A RET::GRB2 fusion in pheochromocytoma defies the classic paradigm of RET oncogenic fusions.

The RET kinase receptor is a target of mutations in neural crest tumors, including pheochromocytomas, and of oncogenic fusions in epithelial cancers. We report a RET::GRB2 fusion in a pheochromocytoma in which RET, functioning as the upstream partner, retains its kinase domain but loses critical C-terminal motifs and is fused to GRB2, a physiological RET interacting protein. RET::GRB2 is an oncogenic driver that leads to constitutive, ligand-independent RET signaling; has transforming capability dependent on RET catalytic function; and is sensitive to RET inhibitors. These observations highlight a new driver event in pheochromocytomas potentially amenable for RET-driven therapy.

Pacemaker-Associated Post-cardiac Injury Syndrome Presenting with Tamponade and Recurrent Pleural Effusion.

Post-cardiac injury syndrome (PCIS) is presumed to be an immune-mediated process. It affects the pericardium and, to a lesser extent, the epicardium, myocardium, and pleura. It has been rarely reported following pacemaker insertion with an estimated incidence of 1% to 2%. We present the case of a 62-year-old female who developed PCIS 8 weeks following pacemaker insertion. She presented with impending cardiac tamponade requiring pericardiocentesis; recurrent pleural effusions subsequently complicated her condition. The pleural effusion recurred despite trials of steroids, eventually requiring talc pleurodesis. This case highlights the need to consider PCIS as a possible etiology of recurrent pleural effusion following pacemaker insertion.

In-Hospital Outcomes with Transfemoral Versus Transapical Access for Transcatheter Aortic Valve Replacement in Patients with Peripheral Arterial Disease.

BACKGROUND: There is a paucity of data regarding outcomes with transfemoral (TF) versus transapical (TA) access for transcatheter aortic valve replacement (TAVR) in patients with peripheral artery disease (PAD). METHODS: We queried the national inpatient sample database (NIS) (2012-2013) to identify patients with PAD who underwent TAVR. We conducted a propensity matching analysis using 25 clinical variables to compare TF-TAVR versus TA-TAVR. The main outcome was in-hospital mortality. RESULTS: The analysis included 22,349 patients who underwent TAVR, among those 6692 (29.9%) had PAD. In the matched cohort, in-hospital mortality was similar between TF-TAVR and TA-TAVR groups (4.8% vs. 5.1%, OR 0.95; 95%CI 0.74-1.21). TF-TAVR was associated with lower rates of cardiogenic shock (OR 0.64; 95%CI 0.50-0.82), use of mechanical circulatory support (OR 0.56; 95%CI 0.42-0.75), acute kidney injury (OR 0.76; 95%CI 0.67-0.86), hemodialysis (OR 0.51; 95%CI 0.36-0.71), major bleeding (OR 0.72; 95%CI 0.64-0.80), blood transfusion (OR 0.65; 95%CI 0.58-0.73), discharge to a skilled nursing facility (OR 0.61; 95%CI 0.54-0.68) as well as shorter length of hospital stay (8.13 ±â€¯6.76 vs. 10.11 ±â€¯7.80 days) compared with TA-TAVR. However, TF-TAVR was associated with higher rate of vascular complications (11.7% vs. 3.7%, OR 3.40; 95%CI 2.63-4.38), complete heart block (OR 1.52; 95%CI 1.23-1.87), and pacemaker insertion (OR = 1.58; 95%CI: 1.28-1.94). There was no difference between both groups in the rate of cerebrovascular accidents (OR 1.26; 95%CI 0.93-1.72). CONCLUSION: In this observational analysis from a large national database, there was no difference in in-hospital mortality between TF-TAVR and TA-TAVR among patients with PAD. Further studies are encouraged to identify the optimal access for TAVR in patients with PAD.

Immune thrombocytopenic purpura.

Immune thrombocytopenic purpura (ITP) is a bleeding disorder characterized by isolated thrombocytopenia (platelet count <150,000 u/L), which is not associated with a systemic illness. ITP is reported in approximately 2 per 100,000 adults. The mean age of diagnosis is 50 years. ITP is more common in females of childbearing age and in pregnancy. In adults, the course is more chronic although spontaneous remission can also occur within months of initial diagnosis. A thorough and timely workup of thrombocytopenia is imperative to rule out other differentials of ITP as it is considered a diagnosis of exclusion. Primary care physicians encounter patients who exhibit signs of thrombocytopenia such as petechiae or purpura on a regular basis. A high index of clinical suspicion is required to accurately diagnose ITP and commence the appropriate treatment including glucocorticoids to increase the chances of a favorable prognosis as described by the authors.

Lyme carditis presenting as atrial fibrillation.

The incidence of Lyme disease in the USA is 8 per 100 000 cases and 95% of those occur in the Northeastern region. Cardiac involvement occurs in only 1% of untreated patients. We describe the case of a 46-year-old man who presented with chest pressure, dyspnoea, palpitations and syncope. He presented initially with atrial fibrillation with rapid ventricular response, a rare manifestation of Lyme carditis. In another hospital presentation, he had varying degrees of atrioventricular block including Mobitz I second-degree heart block. After appropriate antibiotic treatment, he made a full recovery and his ECG normalised. The authors aim to urge physicians treating patients in endemic areas to consider Lyme carditis in the workup for patients with atrial fibrillation and unexplained heart block, as the associated atrioventricular nodal complications may be fatal.

Dilated aortic root and severe aortic regurgitation causing dilated cardiomyopathy in classic Ehlers-Danlos syndrome.

Ehlers-Danlos syndrome (EDS) is a group of heritable disorders characterised by vast clinical heterogeneity ranging from the classic constellation of symptoms including skin hyperextensibility, joint hypermobility and skin fragility to the exceedingly critical consequences of arterial rupture and visceral perforation. We describe the case of a 65-year-old male with a history of classic EDS who reported of dyspnoea on exertion, orthopnoea, fatigue and palpitations. He was found to have dilated cardiomyopathy with an ejection fraction of 35%, aortic root dilation and severe aortic valve regurgitation. The authors intend to draw attention to the rare cardiac manifestations of this condition and the therapeutic challenges involved in managing such patients.

Penicillin-induced liver injury during treatment for ocular neurosyphilis.

A 51-year-old man, homosexual, recently diagnosed with ocular neurosyphilis, presented to the emergency room with a 1-day history of fevers and chills. His vital signs were significant for a temperature of 102.8°F and tachycardia of 125 bpm. The patient had experienced blurred vision in his left eye and was diagnosed with ocular neurosyphilis 10 days prior to the current presentation. He was treated with a 14-day course of high-dose intravenous penicillin and oral prednisone. His laboratory studies were significant for transaminitis, with an aspartate aminotransferase of 1826 U/L, alanine aminotransferase of 1743 U/L, total bilirubin of 1.2 mg/dL and alkaline phosphatase of 68 U/L. After ruling out viral aetiologies and toxin-induced hepatic injury, penicillin was discontinued on the day following admission and transaminases promptly improved with resolution of symptoms. The patient's vision returned to normal within 2 weeks after discharge from hospital.