Erratum regarding missing ethics approval and consent to participate statements in previously published articles.

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Emerging biologic augmentation strategies for meniscal repair: a systematic review.

BACKGROUND: Meniscal repair should be the gold standard. However, the meniscus is poorly vascularized and even an excellent meniscus repair may not heal. Therefore, numerous studies and systematic reviews have been carried out on platelet-rich plasma (PRP), mesenchymal stem cells (MSCs) and fibrin clots for meniscal augmentation, but the results remain controversial. This systematic review aimed to identify other emerging strategies for meniscal repair augmentation and to assess whether there are different avenues to explore in this field. METHODS: A systematic literature review was conducted in August 2022. PubMed, Ovid MEDLINE(R) all, Ovid All EBM Reviews, Ovid Embase and ISI Web of Science databases were searched. In Vivo animal and human studies concerning the biological augmentation of meniscal lesions by factors other than PRP, MSCs or fibrin clots were included. Cartilage-only studies, previous systematic reviews and expert opinions were excluded. All data were analyzed by two independent reviewers. RESULTS: Of 8965 studies only nineteen studies covering 12 different factors met the inclusion criteria. Eight studies investigated the use of growth factors for meniscal biologic augmentation, such as vascular endothelial growth factor or bone morphogenic protein 7. Five studies reported on cell therapy and six studies focused on other factors such as hyaluronic acid, simvastatin or atelocollagen. Most studies (n = 18) were performed on animal models with gross observation and histological evaluation as outcomes. Polymerase chain reaction and immunohistochemistry were also common. Biomechanical testing was the object of only two studies. CONCLUSIONS: Although several augmentation strategies have been attempted, none has yielded conclusive results, testifying to a lack of understanding with regard to meniscal healing. More research is needed to better understand the pathways that regulate meniscus repair and how to act positively on them. LEVEL OF EVIDENCE: Systematic review of case-control and animal laboratory studies.

Seroprevalence of Mycobacterium avium subsp. paratuberculosis in Swiss dairy herds and risk factors for a positive herd status and within-herd prevalence.

Introduction: Bovine paratuberculosis (PTB) is a chronic enteric disease caused by Mycobacterium avium subsp. paratuberculosis (MAP). Control of PTB is important given its negative economic consequences and the potential zoonotic role of MAP in Crohn's disease in humans. Methods: To determine the seroprevalence of MAP in Swiss dairy herds and to identify risk factors associated with seropositive herd status and high within-herd seroprevalence, 10,063 serum samples collected from cattle over 12 months of age in 171 Swiss dairy farms were analyzed using a commercial ELISA test. Eight herds were excluded due to non-interpretable ELISA results. Risk factors associated with seropositive herd status and high within-herd seroprevalence were investigated with regression models using results from a questionnaire on management practices possibly associated with the introduction or spread of MAP in the remaining 163 herds. Univariable logistic regression was performed, carrying forward for multivariable regression analysis when p < 0.2. Results: The calculated between-herd true seroprevalence was 3.6% (95% CI, 0.96-8.4%). Due to the low within-herd seroprevalence, it was not possible to calculate the true seroprevalence at animal level; the apparent within-herd seroprevalence ranged from 2.3 to 5.5% with a median of 3.6% in nine positive farms. Herd size (p = 0.037) and the common grazing of lactating cows with cows from other herds (p = 0.014) were associated with seropositive herd status, while heifers sharing alpine pasture with dairy cattle from other herds were associated with a decreased probability of the herd to test seropositive (p = 0.042). Reliable identification of significant risk factors associated with MAP spread and high seroprevalence of PTB within seropositive herds was not possible due to low observed seroprevalence within herds and low sensitivity of the ELISA test. Discussion: These results highlight the limitation of serology for MAP diagnosis in small herds with low infection prevalence.

Uncovering Unrecognized Heart Failure With Preserved Ejection Fraction Among Individuals With Obesity and Dyspnea.

