Citations

Background: Biomechanical predictors of a second anterior cruciate ligament (ACL) injury after ACL reconstruction (ACLR) and return to sport (RTS) have been identified; however, these measures may not be feasible in a standard clinical environment. Purpose/Hypothesis: The purpose of this study was to evaluate whether standard clinical measures predicted the risk of second ACL injuries. The hypothesis tested was that a combination of strength, function, and patient-reported measures at the time of RTS would predict the risk of second ACL injuries with high sensitivity and specificity. Study Design: Case-control study; Level of evidence, 3 and Cohort study (prognosis); Level of evidence, 1. Methods: A total of 163 participants (mean age, 16.7 ± 3.0 years) who underwent primary ACLR and were able to RTS were evaluated. All participants completed an assessment of isokinetic strength, hop testing, balance, and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Participants were tracked for a minimum of 24 months to identify occurrences of a second ACL injury. The initial 120 participants enrolled were used to develop a clinical prediction model that utilized classification and regression tree (CART) analysis, and the remaining 43 participants enrolled were used as a validation dataset. Additional analyses were performed in all 163 participants using Kaplan-Meier analysis and Cox proportional hazards modeling. Results: Approximately 20% (23/114) of the initial subset of the cohort suffered a second ACL injury. CART analysis identified age, sex, knee-related confidence, and performance on the triple hop for distance at the time of RTS as the primary predictors of a second ACL injury. Using these variables, a model was generated from which high-risk (n = 53) and low-risk groups (n = 61) were identified. A total of 22 participants in the high-risk group and 1 participant in the low-risk group suffered a second ACL injury. High-risk participants fit 1 of 2 profiles: (1) age <19 years, triple hop for distance between 1.34 and 1.90 times body height, and triple hop for distance limb symmetry index (LSI) <98.5% (n = 43) or (2) age <19 years, triple hop for distance >1.34 times body height, triple hop for distance LSI >98.5%, female sex, and high knee-related confidence (n = 10). The validation step identified the high-risk group as being 5 times (odds ratio, 5.14 [95% CI, 1.00-26.46]) more likely to suffer a second ACL injury, with a sensitivity of 66.7% and specificity of 72.0%. Conclusion: These findings recognize measures that accurately identify young patients at high risk of sustaining a second ACL injury within 24 months after RTS. The development of a clinical decision algorithm to identify high-risk patients, inclusive of clinically feasible variables such as age, sex, confidence, and performance on the triple hop for distance, can serve as a foundation to re-evaluate appropriate discharge criteria for RTS.

SummaryBackgroundUp to 80% of patients with Crohn's disease require an abdominal operation in their lifetime. As the use of vedolizumab is increasing for the treatment of Crohn's disease, it is important to understand its potential association with post‐operative complications.AimWe sought to compare 30‐day postoperative infectious complication rate among vedolizumab‐treated Crohn's disease patients vs those who had received TNFα inhibitors or no biologic therapy.MethodsA retrospective review of all Crohn's disease patients who received vedolizumab within 12 weeks of a major abdominal or pelvic operation was performed. Two control cohorts consisted of Crohn's disease patients treated with TNFα inhibitors or no biologic therapy.ResultsOne hundred Crohn's disease patients received vedolizumab within 12 weeks of an abdominal operation. Vedolizumab‐treated patients underwent an equivalent rate of laparoscopic surgery (P = .25), had fewer anastomoses performed (P = .0002), and had equally frequent diversion in the setting of anastomoses (P = .47). Thirty‐two vedolizumab‐treated patients experienced postoperative infectious complications (32%), 26 of which were surgical site infections (26%). The vedolizumab‐treated group experienced no difference in nonsurgical site infections (6% vs 5% anti‐TNFα and 2% nonbiologic; P = .34), but significantly higher rates of surgical site infections (26% vs 8% and 11%; P < .001). On univariate and multivariate analysis, exposure to vedolizumab remained a significant predictor of postoperative surgical site infection (P < .001 and P = .002).ConclusionsTwenty‐six per cent of Crohn's disease patients who received vedolizumab within 12 weeks prior to a major abdominal operation experienced a 30‐day postoperative surgical site infection, significantly higher than that of patients receiving TNFα inhibitors or no biologic therapy. Vedolizumab within 12 weeks of surgery remained a predictor of 30‐day postoperative surgical site infection on multivariable analysis. While vedolizumab‐treated Crohn's disease patients may be a sicker cohort of patients, it is important to consider these findings with regard to preoperative counselling, operative timing and primary closure of wounds.

