United States

Background  

Despite showing remarkable remission rates in patients with refractory hematological malignancy, Chimeric Antigen Receptor T cell (CAR-T) therapy has raised increased concern over its side effects, such as Cytokine release syndrome (CRS) and neurotoxicity. It should be used carefully, especially in hemodynamically unstable patients. This vignette describes a patient with relapsing B Cell-Acute Lymphocytic Leukemia(B-ALL) who was in hemorrhagic shock prior to CAR-T infusion but showed significant improvement after being infused with CAR-T.  

Case Presentation  

A 40-year-old male with an 18-month history of B-ALL was admitted to our hospital due to leukemia relapse, infectious mastoiditis, and pneumonia. Workup suggested extensive liver leukemic infiltration and fungal pneumonia. The following seven hospital days were complicated by severe anemia, thrombocytopenia, neutropenia requiring frequent blood transfusion, and acute hypoxic respiratory failure requiring mechanical ventilatory support. Further, he suffered an episode of hematemesis leading to hemorrhagic shock, which was treated with IV norepinephrine. The CAR-T therapy was planned for refractory leukemia, but the impaired hemodynamic status posed a therapeutic dilemma for us. However, given his poor prognosis and no other option for leukemia, we proceeded with its infusion despite his hemodynamic instability. He continued to require blood product replacements with extensive volume support and norepinephrine infusion to maintain adequate blood pressure. His vitals, inflammatory markers, hemoglobin, and blast cell count started improving six days post-CAR-T. He was extubated to a high-flow nasal cannula and transitioned to hemodialysis from the continuous renal replacement therapy. He maintained adequate BP without any vasopressor and was transferred to the floor. His hospital stay was further complicated by resistant thrombocytopenia, anemia, GI bleeding, and acute renal failure, and increasing circulating blasts limiting treatment options. As such, after a stay in the hospital of more than 30 days, at his family’s request, he was transferred to hospice care, where he died the next day. 

Conclusion 

The case demonstrates the use of CAR-T therapy in a hemodynamically unstable and clinically deteriorating patient. Despite hypotension on therapy initiation, this patient tolerated the infusion well and did not develop severe CRS. In contrast, the patient showed improved hemodynamic stability, decreasing signs of inflammation, and improvements in resistant anemia. The patient was able to be extubated while on the therapy. This case suggests CAR-T therapy may be an option for rapidly progressing patients or when alternative therapies are not an option. 

AMA Research Challenge 2022

Case Report: Chimeric Antigen Receptor T Cell Therapy in Patient with B Cell Acute Lymphocytic Lymphoma Shortly after Developing Shock

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Ricardo Correa, MD, EdD
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Charles Lopresto, DO

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poster

There is a known relationship between Clostridium septicum bacteremia and colorectal malignancies. C. septicum is a gram-positive, anaerobic, spore-forming bacterium that can survive the acidic colorectal tumor microenvironment, where it is thought to enter the blood by tumor-mediated epithelial tissue damage. While in circulation, C. septicum can release exotoxins which may lead to life-threatening sepsis. The patient in this case presented with a mild fever, abdominal pain, and left handed weakness. Imaging of the head and abdomen revealed a right frontal lucency and wall thickening of the ascending colon. Two colonic adenocarcinomas were found and removed via an exploratory laparotomy and right hemicolectomy. The blood culture was positive for C. septicum. Brain MRI confirmed a right frontal mass concerning for metastasis. Here, we discuss the relationship between colonic cancers and Clostridium septicum bacteremia.


Concurrent Clostridium Septicum Bacteremia and Colorectal Adenocarcinoma with Metastasis to the Brain

Abstract Title:
Diffuse Bone Disease as Primary Clinical Manifestation of Adult T-Cell Leukemia/Lymphoma: Time for a Classification Update?

