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Multiple myeloma (MM) is an incurable plasma cell neoplasm. In this study, we aimed to analyze the impact of time to initiation of systemic therapy for MM on overall survival (OS).We identified cases diagnosed with MM from the National Cancer Database from 2004 to 2013.A total of 38,178 MM patients were included in the analysis. The median time to systemic therapy in our cohort was 17 days (range 0-120). The median OS for patients who initiated therapy 30-days after diagnosis was longer than those who received it ≤ 7 days (46 vs. 27-month, p 0.001). On multivariable analysis, patients who received treatment ≤ 7 days from diagnosis had worse mortality compared with those receiving treatment 30 days (HR 1.5; 95% CI 1.4-1.6).In our study, time to initiation of systemic therapy was an independent prognostic factor in MM. Similar to other lymphoid malignancies, this metric may be a surrogate for high-risk disease in MM, and future trials may need to investigate time-to-treatment as a factor to allow enrollment of potentially sick patients.

The ideal non-operative treatment for patients with large, node-negative non-small cell lung cancer (NSCLC) is poorly defined. To inform optimal treatment paradigms for this cohort, we examined patterns of failure and the impact of radiation therapy (RT) and chemotherapy receipt.Node-negative NSCLC patients with 5+ cm primary tumors receiving definitive RT at our institution were identified. Sites of initial progression were analyzed. Local progression, regional/distant progression, progression-free survival, and overall survival were analyzed via cumulative incidence function and Kaplan-Meier. Associations between local vs. regional/distant progression with treatment and clinicopathologic variables were assessed via univariable and multivariable competing risks regression.We identified 88 patients for analysis. Among patients with recurrent disease (N = 36), initial patterns of failure analysis showed that isolated distant (27.8%) and isolated regional progression (22.2%) were most common. Distant or regional failure as a component of initial failure was seen in 88.9% of patients who progressed, while isolated local failure was uncommon (11.1%). Univariable and multivariable competing risks regression showed that receipt of SBRT was associated with reduced risk of local progression (HR 0.23, P = .012), and receipt of chemotherapy was associated with reduced risk of regional/distant progression (HR 0.12, P = .040). In conclusion, patients with large, node-negative NSCLC treated with definitive RT are at high risk of regional and distant progression. SBRT correlates with a reduced risk of local failure while chemotherapy is associated with reduced regional/distant progression in this patient population. Ideal treatment may include SBRT when feasible with appropriate systemic therapy.

BACKGROUND The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was created to establish a standard terminology regarding thyroid nodules that can be shared between endocrinologists, pathologists, radiologists, and surgeons. Since its inception and use in 2009, multiple large hospitals and academic institutions have performed retrospective studies to compare their classification rates, specifically those of atypia of undetermined significance (AUS) and follicular lesion of undetermined significance (FLUS), with the recommended rates created by the National Cancer Institute. The current study compared AUS/FLUS rates at a private suburban endocrine practice with those of previous publications from large institutions and the rates established by the National Cancer Institute. METHODS Charts from 893 patients with fine-needle aspiration (FNA) performed in 2015 were reviewed. Data specific to thyroid aspirates classified as AUS/FLUS were organized into whether patients underwent surgery, underwent subsequent repeat FNA, or required continued observation. These results then were calculated to reveal the rate of malignancy in the AUS/FLUS category with surgical pathology in the study institution. RESULTS A total of 893 patients underwent FNA, with 43 patients (4.82%) shown to have AUS/FLUS. A total of 21 patients proceeded to undergo thyroidectomy or lobectomy, with 7 patients (33.3%) found to have papillary or follicular thyroid carcinoma. CONCLUSIONS The rate of use of the AUS/FLUS category for thyroid nodules examined at the study institution was found to be within the recommended range set forth by TBSRTC. However, the malignancy rates on histopathology in the study institution were found to be higher than the new proposed malignancy rates from TBSRTC published in 2017. This finding is comparable to those of multiple other community and academic institutions performed prior to and after institution of the new guidelines.

Traumatic Brain injury affects at least 1.7 million people in the United States alone each year. The majority of injuries are categorized as mild but these still produce lasting symptoms that plague the patient and the medical field. Currently treatments are aimed at reducing a patient’s symptoms, but there is no effective method to combat the source of the problem, neuronal loss. We tested a mild, closed head traumatic brain injury model for the effects of modulation of the antioxidant transcription factor Nrf2 by the chemical activator, tert-butylhydroquinone (tBHQ). We found that post-injury visual memory was improved by a 7 day course of treatment and that the level of activated caspase-3 in the hippocampus was reduced. The injury-induced memory loss was also reversed by a single injection at 30 min after injury. Since the protective stress response molecule, HSP70, can be upregulated by Nrf2, we examined protein levels in the hippocampus, and found that HSP70 was elevated by the injury and then further increased by the treatment. To test the possible role of HSP70, model neurons in culture exposed to a mild injury and treated with the Nrf2 activator displayed improved survival that was blocked by the HSP70 inhibitor, VER155008. Following mild traumatic brain injury, there may be a partial protective response and patients could benefit from directed enhancement of regulatory pathways such as Nrf2 for neuroprotection. Published by Elsevier Ltd. on behalf of IBRO.

Repetitive mild traumatic brain injury (mTBI) represents a major public health problem. Many individuals who suffer repetitive mTBIs suffer from Post-Concussion Syndrome, a constellation of neuropsychiatric symptoms that includes depression, anxiety, and problems with memory and other cognitive processes. Significantly, Post-Concussion Syndrome is resistant to existing therapeutic strategies. To provide better treatment options for this patient population, the underlying pathophysiology of repetitive mTBI must be understood. A first step in this process is the establishment of an in vitro model system that recapitulates the biological changes that occur in the brains of repetitively injured humans. The availability of a model with immortalized cell lines would remove the considerable barriers of time, expense, and difficulties with genetic manipulation that exist with the use of primary neuronal cultures. Here we report the development and functional characterization of an in vitro laboratory model of repetitive TBI using immortalized neuronal cell lines. These results indicate that the moderate, repetitive injury reduces viability, numbers and lengths of neurites, and that the neuronal loss mechanism includes caspase activation.

Traumatic brain injury (TBI) afflicts approximately 1.4 million people in the United States and TBIs have been labeled a major cause of death and disability on a global scale. Regulatory responses in a variety of neuronal loss conditions have supported the protective involvement of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) transcription factor. Nrf2 regulates antioxidant enzyme genes, and an increase in Nrf2 expression may counteract oxidative damage that results from TBI. Elevated Nrf2 may ultimately act through the upregulation of downstream target genes such as thioredoxin (Trx) and heat-shock protein-70 (HSP70) and this may reduce neuronal loss. We performed multiple mild biaxial stretch injuries to neuroblastoma cells in culture, and examined the effects of the Nrf2 activator, tert-butylhydroquinone (tBHQ). We also compared the stretch injury to oxidative insult. We confirmed that Trx and HSP70 were upregulated by treatment with tBHQ. We observed that tBHQ protected neurons from either insult, and that this was evident by different measures of cell viability and a decrease in annexin V binding. Neuronal health after insult was improved approximately 50% by tBHQ, indicating that neurons exposed to TBI in vitro can be protected.