Familial Associations of Prevalence and Cause-Specific Mortality for Thoracic Aortic Disease and Bicuspid Aortic Valve in a Large-Population Database.

BACKGROUND: Thoracic aortic disease and bicuspid aortic valve (BAV) likely have a heritable component, but large population-based studies are lacking. This study characterizes familial associations of thoracic aortic disease and BAV, as well as cardiovascular and aortic-specific mortality, among relatives of these individuals in a large-population database. METHODS: In this observational case-control study of the Utah Population Database, we identified probands with a diagnosis of BAV, thoracic aortic aneurysm, or thoracic aortic dissection. Age- and sex-matched controls (10:1 ratio) were identified for each proband. First-degree relatives, second-degree relatives, and first cousins of probands and controls were identified through linked genealogical information. Cox proportional hazard models were used to quantify the familial associations for each diagnosis. We used a competing-risk model to determine the risk of cardiovascular-specific and aortic-specific mortality for relatives of probands. RESULTS: The study population included 3 812 588 unique individuals. Familial hazard risk of a concordant diagnosis was elevated in the following populations compared with controls: first-degree relatives of patients with BAV (hazard ratio [HR], 6.88 [95% CI, 5.62-8.43]); first-degree relatives of patients with thoracic aortic aneurysm (HR, 5.09 [95% CI, 3.80-6.82]); and first-degree relatives of patients with thoracic aortic dissection (HR, 4.15 [95% CI, 3.25-5.31]). In addition, the risk of aortic dissection was higher in first-degree relatives of patients with BAV (HR, 3.63 [95% CI, 2.68-4.91]) and in first-degree relatives of patients with thoracic aneurysm (HR, 3.89 [95% CI, 2.93-5.18]) compared with controls. Dissection risk was highest in first-degree relatives of patients who carried a diagnosis of both BAV and aneurysm (HR, 6.13 [95% CI, 2.82-13.33]). First-degree relatives of patients with BAV, thoracic aneurysm, or aortic dissection had a higher risk of aortic-specific mortality (HR, 2.83 [95% CI, 2.44-3.29]) compared with controls. CONCLUSIONS: Our results indicate that BAV and thoracic aortic disease carry a significant familial association for concordant disease and aortic dissection. The pattern of familiality is consistent with a genetic cause of disease. Furthermore, we observed higher risk of aortic-specific mortality in relatives of individuals with these diagnoses. This study provides supportive evidence for screening in relatives of patients with BAV, thoracic aneurysm, or dissection.

The association between parental age differences and perinatal outcomes.

STUDY QUESTION: Are there significant associations existing between parental age differences and adverse perinatal outcomes? SUMMARY ANSWER: Large differences in parental age are associated with adverse perinatal outcomes, particularly with older mothers paired with younger fathers. WHAT IS KNOWN ALREADY: The association between advanced maternal age and perinatal outcomes is well-documented with women over 35 years showing an increased risk of several adverse outcomes. Other studies have identified potential associations between advanced paternal age and adverse perinatal outcomes. STUDY DESIGN, SIZE, DURATION: A historical (retrospective) cohort analysis was performed utilizing a multivariable logistic regression model to evaluate the association between varying differences in parental age and adverse perinatal outcomes while controlling for demographic and health-related covariates. Data were compiled from the National Vital Statistics System for 20 613 704 births between 2012 and 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Parental age differences, categorized into eleven 4-year intervals, were stratified by seven maternal age categories and evaluated for their associations with adverse perinatal outcomes. Main outcome measures included low birth weight, very low birth weight, preterm birth, very preterm birth, small size for gestational age, low 5-min appearance, pulse, grimace, activity, and respiration score, congenital defects, and chromosomal anomalies. MAIN RESULTS AND THE ROLE OF CHANCE: Increased parental age differences, in either direction, were associated with significant risks for all adverse outcomes, aside from congenital defects, even when controlling for maternal age. Restricting maternal age to the reference range of 25-29 years, infants born to fathers aged 9-12 years younger (n = 3773) had 27% (odds ratio (OR) 1.27, 95% CI, 1.17-1.37) higher odds of having any adverse perinatal outcome. Infants born to fathers aged >16 years older (n = 98 555) had 14% (OR 1.14, 95% CI, 1.12-1.16) higher odds of having any adverse perinatal outcome. LIMITATIONS, REASONS FOR CAUTION: Data extracted from US birth certificates may be compromised by errors in reporting or documentation. Information regarding the mother's socioeconomic status was estimated using proxy variables and may be susceptible to uncontrolled factors. Use of a pre-compiled dataset may potentially exclude additional maternal comorbidities that could impact perinatal outcomes. WIDER IMPLICATIONS OF FINDINGS: Older mothers paired with younger fathers demonstrated the highest risk, even when maternal age was below the threshold of 35 years. For the clinical setting, parental age differences should be considered alongside maternal and paternal age when assessing risks of adverse perinatal outcomes for potential parents. This is particularly relevant for older women with younger male partners as this may exacerbate the impact of advanced maternal age. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the NIH Research Fellowship T35 Training Grant. There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Describing patterns of familial cancer risk in subfertile men using population pedigree data.

