Randomized controlled trial of enteral vitamin D supplementation (ViDES) in infants <28 weeks gestational age or <1000 g birth weight: study protocol.

BACKGROUND: Vitamin D is necessary to develop healthy lungs and other organs early in life. Most infants born before 28 weeks' gestation have low vitamin D levels at birth and a limited intake during the first month. Enteral vitamin D supplementation is inexpensive and widely used. The appropriate supplementation regimen for extremely preterm infants is controversial, and the effect of different regimens on their blood levels and outcomes is unclear. METHODS: Randomized, blinded comparative effectiveness trial to compare two vitamin D supplementation regimens for inborn infants <28 weeks gestation or <1000 g birth weight at a large academic center in the United States. Infants are stratified by birth weight and randomized within 96 h after birth to either routine supplementation (400 IU/day with established feedings) or increased supplementation (800 IU/day with any feedings) during the first 28 days after birth. We hypothesize that the higher and early vitamin D dose (800 IU/day with early feeding) compared to placebo plus routine dose (400 IU/day with established feeding) will substantially increase total 25-hydroxyvitamin D3 levels measured as state-of-art at 1 month, reduce respiratory support at 36 weeks' postmenstrual age (on an ordinal scale predictive of later adverse outcomes), and improve or at least not worsen other important secondary outcomes. The infants in the study will follow up at 22-26 months' corrected age (~2 years) with blinded certified examiners to evaluate neurodevelopmental outcomes. The sample size of a minimum of 180 infants provides >90% power to detect a >95% posterior probability of a 33% increase in serum 25-hydroxy vitamin D3 and >80% power to detect a >80% posterior probability of a relative risk decrease of 20% of reducing respiratory support by intention-to-treat Bayesian analyses using a neutral prior probability. DISCUSSION: Our study will help clarify the uncertain relationship of vitamin D supplementation and its associated serum metabolites to clinical outcomes of extremely preterm infants. Confirmation of our hypotheses would prompt reconsideration of the supplementation regimens used in extremely preterm infants and justify a large multicenter study to verify the generalizability of the results. TRIAL REGISTRATION: ClinicalTrials.gov NCT05459298. Registered on July 14, 2022.

Adverse Childhood Experiences, Resilience, and Cardiovascular Disease in Adult Survivors of Childhood Cancer: A Report from the Childhood Cancer Survivor Study.

BACKGROUND: The impact of Adverse Childhood Experiences (ACEs: e.g., abuse, neglect and/or household dysfunction experienced before age 18) and resilience on risk for cardiovascular disease (CVD) has not previously been investigated in adult survivors of childhood cancer. METHODS: We conducted a nested case-control study among long-term, adult-aged survivors of childhood cancer from the Childhood Cancer Survivor Study (CCSS). Self-report questionnaires ascertained ACEs and resilience, and scores were compared between cases with serious/life-threatening CVD and controls without CVD matched on demographic and cardiotoxic treatment factors. RESULTS: Among 95 cases and 261 controls, the mean ACE score was 1.4 for both groups; 53.4% of survivors endorsed ≥1 ACE. There was no association between ACEs or resilience and CVD in adjusted models. CONCLUSIONS: ACEs and resilience do not appear to contribute to CVD risk for adult survivors of childhood cancer with cardiotoxic treatment exposures. IMPACT: Although not associated with CVD in this population, ACEs are associated with serious health issues in other populations. Therefore, future studies could investigate effects of ACEs on other health outcomes affecting childhood cancer survivors.

Hybrid Interventions for Pulmonary Vein Stenosis: Leveraging Intraoperative Endovascular Adjuncts in Challenging Clinical Scenarios.

