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.

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.

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.

Assessment of obstetric characteristics and outcomes associated with pregnancy with Turner syndrome.

OBJECTIVE: To assess national-level trends, characteristics, and outcomes of pregnancies with Turner syndrome in the United States. DESIGN: Cross-sectional study. SETTING: The Healthcare Cost and Utilization Project's National Inpatient Sample. SUBJECTS: A total of 17,865,495 hospital deliveries from 2016-2020. EXPOSURE: A diagnosis of Turner syndrome, identified according to the World Health Organization's International Classification of Disease 10th revision code of Q96. MAIN OUTCOME MEASURES: Obstetrics outcomes related to Turner syndrome, assessed with inverse probability of treatment weighting cohort and multivariable binary logistic regression modeling. RESULTS: The prevalence of pregnant patients with Turner syndrome was 7.0 per 100,000 deliveries (one in 14,235). The number of hospital deliveries with patients who have a diagnosis of Turner syndrome increased from 5.0 to 11.7 per 100,000 deliveries during the study period (adjusted-odds ratio [aOR] for 2020 vs. 2016; 2.18, 95% confidence interval [CI] 1.83-2.60). Pregnant patients with Turner syndrome were more likely to have a diagnosis of pregestational hypertension (4.8% vs. 2.8%; aOR 1.65; 95% CI 1.26-2.15), uterine anomaly (1.6% vs. 0.4%; aOR, 3.01; 95% CI 1.93-4.69), and prior pregnancy losses (1.6% vs. 0.3%; aOR 4.70; 95% CI 3.01-7.32) compared with those without Turner syndrome. For the index obstetric characteristics, Turner syndrome was associated with an increased risk of intrauterine fetal demise (10.9% vs. 0.7%; aOR 8.40; 95% CI 5.30-13.30), intrauterine growth restriction (8.5% vs. 3.5%; aOR 2.11; 95% CI 1.48-2.99), and placenta accreta spectrum (aOR 3.63; 95% CI 1.20-10.97). For delivery outcome, pregnant patients with Turner syndrome were more likely to undergo cesarean delivery (41.6% vs. 32.3%; aOR 1.53; 95% CI 1.26-1.87). Moreover, the odds of periviable delivery (22-25 weeks: 6.1% vs. 0.4%; aOR 5.88; 95% CI 3.47-9.98) and previable delivery (<22 weeks: 3.3% vs. 0.3%; aOR 2.87; 95% CI 1.45-5.69) were increased compared with those without Turner syndrome. CONCLUSIONS: The results of contemporaneous, nationwide assessment in the United States suggest that although pregnancy with Turner syndrome is uncommon this may represent a high-risk group, particularly for intrauterine fetal demise and periviable delivery. Establishing a society-based approach for preconception counseling and antenatal follow-up would be clinically compelling.

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.

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.

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.

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.

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.

Successful Treatment of Recalcitrant Mpox Lesions With Intralesional Cidofovir in a Patient With HIV/AIDS.

This case report describes a man in his 50s with HIV/AIDS who presented with widely scattered recalcitrant mpox lesions.

Opioid tapering after surgery and its association with patient-reported outcomes and behavioral changes: a mixed-methods analysis.

