Citations

» Treatment of the patient with rheumatoid arthritis affecting the hand and wrist can be a challenging endeavor. Optimal management for best outcomes includes careful collaboration between providers managing the medical treatment of the disease, therapists, hand surgeons, and the patient. » In this review, we present a challenging clinical scenario with input from key voices from various medical fields to provide a balanced and unbiased diagnosis and treatment recommendation for a patient with complex rheumatoid pathology affecting her hand and wrist.

AbstractBackgroundThe incidence of human papillomavirus (HPV)‐related oropharyngeal squamous cell carcinoma (OPSCC) is rising, even in elderly patients. The outcomes of transoral surgery (TOS) in this population are not entirely known.MethodsA retrospective review was performed at two institutions from October 2003 to September 2016 on patients 70 years or older with HPV‐related OPSCC treated with TOS.ResultsA total of 75 patients were included with a mean age of 74 years (70‐87 years). At a median follow‐up of 35.7 months, 3‐year overall survival was 81.5% and disease‐specific survival was 94.3%. Advanced cT stage (odds ratio, 2.74; 95% confidence interval, 1.13‐6.64) negatively impacted OS. Conjunctive consolidation was performed to create a staging system with patients older than 80 years, severe comorbidity, and cT3‐4 having worse survival.ConclusionsElderly patients with HPV‐related OPSCC treated with TOS have excellent survival and therefore should not be excluded from such therapy based on age alone.

AbstractEpidemiologic studies show an increased risk of non‐Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen‐stimulation in one disease leads to another. Here we assess shared genetic risk in genome‐wide‐association‐studies (GWAS).Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B‐cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta‐analysis.Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta‐analysis (combing AD with NHL) implicated genes of apoptosis and telomere length.This GWAS‐based analysis four NHL subtypes and three ADs revealed few weakly‐associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.

Abstract PURPOSE: RTOG 0933 demonstrated benefits to memory following HA-WBRT, supporting the hypothesis of hippocampal radiosensitivity and associated memory specificity. However, some patients demonstrated cognitive decline, suggesting mechanisms outside hippocampal radiosensitivity playing a role. WMI has been implicated in RT-induced cognitive decline. This secondary analysis explored the relationship between pre-treatment WMI and memory following HA-WBRT. METHODS AND MATERIALS: 113 patients received HA-WBRT. Standardized cognitive assessments were performed at baseline, 2, 4, and 6 months. The primary endpoint was Hopkins Verbal Learning Test Delayed Recall (HVLT-DR) at 4 mos. Secondary endpoints included HVLT Total Recall (HVLT-TR) and Recognition (HVLT-Recog). Of 113 patients, 34 underwent pre-treatment and 4-month post-treatment HVLT testing and pre-treatment post-contrast volumetric T1 and axial T2/FLAIR MRI. Volumetric analysis of metastatic disease burden and disease-unrelated WMI was conducted on the pre-treatment MRI. Correlational analyses were performed examining the relationship between pre-treatment WMI and HVLT outcomes following HA-WBRT. RESULTS: Correlation was found between larger volumes of pre-treatment WMI and decline in HVLT-Recog (r=.54, p< .05) and a correlational trend was observed between larger volume of pre-treatment WMI and decline in HVLT-DR (r=.31, p=.08). Patients with higher pre-treatment disease burden experienced a greater magnitude of stability or positive shift in HVLT-recall and –delayed recall following HA-WBRT. (r=-.36 and r=-.36, p’s < .05), compared to the magnitude of stability/positive shift in those with lesser disease burden. CONCLUSION: In patients receiving HA-WBRT, pre-treatment-WMI predicts memory decline, suggesting white matter integrity pre-treatment contributes to the pathogenesis of post-WBRT cognitive toxicity independent of hippocampal stem cell radiosensitivity. Less decline or improvement in HVLT following HA-WBRT for patients with higher pre-treatment intracranial metastatic burden supports the importance of WBRT-induced intracranial control on cognition. These imaging biomarkers for cognitive toxicity will be further explored on NRG CC001 and CC003, phase III trials of WBRT with or without HA.

Abstract Lung cancer is the deadliest and most frequently diagnosed type of tumor worldwide, with 1.6 million deaths reported annually. Non-small cell lung cancer (NSCLC) represents 85% of all lung cancer cases and carries a poor 5-year survival rate below 15%. Prognoses remain dismal due to the large number of patients diagnosed with advanced stage disease and the development of resistance to current therapies. A better understanding of acquired drug resistance will help to circumvent the progression of lung cancer and make significant strides in improving NSCLC patient treatment. Our recent work demonstrates that dopamine and cAMP-regulated phosphoprotein, Mr 32000 (DARPP-32) and its amino-terminally truncated splice variant (t-DARPP) promote lung tumor growth in orthotopic mouse models. IHC staining of 62 human lung adenocarcinoma tissues showed that t-DARPP expression is elevated with increasing tumor (T) staging score, which represents the size of the primary tumor and whether it has grown into nearby areas, as a metric of tumor progression and growth. Correspondingly, a computational biology analysis of 513 lung adenocarcinoma patients revealed upregulation of t-DARPP isoform expression correlates with advanced T stage and is associated with poor overall survival. We identified a novel physical interaction between DARPP-32 and inhibitory kappa B kinase-α (IKKα) that promotes NSCLC cell migration through activation of non-canonical NF-κB2 signaling. It has been shown that DARPP-32 overexpression inhibits gefitinib-induced apoptosis in gastric cancer and t-DARPP contributes to the trastuzumab resistance phenotype in breast cancer. Our recent findings suggest DARPP-32 and t-DARPP overexpression in NSCLC promotes resistance to specific molecular targeted inhibitors by enabling tumor cells to evade apoptosis via Akt- and Erk-dependent cell survival mechanisms. Current ongoing studies are focused on manipulating expression of DARPP-32 isoforms in lung tumor cells to prevent resistance to targeted therapies in NSCLC patients. Citation Format: SK Kayum Alam, Matteo Astone, Ping Liu, Li Wang, Abbygail M. Coyle, Erin N. Dankert, Dane K. Hoffman, Stephanie R. Hall, Wei Zhang, Rui Kuang, Anja C. Roden, Aaron S. Mansfield, Luke H. Hoeppner. Molecular mechanisms of non-small cell lung cancer growth and drug resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 873.

