United States

Tumor Lysis Syndrome (TLS) is an oncologic emergency that requires prompt recognition and treatment. It occurs due to the release of nucleic acids, potassium, and phosphate systemically. It is seen more commonly in hematologic than solid malignancies. Dehydration, acute kidney injury, high tumor burden are a few of the risk factors that predispose an individual to TLS. Here, we present a case of TLS in a patient with stage IV ovarian cancer. Our patient presented with nausea, vomiting, and was noted to have acute kidney injury, small bowel obstruction and hydronephrosis. She received cytoreductive chemotherapy and she developed hyperuricemia, hyperkalemia, hyperphosphatemia, and acute kidney injury and was diagnosed to have TLS. She received rasburicase and her creatinine improved. Due to a slower tumor doubling time and delayed chemotherapy effect, TLS is less commonly seen in solid malignancies. In our patient her high tumor burden, chemotherapy administration, acute kidney injury and dehydration predisposed her to tumor lysis. It is important to identify patients who could undergo tumor lysis and risk stratify them since mortality can be as high as 40% in these patients.

2023 AMA Research Challenge

Unraveling the Mystery: A case of tumor lysis in a patient with ovarian cancer


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Join the AMA Research Challenge poster symposium and semifinals to explore top research posters, score posters in the semifinals (an AMA member exclusive opportunity) and attend education sessions with experienced physicians to learn tips to advance your research and career. 

Background: Pigmented Villonodular Synovitis (PVNS) is a rare, benign neoplastic
condition affecting the synovial membrane of joints, bursae, and tendons. It is divided into diffuse and localized PVNS (female predilection). The knees are commonly affected, followed by the hips and ankles. Symptoms include pain, swelling and stiffness around the affected joint with recurrent atraumatic hemarthrosis. Etiology includes chromosomal translocation involving chromosome 1p13 causing over-expression of CSF-1 in neoplastic cells. The patients are often diagnosed between the ages of 20-50 years.

Case Presentation: A 24 year-old female presented with insidious onset of pain, swelling and stiffness of her left knee for 5 months. MRI of the left knee with and without contrast was done with findings suggestive of PVNS along the posterior aspect of the knee with moderate joint effusion. Initial blood-work was performed to establish the baseline results. Pexidartinib 800mg/day was started with regular monitoring for possible hepatotoxicity. 15 days into the treatment, the patient’s symptoms resolved, but the patient developed hypopigmented patches over her face, depigmentation of body hair and loss of appetite. After 2 months of therapy, her creatinine was found to be elevated, hence the dose of Pexidartinib was decreased to 600mg/day. She was also diagnosed with iron deficiency anemia for which 15 cycles of iron infusions were given. MRI 4 months after the therapy
showed images of near complete resolution with no joint effusion. However, a small
amount of hemosiderin deposition was evident, therefore, residual PVNS was not
excluded. Routine labs showed elevated AST/ALT levels, hence Pexidartinib was
discontinued. The patient returned 4 months later with similar complaints. MRI showed findings of recurrent PVNS along the posterior margin of Hoffa's fat pad, posterior joint capsule, intercondylar notch, and popliteus myotendinous junction. Large joint effusion and diffuse synovitis was present. Pexidartinib 250mg was started again, after reviewing her recent labs. She is currently tolerating the medication without any concerns.

Discussion: PVNS is a rare disorder that requires prompt management as it can cause morbidity.
MRI is the standard imaging modality used in both diagnosis and to assess recurrence. The mainstay treatment is surgical excision with total synovectomy but due to high recurrence rate (8-60%), other systemic therapies are being investigated. In August 2019, FDA approved the use of Pexidartinib for PVNS. Pexidartinib is a tyrosine kinase inhibitor that targets CSF1R. Liver function tests are performed periodically to monitor hepatotoxicity with dosage being reduced or discontinued accordingly.

Relapse of pigmented villonodular synovitis

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**Abstract:**



Numerous Recurrent Venous Thromboembolisms in the Setting of Severe Obesity and Anticoagulation: A Case Report