INTRODUCTION: Opioid tapering after surgery is recommended among patients with chronic opioid use, but it is unclear how this process affects their quality of life. The objective of this study was to evaluate how opioid tapering following surgery was associated with patient-reported outcome measures related to pain control and behavioral changes that affect quality of life. METHODS: We conducted an explanatory sequential mixed-methods study at a VA Medical Center among patients with chronic opioid use who underwent a spectrum of orthopedic, vascular, thoracic, urology, otolaryngology, and general surgery procedures between 2018 and 2020. Patients were stratified based on the extent that opioid tapering was successful (complete, partial, and no-taper) by 90 days after surgery, followed by qualitative interviews of 10 patients in each taper group. Longitudinal patient-reported outcome measures related to pain intensity, interference, and catastrophizing were compared using Kruskal Wallis tests over the 90-day period after surgery. Qualitative interviews were conducted among patients in each taper group to identify themes associated with the impact of opioid tapering after surgery on quality of life. RESULTS: We identified 211 patients with chronic opioid use (92% male, median age 66 years) who underwent surgery during the time period, including 42 (20%) individuals with complete tapering, 48 (23%) patients with partial tapering, and 121 (57%) patients with no taper of opioids following surgery. Patients who did not taper were more likely to have a history of opioid use disorder (10%-partial, 2%-complete vs 17%-no taper, p<0.05) and be discharged on a higher median morphine equivalent daily dose (52-partial, 30-complete vs 60-no taper; p<0.05) than patients in the partial and complete taper groups. Pain interference (-7.2-partial taper and -9.8-complete taper vs -3.5-no taper) and pain catastrophizing (-21.4-partial taper and -16.5-complete taper vs -1.7-no taper) scores for partial and complete taper groups were significantly improved at 90 days relative to baseline when compared with patients in the no-taper group (p<0.05 for both comparisons), while pain intensity was similar between groups. Finally, patients achieving complete and partial opioid tapering were more likely to report improvements in activity, mood, thinking, and sleep following surgery as compared with patients who failed to taper. CONCLUSIONS: Partial and complete opioid tapering within 90 days after surgery among patients with chronic opioid use was associated with improved patient-reported measures of pain control as well as behaviors that impact a patient's quality of life.

The longitudinal role of family conflict and neural reward sensitivity in youth's internalizing symptoms.

Adolescence is often associated with an increase in psychopathology. Although previous studies have examined how family environments and neural reward sensitivity separately play a role in youth's emotional development, it remains unknown how they interact with each other in predicting youth's internalizing symptoms. Therefore, the current research took a biopsychosocial approach to examine this question using two-wave longitudinal data of 9353 preadolescents (mean age = 9.93 years at T1; 51% boys) from the Adolescent Brain Cognitive Development study. Using mixed-effects models, results showed that higher family conflict predicted youth's increased internalizing symptoms 1 year later, whereas greater ventral striatum (VS) activity during reward receipt predicted reduced internalizing symptoms over time. Importantly, there was an interaction effect between family conflict and VS activity. For youth who showed greater VS activation during reward receipt, high family conflict was more likely to predict increased internalizing symptoms. In contrast, youth with low VS activation during reward receipt showed high levels of internalizing symptoms regardless of family conflict. The findings suggest that youth's neural reward sensitivity is a marker of susceptibility to adverse family environments and highlight the importance of cultivating supportive family environments where youth experience less general conflict within the family.

Broadening the scope: Multiple functional connectivity networks underlying threat and safety signaling.

Introduction: Threat learning and extinction processes are thought to be foundational to anxiety and fear-related disorders. However, the study of these processes in the human brain has largely focused on a priori regions of interest, owing partly to the ease of translating between these regions in human and non-human animals. Moving beyond analyzing focal regions of interest to whole-brain dynamics during threat learning is essential for understanding the neuropathology of fear-related disorders in humans. Methods: 223 participants completed a 2-day Pavlovian threat conditioning paradigm while undergoing fMRI. Participants completed threat acquisition and extinction. Extinction recall was assessed 48 hours later. Using a data-driven group independent component analysis (ICA), we examined large-scale functional connectivity networks during each phase of threat conditioning. Connectivity networks were tested to see how they responded to conditional stimuli during early and late phases of threat acquisition and extinction and during early trials of extinction recall. Results: A network overlapping with the default mode network involving hippocampus, vmPFC, and posterior cingulate was implicated in threat acquisition and extinction. Another network overlapping with the salience network involving dACC, mPFC, and inferior frontal gyrus was implicated in threat acquisition and extinction recall. Other networks overlapping with parts of the salience, somatomotor, visual, and fronto-parietal networks were involved in the acquisition or extinction of learned threat responses. Conclusions: These findings help confirm previous investigations of specific brain regions in a model-free fashion and introduce new findings of spatially independent networks during threat and safety learning. Rather than being a single process in a core network of regions, threat learning involves multiple brain networks operating in parallel coordinating different functions at different timescales. Understanding the nature and interplay of these dynamics will be critical for comprehensive understanding of the multiple processes that may be at play in the neuropathology of anxiety and fear-related disorders.

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.

Association between reward-related functional connectivity and tri-level mood and anxiety symptoms.

