Pregnancy following assisted reproductive technology in morbidly obese patients: assessment of feto-maternal outcomes.

PURPOSE: To examine feto-maternal characteristics and outcomes of morbidly obese pregnant patients who conceived with assisted reproductive technology (ART). METHODS: This cross-sectional study queried the Healthcare Cost and Utilization Project's National Inpatient Sample. Study population was 48,365 patients with ART pregnancy from January 2012 to September 2015, including non-obesity (n = 45,125, 93.3%), class I-II obesity (n = 2445, 5.1%), and class III obesity (n = 795, 1.6%). Severe maternal morbidity at delivery per the Centers for Disease and Control Prevention definition was assessed with multivariable binary logistic regression model. RESULTS: Patients in the class III obesity group were more likely to have a hypertensive disorder (adjusted-odds ratio (aOR) 3.03, 95% confidence interval (CI) 2.61-3.52), diabetes mellitus (aOR 3.08, 95%CI 2.64-3.60), large for gestational age neonate (aOR 3.57, 95%CI 2.77-4.60), and intrauterine fetal demise (aOR 2.03, 95%CI 1.05-3.94) compared to those in the non-obesity group. Increased risks of hypertensive disease (aOR 1.35, 95%CI 1.14-1.60) and diabetes mellitus (aOR 1.39, 95%CI 1.17-1.66) in the class III obesity group remained robust even compared to the class I-II obesity group. After controlling for priori selected clinical, pregnancy, and delivery factors, patients with class III obesity were 70% more likely to have severe maternal morbidity at delivery compared to non-obese patients (8.2% vs 4.4%, aOR 1.70, 95%CI 1.30-2.22) whereas those with class I-II obesity were not (4.1% vs 4.4%, aOR 0.87, 95%CI 0.70-1.08). CONCLUSIONS: The results of this national-level analysis in the United States suggested that morbidly obese pregnant patients conceived with ART have increased risks of adverse fetal and maternal outcomes.

A Transitional Pain Management Program Is Associated with Reduced Opioid Dependence after Major Shoulder Surgery.

BACKGROUND: Over-prescription of opioids in the United States increases risks of opioid dependence, overdose, and death. Increased perioperative and postoperative opioid use during orthopedic shoulder surgery is a significant risk factor for long term opioid dependence. The authors hypothesized that a multidisciplinary perioperative pain management program (Transitional Pain Service or TPS) for major shoulder surgery would lead to a reduced amount of opioids required postoperatively. METHODS: A TPS was implemented at a Veterans Affairs Medical Center focused on non-opioid pain management and cessation support. Opioid consumption during the implementation of the TPS was compared to a historical cohort. All patients undergoing shoulder arthroplasty or rotator cuff repair were included. The primary outcome was the proportion of patients continuing opioid use at 90 days postoperatively. Secondary outcomes included postoperative pain scores, time to opioid cessation, and median opioid tablets consumed at 90-days. A multivariable model was developed to predict total opioid use at 90-days postoperatively. Kaplan Meier curves were calculated for time to opioid cessation. RESULTS: The TPS group demonstrated decreased persistent opioid use at 90 days post-discharge (12.6% vs. 28.6%; p=0.018). Independent predictors associated with increased total opioid tablet prescriptions at 90 days included length of stay (ß=19.17), anxiety diagnosis (ß=37.627), and number of tablets prescribed at discharge (ß=1.353). Shoulder arthroplasty surgery (TSA) was associated with decreased 90-day opioid utilization (ß= -32.535) when compared to cuff repair (RCR). Median time to cessation was shorter in TSA (6 days) when compared with RCR (8 days). Pain scores were reduced compared to population mean by post-discharge day 2 for TSA and by post-discharge day 7 for RCR. Median number of post-discharge opioid tablets (oxycodone 5 mg) consumed under TPS management was 25 in both RCR and TSA surgery groups (180 MME). DISCUSSION AND CONCLUSIONS: This study demonstrates that a TPS reduces the amount of opioid use of patients undergoing shoulder arthroplasty or cuff repair at 90 days when compared with a historical control. Multivariable regression indicated that fewer opioid tablets at discharge was a modifiable factor that may aid in reducing opioid consumption and that anxiety diagnosis, increased length of stay, and cuff repair surgery were other factors independently associated with increased opioid consumption. This data will assist surgeons in counseling patients, setting narcotic use expectations, and minimizing overprescribing. Use of a similar multidisciplinary perioperative pain management program may greatly reduce opioid over prescriptions nationally.