STUDY QUESTION: Can we simultaneously assess risk for multiple cancers to identify familial multicancer patterns in families of azoospermic and severely oligozoospermic men? SUMMARY ANSWER: Distinct familial cancer patterns were observed in the azoospermia and severe oligozoospermia cohorts, suggesting heterogeneity in familial cancer risk by both type of subfertility and within subfertility type. WHAT IS KNOWN ALREADY: Subfertile men and their relatives show increased risk for certain cancers including testicular, thyroid, and pediatric. STUDY DESIGN, SIZE, DURATION: A retrospective cohort of subfertile men (N = 786) was identified and matched to fertile population controls (N = 5674). Family members out to third-degree relatives were identified for both subfertile men and fertile population controls (N = 337 754). The study period was 1966-2017. Individuals were censored at death or loss to follow-up, loss to follow-up occurred if they left Utah during the study period. PARTICIPANTS/MATERIALS, SETTING, METHODS: Azoospermic (0 × 106/mL) and severely oligozoospermic (<1.5 × 106/mL) men were identified in the Subfertility Health and Assisted Reproduction and the Environment cohort (SHARE). Subfertile men were age- and sex-matched 5:1 to fertile population controls and family members out to third-degree relatives were identified using the Utah Population Database (UPDB). Cancer diagnoses were identified through the Utah Cancer Registry. Families containing ≥10 members with ≥1 year of follow-up 1966-2017 were included (azoospermic: N = 426 families, 21 361 individuals; oligozoospermic: N = 360 families, 18 818 individuals). Unsupervised clustering based on standardized incidence ratios for 34 cancer phenotypes in the families was used to identify familial multicancer patterns; azoospermia and severe oligospermia families were assessed separately. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to control families, significant increases in cancer risks were observed in the azoospermia cohort for five cancer types: bone and joint cancers hazard ratio (HR) = 2.56 (95% CI = 1.48-4.42), soft tissue cancers HR = 1.56 (95% CI = 1.01-2.39), uterine cancers HR = 1.27 (95% CI = 1.03-1.56), Hodgkin lymphomas HR = 1.60 (95% CI = 1.07-2.39), and thyroid cancer HR = 1.54 (95% CI = 1.21-1.97). Among severe oligozoospermia families, increased risk was seen for three cancer types: colon cancer HR = 1.16 (95% CI = 1.01-1.32), bone and joint cancers HR = 2.43 (95% CI = 1.30-4.54), and testis cancer HR = 2.34 (95% CI = 1.60-3.42) along with a significant decrease in esophageal cancer risk HR = 0.39 (95% CI = 0.16-0.97). Thirteen clusters of familial multicancer patterns were identified in families of azoospermic men, 66% of families in the azoospermia cohort showed population-level cancer risks, however, the remaining 12 clusters showed elevated risk for 2-7 cancer types. Several of the clusters with elevated cancer risks also showed increased odds of cancer diagnoses at young ages with six clusters showing increased odds of adolescent and young adult (AYA) diagnosis [odds ratio (OR) = 1.96-2.88] and two clusters showing increased odds of pediatric cancer diagnosis (OR = 3.64-12.63). Within the severe oligozoospermia cohort, 12 distinct familial multicancer clusters were identified. All 12 clusters showed elevated risk for 1-3 cancer types. An increase in odds of cancer diagnoses at young ages was also seen in five of the severe oligozoospermia familial multicancer clusters, three clusters showed increased odds of AYA diagnosis (OR = 2.19-2.78) with an additional two clusters showing increased odds of a pediatric diagnosis (OR = 3.84-9.32). LIMITATIONS, REASONS FOR CAUTION: Although this study has many strengths, including population data for family structure, cancer diagnoses and subfertility, there are limitations. First, semen measures are not available for the sample of fertile men. Second, there is no information on medical comorbidities or lifestyle risk factors such as smoking status, BMI, or environmental exposures. Third, all of the subfertile men included in this study were seen at a fertility clinic for evaluation. These men were therefore a subset of the overall population experiencing fertility problems and likely represent those with the socioeconomic means for evaluation by a physician. WIDER IMPLICATIONS OF THE FINDINGS: This analysis leveraged unique population-level data resources, SHARE and the UPDB, to describe novel multicancer clusters among the families of azoospermic and severely oligozoospermic men. Distinct overall multicancer risk and familial multicancer patterns were observed in the azoospermia and severe oligozoospermia cohorts, suggesting heterogeneity in cancer risk by type of subfertility and within subfertility type. Describing families with similar cancer risk patterns provides a new avenue to increase homogeneity for focused gene discovery and environmental risk factor studies. Such discoveries will lead to more accurate risk predictions and improved counseling for patients and their families. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by GEMS: Genomic approach to connecting Elevated germline Mutation rates with male infertility and Somatic health (Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): R01 HD106112). The authors have no conflicts of interest relevant to this work. TRIAL REGISTRATION NUMBER: N/A.

Single-Photon Emission Computed Tomography/Computed Tomography Utilization for Extremity Melanomas at a High-Volume Center.

