Anti-TNF Thioester Glucocorticoid Antibody-Drug Conjugate Fully Inhibits Inflammation with Minimal Effect on Systemic Corticosterone Levels in a Mouse Arthritis Model.

We describe the discovery of a thioester-containing glucocorticoid receptor modulator (GRM) payload and the corresponding antibody-drug conjugate (ADC). Payload 6 was designed for rapid hepatic inactivation to minimize systemic exposure of nonconjugated GRM. Mouse PK indicated that 6 is cleared 10-fold more rapidly than a first-generation GRM payload, resulting in 10-fold lower exposure and 3-fold decrease in Cmax. The anti-mTNF conjugate ADC5 fully inhibited inflammation in mouse contact hypersensitivity with minimal effects on corticosterone, a biomarker for systemic GRM effects, at doses up to and including 100 mg/kg. Concomitant inhibition of P1NP suggests potential delivery to cells involved in the remodeling of bone, which may be a consequence of TNF-targeting or bystander payload effects. Furthermore, ADC5 fully suppressed inflammation in collagen-induced arthritis mouse model after one 10 mg/kg dose for 21 days. The properties of the anti-hTNF conjugate were suitable for liquid formulation and may enable subcutaneous dosing.

Heavy Metals and Trajectories of Anti-Müllerian Hormone During the Menopausal Transition.

BACKGROUND: Experimental and epidemiological studies have linked metals with women's reproductive aging, but the mechanisms are not well understood. Disrupted ovarian folliculogenesis and diminished ovarian reserve could be a pathway through which metals impact reproductive hormones and outcomes. OBJECTIVE: The study aimed to evaluate the associations of heavy metals with anti-Müllerian hormone (AMH), a marker of ovarian reserve. METHODS: The study included 549 women from the Study of Women's Health Across the Nation with 2252 repeated AMH measurements from 10 to 0 years before the final menstrual period (FMP). Serum AMH concentrations were measured using picoAMH ELISA. Urinary concentrations of arsenic, cadmium, mercury, and lead were measured using high-resolution inductively coupled plasma mass spectrometry. Multivariable linear mixed regressions modeled AMH as a function of time before the FMP interaction terms between metals and time to the FMP were also included. RESULTS: Adjusting for confounders, compared with those in the lowest tertile, women in the highest tertile of urinary arsenic or mercury concentrations had lower AMH concentrations at the FMP (percent change: -32.1%; 95% CI, -52.9 to -2.2, P-trend = .03 for arsenic; percent change: -40.7%; 95% CI, -58.9 to -14.5, P-trend = .005 for mercury). Higher cadmium and mercury were also associated with accelerated rates of decline in AMH over time (percent change per year: -9.0%; 95% CI, -15.5 to -1.9, P-trend = .01 for cadmium; -7.3%; 95% CI, -14.0 to -0.1, P-trend = .04 for mercury). CONCLUSION: Heavy metals including arsenic, cadmium, and mercury may act as ovarian toxicants by diminishing ovarian reserve in women approaching the FMP.

Tele-Neuropsychology: From Science to Policy to Practice.

OBJECTIVE: The primary aim of this paper is to accelerate the number of randomized experimental studies of the reliability and validity in-home tele-neuropsychological testing (tele-np-t). METHOD: We conducted a critical review of the tele-neuropsychology literature. We discuss this research in the context of the United States' public and private healthcare payer systems, including the Centers for Medicare & Medicaid Services (CMS) and Current Procedural Terminology (CPT) coding system's telehealth lists, and existing disparities in healthcare access. RESULTS: The number of tele-np publications has been stagnant since the onset of the COVID-19 pandemic. There are less published experimental studies of tele-neuropsychology (tele-np), and particularly in-home tele-np-t, than other tele-np publications. There is strong foundational evidence of the acceptability, feasibility, and reliability of tele-np-t, but relatively few studies of the reliability and validity of in-home tele-np-t using randomization methodology. CONCLUSIONS: More studies of the reliability and validity of in-home tele-np-t using randomization methodology are necessary to support inclusion of tele-np-t codes on the CMS and CPT telehealth lists, and subsequently, the integration and delivery of in-home tele-np-t services across providers and institutions. These actions are needed to maintain equitable reimbursement of in-home tele-np-t services and address the widespread disparities in healthcare access.