Increasing trends of cervical conization with lymph node evaluation for fertility-sparing surgery in early cervical cancer.

OBJECTIVE: To examine uptake, characteristics, and survival outcome of less-radical fertility-sparing surgery with cervical conization and lymph node evaluation (Cone-LN) in reproductive age patients with early cervical cancer. METHODS: This retrospective cohort study examined the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The study population included 407 patients aged <50 years with stage IA-IB2 (≤4 cm) cervical cancer who received fertility-sparing surgery from 2004 to 2019. The exposure was fertility-sparing surgery type: Cone-LN (n = 196) or trachelectomy with lymph node evaluation (Trach-LN, n = 211). The main co-outcomes were (i) temporal trends of surgery type, assessed with Cochran-Armitage test, and (ii) clinical and tumor characteristics, assessed with multivariable binary logistic regression model. The secondary outcome was overall survival, assessed with inverse probability of treatment weighting propensity score. RESULTS: The number of patients receiving Cone-LN increased from 43.5% in 2004-2007 to 58.4% in 2016-2019 (P-trend = 0.005). Patients receiving conization and sentinel lymph node (SLN) biopsy alone increased from 0% to 14.4% (P-trend < 0.001). In a multivariable analysis, patients in the Cone-LN group were more likely to undergo SLN biopsy (aOR 6.04) compared to those in the Trach-LN group whereas those with adenocarcinoma (aOR 0.49) and T1b tumors (aOR for ≤2 cm 0.21, and aOR for 2.1-4.0 cm 0.10) were less likely to receive Cone-LN. In a propensity score-weighted model, the Cone-LN and Trach-LN groups had comparable overall survival (7-year rates, 98.9% vs 97.8%). Similar associations were observed for patients with squamous, adenocarcinoma / adenosquamous, T1a classification, and T1b(≤2 cm) classification. CONCLUSION: The current population-based analysis suggests that the performance of cervical conization with lymph node evaluation, particularly with SLN biopsy, is gradually increasing for early cervical cancer patients desiring future fertility.

A Multidisciplinary Transitional Pain Management Program Is Associated With Reduced Opioid Dependence After Primary Total Joint Arthroplasty.

BACKGROUND: Overprescription of opioids after total joint arthroplasty (TJA) increases risks of opioid dependence, overdose, and death. The authors hypothesized that a multidisciplinary, perioperative pain management program (the Transitional Pain Service or TPS) for TJA would lead to fewer patients becoming opioid dependent. METHODS: A TPS was implemented at a Veterans Affairs Medical Center focused on nonopioid pain management, cessation support, and prospective data tracking. A historical control, interventional study design was used to assess opioid use at 90 days post-discharge. Secondary analysis of the implementation group included post-operative outcome scores, time to opioid cessation, and median opioid tablets consumed at 90 days. RESULTS: Fewer patients in the TPS group demonstrated persistent opioid use at 90 days post-discharge (0.7% vs 9.9%; P = .004). Independent predictors of total opioid tablet prescriptions included TPS (ß = -19.41; 95% confidence interval [CI] -35.37 to -3.47), number of tablets prescribed at discharge (ß = 1.08; 95% CI 0.86-1.31), and TKA surgery (ß = 16.84; 95% CI 4.58-29.10). Under the TPS, median tablets consumed was 20.5 for THA and 36.5 for TKA; median time to cessation was shorter in THA (7 days; 95% CI 2-10) when compared to TKA (13 days; 95% CI 11-16). CONCLUSION: In opioid-naïve veterans undergoing TJA, the TPS was associated with a 93% reduction in opioid dependence and a 60% reduction in opioid tablet prescriptions at 90 days post-discharge. Under the TPS, median 90-day opioid consumption was 20.5 and 36.5 tablets for THA and TKA, respectively. Widespread adoption of similar programs may greatly reduce opioid use and dependence in orthopedic patients nationally. LEVEL OF EVIDENCE: III.

Hyperoxia Injury in the Developing Lung Is Mediated by Mesenchymal Expression of Wnt5A.

