphedema microsurgery reduced the removal rate of knee prostheses. We recommend that lymphedema microsurgery be considered for patients who require TKA as a treatment for of the knee.

Impacts of arterial ischemia or venous occlusion on vascularized groin lymph nodes in a rat model.

BACKGROUND: Reported ischemia time of vascularized lymph nodes was 5 hours. This study investigated the effects of arterial ischemia and venous occlusion on vascularized lymph node function in rats. METHODS: Bilateral pedicled groin lymph node flaps were raised in 27 Lewis rats. Femoral artery and vein were separated and clamped for 1, 3, 4, or 5 hour(s). Lymph node flap perfusion and drainage were assessed by laser Doppler flowmetry and indocyanine green lymphography. Histologic changes were assessed using hematoxylin and eosin stain, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), and glutathione assays. RESULTS: Perfusion units of 2.84 ± 1.41, 2.46 ± 0.64, 2.42 ± 0.37, and 2.01 ± 0.90 were measured in arterial ischemia groups, and 1.71 ± 0.45, 2.20 ± 0.98, 1.49 ± 0.35, and 0.81 ± 0.20 in venous occlusion groups after 1, 3, 4, and 5 hours of clamping, respectively. Lymphatic drainage showed mean latency periods of 5.33 ± 0.88, 9.00 ± 3.21, 10.00 ± 2.08, and 24.50 ± 11.50 seconds in arterial clamping groups, and 25.00 ± 3.61, 26.00 ± 3.06, 23.33 ± 4.41, and 152.00 ± 0 seconds in venous clamping groups, respectively. Severe medullary and cortical congestion and hemorrhage on histology and cell damage by glutathione levels and TUNEL assay were found after 4 hours of venous clamping. CONCLUSIONS: Arterial ischemia and venous occlusion impact the function and viability of vascularized lymph node flaps differently. The critical venous occlusion time was 4 hours.

Clinical features, microbiological epidemiology and recommendations for management of cellulitis in extremity lymphedema.

BACKGROUND: This high volume, single center study investigated the prevalence, bacterial epidemiology, and responsiveness to antibiotic therapy of cellulitis in extremity lymphedema. METHODS: From 2003 to 2018, cellulitis events from a cohort of 420 patients with extremity lymphedema were reviewed. Demographics, lymphedema grading, symptoms, inflammatory markers, cultures and antibiotic therapy regimens were compiled from cellulitis episodes data. Univariate and multivariate analyses were performed for detailed analysis. RESULTS: A total of 131 separate episodes of cellulitis were recorded from 43 (81.1%) lower limb and 10 (19.9%) upper limb lymphedema patients. The prevalence and recurrence rates for cellulitis in lymphedema patients were 12.6% (53 of 420) and 56.6% (30 of 53), respectively. The most common findings were increased limb circumference (127 of 131; 96.9%) and abnormal C-reactive protein (CRP) level (86 of 113; 76.1%). Blood cultures were obtained in 79 (60.3%) incidents, with 9 (11.4%) returning positive. Streptococcus agalactiae was the most isolated bacterium (5 of 9; 55.5%). CONCLUSIONS: The cellulitis prevalence and recurrence rate in extremity lymphedema were 12.6%, and 56.6%, respectively. Strongest indicators of cellulitis were increased affected limb circumference and elevated CRP level. Empiric antibiotic therapy began with coverage for Steptococcus species before broadening to anti-Methicillin-resistant Staphylococcus aureus and anti-Gram negatives if needed for effective treatment of extremity lymphedema cellulitis.

Intra-abdominal chylovenous bypass treats retroperitoneal lymphangiomatosis.

BACKGROUND: Retroperitoneal lymphangiomatosis (RL) is a rare form of primary lymphedema featuring aberrant retroperitoneal lymphatic proliferation. It causes recurrent cellulitis, repeated interventions, and poor life quality. This study aimed to investigate proper diagnositc criteria and surgical outcomes for RL with extremity lymphedema. METHODS: Between 2012 and 2018, 44 primary lower-extremity lymphedema cases received lymphoscintigraphy, magnetic resonance imaging, and single-photon electron computed tomography to detect RL. RL patients underwent vascularized lymph node transfers (VLNT) for extremity lymphedema and intra-abdominal side-to-end chylovenous bypasses (CVB) for chylous ascites. Complications, CVB patency, and quality of life were evaluated postoperatively. RESULTS: Six RL patients (mean age of 30.3 years) had chylous ascites with five had lower-extremity lymphedema. All CVBs remained patent, though one required re-anastomosis, giving a 100% patency rate. Four unilateral and one bilateral extremity lymphedema underwent six VLNTs with 100% flap survival. Patients reported improved quality of life (P = 0.023), decreased cellulitis incidence (P = 0.041), and improved mean lymphedema circumference (P = 0.043). All patients resumed a normal diet and activity. CONCLUSIONS: Evaluating primary lower-extremity lymphedema patients with MRI and SPECT could reveal a 13.6% prevalence of RL and guide treatment of refractory extremity lymphedema. Intra-abdominal CVB with VLNT effectively treated RL with chylous ascites and extremity lymphedema.

Impact of Maternal Obesity on Perinatal Outcomes in Preterm Prelabor Rupture of Membranes ≥34 Weeks.