Magnetic resonance–guided high-intensity focused ultrasound (MRgHIFU) is a novel treatment for neuroblastoma using ultrasound-induced thermal ablation with real-time MR thermometry. It is unclear which patients would be amenable to MRgHIFU given the retroperitoneal location of many neuroblastomas within the smaller pediatric abdomen. In addition, planning relies on MR scans, which are not routine in the standard pediatric neuroblastoma workup. This study sought to demonstrate that neuroblastomas are targetable with MRgHIFU and available computed tomographic imaging could be utilized for MRgHIFU virtual treatment. Cross-sectional images of 88 pediatric abdominal neuroblastoma patients were retrospectively processed with custom software to be made compatible with the Sonalleve MRgHIFU platform. Targetability measured percent treatment to lesion volume, within adequate safety margins from critical structures. All images were successfully converted into treatment planning files. Median lesion size was 191±195 cm3 and depth was 29±17 mm. Up to 78 (85%) patients had targetable lesions with a median targetable volume of 15% and ranging up to 79%. Targetability was highest in superficial, right upper quadrant lesions >200 cm3, but limited by proximity to bowel and ribs. This study demonstrates the capacity for MRgHIFU to potentially treat the majority of abdominal neuroblastomas and the feasibility of using computed tomographic images for MRgHIFU virtual treatment planning.

Intracerebral haemorrhage (ICH) and small vessel ischaemic stroke (SVS) are the most severe manifestations of cerebral small vessel disease. In a cross-phenotype genome-wide association analysis, Chung et al. identify two novel associations at 2q33 and 13q34 plus a previously identified locus at 1q22 for non-lobar ICH and SVS risk.

ObjectiveThis study was performed to outline and analyze the overall Medicare landscape with respect to otolaryngologists and beneficiaries, services, and reimbursements.MethodsThis is a retrospective analysis of publicly available Medicare utilization and payment data for all otolaryngologists in facility and nonfacility practice settings who provided services to Medicare beneficiaries between January 1, 2012, and December 31, 2016.ResultsIn 2016, a total of $701,195,375 was distributed to 8572 otolaryngology physician providers for 815 unique Healthcare Common Procedure Coding System codes for 13,942,536 procedure claims. Of specialty care, otolaryngology ranks 20th among 54 subspecialties for total Medicare payments. The average number of services coded per provider was 1627. The average otolaryngologist was paid $81,800.67. Thirty‐two percent of otolaryngologists did not receive reimbursement for services from Medicare in 2016.DiscussionIn 2016, the most significant contributors to Medicare payments to otolaryngologists were large‐scale, low‐cost events that are relatively short procedures done in clinic. Utilization of nasal endoscopy was up trending from 2012 to 2016. Some of the Current Procedural Terminology codes with the greatest discrepancies between submitted charge and Medicare payment among nonfacility otolaryngology providers are more involved than simple office procedures.Implications for PracticeIt is increasingly valuable for physicians to know factors that affect reimbursement for procedures and operations in different settings and to be aware of the trends in variation in their specialty. Otolaryngologists should communicate with policy makers in efforts toward sustainable reimbursement models.

Objectives: Clinicians recommend diet and exercise for overweight/obese patients. We conducted a secondary analysis of a randomized controlled clinical trial evaluating goal setting and pedometer use versus usual care on weight, waist circumference, and blood pressure of patients with multiple chronic conditions. Methods: In this trial, we recruited and randomized patients over 18 years with multiple chronic conditions. There were two groups with an immediate intervention group who received behavioral coaching and a pedometer versus a delayed control who received the intervention after 2 months. We evaluated body weight, waist circumference, and blood pressure as outcomes. We used analysis of covariance to evaluate differences between the intervention and the control groups. Results: Of 130 patients, mean age was 63.4 years (SD, 17.3). At 2 months, intervention participants lost 0.2 kg versus a 0.1-kg gain in the control participants ( P = .44). The immediate intervention group had significantly smaller waist circumference change at 2-month follow-up compared to control at −1.6 cm (95% confidence interval = −3.1 to −0.1), which was driven by an increase in waist circumference in the delayed control group. No difference in systolic blood pressure was observed. Discussion: We observed no difference in weight or blood pressure between the groups with obesity and multiple chronic conditions.