Treatment Options for Brain Metastases.

OPINION STATEMENT: Therapies for brain metastasis continue to evolve as the life expectancies for patients have continued to prolong. Novel advances include the use of improved technology for radiation delivery, surgical guidance, and response assessment, along with systemic therapies that can pass through the blood brain barrier. With increasing complexity of treatments and the increased need for salvage treatments, multi-disciplinary management has become significantly more important.

Twelve tips for medical students to conduct a systematic review.

Background: Medical students engaged in research develop general skills that are instrumental to clinical practice. The systematic review, a cornerstone of evidence-based medicine, represents an ideal starting point for student researchers. Aim and methods: To outline twelve tips on conducting a systematic review for medical students with limited research experience. Results: The tips in this article are practical, comprehensive, and informed by the authors experience as medical students. Conclusion: The twelve tips can help medical students contribute to the literature and build a valuable skillset for future research and clinical practice.

Occupational styrene exposure and acquired dyschromatopsia: A systematic review and meta-analysis.

BACKGROUND: Styrene is a chemical used in the manufacture of plastic-based products worldwide. We systematically reviewed eligible studies of occupational styrene-induced dyschromatopsia, qualitatively synthesizing their findings and estimating the exposure effect through meta-analysis. METHODS: PubMed, EMBASE, and Web of Science databases were queried for eligible studies. Using a random effects model, we compared measures of dyschromatopsia between exposed and non-exposed workers to calculate the standardized mean difference (Hedges'g). We also assessed between-study heterogeneity and publication bias. RESULTS: Styrene-exposed subjects demonstrated poorer color vision than did the non-exposed (Hedges' g = 0.56; 95%CI: 0.37, 0.76; P < 0.0001). A non-significant Cochran's Q test result (Q = 23.2; P = 0.171) and an I2 of 32.2% (0.0%, 69.9%) indicated low-to-moderate between-study heterogeneity. Funnel plot and trim-and-fill analyses suggested publication bias. CONCLUSIONS: This review confirms the hypothesis of occupational styrene-induced dyschromatopsia, suggesting a modest effect size with mild heterogeneity between studies.

Federally mandating motorcycle helmets in the United States.

BACKGROUND: Motorcycle helmets reduce both motorcycle-related fatalities and head injuries. Motorcycle crashes are a major public health concern which place economic stress on the U.S. healthcare system. DISCUSSION: Although statewide universal motorcycle helmet laws effectively increase helmet use, most state helmet laws do not require every motorcycle rider to wear a helmet. Herein, we propose and outline the solution of implementing federal motorcycle helmet law, while addressing potential counterarguments. CONCLUSIONS: The decision to ride a motorcycle without a helmet has consequences that affect more than just the motorcyclist. In an effort to prevent unnecessary healthcare costs, injuries, and deaths, public health efforts to increase helmet use through education and legislation should be strongly considered. Helmet use on motorcycles fits squarely within the purview of the federal government public health and economic considerations.

Genomic signature for oligometastatic disease in non-small cell lung cancer patients with brain metastases.