BACKGROUND: Although heart failure with preserved ejection fraction (HFpEF) has become the predominant heart failure subtype, it remains clinically under-recognized. HFpEF diagnosis is particularly challenging in the setting of obesity given the limitations of natriuretic peptides and resting echocardiography. We examined invasive and noninvasive HFpEF diagnostic criteria among individuals with obesity and dyspnea without known cardiovascular disease to determine the prevalence of hemodynamic HFpEF in the community. METHODS: Research volunteers with dyspnea and obesity underwent resting echocardiography; participants with possible pulmonary hypertension qualified for invasive cardiopulmonary exercise testing. HFpEF was defined using rest or exercise pulmonary capillary wedge pressure criteria (≥15 mm Hg or Δpulmonary capillary wedge pressure/Δcardiac output slope, >2.0 mm Hg·L-1·min-1). RESULTS: Among n=78 participants (age, 53±13 years; 65% women; body mass index, 37.3±6.8 kg/m2), 40 (51%) met echocardiographic criteria to undergo invasive cardiopulmonary exercise testing. In total, 24 participants (60% among the cardiopulmonary exercise testing group, 31% among the total sample) were diagnosed with HFpEF by rest or exercise pulmonary capillary wedge pressure (n=12) or exercise criteria (n=12). There were no differences in NT-proBNP (N-terminal pro-B-type natriuretic peptide; 79 [62-104] versus 73 [57-121] pg/mL) or resting echocardiography (mitral E/e' ratio, 9.1±3.1 versus 8.0±2.7) among those with versus without HFpEF (P>0.05 for all). Distributions of HFpEF diagnostic scores were similar, with the majority classified as intermediate risk (100% versus 93.75% [H2FPEF] and 87.5% versus 68.75% [HFA-PEFF (Heart Failure Association Pretest assessment, echocardiography and natriuretic peptide, functional testing, and final etiology)] in those with versus without HFpEF). CONCLUSIONS: Among adults with obesity and dyspnea without known cardiovascular disease, at least a third had clinically unrecognized HFpEF uncovered on invasive cardiopulmonary exercise testing. Clinical, biomarker, resting echocardiography, and diagnostic scores were similar among those with and without HFpEF. These results suggest clinical underdiagnosis of HFpEF among individuals with obesity and dyspnea and highlight limitations of noninvasive testing in the identification of HFpEF.

A Fast-Binding, Functionally Reversible, COX-2 Radiotracer for CNS PET Imaging.

Cyclooxygenase-2 (COX-2) is an enzyme that plays a pivotal role in peripheral inflammation and pain via the prostaglandin pathway. In the central nervous system (CNS), COX-2 is implicated in neurodegenerative and psychiatric disorders as a potential therapeutic target and biomarker. However, clinical studies with COX-2 have yielded inconsistent results, partly due to limited mechanistic understanding of how COX-2 activity relates to CNS pathology. Therefore, developing COX-2 positron emission tomography (PET) radiotracers for human neuroimaging is of interest. This study introduces [11C]BRD1158, which is a potent and uniquely fast-binding, selective COX-2 PET radiotracer. [11C]BRD1158 was developed by prioritizing potency at COX-2, isoform selectivity over COX-1, fast binding kinetics, and free fraction in the brain. Evaluated through in vivo PET neuroimaging in rodent models with human COX-2 overexpression, [11C]BRD1158 demonstrated high brain uptake, fast target-engagement, functional reversibility, and excellent specific binding, which is advantageous for human imaging applications. Lastly, post-mortem samples from Huntington's disease (HD) patients and preclinical HD mouse models showed that COX-2 levels were elevated specifically in disease-affected brain regions, primarily from increased expression in microglia. These findings indicate that COX-2 holds promise as a novel clinical marker of HD onset and progression, one of many potential applications of [11C]BRD1158 human PET.

