Family Planning in Cardiothoracic Surgery: A Comparison Between Male and Female Surgeons.

BACKGROUND: Although work-family balance impacts specialty selection for medical students of both sexes, pregnancy and childbearing experiences are unique to women. Cardiothoracic surgery, with low female representation, must prioritize these issues to support women entering the field. This study compared family planning experiences between male and female cardiothoracic surgeons. METHODS: An anonymous, self-administered questionnaire was distributed to cardiothoracic trainees and surgeons from January to June 2023. Descriptive data were collected on family planning perceptions, assisted reproductive technology use, number of children, and pregnancy characteristics (maternal age, complications, miscarriage). Male surgeons reported pregnancy outcomes of their childbearing partners. RESULTS: Of 378 participants, 45.77% were women, and mean age was 44.40 ± 11.59 years. Compared with male surgeons, female surgeons were more often deterred from pursuing cardiothoracic surgery due to a desire to have children (41.62% vs 22.93%, P = .004), more often used assisted reproductive technology (32.37% vs 15.12%, P < .001), had fewer children (1.92 vs 2.48, P < .001), and had fewer children than desired (40.81% vs 25.14%, P < .001). Compared with partners of male surgeons, female surgeons were older at first live birth (34 vs 32 years, P < .001). Among female surgeons, 73 (42.40%) experienced 155 miscarriages, and 54 (74%) reported taking 0 days off from work after miscarriage. CONCLUSIONS: The path to parenthood varies significantly by sex for cardiothoracic surgeons, with women more likely to be deterred from the profession by perceived challenges. Policies that promote work-family integration, support maternal-fetal health, and provide support following fetal loss are needed.

Risk Factors for Major Pregnancy Complications in Female Cardiothoracic Surgeons.

OBJECTIVE: To describe the incidence of and risk factors for pregnancy complications in female cardiothoracic surgeons compared to women of similar sociodemographic profiles. SUMMARY BACKGROUND DATA: Female cardiothoracic surgeons often postpone childbearing, but little is known about their pregnancy outcomes. METHODS: A self-administered survey was distributed to US cardiothoracic surgeons/trainees in 2023. Surgeons with ≥1 live birth were queried on maternal work hours during pregnancy and major antenatal pregnancy complications. Male surgeons answered on behalf of non-surgeon childbearing partners (female non-surgeons). RESULTS: The study included 255 surgeons (63.53% male; 36.47% female). Compared to female surgeons, male surgeons more often had partners who were not employed outside the home (25.64% vs. 13.33%, P<0.001). Female surgeons were older than female non-surgeons at first live birth (34.494.41 vs. 31.454.16, P<0.001), more often worked >60 hours/week during pregnancy (70.33% vs. 14.08%, P<0.001), and more often had pregnancy complications (45.16% vs. 27.16%, P=0.003; OR 1.78, 95%CI:1.01-3.13). Among female surgeons, 18.28% reduced work hours during pregnancy. During their third trimester, 54.84% worked >6 overnight calls/month and 72.04% operated >12 hours/week. Age35yrs (OR 3.28, 95%CI 1.27-8.45) and operating >12 hours/week during the third trimester (OR 3.72, 95%CI 1.04-13.30) were associated with pregnancy complications. CONCLUSIONS: Female cardiothoracic surgeons are more likely to experience major pregnancy complications than non-surgeon partners of their male peers. Long operative hours during pregnancy and older maternal age are significant risk factors for pregnancy complications. To advance gender equity, policies to protect maternal-fetal health and facilitate childbearing during training and early career are needed.

Adult chicken hens (Gallus gallus) have measurable circulating plasma symmetric dimethylarginine via liquid chromatography-tandem mass spectrometry.

OBJECTIVE: To investigate whether chickens (Gallus gallus) have measurable plasma symmetric dimethylarginine (SDMA) and to establish the diagnostic utility of the commercially available immunoassay (IA) for measurement of SDMA. ANIMALS: 245 chicken hens. METHODS: Blood samples were assessed for renal-focused biochemistry analytes. Plasma SDMA was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS/MS) and a high-throughput IA. A Passing-Bablok regression was used to compare the results of IA to LC-MS/MS/MS and reference intervals SDMA values were calculated. RESULTS: The reference interval for plasma SDMA measured by LC-MS/MS/MS is 5.58 to 10.62 µg/dL (range of values, 5 to 15 µg/dL). The concentration of SDMA measured by IA ranged from 1 to 12 µg/dL with a median of 7 µg/dL. Concentrations measured by SDMA-IA demonstrated a low correlation to the SDMA LC-MS/MS reference method. A Passing-Bablok linear regression analysis had a slope of 1.67 (95% CI, 1.35 to 2.14), an intercept of -5.76 (95% CI, -9.90 to -3.35), and a Kendall τ correlation of 0.39. CLINICAL RELEVANCE: SDMA circulates in chicken plasma and should be investigated as a potential renal biomarker in future studies. Because SDMA-IA exhibits a low correlation to the reference method (LC-MS/MS) future assessments of SDMA in chickens should utilize LC-MS/MS assays and compare them to the reference interval created here.

