BackgroundMost studies of outcomes after myocardial infarction (MI) focus on the acute phase after the index event. We assessed mortality and morbidity trends after the first year in survivors of acute MI, by conducting a systematic literature review.MethodsLiterature searches were conducted in Embase, MEDLINE, and the Cochrane Database of Systematic Reviews to identify epidemiological studies of long-term (>10 years) mortality and morbidity trends in individuals who had experienced an acute MI more than 1 year previously.ResultsThirteen articles met the inclusion criteria. Secular trends showed a consistent decrease in mortality and morbidity after acute MI from early to more recent study periods. The relative risk for all-cause death and cardiovascular outcomes (recurrent MI, cardiovascular death) was at least 30% higher than that in a general reference population at both 1–3 years and 3–5 years after MI. Risk factors leading to worse outcomes after MI included comorbid diabetes, hypertension and peripheral artery disease, older age, reduced renal function, and history of stroke.ConclusionsThere have been consistent improvements in secular trends for long-term survival and cardiovascular outcomes after MI. However, MI survivors remain at higher risk than the general population, particularly when additional risk factors such as diabetes, hypertension, or older age are present.

Funding for this study was provided by Novartis, which manufactures ribociclib and provided input on the study design and data collection, analysis, and interpretation. Mistry, May, Suri, and Young are employees of PAREXEL. Tang, Mishra, D. Bhattacharyya, and Dalal are employees of Novartis. S. Bhattacharyya was an employee of Novartis during the study period. Tang and Dalal hold stock in Novartis. Brixner, Oderda, and Biskupiak were paid by Millcreek Outcomes Group as consultants for work on this project. Brixner has also consulted for AstraZeneca, UCB, Regeneron, and Abbott.

This study has identified risk factors that may help stratify patients into different risk profiles and offer prolonged prophylaxis to patients at increased risk on the basis of preoperative risk factors and postoperative complications.

The sensitivity of Cx45 channels to CO2, transjunctional voltage ( V(j)) and inhibition of calmodulin (CaM) expression was tested in oocytes by dual voltage clamp. Cx45 channels are very sensitive to V(j) and close with V(j) preferentially by the slow gate, likely to be the same as the chemical gate. With a CO2-induced drop in junctional conductance ( G(j)), both the speed of V(j)-dependent inactivation of junctional current ( I(j)) and V(j) sensitivity increased. With 40-mV V(j)-pulses, the tau of single exponential I(j) decay reversibly decreased by;40% during CO2 application, and G(j steady state)/G(j peak) decreased multiphasically, indicating that both kinetics and V(j) sensitivity of chemical/slow V(j) gating are altered by changes in [H(+)](i) and/or [Ca(2+)](i). CaM expression was inhibited with oligonucleotides antisense to CaM mRNA. With 15 min CO2, relative junctional conductance ( G(jt)/ G(jt0)) dropped to 0% in controls, but only by;17% in CaM-antisense oocytes. Similarly, V(j) sensitivity was significantly lessened in CaM-antisense oocytes. The data indicate that both the speed and sensitivity of V(j)-dependent inactivation of the junctional current of Cx45 channels are affected by CO2 application, and that CaM plays a key role in channel gating.

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)1,2. Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive1,2. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma3. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response.

ObjectivesAuthors may choose to work with professional medical writers when writing up their research for publication. We examined the relationship between medical writing support and the quality and timeliness of reporting of the results of randomised controlled trials (RCTs).DesignCross-sectional study.Study samplePrimary reports of RCTs published in BioMed Central journals from 2000 to 16 July 2014, subdivided into those with medical writing support (n=110) and those without medical writing support (n=123).Main outcome measuresProportion of items that were completely reported from a predefined subset of the Consolidated Standards of Reporting Trials (CONSORT) checklist (12 items known to be commonly poorly reported), overall acceptance time (from manuscript submission to editorial acceptance) and quality of written English as assessed by peer reviewers. The effect of funding source and publication year was examined.ResultsThe number of articles that completely reported at least 50% of the CONSORT items assessed was higher for those with declared medical writing support (39.1% (43/110 articles); 95% CI 29.9% to 48.9%) than for those without (21.1% (26/123 articles); 95% CI 14.3% to 29.4%). Articles with declared medical writing support were more likely than articles without such support to have acceptable written English (81.1% (43/53 articles); 95% CI 67.6% to 90.1% vs 47.9% (23/48 articles); 95% CI 33.5% to 62.7%). The median time of overall acceptance was longer for articles with declared medical writing support than for those without (167 days (IQR 114.5–231 days) vs 136 days (IQR 77–193 days)).ConclusionsIn this sample of open-access journals, declared professional medical writing support was associated with more complete reporting of clinical trial results and higher quality of written English. Medical writing support may play an important role in raising the quality of clinical trial reporting.

