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Graft dysfunction following cardiac transplantation is treated aggressively regardless of etiology; however, graft dysfunction requiring durable LVAD implantation has rarely been described. We present a case of cardiac transplantation complicated by late graft dysfunction requiring durable LVAD implantation. A 52 year-old woman presented to hospital in cardiogenic shock (CS) with refractory ventricular arrhythmias (VAs). LVEF was 20% with global hypokinesis. Coronary angiogram revealed mild coronary artery disease, and endomyocardial biopsy (EMB) diagnosed giant cell myocarditis. Due to worsening CS and VAs despite escalating inotropic support and IABP insertion, she underwent temporary LVAD implantation as a bridge to decision, then cardiac transplantation 2 months later due to lack of recovery of cardiac function. Her post-transplant course was complicated by progressive graft dysfunction with LVEF deteriorating from >70% two weeks post-transplant, to 15-20% 8 months post-transplant (Table 1). CT thorax revealed no coronary artery calcification to implicate severe cardiac allograft vasculopathy. EMBs demonstrated ISHLT Grade 2R rejection treated with methylprednisolone and thymoglobulin. Donor-specific antibodies (DSAs) increased to 9,837 MFI 7 months post-transplant despite EMB showing antibody-mediated rejection (AMR) Grade 0. She was diagnosed with presumed AMR causing late graft dysfunction, and treated with thymoglobulin, plasmapheresis/IVIg, then bortezomib, with reduction in DSAs but no improvement in cardiac function. Her invasive hemodynamics remained consistent with CS. Immediate re-transplantation was considered immunologically high risk, thus she underwent durable LVAD implantation 14 months post-transplant, as a bridge to potential re-transplantation. This case report highlights the importance of aggressive intervention for cardiac allograft rejection, and presents an uncommon course of treatment for severe late graft dysfunction. [ABSTRACT FROM AUTHOR]

Lyme carditis is the most well-known cardiac manifestation of tickborne illnesses. However, there exist a multitude of other tickborne infections associated with myocarditis. We present a case of fulminant myocarditis following a tick bite which highlights this diagnostic challenge. A 72-year-old male presented to hospital 3 weeks following a tick bite with fevers, chills and malaise. Initial EKG showed ST elevations in the anterior leads with an elevated troponin T. Coronary angiogram was negative for significant coronary artery disease and echocardiogram revealed left ventricular ejection fraction (LVEF) of 35-40%. On a presumptive diagnosis of Lyme carditis, the patient was initiated on appropriate antimicrobial therapy. Two days later the patient developed complete heart block with asystolic arrest requiring transvenous pacing. He thereafter developed a drop in LVEF to 20-25% with progression to cardiogenic shock despite multiple inotropes and placement of intra-aortic balloon pump. Strong consideration was given to advanced mechanical circulatory support. At this time Borrelia burgdorferi (Lyme) serologies returned negative. The culprit tick was identified as Dermacentor variabilis (dog tick), which is associated with Rocky Mountain Spotted Fever and is not an efficient transmitter of Lyme Disease unlike the pathognomonic organism Ixodes scapularis (deer tick). This reduced the likelihood of Lyme carditis, and a broad workup for other infectious and autoimmune etiologies of myocarditis returned negative. With a presumed diagnosis of acute myocarditis, the patient was treated empirically with pulse steroids. Over the next weeks he progressively improved, was extubated and no longer pacemaker dependent. Cardiac MRI demonstrated myopericarditis and endomyocardial biopsy was consistent with a non-specific lymphocytic myocarditis with no giant cells, granulomas or vasculitis identified. The patient was eventually discharged home on a prolonged steroid taper and 3 months later his LVEF normalized. This case highlights the important workup required for a tick bite associated myocarditis and the importance of maintaining a broad differential diagnosis. Further trials assessing the role of steroid therapy in non-specific lymphocytic myocarditis are required. [ABSTRACT FROM AUTHOR]