Do vasoactive medications impact donor hearts clinical outcomes in pediatric heart transplantation?

OBJECTIVES: There is limited data examining donor vasopressor and/or inotrope medications (vasoactives) on pediatric orthotopic heart transplant (OHT) outcomes. We aim to evaluate the effects of vasoactives on pediatric OHT outcomes. METHODS: The United Network for Organ Sharing database was retrospectively reviewed from January 2000 to March 2018 for donor hearts. Exclusion criteria included multiorgan transplants and recipient age >18. Donors receiving vasoactives at the time of procurement were compared to donors not on vasoactives, including the number of vasoactives and the type. End-points of interest were survival at 30 days and 1 year as well as post-transplant rejection at 1 year. Logistic and Cox models were used to quantify survival end-points. RESULTS: Of 6462 donors, 3187 (49.3%) were receiving at least one vasoactive. Comparing any vasoactive medication versus none, there was no difference in 30-day survival (p = .27), 1 year survival (p = .89), overall survival (p = .68), or post-transplant rejection (p = .98). There was no difference in 30-day survival for donors receiving 2 or more vasoactive infusions (p = .89), 1 year survival (p = .53), overall survival (p = .75), or post-transplant rejection at 1 year (p = .87). Vasopressin was associated with decreased 30-day mortality (OR = 0.22; p = .028), dobutamine with decreased 1-year mortality (OR = 0.37; p = .036), overall survival (HR = 0.51; p = .003), and decreased post-transplant rejection (HR = 0.63; p = .012). CONCLUSIONS: There is no difference in pediatric OHT outcomes when the cardiac donor is treated with vasoactive infusions at procurement. Vasopressin and dobutamine were associated with improved outcomes. This information can be used to guide medical management and donor selection.

Report of the 2022 Society of Thoracic Surgeons Congenital Heart Surgery Practice Survey.

BACKGROUND: The Society of Thoracic Surgeons Workforce on Congenital Surgery performed a practice survey to analyze contemporary data. METHODS: An electronic survey was sent to congenital heart surgeons in North America. Details on demographics, training paradigm, clinical practice, and work satisfaction were queried, tabulated, and analyzed. RESULTS: Of 312 unique contacts, 201 (64.4%) responded. Of these, 178 (89%) were practicing. The median age was 52 years (interquartile range, 43, 59 years), and 157 (88%) were male. The number of female respondents increased from 12 (7%) in 2015 to 18 (11%) at present. Practice composition was predominantly mixed pediatric and adult (141; 79%), although 15 (8%) surgeons practiced exclusively pediatric surgery. Most surgeons (154; 87%) reported performing the Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category 4 and 5 procedures. One-fourth (42; 24%) reported performing fewer than 50 pediatric cases per year, and 18 (10%) stated that their primary role was as a surgical assistant. Individual surgeon case volume was most commonly 100 to 149 total cases (29%). Although one-half (91; 51%) reported their volume as being "just right," 74 (42%) reported that their case volume was "too small." Seventy-six (43%) reported too many surgeons in their region. Of the 201 practicing surgeons, 30 (14.9%) plan retirement in the next 5 years. Most described career satisfaction, with 102 (57%) being very satisfied and 48 (27%) somewhat satisfied. CONCLUSIONS: Although most congenital heart surgeons in North America are satisfied with their careers, more than 40% believe that their caseload is inadequate and that there are too many surgeons in their region. Further analysis is warranted regarding career dissatisfaction and diversity.

The American Association for Thoracic Surgery (AATS) 2022 Expert Consensus Document: Management of infants and neonates with tetralogy of Fallot.