Rationale: Bronchopulmonary dysplasia (BPD) is a leading complication of preterm birth that affects infants born in the saccular stage of lung development at <32 weeks of gestation. Although the mechanisms driving BPD remain uncertain, exposure to hyperoxia is thought to contribute to disease pathogenesis.Objectives: To determine the effects of hyperoxia on epithelial-mesenchymal interactions and to define the mediators of activated Wnt/ß-catenin signaling after hyperoxia injury.Methods: Three hyperoxia models were used: A three-dimensional organotypic coculture using primary human lung cells, precision-cut lung slices (PCLS), and a murine in vivo hyperoxia model. Comparisons of normoxia- and hyperoxia-exposed samples were made by real-time quantitative PCR, RNA in situ hybridization, quantitative confocal microscopy, and lung morphometry.Measurements and Main Results: Examination of an array of Wnt ligands in the three-dimensional organotypic coculture revealed increased mesenchymal expression of WNT5A. Inhibition of Wnt5A abrogated the BPD transcriptomic phenotype induced by hyperoxia. In the PCLS model, Wnt5A inhibition improved alveolarization following hyperoxia exposure, and treatment with recombinant Wnt5a reproduced features of the BPD phenotype in PCLS cultured in normoxic conditions. Chemical inhibition of NF-κB with BAY11-7082 reduced Wnt5a expression in the PCLS hyperoxia model and in vivo mouse hyperoxia model, with improved alveolarization in the PCLS model.Conclusions: Increased mesenchymal Wnt5A during saccular-stage hyperoxia injury contributes to the impaired alveolarization and septal thickening observed in BPD. Precise targeting of Wnt5A may represent a potential therapeutic strategy for the treatment of BPD.

Voluntary wheel running attenuates lipopolysaccharide-induced liver inflammation in mice.

Sepsis induces an acute inflammatory response in the liver, which can lead to organ failure and death. Given the anti-inflammatory effects of exercise, we hypothesized that habitual physical activity could protect against acute sepsis-induced liver inflammation via mechanisms, including heat shock protein (HSP) 70/72. Male C57BL/6J mice (n = 80, ∼8 wk of age) engaged in physical activity via voluntary wheel running (VWR) or cage control (SED) for 10 wk. To induce sepsis, we injected (2 mg/kg ip) LPS or sterile saline (SAL), and liver was harvested 6 or 12 h later. VWR attenuated increases in body and epididymal adipose tissue mass, improved glucose tolerance, and increased liver protein content of PEPCK (P < 0.05). VWR attenuated increases in LPS-induced IL-6 signaling and mRNA expression of other inflammatory markers (TNF-α, chemokine C-C motif ligand 2, inducible nitric oxide synthase, IL-10, IL-1ß) in the liver; however, this was not reflected at the whole body level, as systemic markers of inflammation were similar between SED and VWR. Insulin tolerance was greater in VWR compared with SED at 6 but not 12 h after LPS. The protective effect of VWR occurred in parallel with increases in the liver protein content of HSP70/72, a molecular chaperone that can protect against inflammatory challenges. This study provides novel evidence that physical activity protects against the inflammatory cascade induced by LPS in the liver and that these effects may be mediated via HSP70/72.

Prior exercise training blunts short-term high-fat diet-induced weight gain.

High-fat diets rapidly cause weight gain and glucose intolerance. We sought to determine whether these changes could be mitigated with prior exercise training. Male C57BL/6J mice were exercise-trained by treadmill running (1 h/day, 5 days/wk) for 4 wk. Twenty-four hours after the final bout of exercise, mice were provided with a high-fat diet (HFD; 60% kcal from lard) for 4 days, with no further exercise. In mice fed the HFD prior to exercise training, the results were blunted weight gain, reduced fat mass, and a slight attenuation in glucose intolerance that was mirrored by greater insulin-induced Akt phosphorylation in skeletal muscle compared with sedentary mice fed the HFD. When ad libitum-fed sedentary mice were compared with sedentary high-fat fed mice that were calorie restricted (-30%) to match the weight gain of the previously trained high-fat fed mice, the same attenuated impairments in glucose tolerance were found. Blunted weight gain was associated with a greater capacity to increase energy expenditure in trained compared with sedentary mice when challenged with a HFD. Although mitochondrial enzymes in white adipose tissue and UCP-1 protein content in brown adipose tissue were increased in previously exercised compared with sedentary mice fed a HFD, ex vivo mitochondrial respiration was not increased in either tissue. Our data suggest that prior exercise training attenuates high-fat diet-induced weight gain and glucose intolerance and is associated with a greater ability to increase energy expenditure in response to a high-fat diet.