Animal models used in meniscal repair research from ex vivo to in vivo: A systematic review.

This systematic review, registered with Prospero, aims to identify an optimal animal model for meniscus repair research, moving from ex vivo experimentation to in vivo studies. Data sources included PubMed, Medline, all Evidence-Based Medicine Reviews, Web of Science, and Embase searched in March 2023. Studies were screened using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Extracted data including animal model, type of experiment, type of tear, surgical techniques, and measured outcomes, were recorded, reviewed, and analyzed by four independent reviewers. The SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) Rob tool was used for critical appraisal and risk of bias assessment. Out of 11,719 studies, 72 manuscripts were included for data extraction and analysis; 41 ex vivo extra-articular studies, 20 ex vivo intra-articular studies, and only 11 in vivo studies. Six animal models were employed: porcine, bovine, lapine, caprine, canine, and ovine. Longitudinal lesions were the most frequently studied tear pattern and sutures the most common repair technique. Studied outcomes focused mainly on biomechanical assessments and gross observations. This systematic review can guide researchers in their choice of animal model for meniscus repair research; it highlighted the strengths of the porcine, caprine, and bovine models for ex vivo cadaveric studies, while the porcine and caprine models were found to be more suited to in vivo studies due to their similarities with human anatomy. Research teams should familiarize themselves with the advantages and disadvantages of various animal models before initiating protocols to improve standardization in the field.

A Grading System-Guided Approach to the Severely Contracted Nose.

PURPOSE: Capsular contracture is a rare but serious complication of silicone implant-based augmentation rhinoplasty. When severe, the contracture can affect all layers of the nose, causing significant scarring and disfigurement. There is currently no standardized method of evaluating contracted noses and a paucity of literature on the treatment of severe contracture. Therefore, this study aimed to establish a comprehensive grading system and treatment approach for patients with nasal contracture secondary to silicone implant-based rhinoplasty. METHODS: We conducted a retrospective analysis on patients who presented with nasal contracture from 2012 to 2021. All preoperative photographs were evaluated by two plastic surgeons, twice at 1-month intervals. The proposed grading system comprised: normal (grade I), mild contracture with detectable implant (grade II), moderate contracture with skin thinning (grade III), severe contracture with short nose deformity (grade IV), and destructive contracture with scarring of the dorsal skin (grade Va), or columella deficiency (grade Vb). Inter- and intraobserver agreement was assessed using the kappa value to determine the reliability of the system. RESULTS: Based on 87 patients, interobserver agreement was substantial for both evaluation time points (k = 0.701 and 0.723). Intraobserver agreement was excellent for evaluator 1 (k = 0.822) and substantial for evaluator 2 (k = 0.699). CONCLUSIONS: Using this grading system, we propose a graduated treatment algorithm for contracted noses. Most notable is our use of radial forearm free or forehead flaps to reconstruct the columella in grade Vb patients. By combining reconstructive and aesthetic principles, this treatment approach provides an effective and elegant solution for the management of the severely contracted nose. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Intra-operative evaluation of textured anatomic implant rotation: a prospective study.

BACKGROUND: Textured implants were developed with the goal of reducing rates of capsular contracture and preventing implant malposition (eg., malrotation). Recent evidence has questioned whether textured implants are as resistant to malrotation as previously reported. METHODS: Women presenting to a single healthcare system for removal of textured implants were prospectively enrolled in the study from September 2019 to July of 2022. Patients who underwent removal of an anatomic, textured implant in the operating room were included in the study, while those who did not undergo implant removal, or were found to have a smooth implant, or a round, textured implant were excluded. The degree of implant rotation upon removal of the implant was measured intra-operatively. Implant specific factors, as well as patient demographics, clinical factors, and operative characteristics were collected. RESULTS: A total of 51 patients (80 implants) were included in the study. 45% of implants were malrotated (rotated >30 degrees) and the median degree of rotation was 30. Having more than one previous revision of the breast pocket was predictive of implant rotation (42 degrees) on multivariate linear regression analysis. Patients who presented with a complaint of "aesthetic dissatisfaction" had 2.89 increased odds of having an implant rotated > 30 degrees. CONCLUSION: Our study found a high rate of malrotation of textured, shaped implants upon explantation.

