Citations

Objective To determine the efficacy of high‐volume anesthetic suboccipital nerve blocks (HVSON) for chronic cluster headache (CCH) and to define consistency of response over long‐term use. Background There are studies showing efficacy of greater occipital and suboccipital nerve block injections for CCH and also their possible use as a preventive treatment modality. There are scant data about the long‐term efficacy of repetitive greater occipital and suboccipital nerve injections in CCH. HVSON has not been studied for CH. Methods This was an open label, observational, case series study. Patients with CCH seen at a dedicated headache clinic over a 7‐year time period and injected on at least 2 separate occasions were used for analysis. All were deemed medicinal treatment refractory. HVSON consisted of 9 mL 1% lidocaine and 1 mL triamcinolone 40 mg/mL injected on the side of CH. Results Ten CCH patients were retrospectively studied. Range of mean average response to HVSON (all patients had complete pain freedom) was 1.5–31 weeks (longest: 44 weeks in 2 patients). Only one patient did not respond; 2 patients had 1.5–2 weeks of response; the remainder had at least 4 weeks of response. The mean average duration of effect was 10.3 weeks in the responders. Five patients were injected serially for 2–4 years (30x, 17x, 15x, 10x and 3x, respectively) with a consistent response of 6 weeks, 4 weeks, 12 weeks, 4 weeks, and 31 weeks, respectively, after each injection. Response duration was very reliable per individual patient. All 5 patients felt HVSON was effective as a preventive treatment. Smoking history did not appear to alter treatment response (8/10 were chronic current smokers and 7/8 responded to HVSON). The one patient who received the most injections developed avascular necrosis of the hip; the remainder of the subjects had no adverse events. Conclusion HVSON from this open label study appears to be effective in the preventive treatment of medicinal refractory CCH and shows consistent response over long‐term use with high rates of pain freedom.

Abstract INTRODUCTION AND OBJECTIVES: Patient responses to cancer immunotherapy such as checkpoint inhibitor drugs vary greatly between patients and there remains no biomarker to predict sensitivity to these drugs. We describe a patient derived xenograft (PDX) avatar system that predicts cancer immunotherapy responses in the context of tumor heterogeneity within 8-10 days. This avatar model preserves the original tumor microenvironment and tumor infiltrating lymphocytes (TILs) at a high tumor take rate for evaluation of various immunotherapy drugs. This prediction model also involves tumor infiltrating lymphocyte isolation and primary cell generation for confirming the immunotherapy response in vitro. This PDX avatar platform generates rapid actionable information and readily identifies patients that would maximally benefit from checkpoint inhibitor therapies in a phenotype-based manner. METHODS: Tissue from patients that underwent a nephrectomy for RCC or metastasectomy were engrafted into the chorioallantoic membrane of avian embryos with a portion used for TIL isolation and primary cell generation. PD-1 and PD-L1 checkpoint inhibitors were intravenously injected and high frequency ultrasound imaging and immunophenotyping was used to quantitate changes in tumor volume, vascularity, and TIL expansion in all treatment groups. Isolated TILs were expanded and co-cultured with respective primary cells to confirm and examine immunotherapy response at a molecular level. RESULTS: Patient PDXs demonstrated heterogeneous responses to immunotherapy that relates to presence and expansion of TILs after checkpoint inhibitor injection. Patient #1 demonstrated the greatest response with a >50% reduction in tumor volume and 4X expansion of T-cells over 8 days of treatment. Patient #2 demonstrated intratumoral heterogeneities in terms of tumor volume change after checkpoint inhibitors treatment despite TIL expansion in all treatment groups. Patient #3 showed no response that correlated to lack of TILs in the PDX. In vitro expansion of TILs and co-culture with primary cell line demonstrated a specific immune response via INF-gamma release and changes in immunomodulatory molecules. CONCLUSIONS: This PDX system preserves TILs and permits rapid large scale prediction of tumor specimens to various systemic therapy agents such as checkpoint inhibitors without the need for humanized models. This avatar system is a useful tool to rapidly predict and examine response to checkpoint inhibitors on a per-patient basis to improve the assignment of cancer immunotherapies to specific RCC patients. Citation Format: Mario Cepeda, Matthew Lowerison, Cindy Liu, Yarolslav Fedyshyn, Vidhu Joshi, Paras Shah, John Cheville, R. Houston Thompson, Boorjian Stephen, Bradley Leibovich, Haidong Dong, Hon S. Leong. Rapid patient derived xenograft avatars that consider tumor heterogeneity for prediction of cancer immunotherapy responses in metastatic renal cell carcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-155.