We herein report a case of a 24-year-old female who presented to her primary care physician with the chief complaint of increased forgetfulness and brain fog. Further history revealed that she had also been having shortness of breath, nausea/vomiting, fatigue, myalgias, and a 20 lb weight loss. A chest x-ray was ordered and was read as cardiomegaly with severe pulmonary edema. The patient was notified by her PCP to immediately present to an Emergency Department. Upon initial presentation to the hospital, the patient was normotensive, mildly tachycardic at 104 bpm, with oxygen saturation of 92% on room air. Her BMI was 18.8 kg/m2. Physical examination was significant for an ill-appearing female with generalized weakness and mild respiratory distress. She did not have any cardiac murmurs, her lungs were clear to auscultation, and she did not have any rashes. The most pertinent laboratory findings included leukocytosis (14.31 k/uL), normocytic anemia (9.7g/dL), elevated alkaline phosphatase (578U/L), and elevated C-reactive protein (13.38 mg/dL). CT chest/abdomen/pelvis with contrast revealed severe diffuse miliary lung disease, mild bilateral hilar adenopathy, a large pericardial effusion, and ill-defined bony lesions throughout the entire skeleton. CT head without contrast showed multiple calcifications scattered throughout the brain. Given the typical miliary pattern and concern for disseminated tuberculosis, she was empirically started on RIPE therapy. Pericardiocentesis was urgently done due to finding of large circumferential effusion on transthoracic echocardiography concerning for tamponade physiology. The cytology from the pericardial fluid was suspicious for malignancy. Iliac bone biopsy ultimately confirmed metastatic adenocarcinoma consistent with lung primary. RIPE therapy was discontinued, and the patient was started on carboplatin and pemetrexed. After significant improvement in functional capacity, the patient was discharged home with her family after 31 days in the hospital. She is currently being treated with pembrolizumab and pemetrexed and her disease burden has remained stable for 9 months now.

Lung cancer is extremely rare in young adults <35 years old. In this population, it predominantly presents as non-small cell lung cancer (NSCLC) or more specifically, as adenocarcinoma. While cough is the most common presenting symptom (50-75%) in older patients, non-specific symptoms mimicking other pathologies are often present in younger patients with NSCLC. The most common gene mutations are EGFR, KRAS, FGFR1 and ALK, not necessarily hereditary.

Miliary pattern of lung disease can be seen in a handful of etiologies. These include infectious diseases such as tuberculosis and disseminated fungal infections, autoimmune diseases like sarcoidosis, environmental diseases such as silicosis, and neoplastic diseases such as adenocarcinoma and metastasis. The most common of these, as expected, is tuberculosis. In a young patient without risk factors presenting with symptoms and findings typical of an infectious process, we need to be vigilant of less common, unexpected etiologies and keep a broad differential.

Miliary Disease in a 24-year-old Female- An Unexpected Diagnosis

Background
In the course of chronic Hepatitis C virus (HCV) infection, 70% of patients have one or more extrahepatic manifestations. Therefore, patients can present with a spectrum of clinical symptoms that correlate to mixed cryoglobulinemia, non-Hodgkin’s lymphomas, and more. More specifically, the concurrence of hematologic malignancy and membranoproliferative glomerulonephritis (MPGN) can be fatal. Here we report a lethal cascade of extrahepatic manifestations from untreated HCV infection. 

Case Presentation
A 73-year-old female with history of HCV (diagnosed 16 years ago, untreated due to insurance barriers), chronic polyarthralgia, and splenic marginal zone lymphoma (diagnosed 8 years ago, lost to follow-up) presented with lower extremity edema and worsening joint pain. She had previously been prescribed opioids and prednisone for polyarthralgia. The patient was found to have acute kidney injury, elevated rheumatoid factor, decreased C3 and C4, and sub-nephrotic range proteinuria. Worsening arthralgia and renal impairment were hypothesized to be secondary to HCV-related cryoglobulinemia, and she was advised to follow up for HCV treatment and renal biopsy. Two weeks later, she presented again with new lower extremity purpura. She subsequently developed sepsis, worsening kidney failure requiring hemodialysis, and metabolic encephalopathy requiring intubation. After two days of intravenous methylprednisone for presumed mixed cryoglobulinemia vasculitis, the patient’s mental status improved, and renal and skin biopsies were done. Renal biopsy showed MPGN with evidence of pseudothrombi from known cryoglobulins, and skin lesions were consistent with leukocytoclastic vasculitis. Despite plans to treat the patient’s underlying HCV, the patient’s clinical condition continued to deteriorate, and her family decided to transition her to comfort care. She passed away shortly after. 

Discussion
The concurrence of cryoglobulinemic MPGN in HCV patients with splenic marginal zone lymphoma is rare. While the lymphomagenic role of HCV is debated, literature demonstrates that antiviral treatment could be first-line therapy in HCV-associated lymphomas. However, connecting this patient’s clinical signs and symptoms to her previously diagnosed HCV was complicated by the patient’s use of opioids and prednisone for pain. As these medications improved the patient’s polyarthralgia, it seemed as though agents prescribed for presumed arthritis flares likely masked an underlying cryoglobulinemia. In patients with extrahepatic manifestations and atypical features of cryoglobulinemia, a full evaluation for the underlying cause is critical. Lack of viral diagnosis and delay to treatment can result in significant morbidity and cumulative organ failure. Unfortunately for this patient, serological signs of her extrahepatic manifestations presented themselves early, meaning this fatal outcome could have been avoided with early antiviral therapy. 