False Negative Urine Pregnancy Testing with Complete Molar Pregnancy: An Example of the Hook Effect.

INTRODUCTION: Gestational trophoblastic disease (GTD) encompasses a group of tumors derived from trophoblasts, which normally form the placenta during pregnancy. Human chorionic gonadotropin (hCG) is a glycoprotein composed of an alpha subunit identical to that of thyroid stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). Detection of beta-hCG is achievable in both urine and serum samples, proving useful for the detection of normal pregnancy and GTD. However, in the presence of very high levels of beta-hCG, a false negative result may be obtained due to a phenomenon called the "hook effect" or "prozone phenomenon." In certain circumstances, trophoblastic tumors can produce very high levels of beta-hCG, causing misleading results on urine pregnancy testing. CASE PRESENTATION: A 49-year-old Caucasian female with past medical history pertinent for deep vein thrombosis, ovarian cysts, and osteopenia presented to her internist with report of irregular uterine bleeding for the preceding three months, accompanied by complaints of abdominal bloating, night sweats, and constipation. The patient stated she had completed two negative qualitative urine pregnancy tests and had been seen by both gynecology and gastroenterology, with recommendations to start supplemental estrogen for her symptoms and begin additional fiber intake for irritable bowel syndrome, respectively. Despite negative urine beta-hCG, a quantitative serum beta-hCG was obtained and revealed a level greater than 200,000 international units (IU). The patient was referred to gynecologic oncology and an open abdominal hysterectomy with preservation of her ovaries was performed. Histopathologic examination showed a complete hydatiform mole with no evidence of invasion. CONCLUSION: The case highlights the importance of clinical judgment in modern medicine, where biochemical methods and imaging modalities have become main stays in diagnosis. As mentioned, there are ways to reduce the incidence of the hook effect, but with added time and cost. Clinicians need to consider the possibility of the hook effect for instances where the clinical picture points to a disease entity despite negative test results. Delaying diagnoses, as illustrated with GTD, has the potential to cause significant morbidity and mortality.

Breaking of valley degeneracy by magnetic field in monolayer MoSe2.

Using polarization-resolved photoluminescence spectroscopy, we investigate the breaking of valley degeneracy by an out-of-plane magnetic field in back-gated monolayer MoSe2 devices. We observe a linear splitting of -0.22 meV/T between luminescence peak energies in σ+ and σ- emission for both neutral and charged excitons. The optical selection rules of monolayer MoSe2 couple the photon handedness to the exciton valley degree of freedom; so this splitting demonstrates valley degeneracy breaking. In addition, we find that the luminescence handedness can be controlled with a magnetic field to a degree that depends on the back-gate voltage. An applied magnetic field, therefore, provides effective strategies for control over the valley degree of freedom.

Inhaled technosphere regular insulin powder.

The lungs are an effective way to deliver insulin for patients with diabetes, but an initial inhaled insulin product was withdrawn from the market because of high cost and inconsistent dosing. This article describes a recently approved inhaled insulin that appears to control blood glucose as well as rapid-acting injectable insulin.

Exenatide extended-release: a once-weekly option for patients with type 2 diabetes.

Exenatide extended-release is a new long-acting glucagon-like peptide-1 agonist that may be an attractive option for patients desiring to lose weight, who are prone to hypoglycemic episodes, and who have not achieved desired glycemic control with current therapy.

Repair of facial dog bite wound utilizing cryopreserved umbilical cord allograft.

BACKGROUND: In the United States, craniofacial injuries are the most frequently observed traumas in the pediatric population. Human birth tissue products contain growth factors, cytokines, and signaling molecules that can be potentially harnessed for tissue regeneration and wound healing. PURPOSE: A cryopreserved ultra-thick amniotic membrane (AM) allograft wound dressing was used in a patient with significant facial soft tissue loss due to a dog bite injury. METHODS: This is a single case report of a pediatric patient. After obtaining IRB exemption, operative and postoperative clinic notes were reviewed. RESULTS: A 10-year-old female presented to the emergency department after suffering a dog bite to her left cheek and upper lip, resulting in tissue loss. A cryopreserved ultra-thick AM allograft was used to cover the area of tissue loss as part of surgical reconstruction. The patient was followed up at 1 week, 3 weeks, 4 months, and 1 year after the graft was placed, and rapid healing and full epithelialization were achieved in addition to scar contracture due to wound location. CONCLUSION: In the setting of acute trauma and tissue loss, human birth tissue was found to promote epithelialization and regenerative healing of facial tissues.

