Citations

Abstract Background Radiographic leptomeningeal disease (LMD) develops in up to 30% of patients following postoperative stereotactic radiosurgery (SRS) for brain metastases. However, the clinical relevancy of this finding and outcomes after various salvage treatments are not known. Methods Patients with brain metastases, of which 1 was resected and treated with adjunctive SRS, and who subsequently developed LMD were combined from 7 tertiary care centers. LMD pattern was categorized as nodular (nLMD) or classical (“sugarcoating,” cLMD). Results The study cohort was 147 patients. Most patients (60%) were symptomatic at LMD presentation, with cLMD more likely to be symptomatic than nLMD (71% vs. 51%, P = 0.01). Salvage therapy was whole brain radiotherapy (WBRT) alone (47%), SRS (27%), craniospinal radiotherapy (RT) (10%), and other (16%), with 58% receiving a WBRT-containing regimen. WBRT was associated with lower second LMD recurrence compared with focal RT (40% vs 68%, P = 0.02). Patients with nLMD had longer median overall survival (OS) than those with cLMD (8.2 vs 3.3 mo, P < 0.001). On multivariable analysis for OS, pattern of initial LMD (nodular vs classical) was significant, but type of salvage RT (WBRT vs focal) was not. Conclusions Nodular LMD is a distinct pattern of LMD associated with postoperative SRS that is less likely to be symptomatic and has better OS outcomes than classical “sugarcoating” LMD. Although focal RT demonstrated increased second LMD recurrence compared with WBRT, there was no associated OS detriment. Focal cranial RT for nLMD recurrence after surgery and SRS for brain metastases may be a reasonable alternative to WBRT.

Background: Meniscal repair is desirable over resection to prevent postmeniscectomy arthritis, especially among young and active patients. However, long-term data are currently lacking following isolated meniscal repair, particularly in the pediatric population. Purpose/Hypothesis: To report long-term follow-up of isolated meniscal tears treated by meniscal repair in a pediatric and adolescent population and to compare those results with previous midterm follow-up data reported. The authors hypothesized that these patients would have satisfactory function and reoperation rates at long-term follow-up. Study Design: Case series; Level of evidence, 4. Methods: Forty-four patients aged ≤18 years undergoing repair of an isolated meniscal tear (without concomitant anterior cruciate ligament injury) between 1990 and 2005 were included. At the time of final follow-up, recurrent tear, reoperations, and International Knee Documentation Committee (IKDC) and Tegner scores were determined. With logistic regression, the overall failure among tear types was calculated. Wilcoxon rank sum analysis were performed to calculate the differences in clinical outcome for different time points, and Spearman coefficients were calculated for Tegner and IKDC with different variables. Results: At a mean follow-up of 17.6 years (range, 13.1-25.9 years), 32 patients with 33 isolated meniscal repairs (29 male, 3 female) with a mean age of 16.1 years (range, 9.9-18.7 years) at surgery were included in this study. At early follow-up, the overall failure rate was 14 of 33 (42%); complex tears (80%) and bucket-handle tears (47%) had higher overall failure rates when compared with simple tears (18.2%), although only complex tears had a significantly higher failure rate. However, no further failures occurred since midterm follow-up with any tear type. At final follow-up, the mean IKDC score was 92.3, which was significantly increased when compared with preoperative (65.3, P < .0001) and midterm (90.2, P = .01) scores. The mean Tegner score (6.5) was significantly lower than both preoperative (8.3, P < .0001) and midterm (8.4, P < .0001) scores. There was no difference in Tegner or IKDC score for patients with successful versus failed repair. Conclusion: In conclusion, while there was a high early failure rate, this study demonstrated overall good to excellent long-term clinical outcomes after isolated meniscal repair in an adolescent population, even for those requiring reoperation. Early failure and reoperation rates were variable, depending on tear type, with complex multiplanar tears having more failures at short-term follow-up. However, at long-term follow-up, IKDC and Tegner scores were not significantly different for those with complex tears as compared with other tear types.