Depression and anxiety are associated with abnormalities in brain regions that process rewards including the medial orbitofrontal cortex (mOFC), the ventral striatum (VS), and the amygdala. However, there are inconsistencies in these findings. This may be due to past reliance on categorical diagnoses that, while valuable, provide less precision than may be required to understand subtle neural changes associated with symptoms of depression and anxiety. In contrast, the tri-level model defines symptom dimensions that are common (General Distress) or relatively specific (Anhedonia-Apprehension, Fears) to depression and anxiety related disorders, which provide increased precision. In the current study, eligibility was assessed by quasi-orthogonal screening questionnaires measuring reward and threat sensitivity (Behavioral Activation Scale; Eysenck Personality Questionnaire-Neuroticism). These participants were assessed on tri-level symptom severity and completed the Monetary Incentive Delay task during fMRI scanning. VS-mOFC and VS-amygdala connectivity were estimated during reward anticipation and reward outcome. Heightened General Distress was associated with lower VS-mOFC connectivity during reward anticipation (b = -0.064, p = 0.021) and reward outcome (b = -0.102, p = 0.014). Heightened Anhedonia-Apprehension was associated with greater VS-amygdala connectivity during reward anticipation (b = 0.065, p = 0.004). The present work has important implications for understanding the coupling between the mOFC and vS and the amygdala and the vS during reward processing in the pathophysiology of mood and anxiety symptoms and for developing targeted behavioral, pharmacological, and neuromodulatory interventions to help manage these symptoms.

Postsurgical Opioid Use Among Veterans Discharged to Skilled Care Facilities Compared to Veterans Discharged to Home After Orthopedic Surgery.

OBJECTIVES: To compare opioid use patterns among Veterans who were discharged to a skilled care facility vs home after orthopedic surgery at a VA hospital. DESIGN: We conducted a retrospective cohort study of Veterans who had orthopedic surgery at the Salt Lake City VA Medical Center (VAMC) between January 2018 and December 2021 and were followed by a transitional pain service. The principal outcome of interest was the time to stop opioid use after discharge from the hospital. SETTING AND PARTICIPANTS: Veterans not already on chronic opioid therapy who had orthopedic surgery at the Salt Lake City VAMC and were followed by a transitional pain service. METHODS: 448 patients were included in the study, of which 371 (83%) were discharged to home and 77 (17%) were discharged to a skilled care facility. Median days to opioid cessation were estimated using the Kaplan-Meier method with 95% CIs and compared with discharge disposition using a log-rank test. Time to opioid cessation following hospital discharge was compared to baseline characteristics using univariable and multivariable Cox proportional hazards models. RESULTS: Patients who were discharged to a skilled care facility used opioids for twice as long as those who were discharged home [median days (interquartile range)]: 22 (19, 26) vs 11 (10, 12), P < .001, respectively. When controlling for baseline characteristics in the multivariable analysis, discharge to a skilled care facility was significantly associated with continued opioid use at all time points [hazard ratio 0.63 (95% CI 0.44, 0.89), P = .009]. CONCLUSIONS AND IMPLICATIONS: Veterans discharged to a skilled care facility after orthopedic surgery used opioids for twice as long as those who were discharged to home. As postsurgical pain management guidelines change to focus on nonopioid pain modalities and opioid reduction, skilled care providers should adapt those strategies for their facilities.

Association of Hoover's Sign with Maximal Expiratory-to-Inspiratory Pressure Ratio in Patients with COPD.

Purpose: In chronic obstructive pulmonary disease (COPD) some patients develop paradoxical inspiratory rib motion, which is termed Hoover's sign. Our objective was to determine whether Hoover's sign is associated with a difference in the maximal expiratory pressure (MEP), the maximal inspiratory pressure (MIP), the MEP/MIP ratio, and other features on pulmonary function tests (PFTs). Methods: This observational prospective single-center cohort study enrolled patients with an established diagnosis of COPD with Global initiative for chronic Obstructive Lung Disease (GOLD) stage 3 (severe) and 4 (very severe) based on PFTs. Respiratory pressure measurements were also collected. Patients were examined for the presence or absence of Hoover's sign on physical examination by 2 internal medicine resident physicians trained in examining for Hoover's sign by a pulmonologist. Results: A total of 71 patients were examined for the presence of Hoover's sign. Hoover's sign was present in 49.3% of patients. Observer agreement (k statistic) was 0.8 for Hoover's sign. Median MEP/MIP was significantly greater in patients with Hoover's sign than those without Hoover's sign (1.88 versus 1.16, p<0.001). Patients with Hoover's sign also had a significantly lower MIP (39.0 versus 58.0, p<0.001) and higher residual volume (RV) to total lung capacity (TLC) ratio indicating a higher degree of air trapping (65 versus 59.5, p<0.014). Conclusion: The presence of Hoover's sign in patients with COPD is associated with a higher MEP/MIP ratio. This suggests respiratory pressure measurements can predict diaphragm dysfunction in patients with GOLD stage 3 and 4 COPD. Patients with Hoover's sign were also found to have a lower MIP and more air trapping.

