Effect of Serial Pregnancies on Physical Fitness.

INTRODUCTION: Pregnancy has a profound impact on physical fitness, and delivery does not allow for rapid return to peak performance levels as physiologic changes can persist for greater than 1 year postpartum. Multiple studies across all military services have documented decrements in physical performance with pregnancy among women. The purpose of this study was to determine the impact of serial pregnancies on physical fitness and body composition in a cohort of Army women. We hypothesized that a second pregnancy would be associated with increasing decrements in physical fitness in active duty soldiers beyond that seen following a first delivery. MATERIALS AND METHODS: This retrospective cohort study screened all active duty soldiers who had delivered a singleton pregnancy of ≥32 weeks gestation between January 1, 2011 and March 31, 2017 at a single military medical center. This roster of eligible women was used to extract Army Physical Fitness Test (APFT) and height/weight data from the U.S. Army Digital Training Management System. Soldiers who delivered their first 2 pregnancies over this period were included. Select antepartum, intrapartum, and postpartum data were collected from the electronic medical record. The primary outcome variables were raw scores for push-ups, sit-ups, and run events as well as weight measures across the 2 pregnancies. The secondary outcomes were the failure rates on both the APFT events and body mass index measurements. Data were analyzed using paired t-tests to compare the means of APFT scores across the 2 pregnancies. The subjects served as their own controls. This study was approved by Regional Health Command-Pacific. RESULTS: A total of 2,103 active duty soldiers delivered singleton pregnancies at Tripler Army Medical Center between January 2011 and March 2017. Among these, 16 women delivered both their first- and second-term pregnancies and had APFT data available for analysis. Average age at time of first and second delivery was 26.1 and 28.1 years, respectively. Mean time separating the first postpartum APFT from the delivery was 8.8 months for the first pregnancy and 7.3 months following the second.A significant decrease in mean sit-up score was found comparing APFT-1 with APFT-2 (72.1 vs 65.7, P = .043) and comparing APFT-1 to APFT-3 (72.1 vs 60.9, P = .002). A significant increase in mean run time was found comparing APFT-1 to APFT-3 (16.9 minutes vs 17.9 minutes, P = .010) and APFT-2 to APFT-3 (17.5 minutes vs 17.9 minutes, P = .027). Comparing APFT-1 to APFT-3 showed a significant decrease in sit-up raw scores (P = .002), run times (P = .010), and total APFT scores (P = .01). Overall, the data show a trend of decreasing performance in all APFT events across the 3 APFTs and a trend toward higher failure rates. This cohort of soldiers did not experience weight gain following the pregnancies. CONCLUSIONS: The present study is the first to analyze the association of serial pregnancies on physical fitness utilizing a validated physical fitness test, and the results suggest that a second pregnancy is associated with progressive worsening of performance. This study is limited by the small sample size, and future studies could further elucidate the degree to which serial pregnancies affect physical fitness.

Immuno-Molecular Targeted Therapy Use and Survival Benefit in Patients with Stage IVB Cervical Carcinoma in Commission on Cancer®-Accredited Facilities in the United States.

PURPOSE: To investigate IMT use and survival in real-world stage IVB cervical cancer patients outside randomized clinical trials. METHODS: Patients diagnosed with stage IVB cervical cancer during 2013-2019 in the National Cancer Database and treated with chemotherapy (CT) ± external beam radiation (EBRT) ± intracavitary brachytherapy (ICBT) ± IMT were studied. The adjusted hazard ratio (AHR) and 95% confidence interval (CI) for risk of death were estimated in patients treated with vs. without IMT after applying propensity score analysis to balance the clinical covariates. RESULTS: There were 3164 evaluable patients, including 969 (31%) who were treated with IMT. The use of IMT increased from 11% in 2013 to 46% in 2019. Age, insurance, facility type, sites of distant metastasis, and type of first-line treatment were independently associated with using IMT. In propensity-score-balanced patients, the median survival was 18.6 vs. 13.1 months for with vs. without IMT (p < 0.001). The AHR was 0.72 (95% CI = 0.64-0.80) for adding IMT overall, 0.72 for IMT + CT, 0.66 for IMT + CT + EBRT, and 0.69 for IMT + CT + EBRT + ICBT. IMT-associated survival improvements were suggested in all subgroups by age, race/ethnicity, comorbidity score, facility type, tumor grade, tumor size, and site of metastasis. CONCLUSIONS: IMT was associated with a consistent survival benefit in real-world patients with stage IVB cervical cancer.