INTRODUCTION: Planar lymphoscintigraphy (PL) is commonly used in mapping before sentinel lymph node biopsy (SLNB) for invasive cutaneous melanoma. Recently, single-photon emission computed tomography (SPECT)/ computed tomography (CT) has been utilized, in addition to PL, for detailed anatomic information and detection of sentinel lymph nodes (SLNs) outside of the primary nodal basin in truncal and head and neck melanoma. Following a protocol change due to COVID-19, our institution began routinely obtaining both PL and SPECT-CT imaging for all melanoma SLN mapping. We hypothesized that SPECT-CT is associated with higher instances of SLNBs from "nontraditional" nodal basins (NTNB) for extremity melanomas. METHODS: Patients with extremity melanoma (2017-2022) who underwent SLNB were grouped into SPECT-CT with PL versus PL alone. Outcomes were total SLNs removed, + or-SLN status, total NTNB sampled, and postoperative complication rate. Poisson regression and logistic regression models were used to assess association of SPECT-CT with patient outcomes. RESULTS: Of 380 patients with extremity melanoma, 42.11% had SPECT-CT. There were no differences between the groups with regards to age at diagnosis or sex. From 2020 to 2022, all patients underwent SPECT-CT. SPECT-CT was associated with increased odds of SLNB from an NTNB, (odds ratio = 2.39 [95% confidence interval: 1.25-4.67]). There was no difference in odds of number of SLNs sampled, SLN positivity rate, or postoperative complication rate with SPECT-CT. CONCLUSIONS: Routine SPECT-CT was associated with higher incidence of SLNB in NTNB but did not increase number of SLNs removed or SLN positivity rate. The added value of routine SPECT-CT in cutaneous melanoma of the extremities remains to be defined.

High-intensity statin therapy reduces risk of amputation and reintervention among patients undergoing lower extremity bypass for chronic limb-threatening ischemia.

OBJECTIVE: Statins are considered standard-of-care medical therapy for patients undergoing lower extremity bypass (LEB) procedures for chronic limb-threatening ischemia (CLTI). It is unclear, however, whether up-titrating and maintaining patients on higher-intensity statin medications following LEB improves limb salvage outcomes. This study was designed to evaluate whether high-intensity statin therapy impacts the risk of amputation and reintervention following LEB for patients with CLTI. METHODS: The IBM MarketScan database was used to identify adult patients (18-99 years old) who underwent a LEB for CLTI between 2008 and 2017. Patients lacking insurance covering drug reimbursement or those who already had undergone amputation before time of bypass were excluded. Using pharmacy claims and national drug codes to define statin intensity, patients were stratified into three groups: high-intensity, low-intensity, and limited statin therapy. The association between intensity of statin therapy and need for reintervention and/or major amputation after LEB was analyzed using Kaplan-Meier curves and risk-adjusted Cox proportional hazard models. RESULTS: A total of 25,907 patients who underwent LEB for CLTI were identified, of which 6696 (26%) were maintained on high-dose statins, 9297 (36%) were on low-dose statins, and 9914 (38%) had inconsistent pharmacy claims for statin therapy after surgery. Patients on high-intensity statins were, on average, younger and more likely to be male with comorbid disease (diabetes, hypertension, hyperlipidemia, obesity, renal insufficiency, ischemic heart disease, cerebrovascular disease, and tobacco abuse) than patients on low-intensity statins or limited statin therapy (P < .001 for all comparisons). Following LEB, 6649 patients (25.6%) required a reintervention, and 2550 patients (9.8%) went on to have a major amputation during follow-up. Patients maintained on high-intensity statins after LEB had a significantly lower likelihood of requiring a reintervention (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.45-0.51; P < .001) or amputation (HR, 0.27; 95% CI, 0.24-0.30; P < .001) as compared with patients on limited statin therapy. Further, there was a dose-dependent effect for these outcomes relative to patients on low-intensity statins in risk-adjusted models, and it was independent of whether an autologous vein graft was used for the LEB. Finally, among patients who underwent a reintervention, high-dose statin therapy also significantly reduced the HR for subsequent amputation (HR, 0.21; 95% CI, 0.18-0.25; P < .001). CONCLUSIONS: Patients with CLTI on high-intensity therapy following LEB had a significantly lower risk of requiring subsequent reintervention and amputation when compared with patients on low-intensity statins or with limited statin use. These data suggest that patients with CLTI should be up-titrated and/or maintained on high-intensity statins following revascularization whenever possible.

The Association Between Family History and Diverticulitis Recurrence: A Population-Based Study.