Rare Variant Genetics and Dilated Cardiomyopathy Severity: The DCM Precision Medicine Study.

BACKGROUND: Dilated cardiomyopathy (DCM) can lead to advanced disease, defined herein as necessitating a durable left ventricular assist device or a heart transplant (LVAD/HT). DCM is known to have a genetic basis, but the association of rare variant genetics with advanced DCM has not been studied. METHODS: We analyzed clinical and genetic sequence data from patients enrolled between 2016 and 2021 in the US multisite DCM Precision Medicine Study, which was a geographically diverse, multiracial, multiethnic cohort. Clinical evaluation included standardized patient interview and medical record query forms. DCM severity was classified into 3 groups: patients with advanced disease with LVAD/HT; patients with an implantable cardioverter defibrillator (ICD) only; or patients with no ICD or LVAD/HT. Rare variants in 36 DCM genes were classified as pathogenic or likely pathogenic or variants of uncertain significance. Confounding factors we considered included demographic characteristics, lifestyle factors, access to care, DCM duration, and comorbidities. Crude and adjusted associations between DCM severity and rare variant genetic findings were assessed using multinomial models with generalized logit link. RESULTS: Patients' mean (SD) age was 51.9 (13.6) years; 42% were of African ancestry, 56% were of European ancestry, and 44% were female. Of 1198 patients, 347 had LVAD/HT, 511 had an ICD, and 340 had no LVAD/HT or ICD. The percentage of patients with pathogenic or likely pathogenic variants was 26.2%, 15.9%, and 15.0% for those with LVAD/HT, ICD only, or neither, respectively. After controlling for sociodemographic characteristics and comorbidities, patients with DCM with LVAD/HT were more likely than those without LVAD/HT or ICD to have DCM-related pathogenic or likely pathogenic rare variants (odds ratio, 2.3 [95% CI, 1.5-3.6]). The association did not differ by ancestry. Rare variant genetic findings were similar between patients with DCM with an ICD and those without LVAD/HT or ICD. CONCLUSIONS: Advanced DCM was associated with higher odds of rare variants in DCM genes adjudicated as pathogenic or likely pathogenic, compared with individuals with less severe DCM. This finding may help assess the risk of outcomes in management of patients with DCM and their at-risk family members. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03037632.

Identifying high risk clinical phenogroups of pulmonary hypertension through a clustering analysis.

INTRODUCTION: The classification and management of pulmonary hypertension (PH) is challenging due to clinical heterogeneity of patients. We sought to identify distinct multimorbid phenogroups of patients with PH that are at particularly high-risk for adverse events. METHODS: A hospital-based cohort of patients referred for right heart catheterization between 2005-2016 with PH were included. Key exclusion criteria were shock, cardiac arrest, cardiac transplant, or valvular surgery. K-prototypes was used to cluster patients into phenogroups based on 12 clinical covariates. RESULTS: Among 5208 patients with mean age 64±12 years, 39% women, we identified 5 distinct multimorbid PH phenogroups with similar hemodynamic measures yet differing clinical outcomes: (1) "young men with obesity", (2) "women with hypertension", (3) "men with overweight", (4) "men with cardiometabolic and cardiovascular disease", and (5) "men with structural heart disease and atrial fibrillation." Over a median follow-up of 6.3 years, we observed 2182 deaths and 2002 major cardiovascular events (MACE). In age- and sex-adjusted analyses, phenogroups 4 and 5 had higher risk of MACE (HR 1.68, 95% CI 1.41-2.00 and HR 1.52, 95% CI 1.24-1.87, respectively, compared to the lowest risk phenogroup 1). Phenogroup 4 had the highest risk of mortality (HR 1.26, 95% CI 1.04-1.52, relative to phenogroup 1). CONCLUSIONS: Cluster-based analyses identify patients with PH and specific comorbid cardiometabolic and cardiovascular disease burden that are at highest risk for adverse clinical outcomes. Interestingly, cardiopulmonary hemodynamics were similar across phenogroups, highlighting the importance of multimorbidity on clinical trajectory. Further studies are needed to better understand comorbid heterogeneity among patients with PH.