Survival disparities in non-Hispanic Black and White cervical cancer patients vary by histology and are largely explained by modifiable factors.

PURPOSE: We investigated racial disparities in survival by histology in cervical cancer and examined the factors contributing to these disparities. METHODS: Non-Hispanic Black and non-Hispanic White (hereafter known as Black and White) patients with stage I-IV cervical carcinoma diagnosed between 2004 and 2017 in the National Cancer Database were studied. Survival differences were compared using Cox modeling to estimate hazard ratio (HR) or adjusted HR (AHR) and 95% confidence interval (CI). The contribution of demographic, socioeconomic and clinical factors to the Black vs White differences in survival was estimated after applying propensity score weighting in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC). RESULTS: This study included 10,111 Black and 43,252 White patients with cervical cancer. Black patients had worse survival than White cervical cancer patients (HR = 1.40, 95% CI = 1.35-1.45). Survival disparities between Black and White patients varied significantly by histology (HR = 1.20, 95% CI = 1.15-1.24 for SCC; HR = 2.32, 95% CI = 2.12-2.54 for AC, interaction p < 0.0001). After balancing the selected demographic, socioeconomic and clinical factors, survival in Black vs. White patients was no longer different in those with SCC (AHR = 1.01, 95% CI 0.97-1.06) or AC (AHR = 1.09, 95% CI = 0.96-1.24). In SCC, the largest contributors to survival disparities were neighborhood income and insurance. In AC, age was the most significant contributor followed by neighborhood income, insurance, and stage. Diagnosis of AC (but not SCC) at ≥65 years old was more common in Black vs. White patients (26% vs. 13%, respectively). CONCLUSIONS: Histology matters in survival disparities and diagnosis at ≥65 years old between Black and White cervical cancer patients. These disparities were largely explained by modifiable factors.

Underserved Pacific Islanders With Locally Advanced Cervical Cancer Receive Higher Rates of Standard-of-Care Radiation Treatment Through the Pacific Island Health Care Project and Military Health System Compared to the Average U.S. Population.

INTRODUCTION: Brachytherapy, with external beam radiation, increases survival in the treatment of locally advanced cervical cancer (LACC). In 2016, Robin et al. reported only 44% of patients received standard-of-care (SOC) brachytherapy in the USA. The Pacific Island Health Care Project has provided humanitarian medical care to women from the U.S. Associated Pacific Islands (USAPI) for three decades at Tripler Army Medical Center (TAMC), a military health care system (MHS) facility. We evaluated whether this underserved and understudied patient population received SOC treatment for LACC at TAMC. MATERIALS AND METHODS: The TAMC tumor registry was searched for all cervical cancer cases from 1997 to 2019. Subjects were excluded if they did not have stage IB2-IVA disease and were not from USAPI. The primary outcome was the overall utilization of brachytherapy, and statistical analysis was performed using the chi-square test. RESULTS: We identified 214 women with cervical cancer treated at TAMC, of which 67 met the study criteria. Ninety-two percent had squamous cell carcinoma on histology. Of the patients identified, 48 (71.6%, P < .001) were treated with brachytherapy. Fifteen (22.4%) patients received external radiation alone, and four (6.0%) received chemoradiation without brachytherapy. A post-hoc power analysis was conducted with a power of 91.3%. CONCLUSIONS: Women with cervical cancer from USAPI in the PIHCP program treated at TAMC received significantly higher rates of SOC radiation treatment than the U.S. population on average. This highlights the ability of PIHCP, through the MHS, to deliver SOC treatment for cervical cancer to an otherwise underserved patient population.

Curcumin inhibits human leiomyoma xenograft tumor growth and induces dissolution of the extracellular matrix.

OBJECTIVE: To determine whether a curcumin-supplemented diet would prevent and/or treat uterine leiomyoma growth in our mouse xenograft model. DESIGN: Animal study. SETTING: Laboratory study. PATIENT(S): N/A. INTERVENTION(S): Curcumin-supplemented diet. MAIN OUTCOME MEASURE(S): Dietary intake, blood concentrations, tumor size, extracellular matrix protein concentrations, apoptosis markers. RESULT(S): We found that curcumin was well tolerated as a dietary supplement, free curcumin and its metabolites were detected in the serum, and exposure resulted in approximately 60% less leiomyoma xenograft growth as well as dissolution of the peripheral extracellular matrix architecture of the xenografts. The production of matrix proteins, including collagens, decreased, whereas the number of apoptotic cells in the xenografts increased. Additionally, when xenografts were placed in a uterine intramural location, we found a significantly increased apoptotic response to curcumin in the diet. CONCLUSION(S): Mice on a diet supplemented with curcumin could achieve serum concentrations sufficient to regulate human leiomyoma xenograft growth, and curcumin could play both preventive and curative roles in the treatment of uterine leiomyoma as an oral nutritional supplement.