Failed to turn the tide: Chronic hepatitis C related cryoglobulinemia, lymphoma, and membranoproliferative glomerulonephritis

Background:
Chordae tendineae rupture (CTR) has been linked to several factors as hypertension, rheumatic fever, and ischemic heart disease. Here we report a patient with CTR during COVID-19 infection.

Case
A 79-year-old man with non-stenotic coronary artery disease, ischemic cardiomyopathy with diastolic dysfunction, rheumatic heart disease with chronic moderate mitral regurgitation, pulmonary hypertension, paroxysmal atrial fibrillation on apixaban, hypertension, familial hypercholesterolemia, and obstructive sleep apnea presented with progressive worsening of dyspnea, palpitations, orthopnea, and lightheadedness for 6 months duration with acute deterioration 2 hours before admission.

He was hemodynamically stable but was hypoxic with saturation at 89%, requiring 2L O2 by nasal cannula. On examination, a holosystolic murmur was auscultated at the cardiac apex. The rest of examination was normal.

EKG showed sinus rhythm at 73 BPM without ST changes. Laboratory investigations were within normal limits except for Brain natriuretic peptide, which was 3160 pg/mL. He tested positive for COVID-19. Chest x-ray revealed patchy perihilar, right lower lung zone opacities, and a minor right-sided pleural effusion. Transesophageal echocardiography showed moderate to severe mitral valve regurgitation, left ventricular hypertrophy with normal left ventricular ejection fraction at 60%. Records of previous imaging were not available.

Upon cardiac catheterization, high-grade proximal stenosis was detected in the left anterior descending artery and ostial small circumflex; flail posterior mitral valve leaflet with ruptured chordae tendineae, redundant and hypermobile anterior mitral leaflet and myxomatous degeneration of the mitral valve was noted. He underwent mitral valve replacement with mosaic porcine bioprosthesis, single-vessel bypass grafting in the left anterior descending artery with left internal mammary graft, left-sided maze atrial ablation atricure cryoprobe, and Mitra Clip placement at the base of left atrial appendage after a week of clinical improvement with diuresis, nirmatrelvir/ritonavir, and holding apixaban. Apixaban was not restarted postoperatively due to poor general health and high fall risk, and he was discharged to rehabilitation.

Discussion
Mitral regurgitation (MR) affects 9.3% of Americans 75 and older. Primary MR is caused by mitral valve prolapse from CTR. CTR can be of primary or secondary origin. Hypertension is determined to be an independent predictor of primary CTR. Acute rheumatic fever, osteogenesis imperfecta, ischemic heart disease, chronic rheumatic valvular disease, and bacterial endocarditis are causes of secondary CTR. Myxomatous degeneration is underreported since the microscopic investigation is not routinely performed. The posterior chorda is more commonly affected than the anterior chorda. Mild mitral CTR often entails the separation of a single chorda, resulting in limited hemodynamic sequelae requiring no treatment. Multiple chordae ruptures may cause moderate-to-severe MR requiring surgical intervention. The course of the presentation can be acute or progressive. MR severity grading influences clinical decisions, prognosis, and treatment plans. Echocardiography is the most routinely conducted noninvasive MR test.
In literature, COVID-19 infection is linked to cardiovascular complications as myocarditis, myocardial infarction, and cardiogenic shock. At this juncture, there is not enough evidence to attribute the development of CTR to COVID-19 infection, although a causal association is possible.

Conclusion
This case highlights a complex presentation of Chordae tendineae rupture with concurrent Covid-19 infection.

Chordae Tendineae Rupture in Chronic Mitral Regurgitation and COVID-19 Infection


Background
Widespread organ failure, including renal dysfunction, is significantly influenced by underdiagnosed psychiatric conditions, especially eating disorders, ultimately progressing to hemodialysis and significantly affecting the quality of life. We present a case wherein a 36-year-old female presented with syncope and eventually was diagnosed with hypokalemic nephropathy resembling Pseudobartter syndrome. We want to emphasize the importance of identifying non-psychiatric symptoms of eating disorders and treating them earlier in the course to avoid irreversible complications such as end-organ damage, like end-stage renal disease (ESRD), that could lead to life-altering treatment regimes, like in this case, hemodialysis. A detailed history, physical examination, laboratory investigations, and diagnostic imaging, including renal biopsy, were done in this case vignette. 