Presentation and Management of Uterine Didelphys with Unilateral Cervicovaginal Agenesis/Dysgenesis (CVAD): A Multicenter Case Series.

INTRODUCTION: There are several well-described presentations of uterine didelphys (UD): UD without vaginal septum, UD with non-obstructed longitudinal vaginal septum, or UD with duplicated vaginas and an obstructed hemivagina on one side with ipsilateral renal anomaly. STUDY OBJECTIVE: To describe another variant of UD and compare the presentation and management across different institutions METHODS: This was a retrospective case series approved by the NASPAG Fellows Research Consortium. Participating institutions obtained IRB approval. Inclusion criteria included a diagnosis of UD and unilateral cervicovaginal agenesis/dysgenesis (CVAD). Descriptive statistics were used. RESULTS: Five patients met the inclusion criteria, with ages ranging from 13 to 27 years. Presenting symptoms included dysmenorrhea (80%), irregular bleeding (40%), acute onset left lower quadrant pain (20%), and abdominal mass (20%). Three patients had additional known abnormalities, including solitary kidney and solitary adrenal gland. All patients underwent pelvic magnetic resonance imaging. Two cases were only suspicious for unilateral CVAD on imaging and required pathology review postoperatively to confirm diagnosis. Two cases required a 2-staged approach with an initial diagnostic surgery followed by a second definitive procedure. Three patients were noted to have endometriosis intraoperatively. Postoperative follow-up ranged from 2 months to 2 years, with 1 patient reporting chronic pelvic pain. CONCLUSION: Diagnosis on the basis of pelvic imaging can be difficult, as this unique variant may mimic classic obstructed hemivagina with ipsilateral renal anomaly. In patients with UD with unilateral CVAD, standard management is removal of the obstructed uterine horn. This multicenter series stresses awareness about the clinical presentation, distinguishes cases of cervical agenesis from dysgenesis, and reviews approaches to management.

Graves' Disease-Induced Psychosis Refractory to Intensive Medical Management Requiring Non-voluntary Thyroidectomy for Psychosis Resolution: A Case Report.

Graves' disease is an autoimmune disorder characterized by hyperthyroidism, ophthalmopathy, and dermatopathy. The chief thyroid hormone abnormality is the elevation of thyroid hormone, resulting in an overexcitation of the sympathetic and central nervous systems. Psychosis due to Graves' disease is rarely the first presenting symptom, but it is an essential complication of those with severe or untreated disease. Most patients respond well to standard medical management for Graves' disease, although there exists a small subset of people who do not. There are few cases describing patients with psychosis without underlying psychiatric disorders who require intensive care admission and thyroidectomy for necessary management of refractory psychosis secondary to thyrotoxicosis. Here, we present a case of a patient without medical or surgical history who presented with severe psychosis due to untreated Graves' disease requiring non-voluntary thyroidectomy for definitive management.

Postsurgical opioid prescribing among veterans using community care for orthopedic surgery at non-VA hospitals compared to a VA hospital with a transitional pain service: a retrospective cohort study.

BACKGROUND: The USA provides medical services to its military veterans through Veterans Health Administration (VHA) medical centers. Passage of recent legislation has increased the number of veterans having VHA-paid orthopedic surgery at non-VHA facilities. METHODS: We conducted a retrospective cohort study among veterans who underwent orthopedic joint surgery paid for by the VHA either at the Salt Lake City VHA Medical Center (VAMC) or at non-VHA hospitals between January 2018 and December 2021. 562 patients were included in the study, of which 323 used a non-VHA hospital and 239 patients the VAMC. The number of opioid tablets prescribed at discharge, the total number prescribed by postdischarge day 90, and the number of patients still filling opioid prescriptions between 90 and 120 days after surgery were compared between groups. RESULTS: Veterans who underwent orthopedic surgery at a non-VHA hospital were prescribed more opioid tablets at discharge (median (IQR)); (40 (30-60) non-VHA vs 30 (20-47.5) VAMC, p<0.001) and in the first 90 days after surgery than patients who had surgery at the Salt Lake City VAMC (60 (40-120) vs 35 (20-60), p<0.001). Patients who had surgery at Salt Lake City VAMC were also significantly less likely to fill opioid prescriptions past 90 days after hospital discharge (OR (95% CI) 0.06 (0.01 to 0.48), p=0.007). CONCLUSION: These results suggest that veterans who have surgery at a veterans affairs hospital with a transitional pain service are at lower risk for larger opioid prescriptions both at discharge and within 90 days after surgery as well as persistent opioid use beyond 90 days after discharge than if they have surgery at a community hospital.