Analyzing trends in obstetrics and gynecology fellowship training over the last decade using the normalized competitive index.

BACKGROUND: The objective and relative competitiveness of obstetrical and gynecologic subspecialty training programs remain understudied. Traditional metrics, such as match rate or program fill rate, fail to standardize the application environment. This limits their applicability when examining demographic trends or when comparing data between different fellowship matches. The normalized competitive index was introduced to serve as a comprehensive metric of competitiveness by incorporating disparate indicators and normalizing to enable more detailed analyses. OBJECTIVE: This study aimed to analyze trends in the competitiveness across obstetrical and gynecologic subspecialty fellowship matches during the last decade. STUDY DESIGN: The results and data reports from the National Resident Match Program fellowship for 2010 to 2019 were used to collect data on multiple metrics of competitiveness for 6 obstetrical and gynecologic subspecialties. These data were used to determine the normalized competitive index. Subanalyses were conducted to identify trends over the last decade. RESULTS: Among fellowship programs in obstetrics and gynecology, the overall specialty match rate was 67.6%. The overall specialty program fill rate was 95.7%. According to the normalized competitive index metric, minimally invasive gynecologic surgery was the most competitive fellowship match (normalized competitive index=1.31; P=.002). Maternal-fetal medicine was the least competitive (normalized competitive index=0.94; P≤.005). When comparing the first and second half of the decade, no specialty experienced a significant decrease in match rate. The only significant increase in match rates occurred for female pelvic medicine and reconstructive surgery (P=.035). Subanalyses of the normalized competitive index metric and other indicators of competitiveness demonstrated a strong negative correlation between the normalized competitive index and the subspecialty match rate (r=-0.9444) and a moderately positive correlation between the normalized competitive index and the program fill rate (r=0.4047). CONCLUSION: The normalized competitive index offers trainees a more quantitative understanding of the fellowship application environment. By incorporating multiple metrics and normalizing the result, it uniquely enables comparison between the subspecialty matches and the match process over time. The same standardization offers the potential for future comparisons of competitiveness within a single subspecialty match based on geographic region, applicant demographics, and other important determinants of a diverse and vibrant training environment.

Pre-Pregnancy Physical Fitness, Body Mass Index and Gestational Weight Gain as Risk Factors for Cesarean Delivery: A Study of Active Duty Women.

INTRODUCTION: The World Health Organization considers the optimal rate of delivery by Cesarean among healthy nulliparous women to be <15%. In 2020, the rate of primary Cesarean delivery (CD) in the US among nulliparous women with singleton, vertex pregnancies was 26%. An enhanced understanding of factors associated with women undergoing CD may assist in reducing this rate. One potential factor is the level of physical fitness in women before pregnancy. Active duty (AD) soldiers provide a cohort of women who begin pregnancy while actively pursuing physical fitness. The research team sought to assess the effects of pre-pregnancy physical fitness of AD soldiers as measured by the Army Physical Fitness Test (APFT) on the incidence of CD in AD women, in addition to examining known demographic and pregnancy risk factors in this cohort. MATERIALS AND METHODS: We conducted a retrospective study of healthy AD nulliparous women who delivered their singleton pregnancy of >32 weeks at a tertiary medical center between 2011 and 2016. Soldiers undergoing non-labored CD were excluded. Demographics, pre-pregnancy APFT results, antepartum and labor and delivery data were collected from the Digital Training Management System, the outpatient, and inpatient medical records respectively. Weight gain in pregnancy was assessed using the Institute of Medicine Guidelines for pregnancy. Fisher's exact tests and chi-squared tests assessed associations between categorical outcomes, and unpaired t-tests assessed differences in APFT scores between women who underwent CD vs. vaginal delivery. Multivariable logistic regression analysis was used to assess for independent risk factors among all collected variables. The protocol was approved by the Regional Health Command-Pacific Institutional Review Board. RESULTS: Five-hundred-and-twenty-three women delivering singleton pregnancies between 2011 and 2016 were reviewed for this study. Three-hundred ninety women met inclusion criteria: 316 in the vaginal delivery cohort, and 74 in the CD cohort, with a CD rate of 19%. Twenty non-labored CDs were excluded. Neither total APFT performance nor performance on the individual push-up, sit-up or run events in the 15 months prior to pregnancy was associated with mode of delivery. Excessive gestational weight gain (EWG) and neonatal birth weight were the only two factors independently associated with an increased rate of cesarean delivery. Women who had excessive gestational weight gain, were twice as likely to undergo CD as those who had adequate or insufficient weight gain (24% vs. 12%, p = 0.004). Soldiers delivering a neonate ≥4,000 g were 2.8 times as likely to undergo CD as those delivering a neonate <4,000 g (47% vs. 17%, p < 0.001). Age, race, and rank, a surrogate marker for socioeconomic status, were not associated with mode of delivery. CONCLUSION: Pre-pregnancy fitness levels as measured by the APFT among healthy physically active nulliparous AD women showed no association with the incidence of labored CD. EWG is one modifiable factor which potentially increases the risk for CD in this cohort and has been documented as a risk factor in a recent metanalysis (RR-1.3). Counseling on appropriate weight gain in pregnancy may be the most effective way to reduce the rate of CD among this population of healthy and physically active women.

