Citations

PURPOSE American Society of Radiation Oncology (ASTRO) has developed a guideline on appropriate radiation therapy for brain metastases. ASCO has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations. METHODS “Radiation Therapy for Brain Metastases: An ASTRO Clinical Practice Guideline” 2 was reviewed for developmental rigor by methodologists. An ASCO Endorsement Panel subsequently reviewed the content and the recommendations. RESULTS The ASCO Endorsement Panel determined that the recommendations from the ASTRO guideline, published May 6, 2022, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorses “Radiation Therapy for Brain Metastases: An ASTRO Clinical Practice Guideline.” 2 RECOMMENDATIONS Within the guideline, stereotactic radiosurgery (SRS) is recommended for patients with Eastern Cooperative Oncology Group performance status of 0-2 and up to four intact brain metastases, and conditionally recommended for patients with up to 10 intact brain metastases. The guideline provides detailed dosing and fractionation recommendations on the basis of the size of the metastases. For patients with resected brain metastases, radiation therapy (SRS or whole-brain radiation therapy [WBRT]) is recommended to improve intracranial disease control; if there are limited additional brain metastases, SRS is recommended over WBRT. For patients with favorable prognosis and brain metastases ineligible for surgery and/or SRS, WBRT is recommended with hippocampal avoidance where possible and the addition of memantine is recommended. For patients with brain metastases, limiting the single-fraction V 12Gy to brain tissue to ≤ 10 cm 3 is conditionally recommended. Additional information is available at www.asco.org/neurooncology-guidelines .

Background: Wrestling is a physically demanding sport, with young athletes prone to anterior cruciate ligament (ACL) injuries. There is a paucity of data evaluating the results of ACL reconstruction (ACLR) in this cohort. Purpose: To assess return to sport (RTS), patient-reported outcomes, reoperation rates, and graft survival after ACLR in a large cohort of competitive wrestlers at midterm follow-up. Study Design: Case series; Level of evidence, 4. Methods: We identified all competitive wrestlers (club, high school, collegiate, or professional) with a history of an ACLR at a single institution between 2000 and 2019. Graft failure was defined as a retear (as determined via clinical or advanced imaging evaluation) and/or revision ACLR. All patients were contacted for determination of reinjury rates; current sport status; and pain visual analog scale, International Knee Documentation Committee, and Tegner activity scores. Results: Included were 107 knees in 103 wrestlers, with a median follow-up time of 5.9 years (interquartile range [IQR], 3.9-10.3 years). The median age was 17 years (IQR, 15-18 years), with 106 (99%) male patients, and the distribution of bone–patellar tendon–bone (BTB) and hamstring tendon (HT) autografts was 64 (60%) and 43 (40%), respectively. At final follow-up, 80% of athletes were able to RTP at a median of 280 days (IQR, 212-381 days). Graft failure occurred in 14 (13%) knees at a median time of 1.8 years (IQR, 0.7-5.3 years) after the index ACLR. BTB autograft demonstrated a lower failure rate compared with HT autograft (8% vs 21%; P = .044) and was associated with better survival compared with HT autograft up to 15 years after the index ACLR (90.4% vs 76.3%; P = .030). When compared by graft diameter, HT autografts of at least 7.5 mm were not associated with a lower graft failure than BTB constructs of all sizes ( P = .205). Conclusion: Return to competitive wrestling was observed in 80% of athletes after ACLR, with 14% of wrestlers experiencing graft failure. BTB autograft was associated with better survival than HT autograft.