Abstract Pracinostat, a potent oral pan-histone deacetylase inhibitor with modest single-agent activity in acute myeloid leukemia (AML), has shown synergistic antitumor activity when combined with azacitidine. This single-group, multicenter phase 2 study assessed the safety and efficacy of pracinostat combined with azacitidine in patients who were at least 65 years old with newly diagnosed AML and who were ineligible for standard induction chemotherapy. Patients received pracinostat 60 mg/d, 3 d/wk, for 3 consecutive weeks, plus azacitidine 75 mg/m2 daily for 7 days in a 28-day cycle. Primary endpoints were complete remission (CR), CR with incomplete count recovery (CRi), and morphologic leukemia-free state (MLFS) rates of the combination. Secondary endpoints included safety, progression-free survival (PFS), and overall survival (OS) of the regimen. Fifty patients (33 de novo, 12 secondary, and 5 therapy-related AML) were enrolled. Twenty-six patients (52%) achieved the primary endpoint of CR (42%), CRi (4%), and MLFS (6%). Median OS and PFS were 19.1 months (95% confidence interval [CI], 10-26.5 months) and 12.6 months (95% CI, 10-17.7 months), respectively, with a 1-year OS rate of 62%. Forty-three patients (86%) experienced at least 1 grade 3 or worse treatment-emergent adverse event with the combination, with infections (52%), thrombocytopenia (46%), and febrile neutropenia (44%) reported as the most common toxicities. The 30- and 60-day all-cause mortality rates were 2% and 10%, respectively. DNA sequencing revealed somatic mutations at baseline, and clearance rates correlated with response to treatment. Pracinostat plus azacitidine is a well-tolerated and active regimen in the frontline treatment of older patients with AML unfit for intensive therapy. A larger controlled trial is ongoing. This trial was registered at www.clinicaltrials.gov as #NCT01912274.

ABSTRACTObjectives:The aim of the present study was to investigate the natural history of chronic pancreatitis (CP); patients in the North American Pancreatitis Study2 (NAPS2, adults) and INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE, pediatric) were compared.Methods:Demographics, risk factors, disease duration, management and outcomes of 224 children and 1063 adults were compared using appropriate statistical tests for categorical and continuous variables.Results:Alcohol was a risk in 53% of adults and 1% of children (P < 0.0001); tobacco in 50% of adults and 7% of children (P < 0.0001). Obstructive factors were more common in children (29% vs 19% in adults, P = 0.001). Genetic risk factors were found more often in children. Exocrine pancreatic insufficiency was similar (children 26% vs adult 33%, P = 0.107). Diabetes was more common in adults than children (36% vs 4% respectively, P < 0.0001). Median emergency room visits, hospitalizations, and missed days of work/school were similar across the cohorts. As a secondary analysis, NAPS2 subjects with childhood onset (NAPS2‐CO) were compared with INSPPIRE subjects. These 2 cohorts were more similar than the total INSPPIRE and NAPS2 cohorts, including for genetic risk factors. The only risk factor significantly more common in the NAPS2‐CO cohort compared with the INSPPIRE cohort was alcohol (9% NAPS2‐CO vs 1% INSPPIRE cohorts, P = 0.011).Conclusions:Despite disparity in age of onset, children and adults with CP exhibit similarity in demographics, CP treatment, and pain. Differences between groups in radiographic findings and diabetes prevalence may be related to differences in risk factors associated with disease and length of time of CP.

The Ice Hockey Summit III provided updated scientific evidence on concussions in hockey to inform these five objectives: 1) describe sport-related concussion (SRC) epidemiology, 2) classify prevention strategies, 3) define objective, diagnostic tests, 4) identify treatment, and 5) integrate science and clinical care into prioritized action plans and policy. Our action plan evolved from 40 scientific presentations. The 155 attendees (physicians, athletic trainers, physical therapists, nurses, neuropsychologists, scientists, engineers, coaches, and officials) voted to prioritize these action items in the final Summit session. 1) Establish a national and international hockey data base for SRC at all levels, 2) eliminate body checking in Bantam youth hockey games, 3) expand a behavior modification program (Fair Play) to all youth hockey levels, 4) enforce game ejection penalties for fighting in Junior A and professional hockey leagues, 5) establish objective tests to diagnose concussion at point of care (POC), and 6) mandate baseline testing to improve concussion diagnosis for all age groups. Expedient implementation of the Summit III prioritized action items is necessary to reduce the risk, severity, and consequences of concussion in the sport of ice hockey.