BACKGROUND: After initial nonoperative management of diverticulitis, individuals with a family history of diverticulitis may have increased risk of recurrent disease. OBJECTIVE: This study measured the association between family history and recurrent diverticulitis in a population-based cohort. DESIGN: This is a retrospective, population-based cohort study. SETTINGS: The cohort was identified from the Utah Population Database, a statewide resource linking hospital and genealogy records. PATIENTS: Individuals evaluated in an emergency department or hospitalized between 1998 and 2018 for nonoperatively managed diverticulitis were included. INTERVENTION: The primary predictor was a positive family history of diverticulitis, defined as diverticulitis in a first-, second-, or third-degree relative. MAIN OUTCOME MEASURES: This study measured the adjusted association between family history and the primary outcome of recurrent diverticulitis. A secondary outcome was elective surgery for diverticulitis. Additional analyses evaluated risk by degree of relation of the affected family member. RESULTS: The cohort included 4426 individuals followed for a median of 71 months. Median age was 64 years and 45% were male; 17% had complicated disease, 11% had recurrence, and 15% underwent elective surgery. After adjustment, individuals with a family history of diverticulitis had a similar risk of recurrence when compared to those without a family history (HR 1.0; 95% CI 0.8-1.2). However, individuals with a family history of diverticulitis were more likely to undergo elective surgery (HR 1.4; 95% CI 1.1-1.6). This effect was most pronounced in those with an affected first-degree family member (HR 1.7; 95% CI 1.4-2.2). LIMITATIONS: The use of state-specific data may limit generalizability. CONCLUSIONS: In this population-based analysis, individuals with a family history of diverticulitis were more likely to undergo elective surgery than those without a family history, despite similar risks of recurrence and complicated diverticulitis. Further work is necessary to understand the complex social, environmental, and genetic factors that influence diverticulitis treatment and outcomes. See Video Abstract at http://links.lww.com/DCR/B876 . ASOCIACIN ENTRE LOS ANTECEDENTES FAMILIARES Y LA RECURRENCIA DE LA DIVERTICULITIS UN ESTUDIO POBLACIONAL: ANTECEDENTES:Después del tratamiento inicial no quirúrgico de la diverticulitis, las personas con antecedentes familiares de diverticulitis pueden tener un mayor riesgo de enfermedad recurrente.OBJETIVO:Este estudio midió la asociación entre antecedentes familiares y diverticulitis recurrente en una cohorte poblacional.DISEÑO:Este es un estudio de cohorte retrospectivo de la población.ENTORNO CLÍNICO:La cohorte se identificó a partir de la Base de datos de población de Utah, un recurso estatal que vincula los registros hospitalarios y genealógicos.PACIENTES:Se incluyeron individuos evaluados en un departamento de emergencias u hospitalizados entre 1998 y 2018 por diverticulitis manejada de forma no quirúrgica.INTERVENCIÓN:El predictor principal fue un historial familiar positivo de diverticulitis, definida como diverticulitis en un familiar de primer, segundo o tercer grado.PRINCIPALES MEDIDAS DE VALORACIÓN:Este estudio midió la asociación ajustada entre los antecedentes familiares y el resultado primario de diverticulitis recurrente. Un resultado secundario fue la cirugía electiva por diverticulitis. Análisis adicionales evaluaron el riesgo por grado de parentesco del familiar afectado.RESULTADOS:La cohorte incluyó a 4.426 individuos seguidos durante una mediana de 71 meses. La mediana de edad fue de 64 años y el 45% eran varones. El 17% tenía enfermedad complicada, el 11% recidiva y el 15% se sometió a cirugía electiva. Después del ajuste, los individuos con antecedentes familiares de diverticulitis tenían un riesgo similar de recurrencia en comparación con aquellos sin antecedentes familiares (HR 1,0; IC del 95%: 0,8-1,2). Sin embargo, las personas con antecedentes familiares de diverticulitis tenían más probabilidades de someterse a una cirugía electiva (HR 1,4; IC del 95%: 1,1-1,6). Este efecto fue más pronunciado en aquellos con un familiar de primer grado afectado (HR 1,7; IC del 95%: 1,4-2,2).LIMITACIONES:El uso de datos específicos del estado puede limitar la generalización.CONCLUSIONES:En este análisis poblacional, los individuos con antecedentes familiares de diverticulitis tenían más probabilidades de someterse a una cirugía electiva que aquellos sin antecedentes familiares, a pesar de riesgos similares de recurrencia y diverticulitis complicada. Es necesario seguir trabajando para comprender los complejos factores sociales, ambientales y genéticos que influyen en el tratamiento y los resultados de la diverticulitis. Consulte Video Resumen en http://links.lww.com/DCR/B876 . (Traducción-Dr. Ingrid Melo ).

Exogenous Testosterone Replacement Therapy Is Associated with Increased Risk for Vascular Graft Infections Among Hypogonadal Men.

BACKGROUND: Vascular graft infections (VGIs) are a major source of morbidity following vascular bypass surgery. Hypogonadal men may be at increased risk for impaired wound healing and infections, but it is unclear if testosterone replacement therapy (TRT) mitigates this risk. We designed this study to evaluate the relationship between hypogonadism and the use of testosterone replacement therapy (TRT) with subsequent risk for developing a VGI. METHODS: We performed a retrospective analysis of claims in the MarketScan database identifying men greater than 18 years of age who underwent placement of a prosthetic graft in the peripheral arterial circulation from January 2009 to December 2020. Patients were stratified based on diagnosis of hypogonadism and use of TRT within 180 days before surgery. The primary outcome was VGI and the need for surgical excision. The association between hypogonadism and TRT use on risk of VGI was analyzed using Kaplan-Meier plots and multivariate Cox proportional hazards models. RESULTS: We identified 18,312 men who underwent a prosthetic bypass graft procedure in the upper and lower extremity during the study period, of which 802 (5%) had diagnosis of hypogonadism. Among men with hypogonadism, 251 (31%) were receiving TRT. Patients on TRT were younger, more likely to be diabetic, and more likely develop a VGI during follow-up (14% vs. 8%; P < 0.001) that was in the lower extremity. At 5 years, freedom from VGI was significantly lower for hypogonadal men on TRT than patients not on TRT or without hypogonadism (Log rank P < 0.001). In Cox regression models adjusted for age, diabetes, obesity, smoking, corticosteroid use, and procedure type, hypogonadal men on TRT were at a significantly increased risk of graft infection (hazard ratio (HR):1.94, 95% confidence interval (CI):1.4-2.7; P < 0.001) compared to controls. CONCLUSIONS: This study demonstrates TRT among hypogonadal men is associated with an increased risk of prosthetic VGIs. Temporary cessation of TRT should be considered for men undergoing prosthetic graft implants, particularly those in the lower extremity.