Effect of Multidisciplinary Transitional Pain Service on Health Care Use and Costs Following Orthopedic Surgery.

Background: Opioid use disorder is a significant cause of morbidity, mortality, and health care costs. A transitional pain service (TPS) approach to perioperative pain management has been shown to reduce opioid use among patients undergoing orthopedic joint surgery. However, whether TPS also leads to lower health care use and costs is unknown. Methods: We designed this study to estimate the effect of TPS implementation relative to standard care on health care use and associated costs of care following orthopedic surgery. We evaluated postoperative health care use and costs for patients who underwent orthopedic joint surgery at 6 US Department of Veterans Affairs medical centers (VAMCs) between 2018 and 2019 using difference-in-differences analysis. Patients enrolled in the TPS at the Salt Lake City VAMC were matched to control patients undergoing the same surgeries at 5 different VAMCs without a TPS. We stratified patients based on history of preoperative opioid use into chronic opioid use (COU) and nonopioid use (NOU) groups and analyzed them separately. Results: For NOU patients, TPS was associated with a mean increase in the number of outpatient visits (6.9 visits; P < .001), no change in outpatient costs, and a mean decrease in inpatient costs (-$12,170; P = .02) during the 1-year follow-up period. TPS was not found to increase health care use or costs for COU patients. Conclusions: Although TPS led to an increase in outpatient visits for NOU patients, there was no increase in outpatient costs and a decrease in inpatient costs after orthopedic surgery. Further, there was no added cost for managing COU patients with a TPS. These findings suggest that TPS can be implemented to reduce opioid use following joint surgery without increasing health care costs.

Complete opioid cessation after surgery improves patient-reported pain measures among chronic opioid users.

BACKGROUND: Preoperative chronic opioid use is common, but it is unclear whether complete opioid tapering can be achieved postoperatively without adversely affecting pain control and quality of life. This study was designed to assess the association between complete opioid tapering after surgery and patient-reported outcomes for pain intensity and pain interference. METHODS: We identified chronic opioid use patients undergoing a spectrum of nonemergency surgical procedures at a single Veterans Affairs medical institution between December 2017 and 2021. All patients were prospectively followed by a transitional pain service that promoted opioid tapering, assessed opioid use (morphine milligram equivalent), and patient-reported outcomes measurement information system for pain intensity (PROMIS-3a) and pain interference (PROMIS-6b). After stratifying based on whether complete versus partial/no opioid tapering was achieved after surgery, longitudinal changes in patient-reported outcomes and morphine milligram equivalents were compared over time. Independent predictors of complete opioid tapering were assessed using logistic regression models. RESULTS: In total, 341 surgical patients (91% male, mean age 64 years) with chronic opioid use underwent surgery during the study period, of which 44 (13%) completely tapered off opioids within 60 days after discharge from the hospital. Patients who completely tapered had significant improvement in the change in patient-reported outcomes for pain intensity and interference with significant differences at 30 and 60 days after discharge for both measures when compared to the partial/no taper group (both P < .05). In risk-adjusted analyses, patients with lower baseline morphine milligram equivalents and those staying longer in the hospital were more likely to achieve complete opioid tapering (both P < .01). CONCLUSION: Complete opioid tapering can be successfully achieved after surgery among patients with chronic opioid use with corresponding improvements in self-reported pain intensity and pain interference. Our results suggest that the highest potential for improving patient-reported outcomes with opioid tapering occurs among patients undergoing orthopedic procedures early after surgical discharge.