Citations

Objectives To compare electrical stimulation and speech perception in vestibular schwannoma (VS) patients across treatment modalities and standard cochlear implant (CI) patients. Study Design Retrospective review. Setting Tertiary academic center. Patients Sixty-seven CI ears consisting of 23 standard CI controls and 44 VS patients with ipsilateral CI. VS patients were separated by treatment modality: 24 microsurgical resection, 15 radiation therapy, and 5 observation. Eleven VS patients with CI did not receive auditory sensation from electrical stimulation. Interventions VS microsurgical resection, radiation therapy, and observation. Main Outcome Measures Threshold (T-levels), comfort (C-levels), consonant-nucleus-consonant (CNC) word score, and AzBio sentence recognition scores. Results Patients who underwent microsurgical resection required significantly higher (p < 0.001) T-levels and C-levels compared with the standard CI group. Stimulation levels in the VS radiation therapy and observation groups were higher but not significantly different compared with standard CI controls. Overall rate of CI nonstimulation across all VS patients was 25%: 38% for microsurgery and 13% for radiation. Average CNC score for microsurgery group was 18% compared with 44% for radiation, 55% for observation, and 68.5% for standard CI controls. CNC word and AzBio scores were significantly lower (p < 0.001) for the microsurgery group compared with standard CI group. Conclusions Resection may negatively affect auditory nerve function, leading to higher stimulation levels, increased risk of nonstimulation, and poorer postoperative CI speech outcomes compared with observation or radiosurgery. When medically appropriate, nonsurgical VS management may be used to allow for optimization of CI programming and postoperative hearing outcomes.

Background: Despite mounting clinical evidence for the utility of orthobiologics in nonoperative management of orthopaedic pathology, the market for orthobiologic therapies remains largely unregulated by the Food and Drug Administration, giving rise to a wide range of pricing for these therapeutics by different provider types. Purpose: To determine the availability and pricing for platelet-rich plasma (PRP), amniotic or adipose “stem cell,” and bone marrow aspirate concentrate (BMC) injections for the treatment of knee osteoarthritis among orthopaedic sports medicine and alternative providers (eg, chiropractic clinics and stand-alone “regenerative medicine” clinics) in a major metropolitan city. Study Design: Cross-sectional study. Methods: Orthopaedic sports medicine providers in the Chicagoland area were identified through the American Orthopaedic Society for Sports Medicine (AOSSM) and Arthroscopy Association of North America (AANA) surgeon databases. Alternative clinics offering orthobiologic injections were systematically compiled using Yelp! and Google search listings and reviews. Clinics were contacted using a standardized telephone script. Data were collected for each site on the types of injections offered, whether price was disclosed over the telephone, the price of injections offered, and the source of stem cell injections if they were provided. Mann-Whitney U tests were used to compare the mean price between practices. F tests for equality of variances were used to compare the variability in prices between practice types. Results: A total of 25 unique orthopaedic sports medicine practices (comprising 80 AOSSM/AANA surgeons) and 40 alternative clinics offered PRP, stem cell, and/or BMC injections, as indicated over the telephone. There was no difference in likelihood of offering PRP ( P = .698) or BMC injections ( P = .340). However, alternative clinics were significantly more likely to offer stem cell injections ( P < .001). There was no difference in the willingness to disclose the price for PRP ( P = .269), stem cell injections ( P = .302), and BMC ( P = .528) or the source of what each clinic advertised as stem cell injections ( P = .630). The mean price for a single PRP injection was significantly higher ( P = .011) and significantly more variable ( F statistic = .139; P < .001) at alternative clinics. Similarly, the mean price for a single stem cell injection was significantly higher ( P < .001) and significantly more variable ( F statistic = 0.080; P = .025) at alternative clinics. Conclusion: This study demonstrates that orthobiologic knee injections are highly prevalent for in-clinic use within the Chicago metropolitan area, with PRP being the most commonly used therapeutic. When compared with orthopaedic sports medicine providers, alternative clinics were more likely to offer stem cell injections and charge a significantly greater and more variable amount per PRP and stem cell treatment.