Background: Pediatric pulmonary vein stenosis (PVS) is often progressive and treatment-refractory, requiring multiple interventions. Hybrid pulmonary vein interventions (HPVIs), involving intraoperative balloon angioplasty or stent placement, leverage surgical access and customization to optimize patency while facilitating future transcatheter procedures. We review our experience with HPVI and explore potential applications of this collaborative approach. Methods: Retrospective chart review of all HPVI cases between 2009 to 2023. Results: Ten patients with primary (n = 5) or post-repair (n = 5) PVS underwent HPVI at median age of 12.7 months (range 6.6 months-9.5 years). Concurrent surgical PVS repair was performed in 7/10 cases. Hybrid pulmonary vein intervention was performed on 17 veins, 13 (76%) with prior surgical or transcatheter intervention(s). One patient underwent intraoperative balloon angioplasty of an existing stent. In total, 18 stents (9 bare metal [5-10 mm diameter], 9 drug eluting [3.5-5 mm diameter]) were placed in 16 veins. At first angiography (median 48 days [range 7 days-2.8 years] postoperatively), 8 of 16 (50%) HPVI-stented veins developed in-stent stenosis. Two patients died from progressive PVS early in the study, one prior to planned reintervention. Median time to first pulmonary vein reintervention was 86 days (10 days-2.8 years; 8/10 patients, 13/17 veins). At median survivor follow-up of 2.2 years (2.3 months-13.1 years), 1 of 11 surviving HPVI veins were completely occluded. Conclusions: Hybrid pulmonary vein intervention represents a viable adjunct to existing PVS therapies, with promising flexibility to address limitations of surgical and transcatheter modalities. Reintervention is anticipated, necessitating evaluation of long-term benefits and durability as utilization increases.

Chronic Lymphocytic Thyroiditis May Limit the Utility of Molecular Testing in AUS/FLUS Thyroid Nodules.

INTRODUCTION: Chronic lymphocytic thyroiditis (CLT) may increase the likelihood of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) results in thyroid nodules by fine needle aspiration (FNA). Gene expression classifier (GEC) and Thyroid Sequencing (ThyroSeq) may better stratify rate of malignancy (ROM) of AUS/FLUS thyroid nodules. This study compares the utility of molecular tests in determining malignancy in surgical patients with concomitant AUS/FLUS thyroid nodules and CLT. METHODS: A retrospective review of 1648 patients with index thyroid nodules who underwent FNA and thyroidectomy at a single institution was performed. Patients with concomitant AUS/FLUS thyroid nodules and CLT were subdivided into three diagnostic groups: FNA only, FNA with GEC, and FNA with ThyroSeq. Patients with AUS/FLUS thyroid nodules without CLT were subdivided into similar groups. Final histopathology of the cohorts was further stratified into benignity and malignancy and analyzed using Chi-squared statistics. RESULTS: Of 463 study patients, 86 had concomitant AUS/FLUS thyroid nodules and CLT with a 52% ROM, and the difference of ROM among FNA only (48%), suspicious GEC (50%), or positive ThyroSeq (69%) was not significant. In 377 patients with AUS/FLUS thyroid nodules without CL, ROM was 59%. ROM among these patients was significantly higher when molecular testing was used (FNA only 51%, suspicious GEC 65%, and positive ThyroSeq 68%; P < 0.05). CONCLUSIONS: Molecular tests may have limited value in predicting malignancy in surgical patients with concomitant AUS/FLUS thyroid nodules and CLT.

Pre-Fontan Assessment Utilizing Combined Cardiac Catheterization and Cardiac MRI: Comparison to the Pre-Fontan Catheterization.

