Left-dominant arrhythmogenic cardiomyopathy: an association with desmoglein-2 gene mutation-a case report.

BACKGROUND: Desmosomes are specialized intercellular adhesive junctions of cardiac and epithelial cells that provide intercellular mechanical coupling through glycoproteins, one of which is desmoglein (DSG). DSG-2 mutations are frequently associated with biventricular arrhythmogenic cardiomyopathy (ACM). We report a case of left-dominant ACM in a patient who initially was misclassified as dilated cardiomyopathy (DCM). CASE SUMMARY: A 28-year-old-woman was found to have a moderately reduced left ventricular (LV) systolic function and frequent premature ventricular contractions (PVCs). Targeted genetic testing revealed a heterozygous likely pathogenic variant associated with ACM in exon 15 of the DSG-2 gene (c.3059_3062del; p.Glu1020Alafs*18). Subsequent cardiac magnetic resonance (CMR) imaging showed epicardial and mid-myocardial fatty infiltration involving multiple LV wall segments, multiple areas of mid-myocardial fibrosis/scar, regional dyskinesis involving both ventricles, and an overall reduced left ventricular ejection fraction. The patient's right ventricular (RV) cavity size and overall RV systolic function were normal. Based on the patient's frequent PVCs, family history, fibrofatty myocardial replacement in multiple LV segments, and dyskinetic motion of multiple ventricular wall segments (predominantly affecting the LV), the patient was diagnosed with left-dominant ACM. DISCUSSION: Identifying a likely pathogenic mutation associated with ACM in a patient with ventricular arrhythmias and a family history of sudden cardiac death increased the possibility of ACM. Subsequent CMR imaging confirmed the diagnosis of left-dominant ACM by demonstrating regional biventricular dyskinesia and a characteristic pattern of fibrofatty myocardial replacement. Our case highlights the importance of targeted genetic testing and advanced cardiac imaging in distinguishing left-dominant ACM from DCM.

Twiddler's Syndrome: An Unusual Cause of Repeated Shocks by Implantable Cardioverter-Defibrillator in an Asymptomatic Patient.

Twiddler's syndrome refers to malfunction of pacemaker or implantable cardioverter-defibrillator (ICD) resulting from deliberate or unintentional twisting of pulse generator in device pocket, resulting in lead dislodgment. We report a case of a 65-year-old woman with multiple ICD shocks and antitachycardia pacing events on device interrogation, while she was unaware of the ICD discharges. Twiddler's syndrome is rare and mostly occurs in obese or elderly because of loose subcutaneous tissue allowing pulse generator to rotate in its pocket. It can be prevented by patient education against hand manipulating the generator. Smaller device pocket or suturing generator to fascia can also prevent future episodes.

Presence of gas in left ventricle due to infective endocarditis.

Gas in myocardium is a rare manifestation of infective endocarditis caused by gas producing bacteria. We present a case of infective endocarditis caused by Citrobacter Koseri initially diagnosed by computed tomography and confirmed with transesophageal echocardiogram.

Differences in patient outcomes after conventional versus real time perfusion stress echocardiography in men versus women: a prospective randomised trial.

OBJECTIVE: The purpose of our study was to determine whether sex affects the predictive value of perfusion and wall motion imaging obtained with real time myocardial contrast echocardiography (RTMCE) when compared with conventional stress echocardiography (CSE). METHODS: We prospectively enrolled 1649 age-matched men and women with intermediate pretest probability of coronary artery disease (CAD) undergoing stress echocardiography for suspicion of CAD. Patients with known CAD were excluded. Those who consented to participate in the study were randomised to undergo either CSE or RTMCE. Events were defined as death, non-fatal myocardial infarction (MI) and need for revascularisation. RESULTS: Median follow-up was 2.6 years (927 women, 722 men). Mean age was 58±13 years in both sexes. There were a total of 62 deaths, 12 MIs and 85 revascularisations with a 2-year event rate of 3.5% (95% CI 2.7% to 4.7%). Male sex was a significant independent predictor of adverse outcome (death, non-fatal MI) in both CSE and RTMCE (CSE HR 2.07, 95% CI 1.07 to 4.02, RTMCE HR 2.14; 95% CI 1.04 to 4.33). Higher 2-year event rates were noted in men in comparison with women after a normal CSE (men 5.4%, women 1.6%, p=0.02), but not after a normal RTMCE (men 5.8%, women 3.7%, p=0.41). Event rates were also significantly higher in men after an abnormal RTMCE (men 34.8%, women 16.4%, p=0.02) but no difference in outcome between sexes was observed after an abnormal CSE (men 17.8%, women 18.6%, p=0.90). CONCLUSIONS: The addition of perfusion imaging with RTMCE improves the predictive value of stress echocardiography in men with no known CAD, but does not improve the predictive value in age-matched women.

