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Glioma incidence is highest in non‐Hispanic Whites, and to date, glioma genome‐wide association studies (GWAS) to date have only included European ancestry (EA) populations. African Americans and Hispanics in the US have varying proportions of EA, African (AA) and Native American ancestries (NAA). It is unknown if identified GWAS loci or increased EA is associated with increased glioma risk. We assessed whether EA was associated with glioma in African Americans and Hispanics. Data were obtained for 832 cases and 675 controls from the Glioma International Case–Control Study and GliomaSE Case–Control Study previously estimated to have <80% EA, or self‐identify as non‐White. We estimated global and local ancestry using fastStructure and RFMix, respectively, using 1,000 genomes project reference populations. Within groups with ≥40% AA (AFR ≥0.4 ), and ≥15% NAA (AMR ≥0.15 ), genome‐wide association between local EA and glioma was evaluated using logistic regression conditioned on global EA for all gliomas. We identified two regions (7q21.11, p = 6.36 × 10 −4 ; 11p11.12, p = 7.0 × 10 −4 ) associated with increased EA, and one associated with decreased EA (20p12.13, p = 0.0026) in AFR ≥0.4 . In addition, we identified a peak at rs1620291 ( p = 4.36 × 10 −6 ) in 7q21.3. Among AMR ≥0.15 , we found an association between increased EA in one region (12q24.21, p = 8.38 × 10 −4 ), and decreased EA in two regions (8q24.21, p = 0. 0010; 20q13.33, p = 6.36 × 10 −4 ). No other significant associations were identified. This analysis identified an association between glioma and two regions previously identified in EA populations (8q24.21, 20q13.33) and four novel regions (7q21.11, 11p11.12, 12q24.21 and 20p12.13). The identifications of novel association with EA suggest regions to target for future genetic association studies.

The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts. The NCCN Hepatobiliary Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s discussion and updated recommendations regarding systemic therapy for first-line and subsequent-line treatment of patients with hepatocellular carcinoma.

AbstractMicroglial activation has been recognized as a major contributor to inflammation of the epileptic brain. Seizures are commonly accompanied by remarkable microgliosis and loss of neurons. In this study, we utilize the CX3CR1GFP/+ CCR2RFP/+ genetic mouse model, in which CX3CR1+ resident microglia and CCR2+ monocytes are labeled with GFP and RFP, respectively. Using a combination of time‐lapse two‐photon imaging and whole‐cell patch clamp recording, we determined the distinct morphological, dynamic, and electrophysiological characteristics of infiltrated monocytes and resident microglia, and the evolution of their behavior at different time points following kainic acid‐induced seizures. Seizure activated microglia presented enlarged somas with less ramified processes, whereas, infiltrated monocytes were smaller, highly motile cells that lacked processes. Moreover, resident microglia, but not infiltrated monocytes, proliferate locally in the hippocampus after seizure. Microglial proliferation was dependent on the colony‐stimulating factor 1 receptor (CSF‐1R) pathway. Pharmacological inhibition of CSF‐1R reduced seizure‐induced microglial proliferation, which correlated with attenuation of neuronal death without altering acute seizure behaviors. Taken together, we demonstrated that proliferation of activated resident microglia contributes to neuronal death in the hippocampus via CSF‐1R after status epilepticus, providing potential therapeutic targets for neuroprotection in epilepsy.

PURPOSE Patients with centrally located early-stage non–small-cell lung cancer (NSCLC) are at a higher risk of toxicity from high-dose ablative radiotherapy. NRG Oncology/RTOG 0813 was a phase I/II study designed to determine the maximum tolerated dose (MTD), efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for centrally located NSCLC. MATERIALS AND METHODS Medically inoperable patients with biopsy-proven, positron emission tomography–staged T1 to 2 (≤ 5 cm) N0M0 centrally located NSCLC were accrued into a dose-escalating, five-fraction SBRT schedule that ranged from 10 to 12 Gy/fraction (fx) delivered over 1.5 to 2 weeks. Dose-limiting toxicity (DLT) was defined as any treatment-related grade 3 or worse predefined toxicity that occurred within the first year. MTD was defined as the SBRT dose at which the probability of DLT was closest to 20% without exceeding it. RESULTS One hundred twenty patients were accrued between February 2009 and September 2013. Patients were elderly, there were slightly more females, and the majority had a performance status of 0 to 1. Most cancers were T1 (65%) and squamous cell (45%). Organs closest to planning target volume/most at risk were the main bronchus and large vessels. Median follow-up was 37.9 months. Five patients experienced DLTs; MTD was 12.0 Gy/fx, which had a probability of a DLT of 7.2% (95% CI, 2.8% to 14.5%). Two-year rates for the 71 evaluable patients in the 11.5 and 12.0 Gy/fx cohorts were local control, 89.4% (90% CI, 81.6% to 97.4%) and 87.9% (90% CI, 78.8% to 97.0%); overall survival, 67.9% (95% CI, 50.4% to 80.3%) and 72.7% (95% CI, 54.1% to 84.8%); and progression-free survival, 52.2% (95% CI, 35.3% to 66.6%) and 54.5% (95% CI, 36.3% to 69.6%), respectively. CONCLUSION The MTD for this study was 12.0 Gy/fx; it was associated with 7.2% DLTs and high rates of tumor control. Outcomes in this medically inoperable group of mostly elderly patients with comorbidities were comparable with that of patients with peripheral early-stage tumors.

Abstract Background Transverse abdominis plane (TAP) block is considered an effective alternative to neuraxial analgesia for abdominal surgery. However, limited evidence supports its use over traditional analgesic modalities in colorectal surgery. This study compared the analgesic efficacy of liposomal bupivacaine TAP block with intrathecal (IT) opioid administration in a multicentre RCT. Methods Patients undergoing elective small bowel or colorectal resection were randomized to receive TAP block or a single injection of IT analgesia with hydromorphone. Patients were assessed at 4, 8, 16, 24 and 48 h after surgery. Primary outcomes were mean pain scores and morphine milligram equivalents (MMEs) administered within 48 h after surgery. Secondary outcomes included duration of hospital stay, incidence of postoperative ileus and use of intravenous patient-controlled analgesia. Results In total, 209 patients were recruited and 200 completed the trial (TAP 102, IT 98). The TAP group had a 1·6-point greater mean pain score than the IT group at 4 h after surgery, and this difference lasted for 16 h after operation. The TAP group received more MMEs within the first 24 h after surgery than the IT group (median difference in MMEs 10·0, 95 per cent c.i. 3·0 to 20·5). There were no differences in MME use at 24 and 48 h, or with respect to secondary outcomes. Conclusion IT opioid administration provided better immediate postoperative pain control than TAP block. Both modalities resulted in low pain scores in patients undergoing elective colorectal surgery and should be considered in multimodal postoperative analgesic plans. Registration number: NCT02356198 ( http://www.clinicaltrials.gov).

Clinical pharmacists have been incorporating precision medicine into practice for decades. Drug selection and dosing based on patient‐specific clinical factors such as age, weight, renal function, drug interactions, plasma drug concentrations, and diet are expected as part of routine clinical practice. Newer concepts of precision medicine such as pharmacogenomics have recently been implemented into clinical care, while other concepts such as epigenetics and pharmacomicrobiomics still predominantly exist in the research area but clinical translation is expected in the future. The purpose of this paper is to describe current and emerging aspects of precision medicine as it relates to clinical pharmacy across a variety of specialty areas of practice, with perspectives from the American College of Clinical Pharmacy Practice and Research Network membership.