Background
ATLL is an aggressive mature T-cell leukemia/lymphoma caused by the human T-lymphotropic virus type 1. (HTLV-1). Shimoyama published the first diagnostic criteria and classification of ATLL in 1991, and since then, efforts have been made to keep clinical subclassifications up to date. In this context, we believe it is worthwhile to propose an extranodal primary-bone presentation of ATLL. We describe a novel presentation of ATLL with solely bone lesions.

Case Presentation
A 33-year-old woman presents with 1-year of diffuse bone pain and tumor-like chest wall lesions. Laboratory and radiological examinations were remarkable for hypercalcemia and diffuse osteolytic lesions. Initial concern was for multiple myeloma. Workup was negative for the presence of monoclonal gammopathy. Bone marrow examination of the iliac crest did not show any abnormal B-, T-, or plasma cell population. A repeated sternal bone marrow aspirate and biopsy of one of the chest wall lesions demonstrated a CD3+ T-cell neoplasm. Western blot analysis was positive for HTLV-1. A diagnosis of HTLV-1-associated ATLL was concluded. Patient was managed with multiagent chemotherapy, however, patient died from rapid disease progression after completing 2 cycles of treatment. This case highlights bone disease as primary ATLL presentation.

Discussion
Although the above case represents the first case of extranodal primary bone ATLL-variant ever described in Peru, similar cases have also been encountered in our cohort in Miami where 56% had diffuse bone disease and 44% localized bone disease but that progressed to diffuse bone disease upon relapse. High calcium and LDH levels were found in 25% and 38% of patients, respectively. Three patients had HIV co-infection. The median OS time were 16.8 months.

ATLL cells have the HTLV-1 genome clonally incorporated. Tax-induced NF-kb pathway activation by the HTLV-1 genome promotes cell growth and the progression of ATLL. Deregulation of the NF-B has been linked to the development of lytic bone lesions and hypercalcemia in multiple myeloma. We hypothesized that our patient's distinct clinical presentation was influenced by physiopathology similar to that of multiple myeloma.


Diffuse Bone Disease as Primary Clinical Manifestation of Adult T-Cell Leukemia/Lymphoma: Time for a Classification Update?

Squamous Cell Carcinoma of Breast: a Rare Case

Background
Yolk sac tumors are non-seminomatous germ cell tumors found most often in children and rarely in adults. Even in adult populations, a testicular mass is typically the first presenting sign of a primary testicular malignancy, and seldom is there a testicular cancer diagnosis with no mass palpated on physical exam. 
Case Presentation
We present a 44-year-old man with family history of testicular cancer who presented initially with gastrointestinal symptoms and no testicular mass who was ultimately found to have pure yolk sac tumor pathology per liver metastasis biopsy.
Discussion
We compare our case to the other reports of post-pubertal yolk sac tumors currently reported in the literature. Though not only rare for an adult male to have a pure yolk sac tumor, but also an entirely gastrointestinal presentation, it is important for clinicians to weigh the importance of family oncological history combined with classic metastatic patterns when determining a primary tumor location. Furthermore, despite signs and symptoms pointing toward a likely gastrointestinal pathology, testicular cancer should remain on the differential for patients with any risk factors for malignancy. We present a rare case of yolk sac tumor, and testicular cancer in general, demonstrating the diversity of possible pathologic presentations of this cancer.


Unusual Presentation of a Pure Yolk Sac Tumor in an Adult Male: A Case Report

Case Presentation:

A 50-year-old male patient with a past medical history of well-controlled diabetes mellitus type 2 presented with non-productive cough and worsening dyspnea of 7-day duration. He was diagnosed with COVID-19 infection before presentation in urgent care and was prescribed oral methylprednisolone. He was noted to be febrile with a temp of 101.3 F, tachypneic at 24 CPM. BP was 110/60 mm Hg and HR was 110 bpm. Chest X-ray reported bilateral diffuse groundglass opacities. CRP, Ferritin, LDH were all elevated at 7.4 mg/L, 756 ng/mL, 455 U/L respectively. D-Dimer was also high at 7 mcg/mL. He was diagnosed with ARDS due to COVID-19 pneumonia, admitted to ICU, and was subsequently intubated. He was started on dexamethasone 6 mg iv twice daily, enoxaparin 50 mg bid. He was not a candidate for remdesivir as per institutional protocol. 36 hours into admission, he was noted to have a cold right lower extremity with loss of popliteal and dorsals pedis pulsations. CT angiography Aorta (CTA) revealed a near-occlusive thrombus involving the right common iliac artery and occlusive thrombus of the right popliteal artery. He
underwent urgent thrombectomy with the continuation of anticoagulation, now changed to heparin drip infusion. There was no evidence of intracardiac thrombus on a 2D transthoracic echocardiography. CTA was repeated 4 days later which showed persistent occlusion of the right common iliac artery with now thrombus extending into right external iliac and internal iliac arteries. Thrombectomy and angioplasty were repeated. Unfortunately right lower extremity remained
ischemic and pulseless necessitating above-knee amputation. Hypercoagulable work-up was sought. Blood pressure and platelet counts remained stable throughout. Serology for IgM Anticardiolipin (aCL) antibodies was weakly positive at 38 MPL. Anti-beta2-GP I antibodies (GP) and lupus anti-coagulant were not found. Prothrombin Gene mutation and Factor V Leiden were also not detected.

Discussion:
COVID-19, an acute viral infection caused by SARS-CoV-2, continues to challenge the healthcare system worldwide despite availability of vaccines against it. Some of the complications that are associated with COVID-19 are ARDS, myocardial injury, myocarditis, arrhythmia, strokes, and even opportunistic infections such as aspergillum, mucormycosis. [1, 2] These complications overall increase mortality among COVID-19 patients. Coagulopathy is another complication that is associated with organ dysfunction and mortality, particularly in critically ill COVID-19 patients. [3] The index patient did not have any prior history or evidence of venous or arterial thrombosis. No similar history in his family was found. His anti-cardiolipin antibody was minimally elevated. Although this may indicate anti-phospholipid syndrome, confirmation of this abnormal test requires repeating the test 12 weeks later. We believe that COVID-19 infection is, at least, responsible for decreasing the threshold of developing refractory arterial thrombosis requiring limb amputation in this patient with the probable anti-phospholipid syndrome. Endothelial dysfunction, platelet activation, stasis, and enhanced inflammatory response are some of the
mechanisms that can increase the risk of thrombosis in COVID-19 patients.

Conclusions:
Prothrombotic states are not uncommon in critically ill COVID-19 patients. Early initiation of therapeutic anticoagulation in high-risk COVID-19 patients is necessary to prevent limb or lifethreatening complications.


A Case of Limb-threatening Refractory Arterial Thrombosis in a Patient With Covid-19

Background: Primary infection with varicella zoster virus (VZV) causes varicella (chickenpox), while herpes zoster (shingles) is a secondary infection that occurs when latent VZV is reactivated. Both primary and secondary VZV infections can cause central nervous system manifestations, including encephalitis, which is rare and often fatal.

Case Presentation: A 66-year-old woman with history of rheumatoid arthritis, psoriasis, and coronary artery disease presented to our hospital with sudden-onset altered mental status. She was found naked, confused, and covered in feces and urine at home. At presentation, she was afebrile, tachycardiac (106 bpm), tachypneic (24 breaths/min), saturating 97% breathing ambient air. Labs were unremarkable. Non-contrast head CT revealed disproportionately enlarged ventricles and temporal lobe volume loss. Brain MRI confirmed ventriculomegaly. Blood cultures were drawn, and IV vancomycin, ceftriaxone, and ampicillin were started empirically. Initial blood cultures were negative. On Day 3, lumbar puncture with cerebrospinal fluid (CSF) analysis showed elevated WBC (1,077 cells/mcL) with 97% lymphocytes, low glucose (21 mg/dL) and elevated protein (298 mg/dL). CSF viral PCR panel was positive for VZV, necessitating initiation of IV acyclovir. Given no significant improvement despite treatment, lumbar puncture was repeated on Day 8, with similar findings as the initial CSF analysis. Ampicillin was discontinued because repeated blood cultures and CSF analysis were negative for Listeria. By Day 17, she had completed a 14-day course of IV acyclovir but remained febrile and confused. The patient’s family decided to transition her to comfort care measures, and she expired on Day 23.