Single ventricle patients eligible for Fontan completion undergo pre-Fontan catheterization for hemodynamic and anatomic assessment prior to surgery. Cardiac magnetic resonance imaging may be used to evaluate pre-Fontan anatomy, physiology, and collateral burden. We describe our center's outcomes in patients undergoing pre-Fontan catheterization combined with cardiac magnetic resonance imaging. A retrospective review of patients undergoing pre-Fontan catheterization from 10/2018 to 04/2022 at Texas Children's Hospital was performed. Patients were divided into 2 groups: combined cardiac magnetic resonance imaging and catheterization (combined group) and those who underwent catheterization only (catheterization only group). There were 37 patients in the combined group and 40 in the catheterization only group. Both groups were similar in age and weight. Patients undergoing combined procedures received less contrast, and experienced less in-lab time, fluoroscopy time and catheterization procedure time. Median radiation exposure was lower in the combined procedure group but was not statistically significant. Intubation and total anesthesia times were higher in the combined procedure group. Patients undergoing a combined procedure were less likely to have collateral occlusion performed than in the catheterization only group. Bypass time, intensive care unit length of stay, and chest tube duration were similar in both groups at the time of Fontan completion. Combined pre-Fontan assessment decreases catheterization procedure and fluoroscopy time associated with cardiac catheterization at the expense of longer anesthetic times, and results in similar Fontan outcomes compared to when cardiac catheterization alone is utilized.

The Association of Neighborhood Characteristics and Frailty in Childhood Cancer Survivors: A Report from the St. Jude Lifetime Cohort Study.

BACKGROUND: Childhood cancer survivors experience reduced physiologic reserve, or frailty, earlier and more frequently than peers. In other populations, frailty is impacted by one's neighborhood. This study's purpose was to evaluate associations between neighborhood characteristics and frailty in childhood cancer survivors. METHODS: Participants in the St. Jude Lifetime Cohort Study with geocoded residential addresses were analyzed. Pre-frailty/Frailty was defined as having 1-2/≥3 of sarcopenia, muscle weakness, poor endurance, slow walking speed, and exhaustion from direct assessments. Neighborhood characteristics [e.g., access to exercise opportunities and healthy food, neighborhood socioeconomic status (nSES), and rurality/urbanicity] were determined using publicly available geospatial data. Nested multivariable logistic regression models identified associations between neighborhood characteristics and pre-frailty/frailty, adjusting for chronic health conditions, individual health behaviors and socio-demographics, and high-risk cancer treatment exposures. RESULTS: For our cohort (N = 3,806, 46.79% female, 81.40% white, mean age 33.63±9.91 years), compared with non-frail survivors (n = 2,573; 67.6%), pre-frail (n = 900; 23.6%) and frail survivors (n = 333; 8.7%) were more likely to live in neighborhoods with decreased exercise opportunities (frail OR: 1.62, 1.26-2.09), reduced healthy food access (pre-frail OR: 1.28, 1.08-1.51; frail OR: 1.36, 1.06-1.75), and lower nSES (pre-frail OR: 1.31, 1.12-1.52; frail OR: 1.64, 1.30-2.07). Participants had 8% increased odds (95% confidence interval, 2%-14%) of being pre-frail/frail if they lived in "resource poor" neighborhoods as opposed to "resource rich" neighborhoods after adjusting for other pre-frailty/frailty risk factors. CONCLUSIONS: The neighborhood a childhood cancer survivor resides in as an adult is associated with pre-frailty/frailty. IMPACT: This study provides valuable information for creating interventions using neighborhood-level factors to mitigate frailty and improve health outcomes in survivors. See related commentary by Bhandari and Armenian, p. 997.

Cannabidiol Treatment for Neurological, Cognitive, and Psychiatric Symptoms in Sturge-Weber Syndrome.

BACKGROUND: A prior drug trial of cannabidiol for treatment-resistant epilepsy in patients with Sturge-Weber syndrome (SWS), a rare neurovascular condition, implicated improvements in neurological, quality of life (QOL), neuropsychologic, psychiatric, and motor outcomes. METHODS: Ten subjects with SWS brain involvement, controlled seizures, and cognitive impairments received study drug in this Johns Hopkins institutional review board-approved, open-label, prospective drug trial. Oral cannabidiol was taken for six months (dose ranged from 5 to 20 mg/kg/day). SWS neuroscore, port-wine birthmark score, QOL, and adverse events were recorded every four to 12 weeks. Neuropsychologic, psychiatric, and motor assessments were administered at baseline and six months' follow-up. Most evaluations were conducted virtually due to the coronavirus disease 2019 pandemic. RESULTS: Cannabidiol was generally well tolerated. Six subjects reported mild to moderate side effects related to study drug and continued on drug; one subject withdrew early due to moderate side effects. No seizures were reported. Significant improvements in SWS neuroscore, patient-reported QOL, anxiety and emotional regulation, and report of bimanual ability use were noted. Migraine QOL scores were high at baseline in these subjects, and remained high. Neuropsychologic and other QOL and motor outcomes remained stable, with some within-subject improvements noted. CONCLUSIONS: Further studies are needed to determine whether Epidiolex can improve quality of life and be beneficial for neurological, anxiety, and motor impairments in SWS independent of seizure control. Large multicentered studies are needed to extend these preliminary findings.