Background: Full-thickness radial meniscal tears render the meniscus nonfunctional and have historically been treated with partial meniscectomy. As preservative techniques evolve for radial repair, comparisons with other tear patterns are necessary to evaluate repair efficacy and prognosis. Purpose: To assess clinical outcomes and reoperation rates of radial meniscal repair and to compare them to bucket-handle meniscal repair. Study Design: Cohort study; Level of evidence, 3. Methods: Radial and bucket-handle meniscal tears without concurrent root injuries undergoing surgical repair at a single institution between 2007 and 2015 were analyzed, including both all-inside and inside-out suturing techniques. Propensity matching was performed on the basis of age at surgery, sex, meniscus laterality, body mass index (BMI), and concomitant anterior cruciate ligament reconstruction (ACLR) using a comparison pool of 70 bucket-handle repairs. Reoperation-free survival rates and Tegner, visual analog scale (VAS) for pain, and International Knee Documentation Committee (IKDC) scores were analyzed. Results: Twenty-four patients (18 male, 6 female; mean age, 22.8 ± 11.9 years) who underwent repair of a radial meniscal tear were followed for a mean of 3.5 years (range, 2.0-6.3 years). Significant postoperative improvements in VAS scores at rest and with use and IKDC scores were noted postoperatively ( P < .001). Five patients (20.8%) required a reoperation. Subsequently, 18 patients with radial tears (mean age, 19.1 ± 9.1 years; 12 male; mean BMI, 27.0 ± 6.2 kg/m 2 ; 3 medial; 11 ACLR) were propensity matched to 18 patients with bucket-handle tears (mean age, 20.8 ± 5.1 years; 13 male; mean BMI, 25.0 ± 3.5 kg/m 2 ; 3 medial; 11 ACLR). The matched radial and bucket-handle groups demonstrated similar ( P = .17) reoperation-free survival rates at 2 years (88.9% and 94.4%, respectively) and 5 years (77.8% and 87.7%, respectively). VAS and IKDC scores improved significantly after surgery ( P < .001), with no difference noted between the groups ( P ≥ .17). Patients with radial and bucket-handle meniscal repairs achieved mean postoperative Tegner scores (6.6 and 6.6, respectively) not significantly different from their preinjury levels (6.9 and 6.7, respectively) ( P ≥ .32). Conclusion: Satisfactory clinical outcomes are achievable for radial meniscal tear repair at short-term follow-up. In a robustly matched comparison, radial and bucket-handle meniscal tears demonstrate similar improvements in VAS and IKDC scores, restoration of preoperative Tegner scores, and acceptable reoperation rates. Full-thickness radial meniscal tears should be considered for repair.