Integrating Lifestyle Factor Science into Neuropsychological Practice: A National Academy of Neuropsychology Education Paper.

OBJECTIVE: The primary aim of this paper is to review evidence and clinical implications related to lifestyle activities associated with promoting brain and cognitive health. Our review targets four key lifestyle factors: physical activity and exercise, social engagement, cognitively stimulating activity, and consuming Mediterranean-style diets. METHOD: We conducted a critical review of the lifestyle factor literature in the four domains listed earlier. We contextualize this literature review by translating findings, when possible, into evidence-based recommendations to consider when providing neuropsychological services. RESULTS: There is significant current evidence supporting the role of physical activity and exercise, social engagement, cognitively stimulating activity, and consuming Mediterranean-style diets on positive brain and cognitive health outcomes. While some null findings are present in all four areas reviewed, the weight of the evidence supports the notion that engaging in these activities may promote brain and cognitive functioning. CONCLUSIONS: Clinical neuropsychologists can have confidence in recommending engagement in physical activity, social activity, and cognitively stimulating activity, and adhering to a Mediterranean-style diet to promote brain and cognitive health. We discuss limitations in existing lifestyle factor research and future directions to enhance the existing evidence base, including additional research with historically underrepresented groups and individuals with neurological conditions.

Biological variation of serum thyrotropin and thyroid hormones concentrations determined at 8-week intervals for 1 year in clinically healthy cats.

BACKGROUND: Cats commonly develop thyroid disease but little is known about the long-term biological variability of serum thyroid hormone and thyrotropin (thyroid-stimulating hormone; TSH) concentrations. OBJECTIVES: We aimed to determine the long-term biological variation of thyroid hormones and TSH in clinically healthy cats. METHODS: A prospective, observational study was carried out. Serum samples for analysis of total thyroxine (T4, by radioimmunoassay [RIA] and homogenous enzyme immunoassay [EIA]), triiodothyronine (T3 ), free T4 (by dialysis), and TSH were obtained every 8 weeks for 1 year from 15 healthy cats, then frozen until single-batch analysis. Coefficients of variation (CV) within individual cats ( CV I ) and among individual cats ( CV G ), as well as the variation between duplicates (ie, analytical variation [ CV A ]) were determined with restricted maximum likelihood estimation. The indices of individuality (IoI) and reference change values (RCVs) for each hormone were calculated. RESULTS: Some thyroid hormones showed similar (total T4 by EIA) or greater (TSH) interindividual relative to intraindividual variation resulting in intermediate to high IoI, consistent with previous studies evaluating the biological variation of these hormones weekly for 5-6 weeks. By contrast, total T4 (by RIA) and free T4 had a low IoI. Total T3 had a high ratio of CV A to CV I ; therefore, interindividual variation could not be distinguished from analytical variation. No seasonal variability in the hormones could be demonstrated. CONCLUSIONS: Clinicians might improve the diagnosis of feline thyroid disease by establishing baseline concentrations for analytes with intermediate-high IoI (total T4, TSH) for individual cats and applying RCVs to subsequent measurements.

Cognitive Reserve Moderates the Effects of Fatigue and Depressive Symptoms in Multiple Sclerosis.