Genetic Architecture of Dilated Cardiomyopathy in Individuals of African and European Ancestry.

Importance: Black patients with dilated cardiomyopathy (DCM) have increased familial risk and worse outcomes than White patients, but most DCM genetic data are from White patients. Objective: To compare the rare variant genetic architecture of DCM by genomic ancestry within a diverse population of patients with DCM. Design: Cross-sectional study enrolling patients with DCM who self-identified as non-Hispanic Black, Hispanic, or non-Hispanic White from June 7, 2016, to March 15, 2020, at 25 US advanced heart failure programs. Variants in 36 DCM genes were adjudicated as pathogenic, likely pathogenic, or of uncertain significance. Exposure: Presence of DCM. Main Outcomes and Measures: Variants in DCM genes classified as pathogenic/likely pathogenic/uncertain significance and clinically actionable (pathogenic/likely pathogenic). Results: A total of 505, 667, and 26 patients with DCM of predominantly African, European, or Native American genomic ancestry, respectively, were included. Compared with patients of European ancestry, a lower percentage of patients of African ancestry had clinically actionable variants (8.2% [95% CI, 5.2%-11.1%] vs 25.5% [95% CI, 21.3%-29.6%]), reflecting the lower odds of a clinically actionable variant for those with any pathogenic variant/likely pathogenic variant/variant of uncertain significance (odds ratio, 0.25 [95% CI, 0.17-0.37]). On average, patients of African ancestry had fewer clinically actionable variants in TTN (difference, -0.09 [95% CI, -0.14 to -0.05]) and other genes with predicted loss of function as a disease-causing mechanism (difference, -0.06 [95% CI, -0.11 to -0.02]). However, the number of pathogenic variants/likely pathogenic variants/variants of uncertain significance was more comparable between ancestry groups (difference, -0.07 [95% CI, -0.22 to 0.09]) due to a larger number of non-TTN non-predicted loss of function variants of uncertain significance, mostly missense, in patients of African ancestry (difference, 0.15 [95% CI, 0.00-0.30]). Published clinical case-based evidence supporting pathogenicity was less available for variants found only in patients of African ancestry (P < .001). Conclusion and Relevance: Patients of African ancestry with DCM were less likely to have clinically actionable variants in DCM genes than those of European ancestry due to differences in genetic architecture and a lack of representation of African ancestry in clinical data sets.

Early changes in soluble intracellular adhesion molecule-1 as prognostic biomarkers to immune checkpoint inhibitor.