The effect of pregnancy and the duration of postpartum convalescence on the physical fitness of healthy women: A cohort study of active duty servicewomen receiving 6 weeks versus 12 weeks convalescence.

INTRODUCTION: Pregnancy profoundly affects cardiovascular and musculoskeletal performance requiring up to 12 months for recovery in healthy individuals. OBJECTIVE: To assess the effects of extending postpartum convalescence from 6 to 12 weeks on the physical fitness of Active Duty (AD) soldiers as measured by the Army Physical Fitness Test (APFT) and Body Mass Index (BMI). METHODS: We conducted a retrospective study of AD soldiers who delivered their singleton pregnancy of ≥ 32weeks gestation at a tertiary medical center. Pre- and post-pregnancy APFT results as well as demographic, pregnancy, and postpartum data were collected. Changes in APFT raw scores, body composition measures, and failure rates across the 6-week and 12-week convalescent cohorts were assessed. Multivariable regressions were utilized to associate risk factors with failure. RESULTS: Four hundred sixty women met inclusion criteria; N = 358 in the 6 week cohort and N = 102 in the 12 week cohort. Demographic variables were similar between the cohorts. APFT failure rates across pregnancy increased more than 3-fold in both groups, but no significant differences were found between groups in the decrement of performance or weight gain. With the combined cohort, multivariable regression analysis showed failure on the postpartum APFT to be independently associated with failure on the pre-pregnancy APFT (OR = 16.92, 95% CI 4.96-57.77), failure on pre-pregnancy BMI (OR = 8.44, 95% CI 2.23-31.92), elevated BMI at 6-8 weeks postpartum (OR = 4.02, 95% CI 1.42-11.35) and not breastfeeding at 2 months (OR = 3.23, 95% CI 1.48-7.02). Within 36 months of delivery date, 75% of women had achieved pre-pregnancy levels of fitness. CONCLUSION: An additional 6 weeks of convalescence did not adversely affect physical performance or BMI measures in AD Army women following pregnancy. Modifiable factors such as pre- and post-pregnancy conditioning and weight, weight gain in pregnancy and always breastfeeding were found to be significant in recovery of physical fitness postpartum.

Mandatory HPV Vaccination; Opportunity to Save Lives, Improve Readiness and Cut Costs.

Human papillomavirus (HPV) is the most common sexually transmitted infection (STI) in the U.S. military and accounts for more healthcare visits than the next two most common STIs combined. Human papillomavirus is preventable with a safe, effective, prophylactic vaccine that has been available since 2006, yet vaccination rates remain low. The vaccine is approved for females and males aged 9-45 years for prevention of HPV-related dysplasia and cancers. Although it is recommended by the Centers for Disease Control and Prevention (CDC)'s Advisory Committee on Immunization Practices (ACIP), it is not part of the U.S. military's mandatory vaccine list. Human papillomavirus does not just affect female service members-male service members have a higher reported seropositive rate than their civilian counterparts and can develop oropharyngeal, anal, or penile cancers as sequelae of HPV. Oropharyngeal cancer, more common in males, is the fastest growing and most prevalent HPV-related cancer in the USA. Several countries, such as Australia and Sweden, have successfully implemented mandatory vaccine programs and have seen rates of HPV-related diseases, including cancer, decline significantly. Some models project that cervical cancer, which is the fifth-most common cancer in active duty women, will be eliminated in the next 20 years as a result of mandatory vaccination programs. Between higher seropositive rates and lack of widespread vaccination, HPV dysplasia and cancer result in lost work time, decreased force readiness, negative monetary implications, and even separation from service. With more than half of the 1.3 million service members in the catch-up vaccination age range of less than 26 years of age, we are poised to have a profound impact through mandatory active duty service member vaccination. Although multiple strategies for improving vaccination rates have been proposed, mandatory vaccination would be in line with current joint service policy that requires all ACIP-recommended vaccines. It is time to update the joint service guidelines and add HPV vaccine to the list of mandatory vaccines.