Objectives: The purpose of this study was to report long-term follow-up of skeletally immature OCD lesions treated operatively and non-operatively and determine risk factors for persistent knee pain at final follow-up. Methods: A large, geographic database of over 500,000 patients was reviewed in this case series to identify and confirm patients with OCD of the knee. Presenting radiographs and MRI were reviewed. Clinical course including operative management, persistent knee pain, and conversion to TKA were obtained and analyzed through review of clinical and operative notes. Results: 95 skeletally immature patients (70 males, 25 females) with OCD lesions diagnosed at a mean age of 13 years (range: 7-16) were followed for a mean of 14 years (range: 2-40). 53 patients (56%) were treated operatively and 42 patients (44%) were treated non-operatively. At final follow up, 13 patients with a mean age of 30 years noted persistent knee pain, 8 (15%) treated operatively versus 5 (12%) treated non-operatively. Risk factors for knee pain were female gender, patellar lesion location, and unstable lesions (Table 1). Four patients (8%) treated operatively and two (5%) treated non-operatively developed symptomatic osteoarthritis at a mean of 28.6 years following diagnosis. One patient treated operatively and two treated non-operatively converted to TKA at a mean of 37 years following diagnosis. Mean age at TKA was 52 years, significantly younger than that observed for primary TKA at our institution (p = 0.004). Conclusion: Patients with skeletally immature OCD lesions have an estimated 14% rate of persistent knee pain, 6% risk of symptomatic osteoarthritis, and 3% risk of conversion to TKA at a mean of 14 years following time of diagnosis. Female patients, patellar lesions, and unstable lesions demonstrated increased risk of persistent knee pain at final follow-up. Patients with OCD of the knee convert to TKA at a significantly younger age than that of the general primary TKA population. [Table: see text]

Objective Osteochondritis dissecans (OCD) is a knee disorder of predominately pediatric populations. Because of low incidence, it has traditionally been difficult to study OCD. The purpose of this study was to report long-term outcomes of skeletally immature OCD lesions and determine risk factors for persistent knee pain at final follow-up. Design A geographic database of more than 500,000 patients was reviewed to identify patients with knee OCD. Clinical course including operative management, persistent knee pain, and total knee arthroplasty (TKA) were analyzed through review of radiographs, magnetic resonance images, and physician notes. Results A total of 95 skeletally immature patients (70 male, 25 female, mean age 12.5 ± 2.0 years) were followed for a mean of 14 years (range, 2-40 years). Fifty-three patients were treated operatively and 42 were treated nonoperatively. At final follow-up, 13 patients noted persistent knee pain, 8 treated operatively versus 5 treated nonoperatively. Risk factors for knee pain were female gender, patellar lesions, and unstable lesions. Four patients (8%) treated operatively and 2 patients (5%) treated nonoperatively developed symptomatic osteoarthritis at a mean of 28.6 years following diagnosis. Three patients underwent TKA at a mean age of 52 years, significantly younger than that observed for primary TKA at our institution ( P = 0.004). Conclusions Skeletally immature OCD patients have promising histories, with an estimated 14% risk of persistent knee pain, 6% symptomatic osteoarthritis, and 3% conversion to TKA at 14 years’ mean follow-up. Females, patellar lesions, and unstable lesions demonstrated increased persistent knee pain risk. Patients with OCD undergo TKA at a significantly younger age than the general population.

Ehlers-Danlos Syndrome is a connective tissue disorder that results in joint and generalized tissue hyperlaxity, predisposing patients to early onset arthritis. An institutional database spanning 1999–2016 was reviewed for all patients with symptomatic carpometacarpal arthritis and coexisting Ehlers-Danlos Syndrome, resulting in 14 thumbs amongst nine patients followed clinically for a median of 5.9 years (range 1–15). Patients managed non-operatively demonstrated stable subjective pain and trended towards decreased range of motion over time, whereas patients managed operatively had significant improvements in pain and trended towards increased grip strength. Our findings suggest that patients with Ehlers-Danlos-associated carpometacarpal arthritis can be successfully managed both operatively and non-operatively and that patients with pain refractory to conservative therapy may benefit from relief and increased hand strength following surgical intervention. Level of evidence: IV

Objectives Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early‐onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD‐ and schizophrenia (SCZ)‐associated risk variants is associated with an earlier AAO in BD patients. Methods A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn‐Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18 years] vs adulthood [>18 years]) or considered as a continuous measure. The associations between BD‐ and SCZ‐PRSs and AAO were evaluated with regression models. Results BD‐ and SCZ‐PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment. Conclusions The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.