IgA multiple myeloma-associated mediastinal spinal plasmacytoma presenting as spinal cord compression.

Multiple myeloma associated with extramedullary plasmacytoma at initial presentation is rare. We describe a case of a man in his 30s who initially presented with symptoms of spinal cord compression. Further imaging revealed a mediastinal tumour, with a biopsy confirming plasmacytoma. Immunofixation revealed IgA lambda paraprotein. Bone marrow biopsy demonstrated atypical T-cell cytotoxic proliferation and trilineage hypoplasia. The patient was diagnosed with extramedullary plasmacytoma with active IgA multiple myeloma. The patient received mediastinal radiation to the tumour, followed by anti-myeloma therapy. This diagnosis is critical as managing a solitary plasmacytoma drastically differs from an extramedullary plasmacytoma with active multiple myeloma.

A case report of superior vena cava/right coronary artery fistula secondary to chronic endocarditis.

Background: Coronary arteriovenous fistulas present an abnormal connection between the coronary arteries and an adjacent systemic or pulmonary vessel. They are rare, representing 0.002% of the general population. The majority is congenital but may additionally occur related to trauma or interventional cardiac procedures. Case summary: We present the case of a 48-year-old male with a history of untreated bacterial endocarditis developing a right coronary/superior vena cava fistula. We detail the imaging findings of this rare phenomenon to arrive at this diagnosis. We describe his clinical course and the interventions considered, including surgical extraction. Unfortunately, this patient left against medical advice before completing recommended treatment. Discussion: We present the first documentation of a right coronary/superior vena cava fistula secondary to chronic untreated bacterial endocarditis. Clinicians should be aware of this rare complication.

A case report of a giant coronary artery aneurysm masquerading as a ventricular mass.

Background: A coronary artery aneurysm is a dilation exceeding 1.5 times the diameter of the patient's largest coronary vessel. They are rare, varying in prevalence between 1.4 and 4.9%. Additionally, they carry a high risk of potential complications, including thrombosis and myocardial infarction, with a risk of rupture. We present an interesting case of a patient with initial imaging suggesting a mass in the right ventricle. Case summary: This patient initially presented with acute hypoxic respiratory failure related to pulmonary oedema. His course was complicated by symptomatic ventricular tachycardia and an inferoposterior myocardial infarction. Further investigation revealed a left anterior descending artery and circumflex artery thrombosed aneurysm projecting into the right ventricle. Multimodal imaging was used to arrive at his diagnosis. He continues to do well on medical therapy for coronary artery disease and heart failure. Discussion: Clinicians should be vigilant for this rare pathology, which may be easily missed yet poses a high mortality risk. Our case demonstrates the benefit of multimodal imaging, as this patient's aneurysm was initially mistaken for a ventricular mass.

Cardiotoxicities of Novel Therapies in Hematological Malignancies: Monoclonal Antibodies and Enzyme Inhibitors.

Monoclonal antibodies (mAB) selectively target leukemia surface antigens and work by either blocking cell surface receptors or triggering the target cell's destruction. Similarly, enzyme inhibitors bind to complex molecular platforms and induce downstream mechanisms that trigger cell death. These are used in a variety of hematologic malignancies. Yet, they also elicit severe immune-mediated reactions as biological agents that require careful monitoring. Cardiovascular effects include cardiomyopathy, ventricular dysfunction, cardiac arrest, and acute coronary syndrome. While there have been scattered reviews of mAB and enzyme inhibitors, a consolidated resource regarding their cardiovascular risk profile is lacking. We provide general recommendations for initial screening and serial monitoring based on the literature.

Cardiotoxicities of Novel Therapies in Hematologic Malignancies: Chimeric Antigen Receptor T-Cell Therapy and Bispecific T-Cell Engager Therapy.

The field of malignant hematology is transforming with novel immunotherapeutic approaches. Unfortunately, quality of life, treatment efficacy, and life expectancy are negatively affected by cardiotoxic side effects of treatment. To date, the exact mechanism and incidence of cardiotoxicity associated with these therapies is unclear. These events are believed to be triggered or occur concurrently with cytokine release syndrome. Furthermore, there are no formal guidelines to provide evaluation, treatment, and surveillance. We aim to synthesize available literature with updates on the cardiotoxic effects of novel therapies used in malignant hematologic disorders, with a focus on chimeric antigen receptor T-cell therapy and bispecific T-cell engager therapy, along with a proposed algorithm that may guide pretreatment evaluation, monitoring during treatment, and post-treatment surveillance.