Serologic biomarker to predict clinical outcome is needed for immune checkpoint inhibitors (ICIs). We evaluated soluble intercellular adhesion molecules-1 (sICAM-1) as a predictor of response to ICIs treatment. Ninety-five patients with cancer treated with ICI were studied. The serum sICAM-1 levels of baseline, post two cycle therapy and end of therapy (EOT) were measured by enzyme-linked immunoassay. We randomly assigned the patients into the primary cohort (n = 47) and validation cohort (n = 48). Serum sICAM-1 post two cycle (277.7 ± 181.6 ng/mL) and EOT (403.9 ± 218.9 ng/mL) were significantly elevated compared to baseline (244.8 ± 153.8 ng/mL, p = 0.008 and p = 0.004, respectively). Early changes of sICAM-1 (ΔsICAM-1), deemed as sICAM-1 after two cycles minus baseline, were assessed. Following ICI treatments, responders had significantly lower ΔsICAM-1 compared with nonresponders in the primary cohort (p = 0.040) and the validation cohort (p = 0.026). High ΔsICAM-1 was strongly associated with inferior progression-free survival (PFS; (primary cohort: p = 0.001 and validation cohort: p = 0.002) and overall survival (OS; (primary cohort: p < 0.001 and validation cohort: p = 0.007). The ΔsICAM-1 remained independently associated with worse PFS and OS in the primary cohort and the validation cohort. Subgroup analysis indicated patients whose sICAM-1 significantly elevated had shorter PFS and OS in both anti-PD-1 and anti-PD-L1 treatment groups. Early change of serum sICAM-1 could be used to monitor and predict clinical benefit of ICI therapy in patients with solid cancer.

Screening for Dilated Cardiomyopathy in At-Risk First-Degree Relatives.

BACKGROUND: Cardiovascular screening is recommended for first-degree relatives (FDRs) of patients with dilated cardiomyopathy (DCM), but the yield of FDR screening is uncertain for DCM patients without known familial DCM, for non-White FDRs, or for DCM partial phenotypes of left ventricular enlargement (LVE) or left ventricular systolic dysfunction (LVSD). OBJECTIVES: This study examined the yield of clinical screening among reportedly unaffected FDRs of DCM patients. METHODS: Adult FDRs of DCM patients at 25 sites completed screening echocardiograms and ECGs. Mixed models accounting for site heterogeneity and intrafamilial correlation were used to compare screen-based percentages of DCM, LVSD, or LVE by FDR demographics, cardiovascular risk factors, and proband genetics results. RESULTS: A total of 1,365 FDRs were included, with a mean age of 44.8 ± 16.9 years, 27.5% non-Hispanic Black, 9.8% Hispanic, and 61.7% women. Among screened FDRs, 14.1% had new diagnoses of DCM (2.1%), LVSD (3.6%), or LVE (8.4%). The percentage of FDRs with new diagnoses was higher for those aged 45 to 64 years than 18 to 44 years. The age-adjusted percentage of any finding was higher among FDRs with hypertension and obesity but did not differ statistically by race and ethnicity (16.2% for Hispanic, 15.2% for non-Hispanic Black, and 13.1% for non-Hispanic White) or sex (14.6% for women and 12.8% for men). FDRs whose probands carried clinically reportable variants were more likely to be identified with DCM. CONCLUSIONS: Cardiovascular screening identified new DCM-related findings among 1 in 7 reportedly unaffected FDRs regardless of race and ethnicity, underscoring the value of clinical screening in all FDRs.

Complications Associated with Cervical Cerclage: A Systematic Review.

Cervical cerclages are associated with improved live birth rates and have low short- and long-term risks. However, there have been reports of fistula formation or erosion of cerclage into the surrounding tissue. Those complications are uncommon and yet are serious. The risk factors associated with its development are still unclear. The purpose of our study was to evaluate the incidence of fistula formation or erosion following transvaginal cervical cerclage and the associated clinical and sociodemographic factors. We conducted a systematic search of PubMed, Medline, and Embase databases to retrieve articles related to transvaginal or transabdominal cervical cerclage. Databases were searched up to July 2021. The study protocol was registered (PROSPERO ID 243542). A total of 82 articles were identified describing cervical cerclage and erosion or fistula formation. A total of 9 full-text articles were included. There were seven case reports and series that described 11 patients who experienced late complications following cervical cerclage. Many of the cerclage procedures were done electively (66.7%). The most common type of cerclage was McDonald (80%). While all cases reported fistula formation, the main location was vesicovaginal fistulas (63.6%). One patient (9.1%) had erosion of their cerclage and another (9.1%) had bladder calculi. Of 75 patients who underwent cerclage in two retrospective case reviews, the overall incidence of fistula was 1.3% and abscess was also 1.3%. Although rare, the most common long-term complication of cervical cerclage placement is fistula formation, particularly vesicovaginal fistulas.