To investigate cognitive reserve as a possible moderator in the relationship between fatigue and depressive symptoms in persons with multiple sclerosis (PwMS). Fifty-three PwMS (37 female; mean age, 52.66; mean education, 14.81) completed comprehensive neuropsychological testing and psychosocial questionnaires assessing the perceived effects of fatigue (Fatigue Impact Scale) and depressive symptoms (Beck Depression Inventory-Fast Screen). Cognitive reserve (CR) was operationalized as Fixed CR and Malleable CR. Fixed CR was quantified as the standardized mean of years of education and a vocabulary-based estimate of premorbid intelligence. Malleable CR was quantified as the standardized mean of cognitive exertion, exercise, and socializing items from the Cognitive Health Questionnaire. Regressions on depressive symptoms examining fatigue, both conceptualizations of CR, and their interactions were explored. A Bonferroni correction was used; results were considered significant at an alpha level of p < .01. The interactions between fatigue and both conceptualizations of CR were significant, p = .005 (Fixed CR); p = .004 (Malleable CR). Simple effects tests revealed that fatigue only predicted depressive symptoms in PwMS with low Fixed CR or low Malleable CR (p's < .001), and not in those with high Fixed or high Malleable CR (p > .01). Cognitive reserve moderated the relationship between fatigue and depressive symptoms in PwMS. Specifically, fatigue does not appear to influence depression in PwMS with high cognitive reserve. Having higher cognitive reserve (either Fixed or Malleable) may reduce the likelihood that fatigue will lead to depressive symptoms in MS.

Discovery of a Potent Chloroacetamide GPX4 Inhibitor with Bioavailability to Enable Target Engagement in Mice, a Potential Tool Compound for Inducing Ferroptosis In Vivo.

Compounds that inhibit glutathione peroxidase 4 (GPX4) hold promise as cancer therapeutics in their ability to induce a form of nonapoptotic cell death called ferroptosis. Our research identified 24, a structural analog of the potent GPX4 inhibitor RSL3, that has much better plasma stability (t1/2 > 5 h in mouse plasma). The bioavailability of 24 provided efficacious plasma drug concentrations with IP dosing, thus enabling in vivo studies to assess tolerability and efficacy. An efficacy study in mouse using a GPX4-sensitive tumor model found that doses of 24 up to 50 mg/kg were tolerated for 20 days but had no effect on tumor growth, although partial target engagement was observed in tumor homogenate.

Associations Between Repeated Measures of Urinary Phthalate Metabolites With Hormones and Timing of Natural Menopause.

Phthalates, ubiquitous endocrine-disrupting chemicals, may affect ovarian folliculogenesis and steroidogenesis. We examined the associations of urinary phthalate metabolites with hormones including estradiol, testosterone, follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), and anti-Müllerian hormone (AMH), and timing of natural menopause in midlife women. Data were from 1189 multiracial/multiethnic women aged 45 to 56 years without hormone therapy from the Study of Women's Health Across the Nation (SWAN). Urinary concentrations of 12 phthalate metabolites and hormones were repeatedly measured in 1999 to 2000 and 2002 to 2003, resulting in a total of 2111 observations. Linear mixed-effect models were used to calculate percentage differences (%D) and 95% CIs in serum concentrations of estradiol, testosterone, FSH, SHBG, and AMH. Cox proportional-hazards models were used to calculate hazard ratios (HRs) and 95% CIs of natural menopause. We observed statistically significant associations of phthalate metabolites with lower testosterone concentrations: MCOP with testosterone (%D: -2.08%; 95% CI, -3.66 to -0.47) and MnBP with testosterone (%D: -1.99%; 95% CI, -3.82 to -0.13), after adjusting for multiple comparisons with false discovery rates less than 5%. Lower AMH concentrations were also found with higher MECPP (%D: -14.26%; 95% CI, -24.10 to -3.14), MEHHP (%D: -15.58%; 95% CI, -24.59 to -5.50), and MEOHP (%D: -13.50%; 95% CI, -22.93 to -2.90). No associations were observed for other hormones or timing of natural menopause. These results suggest that exposure to phthalates may affect circulating levels of testosterone and diminish the ovarian reserve in midlife women. Given the widespread exposure, reduced exposure to phthalates may be a key step to prevent reproductive effects of phthalates.

Exposure to heavy metals and hormone levels in midlife women: The Study of Women's Health Across the Nation (SWAN).

