Genetic defects in a His-Purkinje system transcription factor, IRX3, cause lethal cardiac arrhythmias.

AIM: Ventricular fibrillation (VF), the main cause of sudden cardiac death (SCD), occurs most frequently in the acute phase of myocardial infarction: a certain fraction of VF, however, develops in an apparently healthy heart, referred as idiopathic VF. The contribution of perturbation in the fast conduction system in the ventricle, the His-Purkinje system, for idiopathic VF has been implicated, but the underlying mechanism remains unknown. Irx3/IRX3 encodes a transcription factor specifically expressed in the His-Purkinje system in the heart. Genetic deletion of Irx3 provides a mouse model of ventricular fast conduction disturbance without anatomical or contraction abnormalities. The aim of this study was to examine the link between perturbed His-Purkinje system and idiopathic VF in Irx3-null mice, and to search for IRX3 genetic defects in idiopathic VF patients in human. METHODS AND RESULTS: Telemetry electrocardiogram recording showed that Irx3-deleted mice developed frequent ventricular tachyarrhythmias mostly at night. Ventricular tachyarrhythmias were enhanced by exercise and sympathetic nerve activation. In human, the sequence analysis of IRX3 exons in 130 probands of idiopathic VF without SCN5A mutations revealed two novel IRX3 mutations, 1262G>C (R421P) and 1453C>A (P485T). Ventricular fibrillation associated with physical activities in both probands with IRX3 mutations. In HL-1 cells and neonatal mouse ventricular myocytes, IRX3 transfection up-regulated SCN5A and connexin-40 mRNA, which was attenuated by IRX3 mutations. CONCLUSION: IRX3 genetic defects and resultant functional perturbation in the His-Purkinje system are novel genetic risk factors of idiopathic VF, and would improve risk stratification and preventive therapy for SCD in otherwise healthy hearts.

Two Cases of SMARCA4-Deficient Non-small Cell Lung Cancer (NSCLC) with Improved Performance Status (PS) after Treatment with Immune Checkpoint Inhibitors (ICIs).

SWItch/Sucrose Non-Fermentable (SWI/SNF)-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4) mutations are commonly reported in non-small cell lung cancer (NSCLC) and are associated with a poor prognosis. There is insufficient evidence regarding the efficacy of immune checkpoint inhibitors (ICIs) in SMARCA4-deficient NSCLC patients with poor performance status (PS). We report two cases of advanced SMARCA4-deficient NSCLC treated with ICIs, in which marked regression of the tumor and improved general condition of the patients were achieved.

Seven cases of contact dermatitis due to stearyl alcohol contained in topical medications.

Stearyl alcohol is found in various cosmetics and topical medications and is regarded as safe. Allergic contact dermatitis is reported due to this chemical on rare occasions. We report seven cases, comprising three men and four women aged between 36 and 62 between the years 2013 to 2019, of allergic contact dermatitis due to the use of topical medication, where the patient showed a positive result to a patch test using stearyl alcohol. There were 10 topical medications that we considered to be the cause of this: three were from Oronine® H ointment, two from Eurax® cream, one from Eurax H cream, and four from topical antifungal medications. All these medications contained stearyl alcohol. Seven cases of patch tests with stearyl alcohol all showed positive results. Moreover, having done a patch test with cetyl alcohol, two out of three tests showed positive. When researching allergic contact dermatitis due to topical medications, it is important to test for allergy to stearyl alcohol as well as their main ingredients, because it is contained in numerous products and has the ability to cause allergic contact dermatitis.

Massive Pericardial Effusion in a Case of Acute Pericarditis with Slight ST-Segment Elevation of Short Duration.

We present the case of a 77-year-old woman who suffered from chest pain. Her white blood cell count was 10,200/µL and C-reactive protein level was 5.5 mg/dL. There was no electrocardiogram abnormality up to 5 hours after admission. At 15 hours, slight ST-segment elevation occurred, but this disappeared on day 4. Imaging revealed slight pericardial effusion. Nonsteroidal anti-inflammatory drugs and antibiotics were administered. However, the pericardial effusion, inflammatory response, and bilateral heart failure worsened. Pericardiotomy on day 6 released 350 mL of fluid, and symptoms improved. Viral pericarditis was assumed. Massive pericardial effusion is rare in cases of acute viral pericarditis, as is slight, short-duration ST-segment elevation.

Acute Myocardial Infarction with Severe ST Segment Elevation Treated with Percutaneous Coronary Intervention More than Two Days after Onset: A Case with Remarkable Recovery.

The patient was a 65-year-old man with marked ST-elevation myocardial infarction. Cardiac catheterization revealed an occluded middle portion of the left anterior descending artery and no collateral circulation. Percutaneous coronary intervention (PCI) was performed, and ST elevation improved 5 days after PCI. Almost all electrocardiogram (ECG) findings were normal 6 months later. Echocardiographic findings were also normal. This case was very successful and unusual in that no ventricular aneurysm formed despite ST elevation continuing for a few days and that ECG and left ventricular function were nearly normal after PCI performed days after the onset in a case without collateral circulation.

Isolation and characterization of Streptococcus thermophilus possessing prtS gene from raw milk in Japan.

