CMR findings in patients referred for suspected myocarditis following mRNA-based COVID vaccination compared with pre-COVID myocarditis referrals: A single-centre observational study.

Background: Vaccination is considered the key to overcome the COVID pandemic. For the first time mRNA-based vaccinations are used in humans. Case series suggested an increased risk of myocarditis after vaccination. This study sought to describe CMR findings in patients with suspected mRNA-vaccine associated myocarditis. Methods: A total of 33 consecutive patients referred for CMR work-up of suspected myocarditis associated with mRNA-based vaccination were included. A historical cohort of 135 consecutive patients referred for suspected myocarditis in the pre-COVID era served as control group. All patients underwent multi-parametric CMR including CINE and late gadolinium enhancement (LGE) imaging as well as parametric T1/T2 mapping of the left ventricular myocardium. Results: Patients referred for suspected vaccination-related myocarditis were more often female (55 % vs 32 %, p = 0.015) and demonstrated smaller LV dimensions as well as a better LV function compared to patients of the control group. CMR revealed a lower prevalence of non-ischemic LGE in patients with suspected vaccination-myocarditis (6 % vs 22 %, p = 0.04). However, among patients without LGE we observed a higher prevalence of an abnormal T1/T2 mapping result in patients with suspected vaccination-myocarditis compared to the control group (45 % vs 18 %, p = 0.010). Conclusion: In this small single-centre study, compared to myocarditis referrals in the pre-COVID era, patients currently referred for CMR work-up of suspected mRNA-vaccination-associated myocarditis demonstrated lower prevalence of LGE but higher prevalence of abnormal T1/T2 mapping. These hypothesis-generating observations may point towards a rather subtle myocardial damage and support the routine use of T1/T2 mapping in this indication.

Right coronary anomaly in a patient with myocarditis and cardiac arrest: a case report.

INTRODUCTION: Management of coronary anomalies continues to be a controversial topic in medicine, for which only in specific clinical scenarios recommendations for management are clearly defined. We are presenting a previously healthy 18-year-old patient who survived sudden cardiac death (SCD). Multiple potential aetiologies were evaluated, including malignant coronary anomaly, acute myocarditis, potential Brugada type 3 electrocardiographic pattern, and urine drug screening positive for lysergic acid diethylamide (LSD). CASE PRESENTATION: Malignant right coronary anomaly with interarterial course and acute angle takeoff was diagnosed with coronary computed tomography angiography. Signs of acute myocarditis were detected in cardiac magnetic resonance imaging and endomyocardial biopsy. Due to potential Brugada type 3 electrocardiographic pattern flecainide provocation testing was performed to rule out Brugada Syndrome. Confirmatory chromatography revealed that prior LSD drug screening was false positive. Ultimately, the patient underwent cardiothoracic surgery with unroofing of the right coronary artery. Subsequent clinical course was favourable. DISCUSSION: Right coronary artery anomalies are more prevalent than left coronary anomalies but less often associated with SCD. Interarterial course and acute angle takeoff are risk factors for unfavourable outcomes. Myocarditis is a potential trigger of arrhythmias and SCD. In patients with Brugada type 2 and 3 electrocardiographic pattern (saddleback ST-segment elevation), provocation testing with flecainide, ajmalin, or procainamide can be used to unmask Brugada type 1 electrocardiographic pattern. Due to the proarrythmic potential of many recreational drugs, screening for these substances can be useful in young adults presenting after cardiac arrest; cross-reaction of substances as in our patient have to be considered.

31 years of lung cancer in the canton of Zurich, Switzerland: incidence trends by sex, histology and laterality.