Exposure to heavy metals may alter the circulating levels of sex hormones. However, epidemiologic studies on heavy metals and sex hormones have been limited, and results have been inconsistent. We assessed the associations of heavy metals assayed in urine, including arsenic, cadmium, lead, and mercury, with repeated measures of serum estradiol (E2), follicle-stimulating hormone (FSH), testosterone, and sex hormone-binding globulin (SHBG) levels in the Study of Women's Health Across the Nation Multi-Pollutant Study. The sample included 1355 White, Black, Chinese, and Japanese women, aged 45-56 years at baseline (1999-2000), whose serum hormone levels were repeatedly measured through 2017. Urinary metal concentrations were measured at baseline. Linear mixed effect models were used to calculate percent changes in serum hormone levels per doubling of urinary metal concentrations, adjusting for demographics, socioeconomic status, lifestyle, health-related factors, and urinary creatinine. After multivariable adjustment, a doubling of urinary metal concentration was associated with lower E2 levels by 2.2% (95% CI: 4.0%, -0.3%) for mercury and 3.6% (95% CI: 5.7%, -1.6%) for lead; higher FSH levels by 3.4% (95% CI: 0.9%, 5.9%) for lead; and higher SHBG levels by 3.6% (95% CI: 1.3%, 5.9%) for cadmium. The overall joint effect using the Bayesian kernel machine regression showed that metal mixtures were inversely associated with E2 and positively associated with FSH levels. No association was found between metals and testosterone levels. Results from this prospective cohort study demonstrate that environmental heavy metal exposures, including cadmium, mercury, and lead, may disturb circulating levels of E2, FSH, and SHBG in midlife women.

Biological variation of biochemical analytes determined at 8-week intervals for 1 year in clinically healthy cats.

BACKGROUND: Biological variation helps determine whether population-based or subject-based reference intervals are more appropriate to assess changes in serial analytical values. Previous studies have investigated the biological variation of biochemical analytes weekly or with variable frequency over 5-14 weeks in cats, but none have considered biological variation at less frequent intervals over 1 year. OBJECTIVES: We aimed to evaluate the long-term biological variation of 19 biochemical analytes in clinically healthy cats. METHODS: A prospective, observational study in which 15 clinically healthy, client-owned cats were sampled for serum biochemical analyses every 8 weeks for 1 year. Frozen serum samples were single-batch analyzed. Restricted maximum likelihood estimation was used to determine the coefficients of variation (CV), describing variation within each cat, between cats, and the analytical variation. These CVs were used to determine the indices of individuality and reference change values (RCVs). RESULTS: Albumin, alkaline phosphatase, creatine kinase, and globulin had high indices of individuality, indicating that they are best evaluated by RCVs. Phosphorus, potassium, chloride, sodium, symmetric dimethylarginine, and total CO2 had low indices of individuality, indicating that population-based reference intervals are appropriate. Alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, calcium, cholesterol, creatinine, glucose, total bilirubin, and total protein had intermediate indices of individuality, indicating that RCVs may provide additional insight into the interpretation of analyte measurements beyond the population-based reference intervals. CONCLUSIONS: For many analytes, the biological variation detected was similar to that reported in prior studies. Clinicians should consider the biological variation of analytes to best interpret clinically relevant changes in serial analyte measurements.

Discovery of ABBV-3373, an Anti-TNF Glucocorticoid Receptor Modulator Immunology Antibody Drug Conjugate.

Using a convergent synthetic route to enable multiple points of diversity, a series of glucocorticoid receptor modulators (GRM) were profiled for potency, selectivity, and drug-like properties in vitro. Despite covering a large range of diversity, profiling the nonconjugated small molecule was suboptimal and they were conjugated to a mouse antitumor necrosis factor (TNF) antibody using the MP-Ala-Ala linker. Screening of the resulting antibody drug conjugates (ADCs) provided a better assessment of efficacy and physical properties, reinforcing the need to conduct structure-activity relationship studies on the complete ADC. DAR4 ADCs were screened in an acute mouse contact hypersensitivity model measuring biomarkers to ensure a sufficient therapeutic window. In a chronic mouse arthritis model, mouse anti-TNF GRM ADCs were efficacious after a single dose of 10 mg/kg i.p. for over 30 days. Data on the unconjugated payloads and mouse surrogate anti-TNF ADCs identified payload 17 which was conjugated to a human anti-TNF antibody and advanced to the clinic as ABBV-3373.