Adverse childhood experiences and resilience in childhood and adolescent and young adult cancer patients.

Childhood and adolescent and young adult (AYA) cancer survivors experience poor health outcomes in adulthood. Adverse childhood experiences (ACEs) also portend poor health outcomes for the general population. Resilience can mitigate effects of ACEs. We examined the feasibility of assessing ACEs and resilience in childhood and AYA cancer patients. We also described occurrences of ACEs, resilience, and poor health outcomes. Of 52 participants, most rated their study experience favorably, with privacy in answering sensitive questions. Half reported ACEs, and those with ACEs had lower resilience; X2 (3, N = 52) = 9.4, p = .02. Further investigations of ACEs and resilience in larger cohorts are warranted to delineate associations with long-term health outcomes.

African Ancestry-Associated Gene Expression Profiles in Triple-Negative Breast Cancer Underlie Altered Tumor Biology and Clinical Outcome in Women of African Descent.

Women of sub-Saharan African descent have disproportionately higher incidence of triple-negative breast cancer (TNBC) and TNBC-specific mortality across all populations. Population studies show racial differences in TNBC biology, including higher prevalence of basal-like and quadruple-negative subtypes in African Americans (AA). However, previous investigations relied on self-reported race (SRR) of primarily U.S. populations. Due to heterogeneous genetic admixture and biological consequences of social determinants, the true association of African ancestry with TNBC biology is unclear. To address this, we conducted RNA sequencing on an international cohort of AAs, as well as West and East Africans with TNBC. Using comprehensive genetic ancestry estimation in this African-enriched cohort, we found expression of 613 genes associated with African ancestry and 2,000+ associated with regional African ancestry. A subset of African-associated genes also showed differences in normal breast tissue. Pathway enrichment and deconvolution of tumor cellular composition revealed that tumor-associated immunologic profiles are distinct in patients of African descent. SIGNIFICANCE: Our comprehensive ancestry quantification process revealed that ancestry-associated gene expression profiles in TNBC include population-level distinctions in immunologic landscapes. These differences may explain some differences in race-group clinical outcomes. This study shows the first definitive link between African ancestry and the TNBC immunologic landscape, from an African-enriched international multiethnic cohort. See related commentary by Hamilton et al., p. 2496. This article is highlighted in the In This Issue feature, p. 2483.

Depth of mediastinal extension can predict sternotomy need for substernal thyroid goiters.