Background Given the low haemorrhagic risk of intracranial low-grade dural arteriovenous fistulas (dAVFs), the benefits of routine intervention remain controversial. This study compares patient outcomes treated with stereotactic radiosurgery (SRS) versus conservative management. Method Multicentre retrospective analysis of the Consortium for Dural Arteriovenous Fistula Outcomes Research and the International Radiosurgery Research Foundation data. Inclusion criteria were (1) intracranial low-grade dAVF diagnosed by catheter-based angiography, (2) no prior dAVF-related haemorrhage and (3) management with upfront SRS (intervention group) or conservative management (observation group). The primary outcome was symptomatic improvement. Secondary outcomes included dAVF obliteration, up-conversion, haemorrhage, improvement and favourable modified Rankin Scale (mRS) at follow-up. Results 304 patients with a mean age of 56 years (SD 13.5) and a follow-up of 46.7 months (SD 45.5) were included. 135 (44.4%) were managed conservatively and 169 (55.6%) had upfront SRS. Compared with the observation group, symptomatic and mRS Score improvement (≥1-point decrease in baseline score) was more likely in the intervention group (95.1% vs 58.5%; OR=13.75 (5.61–33.69) and 37.0% vs 24.0%; OR=1.85 (1.09–3.15), respectively). These findings remained significant after multiple imputation and propensity score matching. Remaining outcomes were similar between groups. The all-cause mortality rate was 5.4% (n=16), unrelated to the dAVF or treatment. Five (3.0%) SRS-related complications were reported and resolved during the follow-up period. Conclusions SRS was associated with increased symptomatic and mRS Score improvement for low-grade dAVFs compared with conservative management. SRS had a low complication risk and did not appear to alter dAVF obliteration or haemorrhage. Future prospective trials on SRS as a first-line intervention for symptomatic low-grade dAVFs should be considered.

Purpose To perform a prospective, double‐blind, randomized controlled trial to assess differences in integration and patient‐reported outcomes metrics (PROMs) of osteochondral allograft transplantation with and without bone marrow aspirate concentrate (BMAC) augmentation. Methods Patients (n = 36) undergoing osteochondral allograft transplantation of the knee were consented and enrolled in this prospective study. They were randomized to either iliac crest BMAC or sham incision groups and blinded to their allocation. Computerized tomography (CT) scans of the knee were obtained at 6 months postoperatively after the index transplantation and graded by the semiquantitative assessment CT osteochondral allograft system. PROMs, including the International Knee Documentation Committee and Knee injury and Osteoarthritis Outcome Score–Joint Replacement, were obtained at 6 months, 1 year, and 2 years postoperatively. Results On 6‐month postoperative CT scans, patients receiving BMAC‐treated grafts were more likely to have small cystic changes ( P = .01), with an associated trend toward reduction in large cyst formation ( P = .06), but equal osseous integration, graft signal density, and presence of discernible clefts and intra‐articular fragments. The BMAC group was less likely to undergo subsequent surgery for graft debridement or revision (5.3% vs 35.3%; P = .02). There were no significant differences in PROMs between the 2 groups preoperatively or postoperatively at 6 months, 1 year, or 2 years. Patients receiving BMAC trended toward a higher rate of achievement of Knee Documentation Committee and Knee injury and Osteoarthritis Outcome Score–Joint Replacement minimal clinically important difference (88% vs 55%; P = .076). Conclusions Patients receiving BMAC‐treated grafts were more likely to have small cystic changes and were less likely to undergo subsequent surgery for persistent or new symptoms after the index procedure. No difference in postoperative PROMs was shown at the 6‐month, 1‐year, and 2‐year follow‐ups between the 2 groups. Level of Evidence Level I, prospective, randomized controlled trial.

Objectives: To evaluate the performance of noninvasive, elastic scattering spectroscopy, algorithm-powered device (DermaSensor) to detect melanoma and basal and squamous cell cancers in the primary care setting. Patients & Methods: DERM-SUCCESS, a blinded, prospective, multicenter pivotal study, enrolled adult patients between August 17, 2020, and December 9, 2021, with lesions that their primary care physicians (PCPs) suspected of skin cancer at clinics in the US (n = 18) and Australia (n = 4). These lesions were assessed by PCPs and scanned with the DermaSensor device. Biopsy specimens were collected, and histopathologic analysis was performed by dermatopathologists. The diagnostic performance of the device, dermatopathologist discordance, and subgroup analyses of clinical interest were calculated. Results: Of the 1579 skin lesions enrolled, dermatopathologic analysis identified 224 (14.2%) cancers. Device sensitivity was 95.5% (95% CI, 91.7%-97.6%) overall and 96.3% (92.9%-98.4%) for patients in the FDA-approved age group 40 years and older (90.2% for melanoma, 97.8% for basal cell carcinoma, and 97.7% for squamous cell carcinoma). Device specificity was 20.7%. The negative predictive value was 96.6%, and the positive predictive value was 16.6% (NNB 6). The device misclassified as “ monitor ” rather than “ investigate further ” 4 keratinocyte carcinomas and 4 melanomas in patients aged 40 years or older (n = 8, 0.5% of lesions, 3.7% of cancers biopsied). Conclusions: The DermaSensor device is an easy-to-use, point-of-care, hand-held skin cancer adjunctive diagnostic device with high sensitivity and NPV to help inform PCP decision-making about skin lesions suspicious for cancer that need further evaluation and those that may be monitored.