AbstractRecently, practices have begun integrating cell‐free DNA‐based noninvasive prenatal screening as a screening option for a variety of genetic conditions. According to the National Society of Genetic Counselors, the integration of cfDNA screening into clinical prenatal practice may “significantly shift the paradigm of prenatal testing and screening for all women.” The purpose of this study was to determine whether group information sessions can feasibly serve as an alternative to extended one‐on‐one genetic counseling for the increasing number of women making decisions about prenatal testing and screening. This study assessed the effect of group genetic information sessions coupled with abbreviated counseling on pregnant women's knowledge about and attitudes toward prenatal testing and screening.

Background— Postmortem genetic testing for heritable cardiovascular (CV) disorders is often lacking because ideal specimens (ie, whole blood) are not retained routinely at autopsy. Formalin-fixed paraffin-embedded tissue (FFPET) is ubiquitously collected at autopsy, but DNA quality hampers its use with traditional sequencing methods. Targeted next-generation sequencing may offer the ability to circumvent such limitations, but a method has not been previously described. The primary aim of this study was to develop and evaluate the use of FFPET for heritable CV disorders via next-generation sequencing. Methods and Results— Nineteen FFPET (heart) and blood (whole blood or dried blood spot) specimens underwent targeted next-generation sequencing using a custom panel of 101 CV-associated genes. Nucleic acid yield and quality metrics were evaluated in relation to FFPET specimen age (6 months to 15 years; n=14) and specimen type (FFPET versus whole blood and dried blood spot; n=12). Four FFPET cases with a clinical phenotype of heritable CV disorder were analyzed. Accuracy and precision were 100% concordant between all sample types, with read depths >100× for most regions tested. Lower read depth, as low as 40×, was occasionally observed with FFPET and dried blood spot. High-quality DNA was obtained from FFPET samples as old as 15 years. Genomic analysis of FFPET from the 4 phenotype-positive/genotype unknown cases all revealed putative disease-causing variants. Conclusions— Similar performance characteristics were observed for next-generation sequencing of FFPET, whole blood, and dried blood spot in the evaluation of inherited CV disorders. Although blood is preferable for genetic analyses, this study offers an alternative when only FFPET is available.

ABSTRACTU.S. guidelines recommend BRCA1/2 mutation testing for women diagnosed with high‐grade ovarian cancer (HGOC) to increase recognition of carriers, but most remain unidentified and at risk. Accordingly, an approach termed “Traceback” has been proposed in which probands are retrospectively identified by testing archived pathology specimens, and family members are traced to provide genetic counseling and testing. We used population‐based data to estimate the number of family members who might be contacted through such a program. We used incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program to estimate the number of women diagnosed with HGOC from 2005 to 2016, and census data to estimate the number of spouses, offspring, and siblings (both sexes). Using overall survival for HGOC from SEER and all‐cause mortality rates from the Centers for Diseases Control and Prevention, we estimated the number of patients, spouses, offspring, and siblings of HGOC cases living in 2017. Due to the high mortality rate of HGOC, consent from living probands may be possible in only 42% of the cases; consent to test pathology specimens would need to be sought from next of kin for the remainder. In 2017, an estimated 406,919 living next of kin (spouses, siblings, offspring) would be available for potential consent. Testing archived ovarian cancer pathology specimens may enable the identification of BRCA1/2 mutation carriers, but consent from next of kin would be required in in 58% of cases. Although Traceback offers the possibility of identifying unaffected BRCA1/2 mutation carriers, pilot feasibility studies that include assessment of methods to secure consent are needed.

The natriuretic peptides (NPs) B-type NP (BNP) and urodilatin (URO) exert renal protective properties via the particulate guanylyl cyclase A receptor (pGC-A). As a potential renal-enhancing strategy, we engineered a novel designer peptide that we call CRRL269. CRRL269 was investigated in human cell lines and in normal canines to define potential cardiorenal enhancing actions. The mechanism of its cardiorenal selective properties was also investigated. In vitro NP receptor activity was quantified with guanosine 3′,5′-cyclic monophosphate generation. In vivo effects were determined in normal canine acute infusion studies. We observed that CRRL269 demonstrated enhanced pGC-A activity in renal compared with nonrenal cell lines. CRRL269 exerted enhanced resistance to neprilysin compared with URO. Importantly, CRRL269 exhibited significant and greater increases in urinary sodium excretion and diuresis, with less blood pressure reduction, than BNP or URO in normal canines. CRRL269 retained potent renin-angiotensin-aldosterone system (RAAS) suppressing properties shared by URO and BNP. Also, CRRL269 exerted less arterial relaxation and higher cAMP cardiomyocytes generation than BNP. CRRL269 possessed superior renal and pGC-A activating properties compared with BNP or URO in vitro. CRRL269 exerted enhanced renal actions while suppressing RAAS in vivo and with less hypotension compared with URO or BNP. Together, our study suggests that CRRL269 is a promising innovative renal-enhancing drug, with favorable protective actions targeting cardiorenal disease states through the pGC-A receptor.