Abstract Removing fighting from ice hockey is an essential concussion prevention strategy that will improve the safety of the game at all levels.

Level of Evidence : 5 Technical Efficacy : Stage 5 J. Magn. Reson. Imaging 2019.

Abstract Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging–Alzheimer's Association describes a biomarker‐based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood‐brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts.

Background: Surgical reconstruction of the anterior cruciate ligament (ACL) is one of the most common orthopaedic procedures, with an estimated 100,000 to 175,000 procedures performed annually. Recently, the all-inside reconstruction technique has come into favor and is theorized to be superior to the complete tibial tunnel technique. Purpose: To compare clinical and patient-reported outcomes (PROs) for hamstring autograft ACL reconstruction (ACLR) performed with an all-inside versus a complete tibial tunnel technique. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who underwent hamstring autograft ACLR via either an all-inside approach (femoral and tibial sockets) or a complete tibial tunnel approach (femoral socket and full-length, transtibial tunnel) at a single institution between July 2011 and July 2015 were reviewed. Demographic information, preoperative comorbidities, surgical details, physical examination findings, and follow-up outcomes were extracted from the medical record. Physical examination data included pivot-shift, Lachman, and range of motion examinations, whereas PROs included the Tegner activity scale, Lysholm score, and International Knee Documentation Committee (IKDC) score at a minimum of 2 years after surgery. Return to sport and risk factors for failure were analyzed. Results: A total of 82 patients (mean ± SD age, 25.8 ± 10.2 years) who underwent all-inside reconstruction (median PRO follow-up, 30.1 months; range, 24.7-72.9 months) and 54 patients (mean ± SD age, 21.1 ± 7.3 years) who underwent complete tibial tunnel reconstruction (median PRO follow-up, 25.8 months; range, 23.9-74.5 months) met the inclusion criteria. PRO scores at latest follow-up were comparable between the all-inside versus the complete tibial tunnel groups (Lysholm score, 93.8 vs 94.4, P = .621; IKDC score, 93.5 vs 93.3, P = .497; Tegner activity score, 6.4 vs 6.8, P = .048). Complications (including graft failure) were experienced by 20% of patients in the all-inside group compared with 24% in the complete tibial tunnel group ( P = .530). Graft failure before the final follow-up was experienced by 10% of patients in the all-inside group compared with 19% in the complete tibial tunnel group ( P = .200). Mean return to sport was 12.5 months in the all-inside group versus 9.9 months in the complete tibial tunnel group ( P = .028). Conclusion: All-inside and complete tibial tunnel hamstring autograft ACLR resulted in excellent physical examination findings and PROs at minimum 2-year follow-up. Both techniques successfully restored knee stability and patient function.

Background: Despite safety concerns, many young patients with implantable cardioverter-defibrillators (ICDs) participate in sports. We undertook a prospective, multinational registry to determine the incidence of serious adverse events because of sports participation. The primary end points were death or resuscitated arrest during sports or injury during sports because of arrhythmia or shock. Secondary end points included system malfunction and incidence of ventricular arrhythmias requiring multiple shocks for termination. Methods: Athletes with ICDs aged ≤21 years were included in this post hoc subanalysis of the ICD Sports Registry. Data on sports and clinical outcomes were obtained by phone interview and medical records review. ICD shocks and clinical details of lead malfunction were classified by 2 electrophysiologists. Results: A total of 129 young athletes participating in competitive (n=117) or dangerous (n=12) sports were enrolled. The mean age was 16 years (range, 10–21; 40% female; 92% white). The most common diagnoses were long QT syndrome (n=49), hypertrophic cardiomyopathy (n=30), and congenital heart disease (n=16). The most common sports were basketball and soccer, including 79 varsity/junior varsity high school and college athletes. During a median follow-up of 42 months, 35 athletes (27%) received 38 shocks. There were no occurrences of death, arrest, or injury related to arrhythmia, during sports. There was 1 ventricular tachycardia/ventricular fibrillation storm during competition. Freedom from lead malfunction was 92.3% at 5 years and 79.6% at 10 years. Conclusions: Although shocks related to competition/practice are not uncommon, there were no serious adverse sequelae. Lead malfunction rates were similar to previously reported in unselected pediatric ICD populations. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00637754.