OBJECTIVE: Despite decades of experience, aspects of the management of tetralogy of Fallot with pulmonary stenosis (TOF) remain controversial. Practitioners must consider newer, evolving treatment strategies with limited data to guide decision making. Therefore, the TOF Clinical Practice Standards Committee was commissioned by the American Association for Thoracic Surgery to provide a framework on this topic, focused on timing and types of interventions, management of high-risk patients, technical considerations during interventions, and best practices for assessment of outcomes of the interventions. In addition, the group was tasked with identifying pertinent research questions for future investigations. It is recognized that variability in institutional experience could influence the application of this framework to clinical practice. METHODS: The TOF Clinical Practice Standards Committee is a multinational, multidisciplinary group of cardiologists and surgeons with expertise in TOF. With the assistance of a medical librarian, a citation search in PubMed, Embase, Scopus, and Web of Science was performed using key words related to TOF and its management; the search was restricted to the English language and the year 2000 or later. Articles pertaining to pulmonary atresia, absent pulmonary valve, atrioventricular septal defects, and adult patients with TOF were excluded, as well as nonprimary sources such as review articles. This yielded nearly 20,000 results, of which 163 were included. Greater consideration was given to more recent studies, larger studies, and those using comparison groups with randomization or propensity score matching. Expert consensus statements with class of recommendation and level of evidence were developed using a modified Delphi method, requiring 80% of the member votes with 75% agreement on each statement. RESULTS: In asymptomatic infants, complete surgical correction between age 3 and 6 months is reasonable to reduce the length of stay, rate of adverse events, and need for a transannular patch. In the majority of symptomatic neonates, both palliation and primary complete surgical correction are useful treatment options. It is reasonable to consider those with low birth weight or prematurity, small or discontinuous pulmonary arteries, chromosomal anomalies, other congenital anomalies, or other comorbidities such as intracranial hemorrhage, sepsis, or other end-organ compromise as high-risk patients. In these high-risk patients, palliation may be preferred; and, in patients with amenable anatomy, catheter-based procedures may prove favorable over surgical palliation. CONCLUSIONS: Ongoing research will provide further insight into the role of catheter-based interventions. For complete surgical correction, both transatrial and transventricular approaches are effective; however, the smallest possible ventriculotomy should be utilized. When possible, the pulmonary valve should be spared; and if unsalvageable, reconstruction can be considered. At the conclusion of the operation, adequate relief of the right ventricular outflow obstruction should be confirmed, and identification of a significant fixed anatomical obstruction should prompt further intervention. Given our current knowledge and the gaps identified, we propose several key questions to be answered by future research and potentially by a TOF registry: When to palliate or proceed with complete surgical correction, as well as the ideal type of palliation; the optimal surgical approach for complete repair for the best long-term preservation of right ventricular function; and the utility, efficacy, and durability of various pulmonary valve preservation and reconstruction techniques.

CLINICOPATHOLOGIC EVALUATION OF AN EX SITU POPULATION OF ADULT AFRICAN WHITE-BELLIED PANGOLIN (PHATAGINUS TRICUSPIS).

Death due to illegal trade and trafficking serves as the largest threat to pangolins in their geographic range countries. Appropriate veterinary care is essential to the welfare of sick or debilitated pangolins. Given the challenge of comprehensive physical examination of this species due to its unique anatomic features and poorly studied physiology, laboratory diagnostics can provide essential information to guide appropriate medical care. This retrospective study included previously analyzed blood and urine samples collected from adult (n = 17) African white-bellied pangolins (Phataginus tricuspis) under managed care that were sampled over a 4-yr period as part of routine veterinary examinations. Samples from clinically normal animals were used to summarize results for this species. Pangolins had a lymphocyte-predominant leukogram with a mean neutrophil to lymphocyte ratio of 0.83 (min-max: 0.13-4.81). Seasonal, sex, and age differences were present for several hematologic and serum biochemical analytes. Urine samples had a median urine specific gravity (USG) of 1.040 (min-max: 1.006-1.060), a neutral-to-basic urine pH (6.0-8.6), and contained mainly struvite crystals or infrequently calcium oxalate dihydrate crystals. Winter samples had higher USG than summer samples. The clinicopathologic data provided herein offers applicable information useful for the clinical management of pangolins.

Cohesin is required for long-range enhancer action at the Shh locus.

