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.

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.

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.