Background: Cerebral microbleeds (CMBs) are a common vascular pathology associated with future intracerebral hemorrhage. Plasma biomarkers of amyloid, tau, and neurodegeneration may provide a screening avenue to identify those with CMBs, but evidence is conflicting. Objective: To determine the association between plasma biomarkers (Aβ40, Aβ42, t-tau, p-tau181, p-tau217, neurofilament light chain (NfL)) and CMBs in a population-based study of aging and whether these biomarkers predict higher signal on Aβ-PET imaging in patients with multiple CMBs. Methods: 712 participants from the Mayo Clinic Study of Aging with T2* GRE MRI and plasma biomarkers were included. Biomarkers were analyzed utilizing Simoa (Aβ40, Aβ42, t-tau, NfL) or Meso Scale Discovery (p-tau181, p-tau217) platforms. Cross-sectional associations between CMBs, plasma biomarkers and Aβ-PET were evaluated using hurdle models and multivariable regression models. Results: Among the 188 (26%) individuals with≥1 CMB, a lower plasma Aβ42/Aβ40 ratio was associated with more CMBs after adjusting for covariables (IRR 568.5 95% CI 2.8–116,127). No other biomarkers were associated with risk or number CMBs. In 81 individuals with≥2 CMBs, higher plasma t-tau, p-tau181, and p-tau217 all were associated with higher Aβ-PET signal, with plasma p-tau217 having the strongest predictive value (r2 0.603, AIC –53.0). Conclusion: Lower plasma Aβ42/Aβ40 ratio and higher plasma p-tau217 were associated with brain amyloidosis in individuals with CMBs from the general population. Our results suggest that in individuals with multiple CMBs and/or lobar intracranial hemorrhage that a lower plasma Aβ42/Aβ40 ratio or elevated p-tau217 may indicate underlying cerebral amyloid angiopathy.

Hodgkin lymphoma (HL) is an uncommon malignancy of B-cell origin. Classical HL (cHL) and nodular lymphocyte–predominant HL are the 2 main types of HL. The cure rates for HL have increased so markedly with the advent of modern treatment options that overriding treatment considerations often relate to long-term toxicity. These NCCN Guidelines Insights discuss the recent updates to the NCCN Guidelines for HL focusing on (1) radiation therapy dose constraints in the management of patients with HL, and (2) the management of advanced-stage and relapsed or refractory cHL.

AbstractObjectivesPersistent functional impairment is common in bipolar disorder (BD) and is influenced by a number of demographic, clinical, and cognitive features. The goal of this project was to estimate and compare the influence of key factors on community function in multiple cohorts of well‐characterized samples of individuals with BD.MethodsThirteen cohorts from 7 countries included n = 5882 individuals with BD across multiple sites. The statistical approach consisted of a systematic uniform application of analyses across sites. Each site performed a logistic regression analysis with empirically derived “higher versus lower function” as the dependent variable and selected clinical and demographic variables as predictors.ResultsWe found high rates of functional impairment, ranging from 41 to 75%. Lower community functioning was associated with depressive symptoms in 10 of 12 of the cohorts that included this variable in the analysis. Lower levels of education, a greater number of prior mood episodes, the presence of a comorbid substance use disorder, and a greater total number of psychotropic medications were also associated with low functioning.ConclusionsThe bipolar clinical research community is poised to work together to characterize the multi‐dimensional contributors to impairment and address the barriers that impede patients' complete recovery. We must also identify the core features which enable many to thrive and live successfully with BD. A large‐scale, worldwide, prospective longitudinal study focused squarely on BD and its heterogeneous presentations will serve as a platform for discovery and promote major advances toward optimizing outcomes for every individual with this illness.

Abstract Background and study aims Optical coherence tomography (OCT) is a new technology available for evaluation of indeterminate biliary strictures. It allows under-the-surface visualization and preliminary studies have confirmed standardized characteristics associated with malignancy. The aim of this study is to evaluate the first interobserver agreement in identifying previously agreed upon OCT criteria and diagnosing of malignant versus benign disease. Patients and methods Fourteen endoscopists were asked to review an atlas of reference clips and images of eight criteria derived from expert consensus A total of 35 de-identified video clips were then evaluated for presence of the eight criteria and for final diagnosis of malignant versus benign using the atlas as reference Intraclass correlation (ICC) analysis was done to evaluate interrater agreement. Results Clips of 23 malignant lesions and 12 benign lesions were scored. Excellent interobserver agreement was seen with dilated hypo-reflective structures (0.85) and layering effacement (0.89); hyper-glandular mucosa (0.76), intact layering (0.81), and onion-skin layering (0.77); fair agreement was seen with scalloping (0.58), and thickened epithelium (0.4); poor agreement was seen with hyper-reflective surface (0.36). The diagnostic ICC for both neoplastic (0.8) and non-neoplastic (0.8) was excellent interobserver agreement. The overall diagnostic accuracy was 51 %, ranging from 43 % to 60 %. Conclusions Biliary OCT is a promising new modality for evaluation of indeterminate biliary strictures. Interobserver agreement ranged from fair to almost perfect on eight previously identified criteria. Interobserver agreement for malignancy diagnosis was substantial (0.8). Further studies are needed to validate this data.