Objective To provide a comprehensive analysis of initial suicide attempts, covering incidence, risk factors, outcomes, and healthcare use in the month before and the month after the attempts. Design Comprehensive analysis of the Swedish population that included three designs: a retrospective cohort study to investigate incidence and healthcare use, a nested case-control study to investigate risk factors, and a matched cohort study to examine subsequent suicide attempts and mortality. Setting Comprehensive Swedish national registers that include patient diagnoses from hospitals and specialist outpatient care, and cause of death information updated to the end of 2019. Participants 3.7 million people born in Sweden in 1963-98 and followed from age 10 to 57 years. Main outcome measure First lifetime suicide attempt identified in patient and death registers using ICD (international classification of diseases) codes for intentional self-harm, any self-harm with lethal methods or requiring hospital admission, or any self-harm resulting in death. Results The lifetime risk of an initial suicide attempt in the study population was 4.6%, with greater risk in females and highest risk between ages 18 and 24. One in 10 families in Sweden had at least one family member who attempted suicide. Overdose and poisoning were the most common methods. Previous psychiatric disorders, general medical diseases, and adverse life events were associated with increased risk of initial suicide attempt, while higher socioeconomic status was associated with decreased risk. People with an initial suicide attempt were at substantially increased risk of subsequent attempts (hazard ratio 23.4), death by suicide (16.4), and all cause mortality (7.3). At least 60% of those who made an initial suicide attempt had a healthcare contact in the month before the attempt. Conclusions This study provides comprehensive data on the incidence, risk factors, outcomes, and healthcare use of initial suicide attempts in the Swedish population, highlighting the need for systematic prevention efforts for people who have attempted suicide for the first time.

Introduction Bronchoscopic lung volume reduction with endobronchial valves (EBV) is an effective procedure for patient with severe emphysema to improve lung function, exercise tolerance, dyspnoea and quality of life. Optimisation of patient and treatment lobe selection is essential for successful EBV outcomes. While clinical selection criteria are rigorous, many centres use a multidisciplinary team and rely on previous clinical experience for the selection process. To aid objective clinical decision making, we present a mathematical model to facilitate patient and target lobe selection. Methods A multidisciplinary team reviewed quantitative high-resolution computed tomography (HRCT) analysis from 119 patients to select candidates for EBV and to select a treatment lobe. Two logistic regression models, (1) candidacy for EBV placement and (2) target-lobe selection, were developed based on the normalised distributions of the four quantitative HRCT variables (fissure completeness score, per cent of voxel density with HU < −910 and HU < −950, and lobar volumes) across all five lung lobes. An external cohort of 50 patients (25 candidates and 25 non-candidates) was used to validate the prediction model. Results Performance measures of the training cohort demonstrated an area under the curve (AUC) of 0.91, accuracy of 81%, sensitivity of 93% and specificity of 78% compared with the multidisciplinary teams’ target lobe selection. The validation cohort demonstrated an AUC of 0.89, accuracy of 84%, sensitivity of 88% and specificity of 83% compared with the multidisciplinary team decision making. Conclusions Endobronchial valve lung volume reduction remains a potent palliative measure to improve quality of life in patients with hyperinflated emphysema. Our model for target lobe selection harnesses the multidisciplinary experience at a tertiary care centre to objectively select candidates and target lobes to assist clinicians’ decision making. Future studies investigating prediction of lobar collapse and functional improvement after target lobe selection using our model are needed.