Purpose/objectives: Biomarkers for extracranial oligometastatic disease remain elusive and few studies have attempted to correlate genomic data to the presence of true oligometastatic disease. Methods: Patients with non-small cell lung cancer (NSCLC) and brain metastases were identified in our departmental database. Electronic medical records were used to identify patients for whom liquid biopsy-based comprehensive genomic profiling (Guardant Health) was available. Extracranial oligometastatic disease was defined as patients having ≤5 non-brain metastases without diffuse involvement of a single organ. Widespread disease was any spread beyond oligometastatic. Fisher's exact tests were used to screen for mutations statistically associated (p<0.1) with either oligometastatic or widespread extracranial disease. A risk score for the likelihood of oligometastatic disease was generated and correlated to the likelihood of having oligometastatic disease vs widespread disease. For oligometastatic patients, a competing risk analysis was done to assess for cumulative incidence of oligometastatic progression. Cox regression was used to determine association between oligometastatic risk score and oligoprogression. Results: 130 patients met study criteria and were included in the analysis. 51 patients (39%) had extracranial oligometastatic disease. Genetic mutations included in the Guardant panel that were associated (p<0.1) with the presence of oligometastatic disease included ATM, JAK2, MAP2K2, and NTRK1, while ARID1A and CCNE1 were associated with widespread disease. Patients with a positive, neutral and negative risk score for oligometastatic disease had a 78%, 41% and 11.5% likelihood of having oligometastatic disease, respectively (p<0.0001). Overall survival for patients with positive, neutral and negative risk scores for oligometastatic disease was 86% vs 82% vs 64% at 6 months (p=0.2). Oligometastatic risk score was significantly associated with the likelihood of oligoprogression based on the Wald chi-square test. Patients with positive, neutral and negative risk scores for oligometastatic disease had a cumulative incidence of oligometastatic progression of 77% vs 35% vs 33% at 6 months (p=0.03). Conclusions: Elucidation of a genomic signature for extracranial oligometastatic disease derived from non-invasive liquid biopsy appears feasible for NSCLC patients. Patients with this signature exhibited higher rates of early oligoprogression. External validation could lead to a biomarker that has the potential to direct local therapies in oligometastatic patients.

Misrepresentation of mild traumatic brain injury research in press releases.

BACKGROUND: Press releases from academic medical centers often form the basis for health and science news stories. Press release coverage of mild traumatic brain injury (mTBI) research has not been formally appraised in the literature. OBJECTIVE: To perform a systematic content analysis of mTBI-based press releases. DESIGN: Retrospective database study. SETTING: EurekAlert! (eurekalert.org), the main distribution engine for scientific press releases. PARTICIPANTS: Press releases indexed between January 1, 2012 and December 31, 2019 containing a minimum of 150 words. INTERVENTIONS: Pre-established, investigator-generated criteria delineating aspects of misinformation. MAIN OUTCOME MEASUREMENTS: Press releases were evaluated for manifestations of "spin," including misleading title, misleading reporting, misleading claims, and inappropriate extrapolation. RESULTS: Our database search yielded 125 entries within the specified time period. Of these, 66 met inclusion criteria. Fifty-five of 66 (83%) press releases exhibited at least one manifestation of spin. We identified 38 (58%) with misleading titles, 49 (74%) with misleading reporting, 44 (67%) with misleading claims, and 38 (58%) with inappropriate extrapolation. CONCLUSIONS: Our analysis revealed a high degree of spin in recent press releases dedicated to mTBI research. The reports often overstated the strengths and practical impact of the study, publicize substandard research without clinical relevance, while downplaying or failing to report limitations and caveats. Misrepresentation in press releases can affect real-life medical decisions and outcomes.

Impact of Electronic Cigarettes on Various Organ Systems.

The electronic cigarette (e-cigarette) has been regarded by many as a healthier alternative to the combustible cigarette, yet there is a lack of consensus concerning the health consequences and the health benefits associated with e-cigarette use. We review the research on the effects of e-cigarettes on multiple physiological systems, examine the association between e-cigarette use and combustible cigarette uptake and cessation, and highlight research necessary to build consensus. Although the levels of known toxicants and carcinogens tend to be significantly lower in e-cigarettes than in combustible cigarette smoke, toxicants in e-cigarette e-liquid and those that form as part of the vaporization process may produce adverse health consequences in their own right. Acute effects have been noted in the pulmonary, cardiovascular, and immune systems, which highlight the need for research on long-term exposure. The specific chemical constituents and the levels of those constituents that pose harm remain largely uncharacterized. In addition, the efficacy of e-cigarettes for smoking cessation has yet to be established. As the e-cigarette has evolved rapidly, so has the methodology across studies, making cross-study comparisons more difficult to synthesize. The latest generation of e-cigarette devices deliver nicotine and toxicants at higher levels than earlier devices, especially in experienced users. E-cigarettes pose a risk for nicotine exposure, dependence, and combustible cigarette uptake. E-cigarettes and their delivered toxicants appear harmful to multiple organ systems, although the current body of evidence is limited, especially in terms of long-term effects. Further research is warranted with a focus on individual devices, e-liquid constituents, user characteristics, and patterns of use. Any potential benefit of e-cigarettes for smoking cessation must be weighed against the risks. Given the potential longer-term effects, efforts to prevent e-cigarette use in youth are critical.