Case presentation 
A 36-year-old Caucasian with no known medical history except mild intellectual disability presented with syncopal episodes. Further workup revealed macrocytic anemia, hypochloremic alkalosis, hypokalemia, and acute kidney injury. Finally, a renal biopsy revealed moderate chronic kidney disease (CKD) with a similar degree of global glomerulosclerosis to interstitial fibrosis and tubular atrophy. There was no evidence of acute interstitial nephritis, immune complex-mediated glomerulonephritis, or primary podocytopathy. Her renal progressed to the end stage, requiring hemodialysis. 

Discussion
The prevalence of electrolyte abnormalities in eating disorders, including hyponatremia, hypokalemia, and metabolic alkalosis, varies depending on whether or not patients purge. Pseudo-Bartter syndrome is characterized by hyperaldosteronism, hyperreninemia, hypokalemia, metabolic alkalosis, and hyperplasia of the juxtaglomerular apparatus. CKD and hypokalemic nephropathy can result from purging in patients with anorexia nervosa-binge purge subtype (AN-BP). Clinicians need to understand that not all eating disorders present with psychiatric symptoms. There are manifestations of various non-psychiatric self-imposed malnourishment presenting with varied symptoms, as seen in our index case, that may rapidly progress to organ damage, especially ESRD, ultimately requiring renal replacement therapy. When not diagnosed and treated, failure to thrive secondary to psychiatric conditions will cause chronic electrolyte abnormalities, eventually leading to irreversible hypokalemic nephropathy. Dialysis substantially impacts the quality of life, and patients who receive it have shorter life expectancies due to increased risk of infection and cardiovascular disease.

Is End-Stage Renal Disease an irreversible complication of an eating disorder? 
A Case report on pseudo bartter?

Mucosal Infection with Tsukamurella Species Following Nasal Septum Procedure: A Rare Case Report

Introduction:
The main issue that has frequently plagued treatment of OSA is compliance and tolerance of continuous positive airway pressure (CPAP). This has spurred innovation in this field with the development of more tolerable nasal pieces and, most recently, hypoglossal nerve stimulators (HGNS). However, just like any other implantable device, there is a real risk of infection with implantation and subsequent need for removal. A published review in the American Journal of Otolaryngology on a search query of adverse events associated with HGNS implantation from the FDA Manufacturer and User Facility Device Experience (MAUDE) database yielded 180 reports containing a total of 196 adverse events. The most commonly reported adverse events to patients were infection (n = 50, 34.2%). Subsequently, a total of 83 adverse events, whether infection or device migration (42.3%) required re-operation. With the exciting innovation of new implantable devices being developed in medicine, our case stresses the importance to recognize unconventional sources of infection in the undifferentiated septic patient.

Case Description:
Our patient was a middle-aged gentleman with ankylosing spondylitis and OSA status post hypoglossal nerve stimulator (HGNS) implantation presenting with purulent drainage from the implant site on his chest wall, as well as subacute severe left knee pain and swelling. Following HGNS implantation five months prior to presentation, he had poor wound healing requiring multiple outpatient courses of antibiotics. During this time, his Enbrel for ankylosing spondylitis was held due to concerns for immune-compromised state and worsening infection, and his HGNS was never actually activated for use. On presentation there was valid concern for hematogenous spread to his left knee, and an MRI of the left knee was obtained that was not concerning for osteomyelitis. An arthrocentesis was performed showing an inflammatory fluid aspirate with negative grain stain and no growth on bacterial cultures. Wound cultures obtained from the implant site on the chest wall demonstrated MSSA, and he was transitioned from broad spectrum vancomycin and zosyn to IV cefazolin. The HGNS implant was subsequently removed with visible draining pus on the stimulator leads. He was ultimately discharged on a course of cefalexin for two weeks with Rheumatology follow up in the setting of suspected ankylosing spondylitis flare of his left knee.

Discussion:
We treated our patient similarly to a pacemaker lead infection with prompt removal of the device and a course of antibiotics geared towards bacteria that tend to grow on foreign devices. An additional complicating layer to our case was the presentation of a potential septic knee, which required swift evaluation and rule out from the interdisciplinary team. As HGNS products become more popular choices of treatment for OSA, we will be seeing more cases similar to ours in the community and will start to develop more informed and nuanced management. As hospitalists, it is our duty to view our patients on presentation as a whole - innate bodily systems and organs plus their foreign hardware.