CO(2)-guided EVAR is technically feasible and safe; it eliminates or reduces the need for IC use, may expedite the procedure, and avoids deterioration in renal function in patients with pre-existing renal insufficiency. A prospective trial comparing CO(2) with IC during EVAR is warranted.

Objective: Multimodal CT, including noncontrast CT (NCCT), CT with contrast, CT angiography (CTA), and perfusion CT (CTP), is increasingly used in acute stroke patients to identify candidates for endovascular therapy. Our goal is to explore the cost-effectiveness of multimodal CT as a diagnostic test.Methods: A Markov model compared multimodal CT to NCCT in a hypothetical cohort of nonhemorrhagic stroke patients presenting within 3 hours of symptom onset who were potential IV tPA candidates. Patients who failed to improve after IV tPA or in whom IV tPA was contraindicated were candidates for endovascular therapy. Direct costs (2008 USD), outcomes, and probabilities were obtained from the literature.Results: For the 3-month time horizon, multimodal CT had lower costs (Ϫ$1,716), had greater quality-adjusted life-years (QALYs, 0.004), and was the cost-effective choice 100% of the time for a willingness-to-pay of $100,000/QALY (probabilistic sensitivity analysis). The number needed to screen with multimodal CT to avoid 1 diagnostic angiogram was 2. Over a lifetime, multimodal CT had lower costs (Ϫ$2,058), had greater QALYs (0.008), and was cost-effective, with a 90.1% likelihood, for a willingness-to-pay of $100,000/QALY. Conclusions:Multimodal CT appears to be a cost-saving screening tool over the short term. However, additional data regarding clinical outcomes following multimodal CT-guided intra-arterial treatment are needed before the long-term cost-effectiveness can be suitably addressed. This analysis can be incorporated into future discussions of multimodal CT as a diagnostic test for unselected patients, within and beyond the 3-hour IV tPA time window. Neurology ® 2010;75:1678-1685 GLOSSARY CTA ϭ CT angiography; CTP ϭ perfusion CT; IA ϭ intra-arterial; ICER ϭ incremental cost-effectiveness ratio; mRS ϭ modified Rankin Scale; NCCT ϭ noncontrast CT; NE ϭ northeast; NW ϭ northwest; QALY ϭ quality-adjusted life-year; SE ϭ southeast; SW ϭ southwest; tPA ϭ tissue plasminogen activator; WTA ϭ willingness to accept; WTP ϭ willingness to pay.Recommendations for treatment of acute ischemic stroke emphasize timely IV tissue plasminogen activator (tPA) administration. The minimum requirement is imaging excluding hemorrhage while allowing for other MR or CT-based imaging so long as IV tPA is not delayed.1 At some institutions, multimodal CT imaging is performed prior to intra-arterial (IA) procedures. CT-based imaging is typically utilized because it requires less time to complete than MR-based imaging, thus minimizing the time to IA procedures in the setting of acute stroke. Multimodal CT imaging including CT with and without contrast, CT angiography (CTA), and perfusion CT (CTP) rapidly identifies the presence or absence of clot suitable for extraction and salvageable ischemic tissue. 2,3At centers providing endovascular therapies for stroke, multimodal CT rapidly identifies candidates for these therapies in lieu of conventional angiography. However, multimodal CT is a costly screening tool where a proportion o...