Discussion: Nervous system manifestations of VZV include meningitis, encephalitis, cerebellar ataxia, vasculopathy, and myelopathy. Unlike encephalitis caused by herpes simplex virus type-1 and enteroviruses, VZV encephalitis is uncommon, occurring in one out of every 33,000 to 50,000 cases of VZV infection. VZV encephalitis is associated with intense inflammation, and often has an acute presentation. Studies report higher median CSF protein levels and higher CSF lymphocytosis in VZV encephalitis compared to enterovirus encephalitis. Even with appropriate treatment, VZV encephalitis is almost 100% fatal in immunocompromised hosts. A high index of suspicion and early initiation of appropriate treatment for VZV encephalitis is essential, especially in immunocompromised hosts.

A Case of Varicella Zoster Virus Encephalitis – A Rare but Often Fatal Cause of Encephalitis

Abstract Title: Difficult case of refractory hypertension 

Background: Refractory hypertension is a rare but challenging disease to treat. The most updated phenotype helps distinguish it from white coat syndrome, resistant or secondary hypertension. However, controlling blood pressure, in this case, is likely a frustrating process for the patient and doctor alike. 



Case Presentation: 34 years old Caucasian male with a ten-year history of uncontrolled hypertension was referred by his primary care physician's office to a cardiology office for blood pressure (BP) management. On his first visit, his BP was 180s/110s. in addition to the high BP, his history and physical exam were positive for chest pain and palpitation; otherwise, unremarkable. Blood work, echo, and kidney ultrasound results excluded secondary causes and were only significant for hyperlipidemia. Therefore, the patient was started on a statin. Over the course of five months, the patient followed up every 1-3 weeks. Multiple medication adjustments were made by either increasing the dose or switching to another group of medications. He has always been on seven antihypertensive agents, including chlorthalidone and spironolactone. Nevertheless, his BP has always been high (150s -210s/100-150 mmHg). 



Due to the failure of medical management to control the patient's BP, He was referred to Providence hospital/Simplicity study for sympathetic denervation. Unfortunately, he did not meet the study criteria. Furthermore, a recent stress test showed that his refractory hypertension is now complicated by cardiomyopathy with an EF of 35%. Thus, he was switched from Telmisartan to Entresto 49/51 mg twice daily. 



Discussion: The most updated refractory hypertension definition is a failure to control BP after a routine clinical follow-up of ≥3 visits for ≥ 6 months despite being adherent to a regimen of >5 classes of antihypertensive agents, including chlorthalidone 25 mg daily and spironolactone 25 mg daily or eplerenone, 50 mg twice daily and without evidence of underlying secondary causes of hypertension. However, the clear definition of refractory hypertension is not necessarily associated with a clear management plan or promising outcomes for this group of patients. 



A difficult case of refractory hypertension

Background
Inferior Vena Cava (IVC) filters are a versatile tool used in prevention of pulmonary embolism but face many challenges in complications, most notably fracturing. This complication can be as high as 38% depending on the model and remains a significant concern in long term risk-benefit viability of the device. We present the unique case of a patient with a history of sarcoidosis, surgical complications from prior hysterectomy, and fractured IVC filter resulting in multiple repeat pulmonary emboli.

Case Presentation
In July 2021, a 52 year old Caucasian female with history of hysterectomy, sarcoidosis, bariatric surgery and 8 year history of IVC filter placement presented with back pain and on evaluation was found to have filter fracturing. Her filter was prophylactically placed around 2013 after a past provoked pulmonary embolism following a hysterectomy for endometriosis.