Nephrectomy Is Not Associated with Increased Risk of Mortality or Acute Kidney Injury after High-Grade Renal Trauma: A Propensity Score Analysis of the Trauma Quality Improvement Program (TQIP).

PURPOSE: Patients with high-grade renal trauma (HGRT) undergoing nephrectomy may be at higher risk for mortality compared to those treated conservatively. However, no study has controlled for degree of hemorrhage as a measure of shock. We hypothesized that after controlling for blood transfusions and other factors, nephrectomy after HGRT would be associated with increased mortality and acute kidney injury (AKI). MATERIALS AND METHODS: We identified adult patients with HGRT (American Association for the Surgery of Trauma grade III-V) in TQIP (2013-2017). Propensity scoring was used to adjust for the probability of nephrectomy. Conditional logistic regression was used to analyze the association between nephrectomy and mortality and AKI. We adjusted for patient characteristics, injury specifics, and physiological factors including blood transfusions. RESULTS: There were 12,780 patients with HGRT, and 1,014 (7.9%) underwent nephrectomy. Mortality was 10.6% and 4.2% in the nephrectomy and nonnephrectomy groups, respectively (p <0.001). In nephrectomy patients, 8.6% experienced AKI vs 2.4% of nonnephrectomy patients (p <0.001). In the adjusted analysis, there was no association between nephrectomy and mortality (OR=0.367, 95% CI 0.09-1.497, p=0.162). There was also no association between nephrectomy and AKI. Increasing age, nonCaucasian race, increasing Injury Severity Score, decreasing Glasgow Coma Score and blood transfusions were associated with higher mortality. For AKI, independent predictors included increasing age, male sex, and blood transfusions. CONCLUSIONS: After adjusting for volume of blood transfused in the first 24 hours, nephrectomy after HGRT was not associated with increased mortality or AKI. As a clinical principle, trauma nephrectomy should be avoided when possible.

Risk of Postoperative Thromboembolism in Men Undergoing Urological Prosthetic Surgery: An Assessment of 21,413 Men.

PURPOSE: We assessed venous thromboembolism (VTE) and associated risk factors following artificial urinary sphincter (AUS) and inflatable penile prosthesis (IPP) surgery. MATERIALS AND METHODS: Using IBM® MarketScan, a commercial claims database, patients undergoing AUS and IPP surgery were identified using CPT® and ICD (International Classification of Diseases)-10 procedure codes between 2008 and 2017. ICD-9 and -10 codes were used to identify health care visits associated with lower extremity deep vein thrombosis (DVT) and pulmonary embolism (PE) within 90 days of surgery. Covariates were assessed using a multivariable model to determine association with outcome of DVT and/or PE. RESULTS: A total of 21,413 men underwent AUS (4,870) or IPP (16,543) surgery between 2008 and 2017 with a median age of 62 years and 68 years, respectively. DVT and PE events following AUS and IPP surgery occurred in 1.54% and 1.04%, respectively. A history of varicose veins (HR 2.76; 95% CI 1.11-6.79), prior history of DVT (HR 13.65; 95% CI 7.4-25.19), or PE (HR 7.65; 95% CI 4.01-14.6) in those undergoing AUS surgery was highly associated with development of postoperative VTE. Likewise, prior history of DVT (HR 12.6; 95% CI 7.99-19.93) and PE (HR 8.9; 95% CI 5.6-14.13) was strongly associated with a VTE event following IPP surgery. CONCLUSIONS: In a large cohort of men undergoing AUS and IPP surgery, 1.54% and 1.04% of men experienced a VTE event within 90 days of surgery, respectively. Prior history of varicose veins, DVT, and PE was associated with an increased likelihood of developing a postoperative DVT or PE.

Healthcare Burden and Cost in Children with Anorectal Malformation During the First 5 Years of Life.

OBJECTIVE: To identify cumulative 5-year healthcare costs and healthcare days in children with anorectal malformation (ARM) and to compare the cumulative 5-year healthcare costs and healthcare days in children with ARM with 3 control cohorts: healthy, premature, and congenital heart disease (CHD). STUDY DESIGN: We performed a retrospective case-control study using the Truven MarketScan database of commercial claims encounters between 2008 and 2017. The ARM, CHD, and premature cohorts were identified using a targeted list of International Classification of Diseases 9th or 10th Revision diagnosis and Current Procedural Terminology codes. The healthy cohort included patients without ARM, preterm birth, or CHD. RESULTS: We identified 664 children with ARM, 3356 children with heart disease, 63 190 children who were born preterm, and 2947 healthy patients. At 5 years, the total healthcare costs of children with ARM ($273K, 95% CI $168K-$378K) were similar to the premature cohort ($246K, 95% CI $237K-$255K) and lower than the CHD cohort ($466K, 95% CI $401K-$530K, P < .001). Total healthcare days were similar in children with ARM (158 days, 95% CI 117-198) and prematurity (141 days, 95% CI 137-144) but lower than CHD (223 days, 95% CI 197-250, P = .02). In ARM, outpatient care (126 days, 95% CI 93-159) represented the largest contribution to total healthcare days. CONCLUSIONS: Children with ARM accumulate similar healthcare costs to children with prematurity and comparable healthcare days to children with CHD and prematurity in the first 5 years of life. Outpatient care represents the majority of healthcare days in children with ARM, identifying this as a target for quality improvement and demonstrating the long-term impact of this condition.