OBJECTIVE: This study aimed to compare pregnancy outcomes in obese and nonobese women with preterm prelabor rupture of membranes (PPROM) ≥34 weeks. STUDY DESIGN: The present study is a secondary analysis of a multicenter retrospective cohort of singletons with PPROM from 2011 to 2017. Women with a delivery body mass index (BMI) ≥30 kg/m2 (obese) were compared with women with a BMI < 30 kg/m2 (nonobese). Pregnancies were stratified based on delivery policies of expectant management until 35 weeks versus immediate delivery ≥34 weeks. The primary outcome was a composite neonatal outcome (neonatal sepsis, antibiotic administration for duration >72 hours after delivery or respiratory support). Univariate analysis and general estimating equations models including maternal age, delivery timing, mode of delivery, hospital, and gestational age were used with p < 0.05 level of significance. RESULTS: Among 259 pregnancies, 47% were obese. Pregnant women with obesity had increased composite neonatal outcome versus nonobese pregnancies (adjusted odds ratio [aOR] = 1.48 [95% confidence interval (CI): 1.01-2.17]). Obesity was also associated with increased neonatal antibiotic administration for a duration >72 hours after delivery, respiratory support, ventilation, oxygen supplementation, and surfactant administration. When stratified by delivery policies there was no significant difference in perinatal outcomes based on obesity. CONCLUSION: Obese women with PPROM ≥34 weeks have an increased odds of adverse neonatal respiratory and infectious outcomes compared with nonobese women.

Antepartum Contraceptive Counseling in Women with Preterm Birth.

OBJECTIVE: To compare rates of antepartum contraceptive counseling among women with preterm birth (PTB) and term birth. STUDY DESIGN: This is a retrospective cohort study of patients with completed delivery records in New York from January 1, 2004, to December 31, 2014. Exposure was determined based on the timing of delivery. Exposed women delivered at <37 weeks, and nonexposed women delivered at ≥37 weeks. Primary outcome was patient response to questions regarding receipt of prenatal contraceptive counseling (PCC) by a health care provider. Secondary outcome was receipt of interpregnancy interval counseling. Chi-square tests and multivariate logistic regression were used for analysis. RESULTS: Of 724,723 delivery records, PTB rate was 7.9%. Women with PTB < 37 weeks were significantly less likely to receive PCC (odds ratio [OR]: 0.9; 95% confidence interval [CI]: 0.89-0.93) or interpregnancy interval counseling (OR: 0.95; 95% CI: 0.94-0.97). The primary outcome remained significant after adjusting for confounders (adjusted OR: 0.91; 95% CI: 0.89-0.93). PTB < 34 weeks was associated with even lower odds of receiving contraceptive counseling (OR: 0.79; 95% CI: 0.76-0.83). CONCLUSION: Postpartum contraception is an important tool for the prevention of recurrent PTB. Antepartum contraception counseling increases postpartum contraceptive uptake. Women with PTB have less exposure to antepartum contraceptive counseling. Lack of adequate counseling and decreased uptake of postpartum contraception may impact future pregnancy outcomes.

Preterm Prelabor Rupture of Membranes: Outcomes with Expectant Management until 34 versus 35 Weeks.

OBJECTIVE: To evaluate outcomes with expectant management of preterm prelabor rupture of membranes (PROM) until 35 weeks versus immediate delivery at ≥34 weeks. STUDY DESIGN: This was a multicenter retrospective cohort study of singletons with preterm PROM at >20 weeks from 2011 through 2017. Groups were defined as expectant management until 35 weeks versus immediate delivery at ≥34 weeks. Primary outcome was composite neonatal morbidity: need for respiratory support, culture positive neonatal sepsis, or antibiotic administration for >72 hours. Univariate and general estimating equation models were used with p < 0.05 considered significant. RESULTS: A total of 280 mother-infant dyads were included. There was no difference in composite neonatal outcome in pregnancies managed with expectant management compared with immediate delivery (43.4 vs. 37.5%; p = 0.32). Those with expectant management had shorter length of neonatal intensive care unit (NICU) admission but higher rates of neonatal antibiotics for > 72 hours, endometritis, and histological chorioamnionitis. There were no cases of fetal demise, neonatal death, or maternal sepsis, and only three cases of neonatal sepsis. CONCLUSION: There is no difference in composite neonatal morbidity in pregnancies with preterm PROM managed with expectant management until 35 weeks as compared with immediate delivery at 34 weeks. Expectant management is associated with a decreased length of NICU admission but increased short-term infectious morbidity.

Chlamydia trachomatis and Adverse Pregnancy Outcomes: Meta-analysis of Patients With and Without Infection.

OBJECTIVES: We conducted a meta-analysis to determine the association between Chlamydia trachomatis and adverse perinatal outcomes. METHODS: Electronic databases were searched between 1970 and 2013. Included studies reported perinatal outcomes in women with and without chlamydia. Summary odds ratios were calculated using fixed- and random-effects models. Study bias was assessed using a Funnel Plot and Begg's test. RESULTS: Of 129 articles identified, 56 studies met the inclusion criteria encompassing 614,892 subjects. Chlamydia infection in pregnancy was associated with preterm birth (OR = 1.27, 95% CI 1.05, 1.54) with a large quantity of heterogeneity (I2 = 61%). This association lost significance when limiting the analysis to high-quality studies based on the Newcastle-Ottawa Scale. Chlamydia infection in pregnancy was also associated with preterm premature rupture of membranes (OR = 1.81, 95% CI 1.0, 3.29), endometritis (OR 1.69, 95% CI 1.20, 2.38), low birthweight (OR 1.34, 95% CI 1.21, 1.48), small for gestational age (OR 1.14, 95% CI 1.05, 1.25) and intrauterine fetal demise (OR 1.44, 95% CI 1.06, 1.94). CONCLUSIONS: This review provides evidence that chlamydia in pregnancy is associated with a small increase in the odds of multiple adverse pregnancy outcomes. The literature is complicated by heterogeneity and the fact that the association may not hold in higher quality and prospective studies or those that use more contemporary nucleic acid testing.

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.

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.

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.

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.