Perfluoroalkyl Substances and Incident Natural Menopause in Midlife Women: The Mediating Role of Sex Hormones.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been associated with earlier natural menopause; however, the underlying mechanisms are not well understood, particularly the extent to which this relationship is mediated by sex hormones. We analyzed data (1999-2017) on 1,120 premenopausal women from the Study of Women's Health Across the Nation (SWAN). Causal mediation analysis was applied to quantify the degree to which follicle-stimulating hormone (FSH) and estradiol levels could mediate the associations between PFAS and incident natural menopause. Participants with higher PFAS concentrations had shorter times to natural menopause, with a relative survival of 0.82 (95% confidence interval (CI): 0.69, 0.96) for linear perfluorooctane sulfonate (n-PFOS), 0.84 (95% CI: 0.69, 1.00) for sum of branched-chain perfluorooctane sulfonate (Sm-PFOS), 0.79 (95% CI: 0.66, 0.93) for linear-chain perfluorooctanoate (n-PFOA), and 0.84 (95% CI: 0.71, 0.97) for perfluorononanoate (PFNA), comparing the highest tertile of PFAS concentrations with the lowest. The proportion of the effect mediated through FSH was 8.5% (95% CI: -11.7, 24.0) for n-PFOS, 13.2% (95% CI: 0.0, 24.5) for Sm-PFOS, 26.9% (95% CI: 15.6, 38.4) for n-PFOA, and 21.7% (6.8, 37.0) for PFNA. No significant mediation by estradiol was observed. The effect of PFAS on natural menopause may be partially explained by variations in FSH concentrations.

Cellular heterogeneity of human fallopian tubes in normal and hydrosalpinx disease states identified using scRNA-seq.

Fallopian tube (FT) homeostasis requires dynamic regulation of heterogeneous cell populations and is disrupted in infertility and ovarian cancer. Here, we applied single-cell RNA-seq to profile 59,738 FT cells from four healthy, pre-menopausal subjects. The resulting cell atlas contains 12 major cell types representing epithelial, stromal, and immune compartments. Re-clustering of epithelial cells identified four ciliated and six non-ciliated secretory epithelial subtypes, two of which represent potential progenitor pools: one leading to mature secretory cells and the other contributing to either ciliated cells or one of the stromal cell types. To understand how FT cell numbers and states change in a disease state, we analyzed 17,798 cells from two hydrosalpinx samples and observed shifts in epithelial and stromal populations and cell-type-specific changes in extracellular matrix and TGF-ß signaling; this underscores fibrosis pathophysiology. This resource is expected to facilitate future studies aimed at expanding understanding of fallopian tube homeostasis in normal development and disease.

Subgroup Analysis of Individuals with Multiple Sclerosis Showing Cognitive Resilience.

OBJECTIVE: Cognitive dysfunction is known to occur in many individuals with multiple sclerosis (MS). However, little is currently known about MS patients without cognitive impairment, including protective factors associated with intact cognition. The present study considered these issues in a sample of MS patients screened for intact subjective and objective cognitive functioning. METHODS: Two MS participant groups from a larger sample were derived: i) participants within 1 standard deviation of controls on measures of objective cognition, subjective cognition, and informant-observed subjective cognition [cognitively resilient MS group (MScr)], and ii) those classified as not cognitively resilient (MSncr). Both groups were compared with age- and gender-matched controls. RESULTS: Findings indicated that the MScr group was similar to the MSncr group on most disease and demographic variables, and level of fatigue. The MScr group showed higher estimated baseline intellectual ability and reported less anxiety, subclinical depressive symptoms, and pain interference. MScr participants also showed a trend toward more reported compensatory cognitive strategy use than MSncr participants. The MScr group showed comparable reading recognition and pain symptoms to controls. CONCLUSIONS: Our findings provide preliminary information on factors associated with cognitive resilience in MS. Future research should examine resilient individuals with MS to further clarify positive outcomes in this condition.

Bacterial culture and immunohistochemical detection of bacteria and endotoxin in cats with suppurative cholangitis-cholangiohepatitis syndrome.