LBA3509 Background: Systemic inflammation has been implicated in colon cancer progression. We examined whether intake of a proinflammatory diet is associated with survival among patients (pts) with stage III colon cancer. Methods: This prospective cohort study was nested within a randomized phase III trial of adjuvant therapy in pts with stage III colon cancer who had undergone curative-intent resection. EDIP score – a validated tool to classify the inflammatory nature of diets – was derived as a cumulative exposure using data from food-frequency questionnaires completed within 6 weeks of randomization and 14-16 months (mo) after randomization. Cox proportional hazards regression was used to assess the associations of EDIP with disease-free survival (DFS) and overall survival (OS). Results: Of 1625 included pts, the mean (SD) age was 60.9 (10.5) years (yrs). Compared to pts in the lowest EDIP quintile, pts in the highest quintile (a more inflammatory diet) were younger (58.7 ± 10.8 vs 61.3 ± 9.5 yrs old) and more likely to be female (64.0% vs 48.9%) and have worse performance status (ECOG 1-2: 35.7% vs 19.4%). Pts in the highest quintile were less likely to be White (76.6% vs 92.0 %) and more likely to be Black (15.4% vs 3.7%). Baseline aspirin use, assigned chemotherapy (3 mo vs 6 mo), and assigned pharmacotherapy (celecoxib vs placebo) were not significantly different across EDIP quintiles. Compared with pts in the lowest EDIP quintile, pts in the highest quintile had significantly worse OS (multivariable hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.26-2.77, P trend =0.01), but not DFS (HR 1.36, 95% CI 0.99-1.86, P trend =0.22). Diet and physical activity jointly influenced OS. Those with lower EDIP scores (quintiles 1-4, 80% of the study population) and higher physical activity (≥9 MET-h/wk) had the best OS (HR 0.37, 95% CI 0.25-0.53) compared with pts in the highest EDIP quintile (20% of the study population) and lower physical activity (<9 MET-h/wk) ( P interaction <0.001). The association between higher EDIP and OS was consistent when analyzed by celecoxib and placebo treatment arms ( P interaction 0.54). The relationship between EDIP and OS did not differ significantly according to aspirin use, with HR 1.60 (95% CI 0.71-3.60) among aspirin users and HR 2.01 (95% CI 1.27-3.16) among aspirin non-users ( P interaction 0.06). Conclusions: Our findings suggest that greater intake of a proinflammatory dietary pattern is associated with worse OS in pts with stage III colon cancer. Regular physical activity may attenuate the association, and further investigation of diet and physical activity intervention is warranted. Support: U10CA180821, U10CA180882, U24CA196171, U10CA180863, CCS 707213, UG1CA233234, U10CA180820, U10CA180868, U10CA180888; https://acknowledgments.alliancefound.org. Pfizer; ClinicalTrials.gov Identifier: NCT01150045.

Tryptophan hydroxylase (TPH) is a rate-limiting enzyme for serotonin or 5-hydroxytryptamine (5-HT) synthesis. Previously, adipocyte TPH1 has been linked to increased adipose 5-HT, reduced brown adipose tissue (BAT) thermogenesis, and obesity. However, the role of TPH2, a neural isoform highly expressed in obese adipose tissue, is unknown. Here, we report that adipose tissue expression of TPH2 is dramatically elevated in mice with diet-induced obesity (DIO) and ob/ob mice, as well as in obese humans. In mice fed a high-fat diet, adipocyte TPH2 deficiency improved DIO-induced metabolic complications, enhanced BAT thermogenesis, and increased intestinal energy-harvesting efficiency without affecting adiposity. Conversely, TPH2 overexpression in epididymal adipocytes of chow-fed mice raised adipose and plasma 5-HT levels, suppressed BAT thermogenesis, and exacerbated obesity and metabolic dysfunction. We found that obesity-induced hyperinsulinemia upregulated adipocyte TPH2 expression via activation of mechanistic target of rapamycin complex 1 and SREBP1. In humans, TPH2 mRNA levels in subcutaneous adipose tissue, but not those of TPH1 , are positively correlated with fasting plasma insulin concentrations. In summary, our study demonstrates that obesity-associated increases in adipocyte TPH2 can regulate distal tissue physiology and energy metabolism, suggesting that TPH2 could be a potential therapeutic target for obesity and its associated complications.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45–1.12]; P =0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28–2.24]; P =0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35–5.45]; P =0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53–20.13]; P =0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18–0.88]; P interaction =0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.