BACKGROUND: Surgical excision of substernal thyroid goiters is usually achieved through a conventional transcervical approach, and transthoracic excision is rarely necessary. Currently, there are no clear guidelines for substernal thyroid goiters that may require a transthoracic approach. This study examined what preoperative factors were significantly associated with transthoracic surgical excision for substernal thyroid goiters. METHODS: A retrospective review of prospectively collected data of 109 patients with substernal thyroid goiters from a single institution was performed. The patients were stratified by transcervical and transthoracic approaches for substernal thyroid goiters. The factors possibly predictive of a transthoracic approach, including substernal extension beyond the thoracic inlet, patient-reported symptoms, tracheal deviation, and malignancy, were analyzed. Demographics including age, sex, and race, among others, were also studied. RESULTS: Of 1,080 patients who underwent surgical resection for multinodular goiter, there were 109 (10%) patients with substernal thyroid goiters. Of the substernal thyroid goiter group, 11 (10%) patients underwent partial sternotomy, whereas 6 (5.5%) underwent total sternotomy. On logistic regression, only substernal component of the thyroid goiter extending beyond the sternal notch into the mediastinum was statistically significant in predicting sternotomy (odds ratio 3.43, confidence interval 1.65-6.41, P < .001). Substernal thyroid goiters with mediastinal extension of ≥5 cm beyond the sternal notch showed a sensitivity of 94% and specificity of 86.5% to predict need of sternotomy. CONCLUSION: Patients with substernal thyroid goiters who exhibit progressive enlargement and/or compressive symptoms should undergo surgical excision. Although most are removed through the conventional transcervical approach, substernal thyroid goiters with a depth of mediastinal extension ≥5 cm have a high likelihood of requiring sternotomy.

Transient Hypocalcemia After Total Thyroidectomy: The Obesity Paradox at Work?

INTRODUCTION: With increasing rates of obesity worldwide, a correlation between high body mass index (BMI) and postoperative morbidity after thyroid surgery remains unclear. Postoperative transient hypocalcemia is common after total thyroidectomy due to interruption of parathyroid function. This study examines the relationship between BMI and hypocalcemia after total thyroidectomy. MATERIALS AND METHODS: A retrospective review of prospectively collected data for 1135 patients who underwent total thyroidectomy for cancer, multinodular goiter (MNG), or Graves' disease between June 2009 and November 2020 at a single institution was performed. BMI groups followed the World Health Organization classification. Hypocalcemia was defined as serum calcium ≤8 mg/dL. Calcium levels measured on postoperative day 0 and the following morning were compared between the BMI groups. RESULTS: Of 1135 total thyroidectomy patients, 85% were women. The mean age and standard deviation of patients was 49 (± 13) y, with most of Hispanic origin (64%). Overall, 41.5% of patients had cancer, 45% nontoxic MNG, 5.8% toxic MNG, and 12% Graves' disease. Stratified by BMI, 27% of patients were normal, 34% overweight, and 39% obese. Overall, overweight and obese patients experienced less transient hypocalcemia at both time points compared to normal patients postoperatively (P = 0.01 and P = 0.009). Furthermore, overweight and obese patients with Graves' disease experienced less transient hypocalcemia at both time points (P = 0.04 and P = 0.05). There was no statistical difference in other groups. CONCLUSIONS: A protective role of higher BMI or "obesity paradox" for postoperative hypocalcemia may exist in those obese patients after total thyroidectomy.

Clinicians' Perceptions of Collaborative Palliative Care Delivery in Chronic Kidney Disease.

CONTEXT: Guidelines recommend palliative care for patients with chronic kidney disease (CKD), who experience a high pain and symptom burden, and receive intensive treatments that often do not align with their values. A lack of scalable specialty palliative care services has prompted calls for attention to primary palliative care, delivered in primary care and nephrology settings. OBJECTIVES: The objectives of this study were to 1) describe expectations for care to meet the palliative care needs of people living with CKD, and limitations to meeting those expectations in the current model, and 2) identify potential interventions to meet patients' palliative care needs. METHODS: We conducted semi-structured interviews with clinicians from primary care, nephrology, and palliative care to assess 1) reasonable expectations for meeting palliative needs, 2) barriers to integrating primary palliative care, and 3) potential intervention points. RESULTS: Clinicians discussed their expectations for high-quality communication (e.g., discussing disease understanding, assessing goals of care) and better integration of palliative care services. Clinicians expressed barriers to delivering that care, including poor inter-clinician communication. To address barriers, clinicians outlined potential intervention points, such as building collaborative models of care, and structural triggers to identify patients who may be appropriate for palliative care. CONCLUSION: Interventions to address gaps in palliative care delivery for people living with CKD should incorporate systematic identification of patients with palliative care needs and structural mechanisms to meeting those needs via specialty and primary palliative care.