Pregnant patients undergoing cholecystectomy: nationwide assessment of clinical characteristics and outcomes.

BACKGROUND: Gallstone disease in pregnancy is one of the most common indications for nonobstetrical surgery during pregnancy. National-level data on contemporary surgical practice and outcomes are limited. OBJECTIVE: This study aimed to assess the clinical characteristics and outcomes of patients undergoing cholecystectomy during pregnancy. STUDY DESIGN: This cross-sectional study examined the Healthcare Cost and Utilization Project's 2 nationwide databases in the United States: the National Inpatient Sample and the Nationwide Ambulatory Surgery Sample. The study population included 18,630 patients who had cholecystectomy during pregnancy from January 2016 to December 2020. The exposure was gestational age, grouped sequentially into the following 5 groups: first trimester (<14 weeks), early second trimester (14-20 weeks), late second trimester (21-27 weeks), early third trimester (28-36 weeks), and late third trimester (≥37 weeks). The main outcomes were clinical demographics, medical comorbidities, surgical information, and pregnancy characteristics and outcomes, assessed by gestational age. RESULTS: Cholecystectomy was most common in the early second trimester (32.1%), followed by the first trimester (25.2%), late second trimester (23.1%), early third trimester (12.4%), and late third trimester (7.2%). Patients in the first-trimester group were more likely to be aged ≥35 years, to smoke, and to have acute cholecystitis, severe hyperemesis gravidarum including metabolic disturbance, pregestational diabetes, multifetal gestation, and sepsis/shock (P<.001). Patients in the early-third-trimester group were more likely to be obese and have gestational diabetes, Charlson Comorbidity Index of ≥1, premature rupture of membranes, and intrauterine growth restriction, whereas those in the late-third-trimester group were more likely to have gallstone pancreatitis, biliary colic, chorioamnionitis, gestational hypertension, preeclampsia, and severe maternal morbidity including sepsis (P<.001). At the cohort level, a laparoscopic approach was used in most cholecystectomy procedures (97.5%), and bile duct injury was uncommon (<0.1%). Delivery during the admission occurred in 0.3%, 0%, 0.6%, 17.8%, and 60.6% in the 5 gestational age groups, respectively (P<.001). Among the cases that had delivery in the early- and late-third-trimester groups, the delivery event preceded cholecystectomy in 61.4% and 86.2%, respectively, whereas both delivery and cholecystectomy occurred on the same day in 34.3% and 13.8%, respectively. CONCLUSION: This nationwide analysis suggests that clinical and pregnancy characteristics and outcomes of patients undergoing cholecystectomy differ by pregnancy stage with a bimodal distribution. Although patients in the first and third trimesters have distinct medical conditions, more clinically significant pregnancy and maternal outcomes were found in both groups compared with patients in the second trimester.

Pregnancy with endometriosis: Assessment of national-level trends, characteristics, and maternal morbidity at delivery.