OBJECTIVE: To characterize the frequency and type of bacterial infection by culture- and immunohistochemical (IHC)-based methods and determine the impact of infection on clinical features and survival time in cats with suppurative cholangitis-cholangiohepatitis syndrome (S-CCHS). ANIMALS: 168 client-owned cats with S-CCHS (cases). PROCEDURES: Clinical features, bacterial culture results, culture-inoculate sources, and survival details were recorded. Cases were subcategorized by comorbidity (extrahepatic bile duct obstruction, cholelithiasis, cholecystitis, ductal plate malformation, biopsy-confirmed inflammatory bowel disease, and biopsy-confirmed pancreatitis) or treatment by cholecystectomy or cholecystoenterostomy. Culture results, bacterial isolates, Gram-stain characteristics, and IHC staining were compared among comorbidities. Lipoteichoic acid IHC staining detected gram-positive bacterial cell wall components, and toll-like receptor expression IHC reflected pathologic endotoxin (gram-negative bacteria) exposure. RESULTS: Clinical features were similar among cases except for more frequent abdominal pain and lethargy in cats with positive culture results and pyrexia, abdominal pain, and hepatomegaly for cats with polymicrobial infections. Bacteria were cultured in 93 of 135 (69%) cats, with common isolates including Enterococcus spp and Escherichia coli. IHC staining was positive in 142 of 151 (94%) cats (lipoteichoic acid, 107/142 [75%]; toll-like receptor 4, 99/142 [70%]). With in-parallel interpretation of culture and IHC-based bacterial detection, 154 of 166 (93%) cats had bacterial infections (gram-positive, 118/154 [77%]; gram-negative, 111/154 [72%]; polymicrobial, 79/154 [51%]). Greater frequency of bacterial isolation occurred with combined tissue, bile, and crushed cholelith inoculates. Infection and gram-positive bacterial isolates were associated with significantly shorter long-term survival times. CLINICAL RELEVANCE: S-CCHS was associated with bacterial infection, pathologic endotoxin exposure, and frequent polymicrobial infection in cats. Combined tissue inoculates improved culture detection of associated bacteria.

Clinical features, concurrent disorders, and survival time in cats with suppurative cholangitis-cholangiohepatitis syndrome.

OBJECTIVE: To characterize clinical features, comorbidities, frequency of bacterial isolation, and survival time in cats with suppurative cholangitis-cholangiohepatitis syndrome (S-CCHS). ANIMALS: 168 client-owned cats with S-CCHS. PROCEDURES: Data were prospectively (1980 to 2019) collected regarding clinical features, comorbidities, bacterial infection, illness duration, and treatments. Variables were evaluated for associations with survival time. RESULTS: Median age of cats was 10.0 years, with no breed or sex predilection observed. Common clinical features included hyporexia (82%), hyperbilirubinemia (80%), lethargy (80%), vomiting (80%), jaundice (67%), weight loss (54%), and hypoalbuminemia (50%). Comorbidities included extrahepatic bile duct obstruction (53%), cholelithiasis (42%), cholecystitis (40%), and ductal plate malformation (44%) as well as biopsy-confirmed inflammatory bowel disease (60/68 [88%]) and pancreatitis (41/44 [93%]). Bacterial cultures were commonly positive (69%) despite prebiopsy antimicrobial administration in most cats. Of surgically confirmed choleliths, diagnostic imaging identified only 58%. Among 55 cats with "idiopathic pancreatitis," 28 (51%) were documented to have transiting choleliths, and 20 had pancreatic biopsies confirming pancreatitis. Cholelithiasis (with or without bile duct obstruction) and cholecystectomy were associated with survival advantages. Survival disadvantages were found for leukocytosis, ≥ 2-fold increased alkaline phosphatase, and hyperbilirubinemia. Cholecystoenterostomy had no survival impact. Cats with ductal plate malformations were significantly younger at diagnosis and death than other cats. Chronic treatments with antimicrobials, S-adenosylmethionine, and ursodeoxycholic acid were common postbiopsy. CLINICAL RELEVANCE: S-CCHS in cats was associated with bacterial infection and various comorbidities and may be confused with pancreatitis. Surgically correctable morbidities (ie, cholecystitis, cholecystocholelithiasis) and cholecystectomy provided a significant survival advantage.