Immune Checkpoint Inhibitor-Induced Hemophagocytic Lymphohistiocytosis in a Patient With Squamous Cell Carcinoma.

Programmed cell death protein 1 (PD-1) checkpoint inhibitors such as pembrolizumab are novel therapeutics used to treat various advanced malignancies and have been shown to increase patient survival in several studies. However, these drugs have a toxicity profile that ranges from mild side effects such as dermatitis to life-threatening complications. We present a case of pembrolizumab-induced hemophagocytic lymphohistiocytosis (HLH) in an 80-year-old patient with squamous cell carcinoma (SCC) of presumed cutaneous primary. This patient initially presented with weakness and pancytopenia, thought to be immune-related. She developed progressive anemia, after which further workup revealed concern for HLH. She recovered after a course of steroids, tocilizumab, and etoposide. To our knowledge, this patient's course is among a few rare cases of immune checkpoint inhibitor (ICI)-mediated HLH. This case highlights the need for early diagnosis and recognition of HLH as a potential toxicity related to ICI therapy.

Microgravity Modulates Effects of Chemotherapeutic Drugs on Cancer Cell Migration.

Microgravity or the condition of apparent weightlessness causes bone, muscular and immune system dysfunctions in astronauts following spaceflights. These organ and system-level dysfunctions correlate with changes induced at the single cell level both by simulated microgravity on earth as well as microgravity conditions in outer space (as in the international space station). Reported changes in single bone cells, muscle cells and white blood cells include structural/morphological abnormalities, changes in gene expression, protein expression, metabolic pathways and signaling pathways, suggesting that cells mount some response or adjustment to microgravity. However, the implications of such adjustments on many cellular functions and responses are not clear largely because the primary mechanism of gravity sensing in animal cells is unknown. Here, we used a rotary cell culture system developed by NASA to subject leukemic and erythroleukemic cancer cells to microgravity for 48 h and then quantified their innate immune response to common anti-cancer drugs using biophysical parameters and our recently developed quantum-dot-based fluorescence spectroscopy. We found that leukemic cancer cells treated with daunorubicin show increased chemotactic migration (p < 0.01) following simulated microgravity (µg) compared to normal gravity on earth (1 g). However, cells treated with doxorubicin showed enhanced migration both in 1 g and following µg. Our results show that microgravity modulates cancer cell response to chemotherapy in a drug-dependent manner. These results suggest using simulated microgravity as an immunomodulatory tool for the development of new immunotherapies for both space and terrestrial medicine.

Chemotherapy impedes in vitro microcirculation and promotes migration of leukemic cells with impact on metastasis.

Although most cancer drugs target the proliferation of cancer cells, it is metastasis, the complex process by which cancer cells spread from the primary tumor to other tissues and organs of the body where they form new tumors, that leads to over 90% of all cancer deaths. Thus, there is an urgent need for anti-metastasis therapy. Surprisingly, emerging evidence suggests that certain anti-cancer drugs such as paclitaxel and doxorubicin can actually promote metastasis, but the mechanism(s) behind their pro-metastatic effects are still unclear. Here, we use a microfluidic microcirculation mimetic (MMM) platform which mimics the capillary constrictions of the pulmonary and peripheral microcirculation, to determine if in-vivo-like mechanical stimuli can evoke different responses from cells subjected to various cancer drugs. In particular, we show that leukemic cancer cells treated with doxorubicin and daunorubicin, commonly used anti-cancer drugs, have over 100% longer transit times through the device, compared to untreated leukemic cells. Such delays in the microcirculation are known to promote extravasation of cells, a key step in the metastatic cascade. Furthermore, we report a significant (p < 0.01) increase in the chemotactic migration of the doxorubicin treated leukemic cells. Both enhanced retention in the microcirculation and enhanced migration following chemotherapy, are pro-metastatic effects which can serve as new targets for anti-metastatic drugs.