Atrial arrhythmias following CAR-chimeric antigen receptor T-cell therapy: Incidence, risk factors and biomarker profile.

Recent reports have raised concerns about the association of chimeric antigen receptor T cell (CAR-T) with non-negligible cardiotoxicity, particularly atrial arrhythmias. First, we conducted a pharmacovigilance study to assess the reporting of atrial arrhythmias following CD19-directed CAR-T. Subsequently, to determine the incidence, risk factors and outcomes of atrial arrhythmias post-CAR-T, we compiled a retrospective single-centre cohort of non-Hodgkin lymphoma patients. Only commercial CAR-T products were considered. Atrial arrhythmias were nearly fourfold more likely to be reported after CAR-T therapy compared to all other cancer patients in the FAERS (adjusted ROR = 3.76 [95% CI 2.67-5.29]). Of the 236 patients in our institutional cohort, 23 (10%) developed atrial arrhythmias post-CAR-T, including 12 de novo arrhythmias, with most (83%) requiring medical intervention. Atrial arrhythmias frequently co-occurred with cytokine release syndrome and were associated with higher post-CAR-T infusion peak levels of IL-10, TNF-alpha and LDH, and lower trough levels of fibrinogen. In a multivariable analysis, risk factors for atrial arrhythmia were history of atrial arrhythmia (OR = 6.80 [2.39-19.6]) and using CAR-T product with a CD28-costimulatory domain (OR = 5.17 [1.72-18.6]). Atrial arrhythmias following CD19-CAR-T therapy are prevalent and associated with elevated inflammatory biomarkers, a history of atrial arrhythmia and the use of a CAR-T product with a CD28 costimulatory domain.

Biomarkers and cardiovascular outcomes in chimeric antigen receptor T-cell therapy recipients.

AIMS: Chimeric antigen receptor T-cell therapy (CAR-T) harnesses a patient's immune system to target cancer. There are sparse existing data characterizing death outcomes after CAR-T-related cardiotoxicity. This study examines the association between CAR-T-related severe cardiovascular events (SCE) and mortality. METHODS AND RESULTS: From a multi-centre registry of 202 patients receiving anti-CD19 CAR-T, covariates including standard baseline cardiovascular and cancer parameters and biomarkers were collected. Severe cardiovascular events were defined as a composite of heart failure, cardiogenic shock, or myocardial infarction. Thirty-three patients experienced SCE, and 108 patients died during a median follow-up of 297 (interquartile range 104-647) days. Those that did and did not die after CAR-T were similar in age, sex, and prior anthracycline use. Those who died had higher peak interleukin (IL)-6 and ferritin levels after CAR-T infusion, and those who experienced SCE had higher peak IL-6, C-reactive protein (CRP), ferritin, and troponin levels. The day-100 and 1-year Kaplan-Meier overall mortality estimates were 18% and 43%, respectively, while the non-relapse mortality (NRM) cumulative incidence rates were 3.5% and 6.7%, respectively. In a Cox model, SCE occurrence following CAR-T was independently associated with increased overall mortality risk [hazard ratio (HR) 2.8, 95% confidence interval (CI) 1.6-4.7] after adjusting for age, cancer type and burden, anthracycline use, cytokine release syndrome grade ≥ 2, pre-existing heart failure, hypertension, and African American ancestry; SCEs were independently associated with increased NRM (HR 3.5, 95% CI 1.4-8.8) after adjusting for cancer burden. CONCLUSION: Chimeric antigen receptor T-cell therapy recipients who experience SCE have higher overall mortality and NRM and higher peak levels of IL-6, CRP, ferritin, and troponin.

Video Education on Hereditary Breast and Ovarian Cancer (HBOC) for Physicians: an Interventional Study.