Long-term declines in bird populations in tropical agricultural countryside.

Tropical agriculture is a major driver of biodiversity loss, yet it can provide conservation opportunities, especially where protected areas are inadequate. To investigate the long-term biodiversity capacity of agricultural countryside, we quantified bird population trends in Costa Rica by mist netting 57,255 birds of 265 species between 1999 and 2010 in sun coffee plantations, riparian corridors, secondary forests, forest fragments, and primary forest reserves. More bird populations (69) were declining than were stable (39) or increasing (4). Declines were common in resident, insectivorous, and more specialized species. There was no relationship between the species richness of a habitat and its conservation value. High-value forest bird communities were characterized by their distinct species composition and habitat and dietary functional signatures. While 49% of bird species preferred forest to coffee, 39% preferred coffee to forest and 12% used both habitats, indicating that coffee plantations have some conservation value. Coffee plantations, although lacking most of the forest specialists, hosted 185 bird species, had the highest capture rates, and supported increasing numbers of some forest species. Coffee plantations with higher tree cover (7% vs. 13%) had more species with increasing capture rates, twice as many forest specialists, and half as many nonforest species. Costa Rican countryside habitats, especially those with greater tree cover, host many bird species and are critical for connecting bird populations in forest remnants. Diversified agricultural landscapes can enhance the biodiversity capacity of tropical countryside, but, for the long-term persistence of all forest bird species, large (>1,000 ha) protected areas are essential.

Predictors of Adherence to Anti-Impulse Therapy among Patients Treated for Acute Type-B Aortic Dissections.

BACKGROUND: Medical management remains the mainstay of treatment for patients who present with acute Type-B aortic dissections (TBAD). However, it is unclear whether patients maintain adherence to their anti-impulse therapy medication regimen following hospital discharge. This study was designed to evaluate rates and predictors of medication adherence among insured patients treated for acute TBAD. METHODS: We used the Truven MarketScan database to identify US patients who presented with an acute TBAD between 2008 to 2017. Patients with continuous health insurance (Commercial or Medicare Part C) for at least 12 months after TBAD diagnosis were stratified by whether they underwent open surgical repair (OPEN), thoracic endovascular aortic repair (TEVAR), or only medication management (MED). Prescriptions for anti-impulse therapy medications were captured and adherence was defined by the medication possession ratio as > 80% fill rate over the follow-up period. Mixed-effects logistic regression models were used to identify predictors for medication adherence. RESULTS: A total of 6,702 patients were identified that underwent treatment for TBAD (3% TEVAR, 9% OPEN, & 74% MED), whereas 14% received no intervention. The overall mean (±SD) rate of adherence to anti-impulse therapy was 72.6% ( ± 26), and varied based on type of TBAD intervention (73.4% TEVAR, 74.4% OPEN, & 72.4% MED). The majority of patients across all treatment groups were prescribed ≥ 2 agents, with beta-blockers and diuretics being the most common medication classes. The odds of adherence to anti-impulse therapy were significantly lower for patients who were female (OR: 0.93; 95%CI:0.85-0.99; P = 0.03), aged < 45 years (OR: 0.81; 95%CI:0.69-0.96; P < 0.001), nonadherent on preexisting therapy (OR: 0.81; 95%CI: 0.73-0.89; P < 0.001), and when medications were obtained in less than a 90 days supply from retail pharmacies. CONCLUSIONS: Nearly a quarter of patients were nonadherent with anti-impulse therapy prescribed following an acute TBAD, which was more likely among younger female patients not adherent before their event. Adherence was improved among patients who received their medications by mail and when a > 90 days supply was prescribed. These findings may be used by quality improvement initiatives to improve medication adherence following TBAD and help prevent further complications.

Balancing revenue generation with capacity generation: case distribution, financial impact and hospital capacity changes from cancelling or resuming elective surgeries in the US during COVID-19.

BACKGROUND: To increase bed capacity and resources, hospitals have postponed elective surgeries, although the financial impact of this decision is unknown. We sought to report elective surgical case distribution, associated gross hospital revenue and regional hospital and intensive care unit (ICU) bed capacity as elective surgical cases are cancelled and then resumed under simulated trends of COVID-19 incidence. METHODS: A retrospective, cohort analysis was performed using insurance claims from 161 million enrollees from the MarketScan database from January 1, 2008 to December 31, 2017. COVID-19 cases were calculated using Institute for Health Metrics and Evaluation models. Centers for Disease Control (CDC) reports on the number of hospitalized and intensive care patients by age estimated the number of cases seen in the ICU, the reduction in elective surgeries and the financial impact of this from historic claims data, using a denominator of all inpatient revenue and outpatient surgeries. RESULTS: Assuming 5% infection prevalence, cancelling all elective procedures decreases ICU overcapacity from 160 to 130%, but these elective surgical cases contribute 78% (IQR 74, 80) (1.1 trillion (T) US dollars) to inpatient hospital plus outpatient surgical gross revenue per year. Musculoskeletal, circulatory and digestive category elective surgical cases compose 33% ($447B) of total revenue. CONCLUSIONS: Procedures involving the musculoskeletal, cardiovascular and digestive system account for the largest loss of hospital gross revenue when elective surgery is postponed. As hospital bed capacity increases following the COVID-19 pandemic, restoring volume of these elective cases will help maintain revenue. In these estimates, adopting universal masking would help to avoid overcapacity in all states.