Comparative Costs of Management Strategies for Neonates With Symptomatic Tetralogy of Fallot.

BACKGROUND: Recent data have demonstrated that overall mortality and adverse events are not significantly different for primary repair (PR) and staged repair (SR) approaches to management of neonates with symptomatic tetralogy of Fallot (sTOF). Cost data can be used to compare the relative value (cost for similar outcomes) of these approaches and are a potentially more sensitive measure of morbidity. OBJECTIVES: This study sought to compare the economic costs associated with PR and SR in neonates with sTOF. METHODS: Data from a multicenter retrospective cohort study of neonates with sTOF were merged with administrative data to compare total costs and cost per day alive over the first 18 months of life in a propensity score-adjusted analysis. A secondary analysis evaluated differences in department-level costs. RESULTS: In total, 324 subjects from 6 centers from January 2011 to November 2017 were studied (40% PR). The 18-month cumulative mortality (P = 0.18), procedural complications (P = 0.10), hospital complications (P = 0.94), and reinterventions (P = 0.22) did not differ between PR and SR. Total 18-month costs for PR (median $179,494 [IQR: $121,760-$310,721]) were less than for SR (median: $222,799 [IQR: $167,581-$327,113]) (P < 0.001). Cost per day alive (P = 0.005) and department-level costs were also all lower for PR. In propensity score-adjusted analyses, PR was associated with lower total cost (cost ratio: 0.73; P < 0.001) and lower department-level costs. CONCLUSIONS: In this multicenter study of neonates with sTOF, PR was associated with lower costs. Given similar overall mortality between treatment strategies, this finding suggests that PR provides superior value.

A Survivorship Educational Tool for Latino Adolescent and Young Adult Cancer Survivors.

BACKGROUND: Low receipt of survivorship care by Latino adolescent and young adult (AYA) cancer survivors necessitates development of age-appropriate and culturally tailored interventions aimed at increasing their perceived need for survivorship care. METHOD: This study describes the development and acceptability testing of a culturally tailored intervention, a photonovela, as part of a community-partnered participatory research (CPPR) project. A four-step approach to the photonovela's development was implemented: (a) literature review, (b) RAND-modified Delphi method, (c) photonovela booklet development, and (d) photonovela acceptability testing through focus groups. Using the CPPR approach, community and academic experts and members worked together at all stages of this project to identify educational domains for the photonovela and ensure that community views and scientific knowledge were equally represented. RESULTS: Cancer survivors and their families described the photonovela as entertaining and relatable. Its story positively reflected their own experiences, and they connected strongly with its characters. Acceptability testing of the photonovela played a significant role in its final script and content, and provided additional new insights into understanding survivorship care perspectives for Latino AYA survivors and their families. CONCLUSION: Equal and shared community and academic involvement through CPPR is essential in identifying unique needs and developing culturally acceptable educational interventions for Latino AYA cancer survivors. The photonovela was seen as an important educational resource in enhancing knowledge and increasing perceived need for survivorship care in this population.

Palliative Care Attitudes and Experiences among Resident Physicians at Historically Black Colleges and Universities.

CONTEXT: Seriously ill Black patients receive lower quality palliative care than White patients. Equitable access requires palliative care skills training for all physicians. Historically Black Colleges and Universities (HBCUs) play a key role in educating Black physicians and have less access to palliative care resources. OBJECTIVE: To investigate palliative care attitudes and experiences among primary care residents at HBCUs. METHODS: Internal Medicine and Family Medicine residents at two HBCUs completed an online survey assessing attitudes towards palliative care and teaching and clinical experiences in palliative care. We performed a descriptive analysis of survey items. RESULTS: Among 91 residents who completed the survey (response rate 48%), 65% were women and 68% Black. Most (96%) said that learning about palliative care was moderately/very important to their career; however, two-thirds of respondents considered care for dying patients to be depressing and half reported receiving negative messages about palliative care from other physicians. Residents reported receiving less teaching about providing palliative care (5.4 ± 2.3 on 10-point scale) than about managing sepsis (8.3 ± 1.8; P < 0.05). Fewer residents rated their palliative care education as "Excellent" or "Very Good" compared to their overall education (13% vs 70%; P < 0.05). CONCLUSION: In the first survey exploring palliative care education at HBCUs, residents viewed palliative care as important but described the quality of their palliative care education as poor. This study highlights opportunities for improving palliative care education at HBCUs as a step toward addressing disparities in serious illness care.