The National Comprehensive Cancer Network (NCCN) guidelines are the gold standard in hereditary cancer risk assessment, screening, and treatment. A minority of physicians follow NCCN guidelines for BRCA1 or BRCA2 mutations. This study assesses the impact of an interventional educational program on HBOC in terms of knowledge. Physicians were sent an invite to join either an intervention survey (web-training offered prior to the knowledge survey) or control survey (web-training offered after the knowledge survey). Sixty-nine physicians in the intervention arm and 67 physicians in the control arm completed the survey. The interventional group regularly answered items correctly at a higher frequency than the control group. For example, 64.71% (n = 44) of physicians in the intervention group knew that multi-gene testing does not have to include only highly penetrant genes compared to 32.84% (n = 22) of the control group (p < 0.01). Similar results were seen with other specific survey items. The current study is important in that it shows web-based education to be a feasible and effective modality for training on hereditary breast cancer. This type of education may be incorporated into CME programs and can be used as a foundation for further studies as well.

A case report of a massive cardiac intimal sarcoma manifesting as syncope during a stress test.

BACKGROUND: Syncope has many aetiologies but from a cardiac standpoint, if arrhythmogenic and ischaemic causes are not present, obstructive lesions should be considered. Cardiac spindle cell sarcomas are incredibly rare and difficult to cure. CASE SUMMARY: A 62-year-old man presented for exercise stress test and had a syncopal episode on the treadmill. He was found to have a massive mass obstructing the transmitral flow. Patient was taken to the operating room and the mass was resected successfully. Histopathological confirmation revealed the mass to be a cardiac intimal sarcoma. Patient was initiated on a trial regimen of doxorubin, ifosfamide, and mesna. DISCUSSION: Cardiac intimal sarcomas are aggressive cancers and are difficult to treat; there are no established treatment guidelines. They can lead to obstruction of blood flow through the cardiac chambers. From a cardiac perspective, without arrhythmogenic and ischaemic causes of syncope, obstructive lesions should be considered.

Precordial ECG Lead Mispositioning: Its Incidence and Estimated Cost to Healthcare.

BACKGROUND: The study was performed to estimate the incidence and economic burden of electrocardiogram (ECG) precordial lead mispositioning, in an effort to highlight the need for quality improvement. Lead mispositioning may result in further cardiovascular testing to rule out significant cardiac disease, thus adding to the national healthcare financial burden. METHODS: All consecutive adult ECGs done during 2018, were reviewed. ECGs with acute anterior myocardial infarction (AMI), bundle branch blocks, left ventricular hypertrophy (LVH), left anterior fascicular block (LAFB), pre-excitation, left axis deviation, ventricular pacing and low voltage QRS were excluded. Septal infarcts identified automatically by the computerized software or identified manually using the criteria of QS composite in V2 were not excluded. Computer interpreted ECGs as "cannot rule-out anterior infarct" were also not excluded from this data. Reimbursement of various stress test types was used to estimate the cost burden of misdiagnosed ECGs. RESULTS: A total of 9424 adult ECGs were evaluated. Poor R-wave progression (PRWP) or reversed R-wave progression (RRWP) accounted for 497 (5.27%) and 102 (1.08%) ECGs, respectively. A total of 335 septal infarct interpretations constituted about 3.55% of all ECGs. ECGs categorized as "cannot rule-out AMI" due to PRWP constituted about 0.89%. Therefore, a total of 1018 ECGs (10.8%) could be possibly falsely labelled as some type of myocardial infarction. CONCLUSION: Precordial ECG lead mispositioning can lead to significantly abnormal ECG patterns, leading to false diagnoses and further unnecessary cardiovascular testing. This not only increases risk and cost to the patient, but also adds to the national healthcare financial burden.

Atypical Manifestation of COVID-19-Induced Myocarditis.

We present a case of a 39-year-old male who presented with chest pain without fever or respiratory symptoms. Troponins were elevated and electrocardiogram (ECG) was inconclusive for ST-elevation myocardial infarction (STEMI). Angiography revealed normal coronaries and the patient was found to be coronavirus disease 2019 (COVID-19) positive; he was diagnosed with COVID-19 myocarditis. With the global pandemic, more cases are emerging regarding myocardial injury induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Although COVID-19 manifests primarily as respiratory disease, few cases of cardiac injury without respiratory involvement or febrile illness have been reported. This case illustrates that COVID-19 can present atypically and affect an isolated non-respiratory organ system.