The regulatory landscapes of developmental genes in mammals can be complex, with enhancers spread over many hundreds of kilobases. It has been suggested that three-dimensional genome organization, particularly topologically associating domains formed by cohesin-mediated loop extrusion, is important for enhancers to act over such large genomic distances. By coupling acute protein degradation with synthetic activation by targeted transcription factor recruitment, here we show that cohesin, but not CTCF, is required for activation of the target gene Shh by distant enhancers in mouse embryonic stem cells. Cohesin is not required for activation directly at the promoter or by an enhancer located closer to the Shh gene. Our findings support the hypothesis that chromatin compaction via cohesin-mediated loop extrusion allows for genes to be activated by enhancers that are located many hundreds of kilobases away in the linear genome and suggests that cohesin is dispensable for enhancers located more proximally.

PHARMACOKINETICS OF A SINGLE DOSE OF INTRAMUSCULAR AND ORAL MELOXICAM IN YELLOW STINGRAYS (UROBATIS JAMAICENSIS).

Elasmobranchs are popular display animals in public aquaria and zoos, but medical management gaps remain in the understanding of the pharmacokinetics of analgesics and pain management in these species. Meloxicam is a nonsteroidal anti-inflammatory drug that has been evaluated intravenously and intramuscularly in teleosts, but has yet to be studied in any elasmobranch species. The pharmacokinetics of meloxicam were determined in 17 yellow stingrays (Urobatis jamaicensis). All stingrays were determined to be healthy from complete physical examinations and baseline bloodwork performed prior to study inclusion. A single dose of 1 mg/kg meloxicam intramuscularly was administered to all rays, followed by a 2 mg/kg oral dose after an 8 wk washout period. Blood samples were collected from the mesopterygial vein at baseline and nine time points up to 96 h after administration of meloxicam. Plasma concentrations were determined using reversed-phase high-performance liquid chromatography. Pharmacokinetic analysis was performed using a noncompartmental technique. The mean peak plasma concentrations for intramuscular and oral meloxicam were 1.29 and 0.42 µg/ml, respectively. The mean terminal half-lives of meloxicam after intramuscular and oral administration were 5.75 and 15.46 h, respectively. Based on these findings, the recommended meloxicam dosage and frequency for yellow stingrays is 2 mg/kg orally once daily. Due to rapid elimination with the intramuscular administration, maintaining clinically relevant plasma concentrations may be difficult using this route. Further studies are needed to determine multidose pharmacokinetics of meloxicam in yellow stingrays, as well as single-dose and multidose pharmacokinetics in other elasmobranch species.

Women in Thoracic Surgery 2020 Update-Subspecialty and Work-Life Balance Analysis.

BACKGROUND: While women comprise nearly half of medical school graduates, they remain underrepresented in cardiothoracic (CT) surgery. To better understand ongoing barriers, we aimed to delineate issues relevant to the CT subspecialities, emphasizing personal life. METHODS: An anonymous Research Electronic Data Capture (REDCap; hosted at Indiana University School of Medicine) survey link was emailed to female diplomats of the American Board of Thoracic Surgeons (ABTS). The survey included questions on demographics, professional accolades, practice details, and personal life. Survey responses were compared across subspecialities using χ2 testing. RESULTS: Of 354 female ABTS diplomats, we contacted 309, and 176 (57%) completed the survey. By subspecialty, 42% practice thoracic, 26% adult cardiac, and 10% congenital cardiac; 19% report a mixed practice. The subspecialties differed in length of training (congenital-the longest), practice location (mixed practice-less urban), and academic rank (thoracic-most full professors at 17%), but were largely similar in their personal lives. Among all respondents, 65% are in a committed relationship, but 40% felt that being a CT surgeon negatively impacted their ability to find a partner. Sixty percent have children, but 31% of those with children reported using assisted reproductive technology, surrogacy, or adoption. The number with leadership roles (eg, division chief, committee chair of national organization) did not differ among subspecialities, but was low, ranging from 0 to <30%. CONCLUSIONS: Women remain underrepresented in CT surgery, particularly in the academic rank of full professor and in leadership positions. We advocate for scholarship and mentorship opportunities to encourage women to enter the field, increased female leadership, and policies to enable families.

Letter to the Editor: "Use of inhaled epoprostenol with high flow nasal oxygen in non-intubated patients with severe COVID-19".