Myocarditis is an inflammatory disease of cardiac muscle caused by a variety of infectious and non-infectious conditions. Viral infection is the most frequent cause of myocarditis; however, herpes simplex virus 1 (HSV-1) infection causing myocarditis has been rarely described. We present a case of a young woman with HSV-1 viremia and fulminant myocarditis presenting with cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation (VA-ECMO), complicated by hyperhemolysis. A 35 year-old immunocompetent woman with moderate alcohol consumption presented to hospital with a 4-day history of fever and flu-like symptoms. She was fully vaccinated for COVID-19 two months prior to symptom onset. Her COVID-19 testing was negative and she was discharged home. She returned to hospital 4 days later in cardiogenic shock. Transthoracic echocardiogram demonstrated LVEF of 30% with a small pericardial effusion. Coronary angiogram revealed normal coronaries. She was placed on peripheral VA-ECMO for worsening cardiogenic shock. Due to inadequate LV unloading, she underwent atrial septostomy. Five days after VA-ECMO cannulation, HSV-1 was detected in the blood and she was started on intravenous acyclovir. Her ECMO course was complicated by acute kidney injury requiring dialysis, and hyperhemolysis with a peak LDH of 12,000 U/L. The mechanism of hemolysis was attributed to an intravascular process (plasma free hemoglobin 7487 mg/L, normal < 150 mg/L) likely from a combination cold agglutinins and the mechanical circuit. Interestingly the membrane pressure gradient was within normal. The patient received treatment with plasmapheresis (Table 1), and was eventually decannulated after 12 days following hemodynamic improvement. This case report highlights a rare viral cause of fulminant myocarditis and emphasizes the need for collaboration among various specialists in the management of complex cases. [ABSTRACT FROM AUTHOR]

The study of the structural and magnetic phase diagram of the manganites La1−xAgxMnO3 shows similarity with the La1−x′Srx′MnO3 series, involving a metallic ferromagnetic domain at relatively high temperature (&ap;300 K). The Ag-system differs from the Sr-one by a much smaller homogeneity range (x≤1/6) and the absence of charge ordering. But the most important feature of the Ag-manganites deals with the exceptionally high magnetoresistance (−25%) at room temperature under 1.2 T, that appears for the composition x=1/6. The latter is interpreted as the coincidence of the optimal double exchange condition (Mn3+:Mn4+=2) with Tmax=300 K (maximum of the ρ(T) curve in zero field). [Copyright &y& Elsevier]

• Ten inhibitors of MDM2 have been used in 18 studies of adult cancer. • Two thirds of studies did not define a dose limiting toxicity a priori. • The most common toxicities were cytopenias, GI toxicity and metabolic disturbances. • There was one death attributed to treatment with MDM2 inhibitors. • MDM2 inhibitors may represent a safe adjuvant therapy for acute leukemia. Mouse double minute 2 protein (MDM2), a negative regulator of the p53 tumour suppressor gene, is frequently amplified in malignancies. MDM2 antagonists have shown efficacy in treating malignancies with MDM2 overexpression and can overcome chemoresistance in acute myeloid leukemia. We systematically evaluated the safety profile of MDM2 inhibitors in the treatment of solid organ and hematologic malignancies. We searched Medline and EMBASE from January 1947 to November 2018 for prospective clinical studies, in English or French, investigating any MDM2 inhibitor in pediatric or adult cancers, and reporting dose and toxicity outcomes. Primary outcome was dose-limiting toxicity (DLT) and secondary outcome was death. The search yielded 493 non-duplicate citations. Eighteen studies of 10 inhibitors met inclusion criteria (total N = 1005 patients). Two-thirds of included studies did not define DLTs and the reporting of toxicities was highly variable. The most commonly reported DLTs were cytopenias, gastrointestinal toxicity, metabolic disturbances, fatigue and cardiovascular toxicity; there was one death attributed to treatment toxicity. MDM2 antagonists have been studied in a variety of malignancies with toxicities similar to other commonly used chemotherapy agents and may represent a safe adjuvant treatment for further study in in acute leukemia. [ABSTRACT FROM AUTHOR]

La0.67Sr0.33MnO3−δ films, fabricated on (1 1 1) LaAlO3 single-crystal substrates using a direct current magnetron sputtering technique, are demonstrated by X-ray diffraction patterns and pole figures to be high quality epitaxial films and there is a perfect matching relationship between the films and the substrates. We observed an obvious difference of the electronic–magnetic transportation properties among films sputtered on (1 1 1), (1 0 0) and (1 1 0) LaAlO3 substrates, respectively. A mechanism for the difference is discussed briefly. [Copyright &y& Elsevier]

Competing Interests: Conflict of interest The authors declare that they have no conflict of interest.