Neutropenic Enterocolitis and Rapid Spontaneous Resolution of Portal Venous Gas: A Non-Respiratory Manifestation of COVID-19.

The COVID-19 pandemic is affecting millions across the globe. The population of immunosuppressed individuals are at greatest risk of morbidity and mortality. Data on COVID-19 induced illness in the immunocompromised host are sparse. We aim to highlight the possibility of atypical and non-respiratory presentations of COVID-19 (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) in immunosuppressed individuals as our case reveals a rare COVID-19 associated GI presentation of neutropenic enterocolitis with bloody diarrhea.

Incidental intrathorcic schwannoma post upper respiratory tract infection associated with Horner's syndrome: A case report.

BACKGROUND: Schwannomas may remain asymptomatic, and may be discovered incidentally. CASE PRESENTATION: Here we describe a case of a young female complaining of upper respiratory tract symptoms who was incidentally found to have an intrathoracic neurogenic tumor consistent with schwannoma associated with Horner's syndrome. Biopsy of the tumor revealed S100, BCL-2 and CD 99+ compatible with schwannoma. Patient had brachial plexus exploration and dissection of thoracic inlet tumor resected through video assisted thoracoscopic surgery (VATS). Patient did exceptionally well afterwards with no documented Horner's symptoms. CONCLUSION: Characterized as a rare case, this patient presented post viral infection and found to have a rare tumor. Successful surgical treatment alleviated her symptoms.

The validity and reliability of preoperative radiographic canal diameter measurements of the femur.

BACKGROUND: The femoral canal is frequently measured preoperatively in cases where an intramedullary device is planned for operative fixation of a fracture. To our knowledge, a formal assessment of validity and reliability of preoperative canal measurements has not been previously performed. QUESTIONS/PURPOSES: This study aims to determine the validity and reliability of preoperative canal measurements of the femur made on plain radiographs using comparison with curved planar reformation software as the gold standard. METHODS: Fifty-six patients were identified based on availability of anterior-posterior (AP) and lateral radiographs of the femur and computed tomography (CT) of the lower extremity. Four "raters" measured the canal diameter at its narrowest point and the distance from the lesser trochanter to the isthmus on the AP, lateral radiograph, and CT. The width of the femoral nail on AP radiographs was also measured to determine magnification error. Curved planar reformation (CPR) was used to provide the most accurate calculation of the canal diameter. RESULTS: Compared to the isthmus position determined by CPR, the measurement was most accurate on an AP and the diameter of the canal was most accurate using coronal CT, followed by AP radiographs. The measured canal diameter of the fractured femur on APs was compared to that of the used implant and varied by 1 mm. DISCUSSION/CONCLUSION: The AP plain radiographic measurement was found to be more accurate for determination of the canal diameter compared to the lateral radiograph. These findings confirm the utility of preoperative canal measurements in predicting the feasibility of placing a specific size intramedullary implant.

Gunshot femoral fractures with vascular injury: a retrospective analysis.

OBJECTIVE: To retrospectively investigate the experience at one urban level one trauma center with gunshot femoral fractures with vascular injury and to examine the implication of surgical sequence with regards to short-term complications and ischaemia time. METHODS: We performed a retrospective study of 24 patients treated at an urban level one trauma center over a 10-year period with low velocity gunshot wounds resulting in femur fractures and major vascular injury. Data were stratified according to sequence of surgical intervention. RESULTS: The mean age was 31.3 years. Mean time to revascularization was highest in patients undergoing definitive orthopaedic fixation first (660 min) and lowest in patient undergoing shunting first (210 min). Most complications in patients undergoing vascular repair first, included two disrupted repairs requiring immediate revision after subsequent orthopaedic fixation. Other complications included compartment syndrome and one amputation. CONCLUSION: Surgical sequence did not appear to impact the outcome with regard to limb loss, compartment syndrome, or mortality. Orthopaedic repair following vascular repair, however, is a risk for disruption of the vascular repair. We suggest that close and early direct communication between the orthopaedic and vascular surgeons take place in order to facilitate a satisfactory outcome.