Retrieval of fractured IVC filter parts was attempted with 3 struts remaining. CT angiogram evaluation revealed presence of multiple pulmonary emboli in the right upper and left lower lobes. The patient was hemodynamically stable and was discharged on 10mg Eliquis BID.

One month later, she presented to the ED with severe fatigue and was found to have new emboli in the left lower lateral segmental lobe. Patient was hemodynamically stable and was started on heparin, eventually transitioning to Eliquis outpatient management.

Discussion
Recurrent emboli following IVC fracture is a novel event. We postulate this phenomenon is attributable to compounded risk of thrombosis in those with prior risks of hypercoagulability.

The pathophysiology of IVC filter fracturing is not well documented. Fracturing is related to metal fatigue from tilting and repetitive flexion. It is possible that recurrent emboli following filter fracture is secondary to underlying hypercoagulability disorders such as sarcoidosis. Sarcoidosis compounds the risk of embolism through inflammatory mediators and increased turbulence within vessel lumens from extrinsic lymphadenopathy compression. Combined with endothelial damage from fractured parts, these risk factors intensify embolism risk.

Although filters may be used for prevention of embolisms, they paradoxically may also increase the risk. Thus, usage is cautioned, and timely removal is highly advised.

A patient with sarcoidosis and multiple pulmonary embolism from IVC filter fracture: A Rare Case Report

A rare case of anti-tubercular drug induced cardiomyopathy

Abstract Title: 
A Rare Case of Infective Endocarditis caused by Serratia marcescens

Background: 
Serratia marcescens is a gram-negative bacillus that usually causes respiratory and CNS infections but it rarely can cause infective endocarditis.

Case Presentation: 
A 62-year-old male with PMH of intravenous drug use and Hepatitis C presented to the ED with palpitations and back pain for three weeks with no reported fevers. In the ED, his vitals were: temperature 103.9° F, BP 105/72, HR 125, RR 20 and O2 saturation 100% on room air. The remainder of his examination revealed bilateral subconjunctival hemorrhages and multiple track marks; there were no neurological deficits, petechiae, or murmurs. Laboratory studies revealed WBC 12.82, bandemia of 13%, and lactic acid 4.1. An MRI brain revealed scattered acute infarcts; subsequent spinal MRIs were negative for abscesses. He was admitted for sepsis possibly secondary to endocarditis and started on broad spectrum antibiotics; an initial TTE was negative for vegetations, and blood cultures later grew S. marcescens. The patient subsequently developed an intermittent AV block. Repeat TTE revealed a linear echo-density on the aortic leaflets; TEE showed a 2cm vegetation on the aortic valve with perforation. He was transferred to a tertiary center for further care; he underwent aortic valve replacement, which was complicated by aortic root rupture. He also developed sick sinus syndrome and required a pacemaker. The remainder of his hospitalization was unremarkable and he was discharged on a prolonged antibiotic course.

Discussion: 
Infective endocarditis with S. marcescens is rare; some studies report only 0.14% of IE cases are caused by Serratia. Although IV drug users typically have higher rates of right-sided valvular endocarditis, S. marcescens tends to involve left-sided valves. S. marcescans is rapidly progressive. Typical symptoms include fever, myalgias, or dyspnea. Exam findings can include cardiac murmurs, splinter hemorrhages, Janeway lesions, Osler nodes, and Roth spots. IE diagnosis is made via positive blood cultures and vegetations on echocardiography. Surgical intervention is recommended within 7-10 days; mortality is as high as 85% in patients with Serratia who only received medical therapy. After prompt surgical intervention, antimicrobial treatment includes combination therapy of B-lactam and an aminoglycoside or fluroquinolone for at least six weeks. 


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Case Report: Chimeric Antigen Receptor T Cell Therapy in Patient with B Cell Acute Lymphocytic Lymphoma Shortly after Developing Shock

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