Coronavirus Disease 2019 (COVID-19) and Venous Thromboembolism During Pregnancy and Postpartum.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with increased risk for macro- and micro-thrombi. Consensus guidelines recommend use of thromboprophylaxis in nonobstetric patients with SARS-CoV-2 infection admitted to the hospital. National-level studies evaluating venous thromboembolism (VTE) among pregnant and postpartum individuals with and without SARS-CoV-2 infection have not been completed. We performed a retrospective cohort study of individuals aged 18 years or older delivering at more than 20 weeks of gestation with data in the MarketScan Commercial Insurance Database from 2016 through 2020. Of 811,008 deliveries, SARS-CoV-2 infection during pregnancy or through 6 weeks postpartum was associated with increased risk for VTE compared with no infection (1.0% vs 0.5%, adjusted hazard ratio 2.62, 95% CI 1.60-4.29). Findings support further consideration of thromboprophylaxis in the obstetric population with SARS-CoV-2 infection.

Untreated hypogonadism and testosterone replacement therapy in hypogonadal men are associated with a decreased risk of subsequent prostate cancer: a population-based study.

We sought to understand the relationship between hypogonadism and testosterone replacement therapy (TRT) in hypogonadal men on the risk of developing localized and metastatic prostate cancer. We used the Merative MarketScan database of commercial claims encounters to identify men diagnosed with hypogonadism. These men were matched to eugonadal men who served as controls. Multivariate negative binomial regression analysis of prostate cancer diagnoses, hypogonadism, and TRT in hypogonadal men adjusting for various known confounding factors was used to understand the impact of hypogonadism and TRT on prostate cancer risk. We identified 3,222,904 men who met inclusion criteria, of which 50% were diagnosed with hypogonadism (1,611,452) and each were matched to a control (1,611,452). The incidence of prostate cancer was 2.16%, 1.55%, and 1.99% in eugonadal controls, hypogonadal men on TRT, and hypogonadal men without TRT, respectively (p < 0.001). Untreated hypogonadism was independently associated with a decreased risk of localized prostate cancer (IRR 0.46, 95% CI 0.43-0.50, p < 0.001) compared to eugonadal controls. Hypogonadal men on TRT also had a significantly decreased risk of localized prostate cancer (IRR 0.49, 95% CI 0.45-0.53, p < 0.001). Furthermore, hypogonadal men on TRT (IRR 0.21, 95% CI 0.19-0.24, p < 0.001) or without TRT (IRR 0.20, 95% CI 0.18-0.22, p < 0.001) both had significantly decreased risk of metastatic prostate cancer, respectively. Our population-based analysis suggests that untreated hypogonadism in men is associated with a 50% decreased incidence of localized prostate cancer and an 80% decreased incidence of metastatic prostate cancer. TRT in hypogonadal men was also associated with a decreased risk of subsequent prostate cancer. Further research is needed to better understand the relationship between hypogonadism and TRT in hypogonadal men on the risk of subsequent prostate cancer.

Cost and utilization analysis of concurrent versus staged testicular prosthesis implantation for radical orchiectomy.

PURPOSE: American Urological Association guidelines recommend testicular prosthesis discussion prior to orchiectomy. Utilization may be low. We compared outcomes and care utilization between concurrent implant (CI) and staged implant (SI) insertion after radical orchiectomy. MATERIALS & METHODS: The MarketScan Commercial claims database (2008-2017) was queried for men ages >18 years who underwent radical orchiectomy for testicular mass, stratified as orchiectomy with no implant, CI, or SI. 90-day outcomes included rate of reoperation, readmission, emergency department (ED) presentation, and outpatient visits. Regression models provided rate ratio comparison. RESULTS: 8803 patients (8564 no implant, 190 CI, 49 SI; 2.7% implant rate) were identified with no difference in age, Charlson Comorbidity Index, insurance plan, additional cancer treatment, or metastasis. Median perioperative cost at orchiectomy (+/- implant) for no implant, CI, and SI were $5682 (3648-8554), $7823 (5403-10973), and $5380 (4130-10521), respectively (p<0.001). Median perioperative cost for SI at implantation was $8180 (4920-14591) for a total cost (orchiectomy + implant) of $13650 (5380 + 8180). CI patients were more likely to have follow-up (p = 0.006) with more visits (p = 0.030) compared to the SI group post-implantation but had similar follow-up (p = 0.065) and less visits (p = 0.025) compared to the SI patients' post-orchiectomy period. Overall explant rates were 4.7% for CI and 14.3% for SI (p = 0.04) with a median time to explant of 166 (IQR: 135-210) and 40 days (IQR: 9.5-141.5; p = 0.06). Median cost of removal was $2060 (IQR: 967-2880). CONCLUSIONS: CI placement has less total perioperative cost, lower explant rate, and similar postoperative utilization to SI.

Transgenerational effects of paternal exposures: the role of germline de novo mutations.