Background: Myocarditis may predispose to dilated cardiomyopathy (DCM) and sudden cardiac death (SCD). Familial data indicate a potential genetic susceptibility shared with arrhythmogenic cardiomyopathy (ACM). We present the first large-scale genotype-phenotype study of adults with acute myocarditis. Methods: A cohort comprising 336 consecutive patients with acute myocarditis was enrolled in London and Maastricht. All participants underwent targeted DNA sequencing for well-characterised cardiomyopathy-associated genes. The burden of rare protein altering variants (PAV) in ACM genes, DCM genes, and TTN specifically, were compared with local healthy controls sequenced on the same platform (n=1053). Case ascertainment was assessed against national hospital admission data. Results: We identified rare protein-altering variants in 23% of cases compared to 16% in controls (Δ+6.8%; p=0.021), with rare truncating variants (tv) in 6% of cases compared to <1% of controls ((Δ+5%; p=0.0097). In London (n=230; median left ventricular ejection fraction (LVEF) 63%), which was representative of national myocarditis admissions, 4.8% of cases carried rare tv, particularly within ACM genes (3% cases vs 0% controls; odds ratio 8.2; p=0.001). This was predominantly driven by desmoplakin (DSP)-tv in patients with normal LVEF. In Maastricht (n=106; median LVEF 30%), rare tv in DCM genes were enriched, particularly TTN-tv found in 7% (all with LVEF<50%) compared to 1% in controls (OR 3.6; p=0.0116). During a median follow-up of 1.9 years, all-cause mortality was greatest in those with a DCM variant (18% vs 4% with no variant; OR 5.0; p=0.004). Conclusion: We identified enrichment of cardiomyopathy gene variants in acute myocarditis patients, dominated by DSP-tv in those with normal LVEF and TTN-tv in those with reduced LVEF. Incorporation of genetic testing may be beneficial to identify such high-risk individuals and guide family screening in acute myocarditis patients.

Background: Proximal tibial osteotomy (PTO) is a well-established treatment for coronal deformity and focal cartilage defects. However, the utility of joint-preserving interventions must be weighed against potential effects on subsequent total knee arthroplasty (TKA). The purpose of this study was to determine the effect of PTO on subsequent TKA by comparing outcomes in patients with bilateral TKAs following unilateral PTO. Methods: Patients who underwent bilateral TKAs from 2000 to 2015 at a single institution and had previously undergone a unilateral valgus-producing PTO were reviewed. We evaluated 140 TKAs performed in 70 patients (24 female, 46 male) with a mean age at PTO of 50 ± 8 years. The patients underwent conversion to TKA at a mean of 14 ± 7 years following ipsilateral PTO and were followed for a mean of 25 ± 7 years (range, 6 to 40 years) following PTO. The Knee Society Score (KSS), Forgotten Joint Score-12 (FJS-12), subjective knee preference, and revision were compared between the PTO-TKA and contralateral TKA-only sides. Results: The PTO side demonstrated similar KSS Knee subscores (41 ± 16) compared with the contralateral side (39 ± 16, p = 0.67) immediately prior to arthroplasty. Patients had significant improvements in KSS (p < 0.001) after TKA, with clinically similar KSS values at 2 to 15 years of follow-up when knees were compared in a pairwise fashion (p = 0.10 to 0.83). Five PTO-TKA knees (7%) and 4 control TKA-only knees (6%) underwent revision at a mean of 5 years postoperatively (p = 0.76). The number of all-cause reoperations was approximately twice as high in PTO-TKA knees (13% compared with 6% in TKA-only knees, p = 0.24). At the time of final follow-up, PTO-TKA knees demonstrated similar FJS-12 scores (72 ± 26) compared with the contralateral knees (70 ± 28, p = 0.57). Nineteen percent of patients preferred the PTO-TKA knee, 19% preferred the contralateral TKA-only knee, and 62% stated that their knees were equivalent (p > 0.99). The final Tegner activity score was 2.5 ± 1.4. Conclusions: Long-term clinical function of TKA following PTO was excellent, with patients demonstrating comparable subjective outcomes and equivalent knee preference compared with the contralateral TKA-only knees. Further, well-matched studies are needed to evaluate long-term revision and reoperation rates following PTO-TKA. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.