Patient education strategies in cataract surgery: A systematic review.

OBJECTIVE: To systematically review the comparative effectiveness of patient education strategies in cataract surgery. METHODS: A comprehensive literature search of five electronic databases was conducted for randomized controlled trials (RCTs) studying the efficacy of educational interventions for cataract surgery patients. Peer-reviewed articles published in English were considered for inclusion without restriction limits on publication date. General study characteristics, measurement methodologies, and outcome measures were narratively synthesized. Quality appraisal was conducted using the Oxford quality rating system (for individual studies) and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidelines (for bodies of evidence). RESULTS: Sixteen RCTs were compiled for qualitative review. We identified 21 distinct patient outcomes, four (19%) with a multi-study evidence base: knowledge of cataracts/cataract surgery, knowledge of postoperative care, proficiency in postoperative care, and anxiety. Targeted interventions significantly increased educational efficacy in 11 (69%) studies, but there were consistent improvements only for patient understanding of cataracts/cataract surgery and postoperative care. Quality of evidence was poor for all outcomes examined in multiple studies, as well as for deciding to undergo cataract surgery (measured in one study). Cross-study examination revealed appreciable clinical and methodological heterogeneity. CONCLUSIONS: Targeted interventions fostered patients' understanding of cataract surgery and postoperative care. Additional high-quality studies are needed to determine appropriate educational strategies that improve other clinical, performance, and humanistic outcomes.

Oxidized Lipoprotein Uptake Through the CD36 Receptor Activates the NLRP3 Inflammasome in Human Retinal Pigment Epithelial Cells.

PURPOSE: Accumulation of oxidized phospholipids/lipoproteins with age is suggested to contribute to the pathogenesis of AMD. We investigated the effect of oxidized LDL (ox-LDL) on human RPE cells. METHODS: Primary human fetal RPE (hf-RPE) and ARPE-19 cells were treated with different doses of LDL or ox-LDL. Assessment of cell death was measured by lactate dehydrogenase release into the conditioned media. Barrier function of RPE was assayed by measuring transepithelial resistance. Lysosomal accumulation of ox-LDL was determined by immunostaining. Expression of CD36 was determined by RT-PCR; protein blot and function was examined by receptor blocking. NLRP3 inflammasome activation was assessed by RT-PCR, protein blot, caspase-1 fluorescent probe assay, and inhibitor assays. RESULTS: Treatment with ox-LDL, but not LDL, for 48 hours caused significant increase in hf-RPE and ARPE-19 (P < 0.001) cell death. Oxidized LDL treatment of hf-RPE cells resulted in a significant decrease in transepithelial resistance (P < 0.001 at 24 hours and P < 0.01 at 48 hours) relative to LDL-treated and control cells. Internalized ox-LDL was targeted to RPE lysosomes. Uptake of ox-LDL but not LDL significantly increased CD36 protein and mRNA levels by more than 2-fold. Reverse transcription PCR, protein blot, and caspase-1 fluorescent probe assay revealed that ox-LDL treatment induced NLRP3 inflammasome when compared with LDL treatment and control. Inhibition of NLRP3 activation using 10 µM isoliquiritigenin significantly (P < 0.001) inhibited ox-LDL induced cytotoxicity. CONCLUSIONS: These data are consistent with the concept that ox-LDL play a role in the pathogenesis of AMD by NLRP3 inflammasome activation. Suppression of NLRP3 inflammasome activation could attenuate RPE degeneration and AMD progression.