PURPOSE: Acute lung injury associated with COVID-19 contributes significantly to its morbidity and mortality. Though invasive mechanical ventilation is sometimes necessary, the use of high flow nasal oxygen may avoid the need for mechanical ventilation in some patients. For patients approaching the limits of high flow nasal oxygen support, addition of inhaled pulmonary vasodilators is becoming more common but little is known about its effects. This is the first descriptive study of a cohort of patients receiving inhaled epoprostenol with high flow nasal oxygen for COVID-19. MATERIALS AND METHODS: We collected clinical data from the first fifty patients to receive inhaled epoprostenol while on high flow nasal oxygen at our institution. We compared the characteristics of patients who did and did not respond to epoprostenol addition. RESULTS: The 18 patients that did not stabilize or improve following initiation of inhaled epoprostenol had similar rates of invasive mechanical ventilation as those who improved or stabilized (50% vs 56%). Rates of mortality were not significantly different between the two groups (17% and 31%). CONCLUSIONS: In patients with COVID-19 induced hypoxemic respiratory failure, the use of inhaled epoprostenol with high flow nasal oxygen is feasible, but physiologic signs of response were not related to clinical outcomes.

2020 Women in Thoracic Surgery Update on the Status of Women in Cardiothoracic Surgery.

BACKGROUND: Women in Thoracic Surgery (WTS) has previously reported on the status of women in cardiothoracic (CT) surgery. We sought to provide a 10-year update on women in CT surgery. METHODS: An anonymous research electronic data capture survey link was emailed to female diplomats of the American Board of Thoracic Surgery. Survey questions queried respondents regarding demographics, training, accolades, practice details, and career satisfaction. The survey link was open for 30 days. Results were compared with The Society of Thoracic Surgeons 2019 workforce survey. Descriptive analyses were performed using frequency and proportions. Comparisons were performed using Student's t tests, Fisher's exact tests, and χ2 tests. RESULTS: Of 354 female diplomats, 309 were contacted and 176 (57%) responded. The majority of respondents were aged 36 to 50 years (59%), white (67.4%), and had graduated from traditional-track programs (91.4%). Most respondents reported practicing in an urban (64%) and academic setting (73.1%). 36.4% and 23.9% reported a general thoracic and adult cardiac practice (22.7% mixed practice, 9.6% congenital). Fifty percent of respondents reported salaries between $400,000 and $700,000 annually; 37.7% reported salaries less than 90% of their male colleagues; 21.6% of respondents in academia are full professor; 53.4% reported having a leadership role. Whereas 74.1% would pursue a career in CT surgery again, only 27.3% agreed that CT surgery is a healthy and positive environment for women. CONCLUSIONS: The number of women in CT surgery has steadily increased. Although women are rising in academic rank and into leadership positions, salary disparities and the CT surgery work environment remain important issues in achieving a diverse work force.

Opsoclonus-myoclonus-ataxia syndrome in children.

Opsoclonus-myoclonus-ataxia syndrome is a rare neuroimmunologic disorder typically presenting in previously healthy infants and toddlers. It is characterized by a clinical triad of (1) erratic saccadic intrusions; (2) myoclonus and/or ataxia; (3) behavioral features, typified by developmental plateauing, irritability and insomnia. About half of cases are associated with an underlying neuroblastoma and diagnostic imaging is essential once OMAS is suspected. A thorough workup, including serum, urine, and cerebrospinal fluid studies is critical to identify underlying biomarkers of OMAS itself or neuroblastoma. Historically, many children had relatively poor long-term outcomes, with residual neurologic and/or neuropsychiatry sequelae typical. More recent concepts have emphasized combined immunotherapy regimens that offer hope for better outcomes in children with this remarkable, challenging disease.

Enhancing Support for Women in Cardiothoracic Surgery Through Allyship and Targeted Initiatives.

BACKGROUND: Issues of diversity, equity, and inclusion in cardiothoracic surgery have garnered increased attention. Although barriers persist for women in our field, they may be ameliorated through enhanced support from allies. We aimed to determine best practices for allyship to better support female cardiothoracic surgeons. METHODS: A survey was electronically distributed to members of Women in Thoracic Surgery, addressing presence of female colleagues, sense of allyship among colleagues and leadership, and supportive versus detrimental characteristics of colleagues. Qualitative responses were grouped and coded to identify key themes. RESULTS: Of 309 Women in Thoracic Surgery members, 87 (28%) responded. More than half of respondents felt supported by their male colleagues in the areas of clinical practice, research, teaching, and personal life. Whereas 64% of respondents considered at least one woman in their division an ally, only 48% considered at least one man in their division an ally, and 53% considered their division chief or department chair an ally. A theme of mentorship, support, and sponsorship was reported as the most important quality of allies, regardless of gender. A theme of disrespect, discrimination, stereotyping, and unconscious bias was reported as the most detrimental characteristic of male colleagues, whereas a theme of competitiveness and undermining was reported as the most detrimental of female colleagues. Initiatives to enhance support for female cardiothoracic surgeons were identified, with increased access to mentorship and sponsorship consistently identified as an important endeavor. CONCLUSIONS: Increasing access to mentors, promoting positive behavior, and minimizing detrimental behavior may enhance support for female cardiothoracic surgeons.