Germline de novo mutations (DNMs) refer to spontaneous mutations arising during gametogenesis, resulting in genetic changes within germ cells that are subsequently transmitted to the next generation. While the impact of maternal exposures on germline DNMs has been extensively studied, more recent studies have begun to highlight the increasing importance of the effects of paternal factors. In this review, we have summarized the existing literature on how various exposures experienced by fathers affect the germline DNM burden in their spermatozoa, as well as their consequences for semen analysis parameters, pregnancy outcomes, and offspring health. A growing body of literature supports the conclusion that advanced paternal age (APA) correlates with a higher germline DNM rate in offspring. Furthermore, lifestyle choices, environmental toxins, assisted reproductive techniques (ART), and chemotherapy are associated with the accumulation of paternal DNMs in spermatozoa, with deleterious consequences for pregnancy outcomes and offspring health. Ultimately, our review highlights the clear importance of the germline DNM mode of inheritance, and the current understanding of how this is affected by various paternal factors. In addition, we explore conflicting reports or gaps of knowledge that should be addressed in future research.

Recurrence of severe diverticulitis is associated with age and birth decade.

BACKGROUND: The risk of recurrence is an important consideration when deciding to treat patients medically or with elective colectomy after recovery from diverticulitis. It is unclear whether age is associated with recurrence. This study aimed to examine the relationship between age and the risk of recurrent diverticulitis while considering important epidemiologic factors, such as birth decade. METHODS: The Utah Population Database was used to identify individuals with incident severe diverticulitis, defined as requiring an emergency department visit or hospitalization, between 1998 and 2018. This study measured the relationship between age and recurrent severe diverticulitis after adjusting for birth decade and other important variables, such as sex, urban/rural status, complicated diverticulitis, and body mass index using a Cox proportional hazards model. RESULTS: The cohort included 8606 individuals with a median age of 61 years at index diverticulitis diagnosis. After adjustment, among individuals born in the same birth decade, increasing age at diverticulitis onset was associated with an increased risk of recurrent diverticulitis (hazard ratio [HR] for 10 years, 1.8; 95% CI, 1.5-2.1). Among individuals with the same age of onset, those born in a more recent birth decade were also at greater risk of recurrent diverticulitis (HR, 1.9; 95% CI, 1.6-2.3). CONCLUSION: Among individuals with an index episode of severe diverticulitis, recurrence was associated with increasing age and more recent birth decade. Clinicians may wish to employ age-specific strategies when counseling patients regarding treatment options after a diverticulitis diagnosis.

Hispanic Ethnicity and Fertility Outcomes.

OBJECTIVE: To assess the association between ethnicity and fertility outcomes for men in a statewide cohort. METHODS: We linked data from the Utah Population Database and Subfertility Health Assisted Reproduction and Environment database, to comprise a cohort of sub-fertile men who underwent semen analysis between 1998 and 2017 in Utah. A multivariable Cox proportional hazard model was constructed to understand the impact of ethnicity on fertility outcomes in our cohort. RESULTS: A total of 11,363 men were included. 1039 (9.1%) were Hispanic. 39.7% of men in the lowest socioeconomic status group were Hispanic (P <.001). When controlling for demographic and clinical factors, the number of live births was reduced for Hispanic men (hazard ratios [HR] = 0.62 [0.57-0.67], P <.001). Though fertility treatment had a positive effect (HR 1.242 [1.085-1.421], P <.001), in competing risks models, Hispanic men were less likely to use fertility treatment (HR = 0.633 [0.526-0.762], P <.001). CONCLUSION: Hispanic ethnicity is significantly associated with a lower likelihood of successful fertility outcomes in Utah. Hispanic men had nearly a 40% reduced likelihood of live births when controlling for sociodemographic factors. Our results indicate that, depending on age, Hispanic men have up to approximately 14 fewer live births per 100 men per year, pointing to a significant disparity in fertility outcomes in the state of Utah. Given 15.1% of Utah's population identifies as Hispanic and 18.7% of the United States population identifies as Hispanic on the 2020 Census, a better understanding of the association of ethnicity and fertility outcomes is imperative.

Animal migration in the Anthropocene: threats and mitigation options.

Animal migration has fascinated scientists and the public alike for centuries, yet migratory animals are facing diverse threats that could lead to their demise. The Anthropocene is characterised by the reality that humans are the dominant force on Earth, having manifold negative effects on biodiversity and ecosystem function. Considerable research focus has been given to assessing anthropogenic impacts on the numerical abundance of species/populations, whereas relatively less attention has been devoted to animal migration. However, there are clear linkages, for example, where human-driven impacts on migration behaviour can lead to population/species declines or even extinction. Here, we explore anthropogenic threats to migratory animals (in all domains - aquatic, terrestrial, and aerial) using International Union for the Conservation of Nature (IUCN) Threat Taxonomy classifications. We reveal the diverse threats (e.g. human development, disease, invasive species, climate change, exploitation, pollution) that impact migratory wildlife in varied ways spanning taxa, life stages and type of impact (e.g. from direct mortality to changes in behaviour, health, and physiology). Notably, these threats often interact in complex and unpredictable ways to the detriment of wildlife, further complicating management. Fortunately, we are beginning to identify strategies for conserving and managing migratory animals in the Anthropocene. We provide a set of strategies that, if embraced, have the potential to ensure that migratory animals, and the important ecological functions sustained by migration, persist.