Effectiveness of the Family Heart Talk Communication Tool in Improving Family Member Screening for Dilated Cardiomyopathy: Results of a Randomized Trial.

BACKGROUND: Managing disease risk among first-degree relatives of probands diagnosed with a heritable disease is central to precision medicine. A critical component is often clinical screening, which is particularly important for conditions like dilated cardiomyopathy (DCM) that remain asymptomatic until severe disease develops. Nonetheless, probands are frequently ill-equipped to disseminate genetic risk information that motivates at-risk relatives to complete recommended clinical screening. An easily implemented remedy for this key issue has been elusive. METHODS: The DCM Precision Medicine Study developed Family Heart Talk, a booklet designed to help probands with DCM communicate genetic risk and the need for cardiovascular screening to their relatives. The effectiveness of the Family Heart Talk booklet in increasing cardiovascular clinical screening uptake among first-degree relatives was assessed in a multicenter, open-label, cluster-randomized, controlled trial. The primary outcome measured in eligible first-degree relatives was completion of screening initiated within 12 months after proband enrollment. Because probands randomized to the intervention received the booklet at the enrollment visit, eligible first-degree relatives were limited to those who were alive the day after proband enrollment and not enrolled on the same day as the proband. RESULTS: Between June 2016 and March 2020, 1241 probands were randomized (1:1) to receive Family Heart Talk (n=621) or not (n=620) within strata defined by site and self-identified race/ethnicity (non-Hispanic Black, non-Hispanic White, or Hispanic). Final analyses included 550 families (n=2230 eligible first-degree relatives) in the Family Heart Talk arm and 561 (n=2416) in the control arm. A higher percentage of eligible first-degree relatives completed screening in the Family Heart Talk arm (19.5% versus 16.0%), and the odds of screening completion among these first-degree relatives were higher in the Family Heart Talk arm after adjustment for proband randomization stratum, sex, and age quartile (odds ratio, 1.30 [1-sided 95% CI, 1.08-∞]). A prespecified subgroup analysis did not find evidence of heterogeneity in the adjusted intervention odds ratio across race/ethnicity strata (P=0.90). CONCLUSIONS: Family Heart Talk, a booklet that can be provided to patients with DCM by clinicians with minimal additional time investment, was effective in increasing cardiovascular clinical screening among first-degree relatives of these patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03037632.

Outcomes of two different unbalanced segregations from a maternal t(4;10)(q33;p15.1) translocation.

BACKGROUND: Unbalanced translocations can cause developmental delay (DD), intellectual disability (ID), growth problems, dysmorphic features, and congenital anomalies. They may arise de novo or may be inherited from a parent carrying a balanced rearrangement. It is estimated that 1/500 people is a balanced translocation carrier. The outcomes of different chromosomal rearrangements have the potential to reveal the functional consequences of partial trisomy or partial monosomy and can help guide genetic counseling for balanced carriers, and other young patients diagnosed with similar imbalances. METHODS: We performed clinical phenotyping and cytogenetic analyses of two siblings with a history of developmental delay (DD), intellectual disability (ID) and dysmorphic features. RESULTS: The proband, a 38-year-old female, has a history of short stature, dysmorphic features and aortic coarctation. She underwent chromosomal microarray analysis, which identified partial monosomy of 4q and partial trisomy of 10p. Her brother, a 37-year-old male, has a history of more severe DD, behavioral problems, dysmorphic features, and congenital anomalies. Subsequently, karyotype confirmed two different unbalanced translocations in the siblings: 46,XX,der(4)t(4;10)(q33;p15.1) and 46,XY,der(10)t(4;10)(q33;p15.1), respectively. These chromosomal rearrangements represent two possible outcomes from a parent who is a carrier for a balanced translocation 46,XX,t(4;10)(q33;p15.1). CONCLUSION: To our knowledge, this 4q and 10p translocation has not been described in literature. In this report we compare clinical features due to the composite effects of partial monosomy 4q with partial trisomy 10p and partial trisomy 4q with partial monosomy 10p. These findings speak to the relevance of old and new genomic testing, the viability of these segregation outcomes, and need for genetic counseling.