Single Embryo Transfer Versus Double Embryo Transfer: A Cost-Effectiveness Analysis in a Non-IVF Insurance Mandated System.

INTRODUCTION: Because of increased morbidity seen in multiple gestations, the American Society of Reproductive Medicine recommends transfer of blastocysts one at a time for most patients. While cost-effectiveness models have compared single embryo transfer (SET) versus double embryo transfer (DET), few incorporate maternal and neonatal morbidity, and none have been performed in U.S. Military facilities. The purpose of this study was to determine the cost effectiveness of sequential SET versus DET in a U.S. Military treatment facility. MATERIALS AND METHODS: A cost-effectiveness model was created based on 250 patients between the ages of 20-44 who previously underwent in vitro fertilization (IVF) at our facility. The model consisted of patients pursuing either SET or DET with two total embryos. Cycle outcomes were determined using the published SARTCORS success calculator. Neonatal and obstetrical outcomes were simulated based on singleton and twin IVF pregnancies. Neonatal and obstetrical cost estimates were based on internal data as well. RESULTS: If 250 model patients pursue SET, 140 live births would occur, with total cost of $5.7 million, and cost per delivery of $40,500. If the model patients pursued DET, 117 live births would occur, with total cost of $9.2 million and a cost per delivery of $77.700. DET would lead to more total infants (207 vs. 143 in SET cohort). Personal costs are higher in SET versus DET cohorts ($23,036 vs. $20,535). CONCLUSIONS: SET in a system with no infertility coverage saves approximately $3.5 million per 250 patients. Higher personal costs as seen with SET may incentivize patients to seek DET. The total savings should encourage alteration to practice patterns with the U.S Military Healthcare System.

A Case of Vulvar Cavernous Lymphangioma.

Cystic (cavernous) lymphangioma of the vulva is a benign tumor of lymphatic vessels with only 10 cases previously reported in the medical literature worldwide. The following is a case of bilateral vulvar cavernous lymphangiomas in a 23-year-old woman with bilateral soft tissue masses of the labia majora. Prior unsuccessful management included aspiration, incision, and drainage. Surgical marsupialization of both masses led to resolution and the subsequent histologic diagnosis of cavernous lymphangioma. Although rare, cavernous lymphangioma should be included in the differential diagnosis of soft tissue masses of the distal labia. Cavernous lymphangioma can mimic other more common vulvar soft tissue masses such as Bartholin's cyst.

HSV Hepatitis in Pregnancy: A Review of the Literature.

IMPORTANCE: Herpes simplex virus (HSV) hepatitis is a rare condition with a high mortality rate. Immunocompromised individuals, including pregnant women, are the most susceptible. When primary infection occurs during pregnancy, risk for disseminated HSV is greatly increased. Disseminated HSV can manifest in the form of HSV hepatitis. OBJECTIVE: We aim to review the literature and summarize what is known about HSV hepatitis in pregnancy to aid in the diagnosis and treatment of this condition. EVIDENCE ACQUISITION: A literature search of PubMed and Web of Science was performed. A total of 237 citations were found. All citations were independently reviewed. Thirty-eight full-text articles were identified and included in this review. Additional data from 1 unpublished case from our institution was included. RESULTS: Fifty-six cases were included with average gestational age at diagnosis of 30 weeks. Patients presented with a wide variety of gastrointestinal, respiratory, neurologic, and urogenital symptoms. The most common examination findings were fever and abdominal tenderness. Only 18.2% of patients had a vesicular rash. All patients had a transaminitis, and 85% had positive viral cultures. A multitude of treatments were used with the majority of favorable outcomes occurring after treatment with acyclovir. CONCLUSIONS AND RELEVANCE: Although HSV hepatitis is rare, it carries a mortality rate of up to 39% for mothers and neonates. Therefore, it is crucial that HSV hepatitis be included on the differential diagnosis when a patient presents with fever and transaminitis. When HSV hepatitis is suspected, empiric therapy with acyclovir can be initiated with no additional risk to the fetus.