OBJECTIVE: To examine pregnancy characteristics and maternal morbidity at delivery among pregnant patients with a diagnosis of endometriosis. STUDY DESIGN: This cross-sectional study queried the Healthcare Cost and Utilization Project's National Inpatient Sample. Study population was 17,796,365 hospital deliveries from 2016 to 2020, excluded adenomyosis and uterine myoma. The exposure was endometriosis diagnosis. Main outcome measures were clinical and pregnancy characteristics and severe maternal morbidity at delivery related to endometriosis, assessed with multivariable regression model. RESULTS: Endometriosis was diagnosed in 17,590 patients. The prevalence of endometriosis increased by 24 % from one in 1,191 patients in 2016 to one in 853 patients in 2020 (adjusted-odds ratio [aOR] 1.24, 95% confidence interval [CI] 1.19-1.30). Clinical and pregnancy characteristics that had greater than two-fold association to endometriosis included polycystic ovary syndrome, placenta previa, cesarean delivery, maternal age of ≥30 years, prior pregnancy loss, and anxiety disorder. Pregnant patients with endometriosis were more likely to have the diagnosis of measured severe maternal morbidity during the index hospitalization for delivery (47.8 vs 17.3 per 1,000 deliveries, aOR 1.91, 95%CI 1.78-2.06); these associations were more prominent following vaginal (aOR 2.82, 95%CI 2.41-3.30) compared to cesarean (aOR 1.85, 95%CI 1.71-2.00) deliveries. Among the individual morbidity indicators, endometriosis was most strongly associated with thromboembolism (aOR 5.05, 95%CI 3.70-6.91), followed by sepsis (aOR 2.39, 95%CI 1.85-3.09) and hysterectomy (aOR 2.18, 95%CI 1.85-2.56). When stratified for endometriosis anatomical site, odds of thromboembolism was increased in endometriosis at distant site (aOR 9.10, 95%CI 3.76-22.02) and adnexa (aOR 7.37, 95%CI 4.43-12.28); odds of sepsis was most increased in endometriosis at multi-classifier locations (aOR 7.33, 95%CI 2.93-18.31) followed by pelvic peritoneum (aOR 5.54, 95%CI 2.95-10.40); and odds of hysterectomy exceeded three-fold in endometriosis at adnexa (aOR 3.00, 95%CI 2.30-3.90), distant site (aOR 5.36, 95%CI 3.48-8.24), and multi-classifier location (aOR 4.46, 95%CI 2.11-9.41). CONCLUSION: The results of this nationwide analysis suggest that pregnancy with endometriosis is uncommon but gradually increasing over time in the United States. The data also suggest that endometriosis during pregnancy is associated with increased risk of severe maternal morbidity at delivery, especially for thromboembolism, sepsis, and hysterectomy. These morbidity risks differed by the anatomical location of endometriosis.

A randomized, controlled clinical trial demonstrates improved owner-assessed cognitive function in senior dogs receiving a senolytic and NAD+ precursor combination.

Age-related decline in mobility and cognition are associated with cellular senescence and NAD + depletion in dogs and people. A combination of a novel NAD + precursor and senolytic, LY-D6/2, was examined in this randomized controlled trial. Seventy dogs with mild to moderate cognitive impairment were enrolled and allocated into placebo, low or full dose groups. Primary outcomes were change in cognitive impairment measured with the owner-reported Canine Cognitive Dysfunction Rating (CCDR) scale and change in activity measured with physical activity monitors. Fifty-nine dogs completed evaluations at the 3-month primary endpoint, and 51 reached the 6-month secondary endpoint. There was a significant difference in CCDR score across treatment groups from baseline to the primary endpoint (p = 0.02) with the largest decrease in the full dose group. No difference was detected between groups using in house cognitive testing. There were no significant differences between groups in changes in measured activity. The proportion of dogs that improved in frailty and owner-reported activity levels and happiness was higher in the full dose group than other groups, however this difference was not significant. Adverse events occurred equally across groups. All groups showed improvement in cognition, frailty, and activity suggesting placebo effect and benefits of trial participation. We conclude that LY-D6/2 improves owner-assessed cognitive function over a 3-month period and may have broader, but more subtle effects on frailty, activity and happiness as reported by owners.

Diagnosis Shift in Site of Origin of Tubo-Ovarian Carcinoma.