Complications associated with total hip arthroplasty in four large nondomestic felids.

CASE DESCRIPTION: A 9-year-old 37-kg sexually intact male snow leopard (Panthera uncia) with no history of lameness but radiographic evidence of right femoral subluxation and flattening of both femoral heads, 2 juvenile (< 1 year old) 25-kg sexually intact male cheetahs (Acinoynx jubatus) with unilateral hind limb lameness resulting from trauma, and an 11-year-old 110-kg sexually intact female Amur tiger (Panthera tigris altaica) with a 2-year history of left hip joint osteoarthritis were examined. CLINICAL FINDINGS: No clinically relevant clinical findings other than hip joint problems were identified. All 4 felids underwent staged bilateral (snow leopard) or unilateral (cheetahs and tiger [Panthera tigris]) total hip arthroplasty (THA). TREATMENT AND OUTCOME: In the snow leopard, both femoral THA components were found to be luxated 1 year after surgery. Treatment consisted of autogenous corticocancellous rib graft augmentation of the dorsal acetabular rims and synthetic suture capsulorrhaphies. The snow leopard lived for an additional 4 years with no additional THA-related complications. In the other 3 animals, catastrophic complications (luxation in the cheetahs and femoral fracture in the tiger) occurred shortly after THA. The THA implants were removed, and excision arthroplasty was performed. Long-term outcomes were good in all 3. CLINICAL RELEVANCE: Findings underscore the challenges associated with THA in large nondomestic felids. Given the high risk for early catastrophic failure as a result of luxation or fracture, plans must be made and resources must be available in case revision surgery or implant removal with excision arthroplasty becomes necessary.

REVIEW OF HISTOLOGIC LESIONS AND MORTALITY IN RIO CAUCA CAECILIANS (TYPHLONECTES NATANS) OVER A 22-YEAR PERIOD.

Rio Cauca caecilians (Typhlonectes natans) are a unique, fully aquatic species of amphibian from the order Gymnophiona. They are housed in several zoological institutions and aquaria with limited information available regarding health and disease. This retrospective study evaluates common pathologic findings and causes of mortality of Rio Cauca caecilians from three different institutions over a 22-y period. Comparisons to previous medical health surveys were conducted with evaluation according to age class and sex to determine whether the primary causes of mortality and common histologic findings have remained similar over time and between institutions. Between 1997 and 2019, the 62 mortalities included males (15/62; 24.2%), females (26/62; 41.9%), and undetermined sex (21/62; 33.9%). The majority of examined individuals were adult (38/62; 61.3%), followed by juveniles (13/62; 21.0%), neonates (9/62; 14.5%), and undetermined age class (2/62; 3.2%). Thirteen (21.0%) individuals were euthanatized. Adult females (16/62; 25.48%) represented the largest group. In adults, the most common lesion and contributor to death was renal disease (28/38; 73.7%) followed by skin disease (16/38; 42.1%), including oomycete dermatitis (8/38; 21.1%) from Saprolegnia sp. Other common findings included bacterial dermatitis, gastrointestinal nematodiasis, and adrenal hyperplasia. This retrospective study will provide a useful reference to help guide veterinary care, management decisions, and collection management planning for this caecilian species in managed care.

Deletion of CTCF sites in the SHH locus alters enhancer-promoter interactions and leads to acheiropodia.

Acheiropodia, congenital limb truncation, is associated with homozygous deletions in the LMBR1 gene around ZRS, an enhancer regulating SHH during limb development. How these deletions lead to this phenotype is unknown. Using whole-genome sequencing, we fine-mapped the acheiropodia-associated region to 12 kb and show that it does not function as an enhancer. CTCF and RAD21 ChIP-seq together with 4C-seq and DNA FISH identify three CTCF sites within the acheiropodia-deleted region that mediate the interaction between the ZRS and the SHH promoter. This interaction is substituted with other CTCF sites centromeric to the ZRS in the disease state. Mouse knockouts of the orthologous 12 kb sequence have no apparent abnormalities, showcasing the challenges in modelling CTCF alterations in animal models due to inherent motif differences between species. Our results show that alterations in CTCF motifs can lead to a Mendelian condition due to altered enhancer-promoter interactions.