Knowledge of Genome Sequencing and Trust in Medical Researchers Among Patients of Different Racial and Ethnic Groups With Idiopathic Dilated Cardiomyopathy.

Importance: Cardiovascular disease contributes outsized mortality in patients from underrepresented racial and ethnic groups. Understanding levels of trust in medical researchers and knowledge of genome sequencing may help identify barriers to research participation and develop strategies to educate patients about the role of genetics in cardiovascular disease. Objective: To assess racial and ethnic differences in trust in medical researchers and genome-sequencing knowledge among patients with idiopathic dilated cardiomyopathy and determine the association between trust in medical researchers and genome-sequencing knowledge. Design, Setting, and Participants: This cross-sectional study conducted by a consortium of 25 US heart failure programs included patients with idiopathic dilated cardiomyopathy defined as left ventricular systolic dysfunction and left ventricular enlargement after excluding usual clinical causes. Enrollment occurred from June 7, 2016, to March 15, 2020. Main Outcomes and Measures: Percent distributions, means, and associations of genome-sequencing knowledge scores and research trust scores for Hispanic, non-Hispanic Black (hereafter referred to as Black), and non-Hispanic White participants (hereafter referred to as White). Results: Among 1121 participants, mean (SD) age was 51.6 (13.6) years with 41.4% Black, 8.5% Hispanic, and 43.4% female. After accounting for site effects, the level of genome-sequencing knowledge was lower in Hispanic and Black participants compared with White participants (mean score difference, -2.6; 95% CI, -3.9 to -1.2 and mean score difference, -2.9; 95% CI, -3.6 to -2.2, respectively). The level of trust in researchers was lowest in Black participants (mean score, 27.7), followed by Hispanic participants (mean score, 29.4) and White participants (mean score, 33.9). Racial and ethnic differences remained after adjusting for education, age at enrollment, duration of dilated cardiomyopathy, and health status. A higher level of trust was associated with a higher level of genome-sequencing knowledge within different racial and ethnic groups. Conclusions and Relevance: In this cross-sectional study, large racial and ethnic differences in levels of genome-sequencing knowledge and trust in medical researchers were observed among patients with dilated cardiomyopathy. Findings from this study can inform future studies that aim to enhance the uptake of genomic knowledge and level of trust in medical researchers.

Strategies for Enhancing the Implementation of Universal Mental Health Prevention Programs in Schools: A Systematic Review.

A number of school-based mental health prevention programs have been found to be effective in research trials, but little is known about how to support implementation in real-life settings. To address this translational problem, this systematic review aims to identify effective strategies for enhancing the implementation of mental health prevention programs for children in schools. Four electronic databases were searched for empirical, peer-reviewed articles in English from January 2000 to October 2021 reporting the effects of implementation strategies for school-based universal mental health programs. Twenty-one articles were included in the narrative synthesis and assessed for quality using the Mixed Methods Appraisal Tool. Twenty-two strategies were found to be effective at improving program fidelity or adoption. The strategies with the strongest positive evidence base were those that involved monitoring and provision of feedback, engaging principals as program leaders, improving teachers' buy-in and organising school personnel implementation meetings. We recommend school-based practitioners trial strategies with positive findings from this review as part of their continuous quality improvement. This review highlights the pressing need for large-scale, randomised controlled trials to develop and trial more robust strategies to enhance adoption, as the five implementation studies found to measure adoption used qualitative methods limited by small samples sizes and case study designs.