Patient Preferences for Receiving Gender-Affirming Hormone Therapy.

Purpose: To characterize patient preferences regarding gender-affirming hormone therapy (HT) providers and telemedicine use. Methods: Between May and October 2019, a survey was administered to adult patients attending a tertiary medical center's HT clinic. The survey included questions on demographics, barriers to care, and preferences for HT follow-up care. Interest in telemedicine was measured using a Likert scale. Multivariable logistic regression was used to identify patient factors associated with interest in telemedicine. Results: Among 111 patients, 63.1% (n=70) preferred an in-person visit with a specialist and 21.6% (n=24) preferred a video visit with their specialist. While only 15.3% (n=17) preferred follow-up with a primary care provider (PCP), 71.0% (n=80) felt comfortable transitioning future care to a PCP. Notably, 52.3% (n=58) of patients were interested in a telemedicine visit. Factors associated with interest in telemedicine included identifying as a transgender man (aOR 3.94, 95% CI [1.24-12.53], p=0.02), minority race/ethnicity (aOR 6.71, 95% CI [1.79-25.17], p=0.005), no need to travel (aOR 3.34, 95% CI [1.14-9.85], p=0.03), no concerns about video visits (aOR 14.66, 95% CI [4.34-49.56], p<0.0001), and concern about their PCP offering a broad range of gender services (aOR 8.63, 95% CI [2.41-29.67], p=0.0006). Conclusions: Patients presenting for HT follow-up prefer continued care with a specialist. However, patients were willing to transition care to PCPs and were interested in telemedicine before the COVID-19 pandemic.

Relationships between congenital peritoneopericardial diaphragmatic hernia or congenital central diaphragmatic hernia and ductal plate malformations in dogs and cats.

OBJECTIVE: To characterize the association between peritoneopericardial diaphragmatic hernia (PPDH) or congenital central diaphragmatic hernia (CCDH) and ductal plate malformations (DPMs) in dogs and cats. ANIMALS: 18 dogs and 18 cats with PPDH or CCDH and 19 dogs and 18 cats without PPDH or CCDH. PROCEDURES: Evaluation of clinical details verified PPDH or CCDH and survival times. Histologic features of nonherniated liver samples were used to categorize DPM. Immunohistochemical staining for cytokeratin-19 distinguished bile duct profiles per portal tract and for Ki-67-assessed cholangiocyte proliferation. Histologic features of herniated liver samples from PPDH or CCDH were compared with those of pathological controls (traumatic diaphragmatic hernia, n = 6; liver lobe torsion, 6; ischemic hepatopathy, 2). RESULTS: DPM occurred in 13 of 18 dogs with the proliferative-like phenotype predominating and in 15 of 18 cats with evenly distributed proliferative-like and Caroli phenotypes. Congenital hepatic fibrosis DPM was noted in 3 dogs and 2 cats and renal DPM in 3 dogs and 3 cats. No signalment, clinical signs, or clinicopathologic features discriminated DPM. Kaplan Meier survival curves were similar in dogs and cats. Bile duct profiles per portal tract in dogs (median, 5.0; range, 1.4 to 100.8) and cats (6.6; 1.9 to 11.0) with congenital diaphragmatic hernias significantly exceeded those in healthy dogs (1.4; 1.2 to 1.6) and cats (2.3; 1.7 to 2.6). Animals with DPM lacked active cholangiocyte proliferation. Histologic features characterizing malformative bile duct profiles yet without biliary proliferation were preserved in herniated liver lobes in animals with DPM. CONCLUSIONS AND CLINICAL RELEVANCE: DPM was strongly associated with PPDH and CCDH. Because DPM can impact health, awareness of its coexistence with PPDH or CCDH should prompt biopsy of nonherniated liver tissue during surgical correction of PPDH and CCDH.