Galectin-1 induces gene and protein expression related to maternal-conceptus immune tolerance in bovine endometrium†.

Conceptus secretory factors include galectins, a family of carbohydrate binding proteins that elicit cell adhesion and immune suppression by interacting with intracellular and extracellular glycans. In rodents, galectin-1 (LGALS1) promotes maternal-fetal immune tolerance in the decidua through expansion of tolerogenic cluster of differentiation 11c (CD11c) positive dendritic cells, increased anti-inflammatory interleukin (IL)-10, and activation of forkhead box P3 (FOXP3) positive regulatory T cells (Treg). This study characterized galectin expression in early ruminant conceptuses and endometrium. We also tested the effect of recombinant bovine LGALS1 (rbLGALS1) and progesterone (P4) on endometrial expression of genes and protein related to maternal-conceptus immune tolerance in cattle. Elongating bovine and ovine conceptuses expressed several galectins, particularly, LGALS1, LGALS3, and LGALS8. Within bovine endometrium, expression of LGALS3, LGALS7, and LGALS9 was greater on Day 16 of pregnancy compared to the estrous cycle. Within ovine endometrium, LGALS7 was greater during pregnancy compared to the estrous cycle and endometrium of pregnant sheep tended to have greater LGALS9 and LGALS15. Expression of endometrial LGALS4 was less during pregnancy in sheep. Treating bovine endometrium with rbLGALS1 increased endometrial expression of CD11c, IL-10, and FOXP3, within 24 h. Specifically, within caruncular endometrium, both rbLGALS1 and P4 increased FOXP3, suggesting that both ligands may promote Treg expansion. Using IHC, FOXP3+ cells with a leukocyte phenotype were localized to the bovine uterine stratum compactum near the uterine surface and increased in response to rbLGALS1. We hypothesize that galectins have important functions during establishment of pregnancy in ruminants and bovine conceptus LGALS1 and luteal P4 confer mechanisms of maternal-conceptus immune tolerance in cattle.

Sex Differences in Papillary Thyroid Cancer.

BACKGROUND: Papillary thyroid cancer (PTC) is three times more common in women than men. However, PTC in men appears to be associated with poorer outcomes than in women. This study compares the clinical presentation and pathologic features of men and women with PTC. MATERIALS AND METHODS: A retrospective review of prospectively collected data for patients with PTC who underwent fine needle aspiration (FNA) of a solitary thyroid nodule and thyroidectomy at a single institution was performed. Factors including age, ultrasound features, FNA results, extent of surgical operation and final histopathology were compared between male and female patients. Descriptive statistics using chi-square and t-test statistics compared outcomes by sex. RESULTS: Of the 851 patients with PTC, 158 (19%) were men and 693 (81%) were women. Mean age and standard deviation (SD) of patients was 48 (± 14) years, and most were of Hispanic origin (69%). Men had a significantly higher rate of radiation exposure relative to women, respectively (8% vs. 2%, P<0.01). There were no ultrasonographic or FNA cytologic differences among sexes. Men had more aggressive pathologic features including lymphovascular invasion (LVI) (47% vs. 34%, P<0.01) and positive lymph nodes (LN) (36% vs. 27%, P<0.05) compared to women. Thyroid lobectomy with isthmusectomy was more commonly performed among men compared to women (24% vs. 13%, P<0.01). CONCLUSION: Men with PTC have higher rates of radiation exposure associated with more aggressive disease with LVI and LN involvement on final histopathology compared to women. Total thyroidectomy with possible central neck dissection should further be considered when counseling men with PTC.