QUESTIONS UNDER STUDY: Lung cancer belongs to the most common cancers in Switzerland. We examined trends in lung cancer incidence, with focus on sex, histology and laterality, in the Canton of Zurich since 1980. MATERIAL AND METHODS: Registry data consisting of 16 798 lung cancer cases from 1980 to 2010 were analysed. Cases were classified into adenocarcinoma (ADC), squamous cell carcinoma (SCC), small-cell carcinoma (SCLC), large cell tumour and carcinoid tumour. Age-standardised (European standard) incidence rates (IR) per 100 000 person-years, male-to-female incidence-rate ratio (M/F-IRR), and left-to-right lung incidence-rate ratio (L/R-IRR) were calculated. RESULTS: Over the study period, ADC occurred most frequently (31.9%), followed by SCC (29.1%), SCLC (15.4%), large cell carcinoma (6.3%), and carcinoid tumour (1.5%). Other/unspecified subtypes accounted for 15.7%. In men, the IR of SCC decreased from 34.2/100 000 (95% confidence interval [CI] 32.5-35.9) in 1980 to 12.8/100 000 (12.0-13.6) in 2010, but increased in women from 3.4/100 000 (2.7-4.0) to 4.0/100 000 (3.4-4.5). The IR of ADC increased in women from 5.1/100 000 (4.1-5.8) to 12.6/100 000 (11.8-13.4) and in men from 15.1/100 000 (14.0-16.3) to 19.4/100 000 (18.4-20.4). Overall M/F-IRR was 2.61; the highest ratio (5.8) was seen for SCC and the lowest (0.77) for carcinoid tumour. All histological subtypes showed a higher susceptibility of the right lung. CONCLUSION: Our data reflect the global increase of lung cancer in women. ADC increased over time in women and men, whereas SCC decreased markedly among men. These trends may have occurred owing to changes in smoking behaviour and cigarette composition.

Colocalization of the (Pro)renin Receptor/Atp6ap2 with H+-ATPases in Mouse Kidney but Prorenin Does Not Acutely Regulate Intercalated Cell H+-ATPase Activity.

The (Pro)renin receptor (P)RR/Atp6ap2 is a cell surface protein capable of binding and non-proteolytically activate prorenin. Additionally, (P)RR is associated with H(+)-ATPases and alternative functions in H(+)-ATPase regulation as well as in Wnt signalling have been reported. Kidneys express very high levels of H(+)-ATPases which are involved in multiple functions such as endocytosis, membrane protein recycling as well as urinary acidification, bicarbonate reabsorption, and salt absorption. Here, we wanted to localize the (P)RR/Atp6ap2 along the murine nephron, exmaine whether the (P)RR/Atp6ap2 is coregulated with other H(+)-ATPase subunits, and whether acute stimulation of the (P)RR/Atp6ap2 with prorenin regulates H(+)-ATPase activity in intercalated cells in freshly isolated collecting ducts. We localized (P)PR/Atp6ap2 along the murine nephron by qPCR and immunohistochemistry. (P)RR/Atp6ap2 mRNA was detected in all nephron segments with highest levels in the collecting system coinciding with H(+)-ATPases. Further experiments demonstrated expression at the brush border membrane of proximal tubules and in all types of intercalated cells colocalizing with H(+)-ATPases. In mice treated with NH4Cl, NaHCO3, KHCO3, NaCl, or the mineralocorticoid DOCA for 7 days, (P)RR/Atp6ap2 and H(+)-ATPase subunits were regulated but not co-regulated at protein and mRNA levels. Immunolocalization in kidneys from control, NH4Cl or NaHCO3 treated mice demonstrated always colocalization of PRR/Atp6ap2 with H(+)-ATPase subunits at the brush border membrane of proximal tubules, the apical pole of type A intercalated cells, and at basolateral and/or apical membranes of non-type A intercalated cells. Microperfusion of isolated cortical collecting ducts and luminal application of prorenin did not acutely stimulate H(+)-ATPase activity. However, incubation of isolated collecting ducts with prorenin non-significantly increased ERK1/2 phosphorylation. Our results suggest that the PRR/Atp6ap2 may form a complex with H(+)-ATPases in proximal tubule and intercalated cells but that prorenin has no acute effect on H(+)-ATPase activity in intercalated cells.