OBJECTIVE: To assess population-level trends, characteristics, and outcomes of high-grade serous tubo-ovarian carcinoma in the United States. METHODS: This retrospective cohort study queried the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The study population was 27,811 patients diagnosed with high-grade serous tubo-ovarian carcinoma from 2004 to 2020. The exposure was the primary cancer site (ovary or fallopian tube). Main outcome measures were temporal trends, clinical characteristics, and overall survival associated with primary cancer site assessed in multivariable analysis. RESULTS: The study population comprised 23,967 diagnoses of high-grade serous ovarian carcinoma and 3,844 diagnoses of high-grade serous fallopian tubal carcinoma. The proportion of diagnoses of high-grade serous fallopian tubal carcinoma increased from 365 of 7,305 (5.0%) in 2004-2008 to 1,742 of 6,663 (26.1%) in 2017-2020. This increase was independent in a multivariable analysis (adjusted odds ratio [aOR] vs 2004-2008, 2.28 [95% CI, 1.98-2.62], 3.27 [95% CI, 2.86-3.74], and 6.65 [95% CI, 5.84-7.57] for 2009-2012, 2013-2016, and 2017-2020, respectively). This increase in high-grade serous fallopian tubal carcinoma was seen across age groups (4.3-5.8% to 22.7-28.3%) and across racial and ethnic groups (4.1-6.0% to 21.9-27.5%) (all P for trend <.001). Among the cases of tumors smaller than 1.5 cm, the increase was particularly high (16.9-67.6%, P for trend <.001). Primary-site tumors in the high-grade serous fallopian tubal carcinoma group were more likely to be smaller than 1.5 cm (aOR 8.26, 95% CI, 7.35-9.28) and unilateral (aOR 7.22, 95% CI, 6.54-7.96) compared with those in high-grade serous ovarian carcinoma. At the cohort level, the diagnosis shift to high-grade serous fallopian tubal carcinoma was associated with narrowing differences in survival over time between the two malignancy groups: adjusted hazard ratio 0.84 (95% CI, 0.74-0.96), 0.91 (95% CI, 0.82-1.01), 1.01 (95% CI, 0.92-1.12), and 1.12 (95% CI, 0.98-1.29) for 2004-2008, 2009-2012, 2013-2016, and 2017-2020, respectively. CONCLUSION: This population-based assessment suggests that diagnoses of high-grade serous tubo-ovarian carcinoma in the United States have been rapidly shifting from high-grade serous ovarian to fallopian tubal carcinoma in recent years, particularly in cases of smaller, unilateral tumors.

Fertility-Sparing Surgery for Stage I Epithelial Ovarian Cancer.

OBJECTIVE: To describe population-level utilization of fertility-sparing surgery and outcome of reproductive-aged patients with early epithelial ovarian cancer who underwent fertility-sparing surgery in the United States. METHODS: This retrospective study queried the National Cancer Institute's Surveillance, Epidemiology, and End Result Program. The study included 3,027 patients younger than age 50 years with stage I epithelial ovarian cancer receiving primary surgical therapy from 2007 to 2020. Fertility-sparing surgery was defined as preservation of one ovary and the uterus for unilateral lesion and preservation of the uterus for bilateral lesions. Temporal trend of fertility-sparing surgery was assessed with linear segmented regression with log-transformation. Overall survival associated with fertility-sparing surgery was assessed with Cox proportional hazard regression model. RESULTS: A total of 534 patients (17.6%) underwent fertility-sparing surgery. At the cohort level, the utilization of fertility-sparing surgery was 13.4% in 2007 and 21.8% in 2020 ( P for trend=.009). Non-Hispanic White individuals (2.8-fold), those with high-grade serous histology (2.2-fold), and individuals with stage IC disease (2.3-fold) had a more than twofold increase in fertility-sparing surgery utilization during the study period (all P for trend<.05). After controlling for the measured clinicopathologic characteristics, patients who received fertility-sparing surgery had overall survival comparable with that of patients who had nonsparing surgery (5-year rates 93.6% vs 92.1%, adjusted hazard ratio 0.87, 95% CI, 0.57-1.35). This survival association was consistent in high-grade serous (5-year rates 92.9% vs 92.4%), low-grade serous (100% vs 92.2%), clear cell (97.5% vs 86.1%), mucinous (92.1% vs 86.6%), low-grade endometrioid (95.7% vs 97.7%), and mixed (93.3% vs 83.7%) histology (all P >.05). In high-grade endometrioid tumor, fertility-sparing surgery was associated with decreased overall survival (5-year rates 71.9% vs 93.8%, adjusted hazard ratio 2.90, 95% CI, 1.09-7.67). Among bilateral ovarian lesions, fertility-sparing surgery was not associated with overall survival (5-year rates 95.8% vs 92.5%, P =.364). Among 41,914 patients who had epithelial ovarian cancer with any age and stage, those younger than age 50 years with stage I disease increased from 8.6% to 10.9% during the study period ( P for trend=.002). CONCLUSION: Nearly one in five reproductive-aged patients with stage I epithelial ovarian cancer underwent fertility-sparing surgery in recent years in the United States. More than 90% of reproductive-aged patients with stage I epithelial ovarian cancer who underwent fertility-sparing surgery were alive at the 5-year timepoint, except for those with high-grade endometrioid tumors.