Exemptions to state laws regulating opioid prescribing for patients with cancer-related pain: A summary.

BACKGROUND: Cancer-related pain is highly prevalent and is commonly treated with prescription opioids. The Centers for Disease Control and Prevention (CDC) now encourages conservative opioid prescribing in recognition of potential opioid-related risks. However, CDC guidelines have been misapplied to patients with cancer. Recent laws at the state level reflect the CDC's guidance by limiting opioid prescribing. It is unclear whether states exempt cancer-related pain, which may affect cancer pain management. Thus, the objective of this study was to summarize current state-level opioid prescribing laws and exemptions for patients with cancer. METHODS: Two study authors reviewed publicly available state records to identify the most recent opioid prescribing laws and cancer-related exemptions. Documents were required to have the force of law and be enacted at the time of the search (November 2020). RESULTS: Results indicated that 36 states had enacted formal legislation limiting the duration and/or dosage of opioid prescriptions, and this was largely focused on acute pain and/or initial prescriptions. Of these states, 32 (89%) explicitly exempted patients with cancer-related pain from opioid prescribing laws. Exemptions were broadly applied, with few states providing specific guidance for cancer-related pain prescribing. CONCLUSIONS: The results of this study indicate that most states recognize the importance of prescription opioids in cancer-related pain management. However, drafting nuanced and clinically relevant opioid legislation is challenging for a heterogenous population. Additionally, current attempts to regulate opioid prescribing by state law may unintentionally undermine patient-centered approaches to pain management. Additional resources are needed to facilitate clarity at the intersection of opioid-related legislation and clinical management for cancer-related pain. LAY SUMMARY: In this review of state-level legislation, current limitations on opioid prescribing are summarized and detailed information is provided on exemptions for patients with cancer. The majority of states have enacted specific dosage and/or duration limitations on opioid prescribing while including broad exemptions for cancer-related pain. Cancer-related pain exemptions are important to include, as is consistent with national and professional guidelines (eg, the Centers for Disease Control and Prevention). However, these exemptions may also unintentionally undermine patient-centered approaches to pain management. Additional resources, including specific guidance for patients with cancer, are needed to facilitate clarity at the intersection of opioid-related legislation and clinical pain management. ​.

Multicenter Research Data of Epilepsy Management in Patients With Sturge-Weber Syndrome.

BACKGROUND: Epilepsy in typical Sturge-Weber syndrome (SWS) is common, and many questions remain regarding the treatment outcomes. We analyzed a large multicenter database with focus on neurological drug treatment in different demographic and SWS characteristic groups. METHODS: A total of 268 patients with brain involvement and a history of seizures were selected from a research data registry generated from a multicenter cross-sectional questionnaire. We examined associations between medication use and binary variables such as sex, ethnicity, and brain, skin, and eye involvement laterality. We analyzed group differences in mean number of antiseizure medications and age at diagnosis, enrollment, and seizure onset and examined differences in median SWS neurological scores in groups of interest. RESULTS: The most frequently used medications were levetiracetam (48.1%), low-dose aspirin (44.8%), oxcarbazepine (39.9%), and phenobarbital (14.9%). Lamotrigine was more frequently used in adults than in children (P = 0.001). History of neurosurgery was associated with no current antiseizure medication use (P = 0.001), whereas bilateral brain involvement and family history of seizures were associated with using a higher number of antiseizure medications (P = 0.002, P = 0.027, respectively). Subjects with bilateral brain involvement and early seizure onset were associated with using a higher number of antiseizure medications (P = 0.002) and phenobarbital use (0.003). CONCLUSIONS: Levetiracetam, low-dose aspirin, and oxcarbazepine were the most frequently used medications. More severely affected patients were frequently on a greater number of antiseizure medications. Surgery for epilepsy was associated with the ability to discontinue antiseizure medication. Longitudinal studies are needed to further investigate medication use in patients with SWS.