Hypoglossal nerve stimulator (HGNS) implant infection: a feared
complication for a novel treatment of obstructive sleep apnea

Numerous studies have established a strong connection between the heart and brain, especially in response to stressful stimuli. One condition, Takotsubo cardiomyopathy (TC), is characterized by a temporarily weakened left ventricle apex resulting from excess catecholamines and microvascular dysfunction. Another different condition, posterior reversible encephalopathy syndrome (PRES), is associated with acute neurological changes and changes in the occipital lobe. These two conditions share similarities despite presenting different clinical features and requiring distinct diagnostic workups and treatments.

Case Description
A 49-year-old woman with a past medical history of hypertension and migraines presented after a witnessed seizure following a few hours of worsening headaches. She reported high stress, with her husband diagnosed with blood cancer and her dog recently passing away. Her blood pressure was mildly elevated at 156/92. Initially, she appeared to have right-sided muscle weakness, which resolved. A CT brain scan demonstrated occipital lobe changes, suggesting PRES. A CTA brain revealed no major vascular blockages, and an EEG revealed no epileptiform activity. The next day, she reported substernal chest pain and an ECG revealed new dynamic T-wave inversions in the anterior leads. Her troponins were elevated (peaking at 2222 ng/ml), and a TTE showed apical wall abnormalities. A subsequent cardiac catheterization revealed no coronary occlusion, suggesting TC. The patient improved clinically with conservative therapy during the hospitalization and was eventually discharged home.

Discussion
The "heart and brain connection" was previously identified in patients with acute neurologic insults. PRES is a rare neurologic entity; manifestations include headaches, focal neurologic deficits, seizures, vision loss, or encephalopathy. PRES is believed to involve cerebral blood flow alterations and brain autoregulation dysfunction. Imaging findings include vasogenic edema involving the posterior regions of the brain. It can be seen in hypertensive emergencies, renal failure, autoimmune diseases, and sometimes medication-induced flares. PRES is usually reversible. However, a recent small study showed a mortality rate of 4% and residual damage of 5.5%. TC, aka apical ballooning syndrome, previously known as stress-induced cardiomyopathy, has a 1–3% prevalence in postmenopausal females and 5–6% in those with ACS. It is usually triggered by underlying physical or emotional stress, as reported in 60–70% of cases. Studies have shown that 2% of ACS is due to TC. Hence, it is considered one of the ACS-mimicking diseases. Usually present with chest pain or new onset heart failure with characteristic echo findings of apical balloon shaping. The cardiac catheter is usually negative for any obstruction. 
Based on the available data, there is a possible association between PRES and TC. One study reported a prevalence of 2.7%, and around 14 cases were found in the literature, eight of which are in PubMed journals. It is noteworthy that 13 of the 14 cases involved postmenopausal women over the age of 45 years old. While these conditions can be serious, most patients have a good prognosis with appropriate treatment and support. Further research is needed to understand better the connection between these two conditions and their long-term implications. Treatment approaches may vary depending on the patient's circumstances, so seeking a multidisciplinary approach to care is important.

Conclusion
Healthcare providers should keep a high clinical index of suspicion for potential heart and neurological issues like PRES and TC in postmenopausal women with acute coronary syndrome. Neglecting or ignoring TC can lead to a worse prognosis. It is worth noting that neurological deficits associated with TC may indicate PRES. Further research must be conducted to understand and treat these serious illnesses.



A Rare Combination: A Case of a Patient with Takotsubo Cardiomyopathy and 
Posterior Reversible Encephalopathy Syndrome (PRES)

A venous air embolism occurs when gas enters a venous structure that is under negative pressure. This arises most frequently through central venous catheterization. We report the case of a man in his 70s who underwent computed tomography (CT) guided biopsy of a 14 millimeter nodule in the left upper lobe of the lung. This procedure was complicated by an anterior left-sided pneumothorax as well as pulmonary hemorrhage due to nicking of the left superior pulmonary vein. This nicking is believed to have introduced an air embolism, which then circulated to the heart as visualized on CT. The patient required bilevel positive airway pressure (BiPAP) for about twelve hours, as well as placement of a thoracostomy tube for three days. Following the event an echocardiogram and CT head were performed in order to track the air embolism, however the embolism was not visualized. The patient continued to have pleuritic chest pain and hemoptysis at the time of discharge, and was followed closely outpatient by pulmonology.

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Unraveling the Mystery: A case of tumor lysis in a patient with ovarian cancer

Next from 2023 AMA Research Challenge

Relapse of pigmented villonodular synovitis