Streptococcus thermophilus is widely used for producing fermented dairy products such as yogurt and cheese. Some S. thermophilus strains possessing the cell-wall protease PrtS show high proteolytic activity and fast acidification properties, which are very useful in industrial starters. However, few S. thermophilus strains possessing the prtS gene have been isolated from the environment. To clarify whether or not S. thermophilus strains possessing the prtS gene are present in Japan, we isolated S. thermophilus from raw milk collected in Japan from 2011 to 2017 and investigated the strains for the presence of prtS by PCR. A total of 172 S. thermophilus strains were isolated, and 59 strains were confirmed to possess prtS. We measured fermentation times of 59 prtS-positive strains in skim milk broth and found that 53 strains showed fast acidification properties, finishing fermentation within 10 hr. However, the remaining 6 prtS-positive strains showed slow acidification properties, and they had several amino acid mutations in PrtS compared with fast acidifying S. thermophilus LMD-9 and 4F44. These results demonstrate that S. thermophilus strains possessing prtS are prevalent in Japan and that some prtS-positive strains could lose their fast acidifying properties through mutations in PrtS.

Pityriasis Rubra Pilaris Type V as an Autoinflammatory Disease by CARD14 Mutations.

Importance: We found CARD14 mutations (2 de novo novel mutations and another previously reported mutation) in 3 of 3 patients with pityriasis rubra pilaris (PRP) type V, but not in patients with PRP of other types. Our findings, combined with the published literature, suggest that type V PRP, both familial and sporadic, can be caused by CARD14 mutations. Detailed clinical observation revealed that all 3 patients displayed unique patchy macular brown hyperpigmentation. Objective: To further determine how often patients with PRP have pathogenic mutations in CARD14 and to elucidate which clinical subtype of PRP is caused by CARD14 mutations. Design, Setting, and Participants: We sequenced the entire coding regions of CARD14 in genomic DNA from patients with 5 clinical subtypes of PRP. The detailed clinical features were analyzed in all the patients. The pathogenicity of each mutation was evaluated by several computational predictions. PRP was classified into 6 subgroups, types I to VI, based on clinical criteria. We categorized all the patients with PRP into the clinical subtypes using the classic PRP classification; 22 cases of PRP with varying subtypes were studied. Main Outcomes and Measures: The prevalence of CARD14 mutations in each subtype of PRP was evaluated. Clinical features and characteristics of patients with PRP with CARD14 mutations were analyzed. Results: Overall 22 patients with PRP were included in our study (12 men, 10 women; mean [SD] age, 26 [18] years). Among 3 patients with PRP type V, all were found to have CARD14 mutations: 2 de novo novel mutations (p.Cys127Ser and p.Gln136Leu), and another previously reported mutation (p.Gly117Ser). All were close to the reported pathogenic domains. In silico analysis of all 3 mutations suggested that they are functionally relevant to pathogenesis. All 3 patients displayed unique patchy macular brown hyperpigmentation additionally to other typical features of PRP. Patients with PRP type I and type IV, 1 patient each, had the rare variants in CARD14. Conclusions and Relevance: Pityriasis rubra pilaris type V is a distinct variant of PRP that is caused by CARD14 mutations. In addition, a rare variant of CARD14 might also be implicated in the pathophysiology of other forms of PRP.

Angina pectoris with pharyngeal pain alone: a case report.

Patients with pharyngeal pain are frequently encountered in the department of otorhinolaryngology. The pharyngeal pain is usually caused by an inflammation or a malignant disease. In some cases, anginal pain radiates to the pharynx. However, patients with angina pectoris who suffer from pharyngeal pain without chest pain are believed to be very rare. The patient was a 70-year-old man whose chief complaint was only pharyngeal pain on exertion. The pharyngeal pain was similar to acute pharyngitis with burning pain. Upon cardiac catheterization, no abnormality was found in the right coronary artery or in the circumflex artery, but 99% stenosis was found in the middle portion of the left anterior descending artery. There was no collateral circulation to the left anterior descending artery. Thus, percutaneous coronary intervention was performed, and the pharyngeal pain vanished.

Intravascular ultrasound assessment of atherosclerotic plaque in the aorta.

BACKGROUND: Intravascular ultrasound (IVUS) has been used for assessment of the coronary arteries. However, few IVUS studies have been reported on the aorta. MATERIALS AND METHODS: To assess the presence of atherosclerotic disease in the aorta by the use of IVUS, 29 patients with heart disease (24 men and 5 women; mean age, 61+/-11 years) including ischemic heart disease (n=21) and valvular disease or dilated cardiomyopathy (n=8) were enrolled in the study. An IVUS catheter was inserted through the femoral artery, and IVUS images were obtained in the descending aorta (DA) at the level of the pulmonary artery bifurcation, and in the proximal and distal regions of the abdominal aorta (AA) at the level of the renal artery bifurcation. Percent plaque area (%PA) was calculated as vessel cross-sectional area surrounded by media minus lumen cross-sectional area divided by vessel cross-sectional area. RESULTS: %PAs differed significantly between the three aortic levels: DA, 14.9+/-5.5%; proximal AA, 19.0+/-6.9%; and distal AA, 28.3+/-9.7% (p<0.05). However, PA did not differ significantly between the three levels (DA, 94.7+/-38.0 mm2; proximal AA, 90.9+/-35.0 mm2; distal AA, 79.7+/-32.3 mm2). %PA and PA in the DA and proximal AA correlated with age (r=0.39-0.46, p<0.05), but not with coronary angiography findings or multiple risk factors. CONCLUSIONS: The aortic plaque is clearly observed by IVUS. The plaque is diffuse at the 3 levels, had little relationship with risk factor of arteriosclerosis or coronary artery disease, and aging affected the increase of plaque.