Liver lesions in children and adolescents: cytopathologic analysis and clinical correlates in 44 cases.

The role of fine needle aspiration (FNA) as a first-line diagnostic modality is well-established for neoplastic and nonneoplastic liver masses in adults. However, cytopathologic analysis of such lesions in children and adolescents has not been well studied. An 18-year retrospective review of the cytopathology archives at The Johns Hopkins Hospital identified 44 cases of hepatic FNA in children and adolescents (i.e., 21 years and younger). The cytopathologic material was reviewed and correlated with subsequent surgical pathology diagnoses and/or clinical follow-up. Among the 44 FNAs studied, 40 (90.9%) were deemed diagnostic for evaluation and 4 (9.1%) were nondiagnostic. Twenty four (60%) of the diagnostic FNAs were neoplasms, 10 (25%) were nonneoplastic lesions, and 6 (15%) were "atypical" or "suspicious." There were 21 (87.5%) malignant and 3 (12.5%) benign tumors. Among the malignant cases, metastases/secondary tumors accounted for 12 (54.5%) followed by hepatocellular carcinoma (HCC)--7 (38.1%). The types of metastatic/secondary neoplasms were Wilms tumor (2), germ cell tumor (2), acute leukemias (2), and miscellaneous others (6). Among the nonneoplastic lesions focal nodular hyperplasia was most common--4 (40%). Among the "atypical" cases, 4 (66.6%) turned out to be benign on follow-up, 2 were HCC, and 1 was Hodgkin lymphoma. Immunoperoxidase (IPOX) studies were done in 20 (45.5%) cases to confirm the cytopathologic diagnoses. Overall, FNA showed a sensitivity of 95.2% and a specificity of 100% for a malignant diagnosis.

Continuous requirement of ErbB2 kinase activity for loss of cell polarity and lumen formation in a novel ErbB2/Neu-driven murine cell line model of metastatic breast cancer.

BACKGROUND: Well over a quarter of human breast cancers are ErbB2-driven and constitute a distinct subtype with substantially poorer prognosis. Yet, there are substantial gaps in our understanding of how ErbB2 tyrosine kinase activity unleashes a coordinated program of cellular and extracellular alterations that culminate in aggressive breast cancers. Cellular models that exhibit ErbB2 kinase dependency and can induce metastatic breast cancer in immune competent hosts are likely to help bridge this gap. MATERIALS AND METHODS: Here, we derived and characterized a cell line model obtained from a transgenic ErbB2/Neu-driven mouse mammary adenocarcinoma. RESULTS: The MPPS1 cell line produces metastatic breast cancers when implanted in the mammary fat pads of immune-compromised as well as syngeneic immune-competent hosts. MPPS1 cells maintain high ErbB2 overexpression when propagated in DFCI-1 or related media, and their growth is ErbB2-dependent, as demonstrated by concentration-dependent inhibition of proliferation with the ErbB kinase inhibitor Lapatinib. When grown in 3-dimensional (3-D) culture on Matrigel, MPPS1 cells predominantly form large irregular cystic and solid structures. Remarkably, low concentrations of Lapatinib led to a switch to regular acinar growth on Matrigel. Immunofluorescence staining of control vs. Lapatinib-treated acini for markers of epithelial polarity revealed that inhibition of ErbB2 signaling led to rapid resumption of normal mammary epithelium-like cell polarity. CONCLUSIONS: The strict dependence of the MPPS1 cell system on ErbB2 signals for proliferation and alterations in cell polarity should allow its use to dissect ErbB2 kinase-dependent signaling pathways that promote loss of cell polarity, a key component of the epithelial mesenchymal transition and aggressiveness of ErbB2-driven breast cancers.