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Multiple myeloma (MM) is a plasma cell disorder that is on the rise throughout the world, especially in the US, Australia, and Western Europe. In the US, MM accounts for almost 2% of cancer diagnoses and over 2% of cancer deaths (more than double the global proportion). Incidence has risen by 126% globally and over 40% in the US since 1990, while global mortality has risen by 94% and US mortality has fallen by 18%. The 5 year survival in the US has more than doubled over the past decades with the introduction of new targeted therapies and transplant techniques. Risk factors for MM include age (average age of diagnosis is 69), race (African Americans are over double as likely to be diagnosed), sex (men are at a 1.5× risk), and family history. Diagnosis includes serum or urine electrophoresis and free light-chain assay but requires bone marrow biopsy. It is distinguished from smoldering myeloma and monoclonal gammopathy of undetermined significance by a high (>3 g/dL) level of M-protein (monoclonal light chains) and the presence of CRAB (Hypercalcemia, Renal failure, Anemia, Bone pain) symptoms, which include hypercalcemia, renal failure, anemia, and bone pain, suggesting an end-organ damage. International staging system staging involves beta 2 microglobulin and albumin levels, while the revised system considers prognostic factors such as lactate dehydrogenase levels and chromosomal abnormalities. Front-line management includes induction regimen, maintenance therapy and hematopoietic cell transplantation for eligible patients and bisphosphonates or bone-stimulating agents for the prevention of skeletal events. Treatment for relapsed disease includes newly approved monoclonal antibodies like the CD38-targeting daratumumab, proteasome inhibitors, immunomodulating agents, and investigational therapies such as B cell maturation antigen Chimeric antigen receptor T cells.
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Mieloma Múltiple , Anemia , Humanos , Hipercalcemia , Agentes Inmunomoduladores , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/epidemiología , Dolor , Paraproteinemias , Insuficiencia RenalRESUMEN
INTRODUCTION: Pembrolizumab is a selective anti-programmed cell death protein-1 (PD-1) humanized monoclonal antibody that inhibits PD-1 activity by binding to the PD-1 receptor that is found on activated T-cells. The goal of the treatment is to allow the immune system to target and destroy cancer cells by preventing cancer cells from binding to PD-1 receptors, leading to decreased tumor growth. The activation of T-cells by pembrolizumab not only leads to the destruction of malignant cells but also attacks the donor alloantigens that are present in a renal transplant, resulting in graft rejection. CASE REPORT: We present a case of a 46-year-old African American female with history of renal transplant who was treated with pembrolizumab for stage IV B endometrial adenocarcinoma and experienced renal transplant rejection and severe graft intolerance syndrome.Management and outcome: Due to ongoing graft intolerance, a transplant nephrectomy was performed. Allograft pathology was consistent with non-viable kidney with tubulitis, interstitial fibrosis and necrosis consistent with transplant rejection without any evidence of malignancy. DISCUSSION: As emphasized in our case, there is a very high risk of graft rejection in patients who need to be placed on immunomodulators such as pembrolizumab, so the risk versus benefit needs to be assessed and discussed. Our case is unique because pembrolizumab not only caused graft rejection but also severe graft intolerance syndrome which led to transplant nephrectomy. Further guidelines are needed in renal transplant patients requiring PD-1 inhibitors to establish the ideal treatment plan of immunosuppression management and anti-cancer treatments.
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Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos/efectos adversos , Rechazo de Injerto/inducido químicamente , Rechazo de Injerto/cirugía , Factores Inmunológicos/efectos adversos , Trasplante de Riñón/efectos adversos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Adenocarcinoma/complicaciones , Adenocarcinoma/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias Endometriales/complicaciones , Neoplasias Endometriales/tratamiento farmacológico , Femenino , Humanos , Factores Inmunológicos/uso terapéutico , Enfermedades Renales/inducido químicamente , Enfermedades Renales/cirugía , Persona de Mediana Edad , Nefrectomía , Resultado del TratamientoRESUMEN
BACKGROUND: Improved hepatitis C virus (HCV) clearance due to directly acting antiviral agents has led to remarkably improved outcomes of indolent HCV-associated non-Hodgkin lymphoma (NHL). The impact of directly acting antivirals on the outcomes of aggressive NHL is still under investigation. Characteristics of HCV-associated NHL in black patients are not well characterized. We report outcomes of HCV-associated NHL compared to their HCV-negative counterparts in a predominantly black population. PATIENTS AND METHODS: Patients with lymphoma between January 2007 and December 2017 were retrospectively studied. Depending on presence or absence of HCV RNA, patients were grouped into HCV positive (HCV+) and HCV negative (HCV-) cohorts. Depending on virologic clearance (VC), HCV+ were classified into HCV+ with VC and HCV+ without VC. Overall response rate (ORR), complete response, overall survival (OS), and progression-free survival (PFS) of HCV+ patients with and without VC were compared to HCV- patients. RESULTS: Of 397 patients with lymphoma, 40 had HCV. Black comprised 90% of HCV+ patients. Diffuse large B-cell lymphoma was most frequent (47%) in the HCV+ group. HCV+ patients without VC had significantly worse OS and PFS compared to HCV- patients. There were no differences in ORR, complete response, PFS, and OS of HCV+ patients with VC and HCV- patients. These results were consistent in subgroups of diffuse large B-cell lymphoma and aggressive lymphoma. CONCLUSION: HCV clearance is positively associated with lymphoma outcomes in black patients. Patients who clear HCV have noninferior outcomes to HCV- patients, while those who fail to clear HCV have significantly worse outcomes.
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Antivirales/uso terapéutico , Hepacivirus/aislamiento & purificación , Hepatitis C/tratamiento farmacológico , Linfoma no Hodgkin/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Población Negra/estadística & datos numéricos , Femenino , Hepacivirus/genética , Hepatitis C/virología , Humanos , Linfoma no Hodgkin/terapia , Linfoma no Hodgkin/virología , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , ARN Viral/aislamiento & purificación , Estudios Retrospectivos , Adulto JovenAsunto(s)
Betacoronavirus , Cardiomiopatías/complicaciones , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/terapia , Inmunosupresores/administración & dosificación , Neumonía Viral/complicaciones , Neumonía Viral/terapia , Sarcoidosis Pulmonar/complicaciones , COVID-19 , Cardiomiopatías/tratamiento farmacológico , Infecciones por Coronavirus/diagnóstico , Femenino , Humanos , Persona de Mediana Edad , Pandemias , Neumonía Viral/diagnóstico , SARS-CoV-2 , Sarcoidosis Pulmonar/tratamiento farmacológicoRESUMEN
Prostate cancer is the second most common and fifth most aggressive neoplasm among men worldwide. It is particularly incident in high human development index (HDI) nations, with an estimated one in seven men in the US receiving a prostate cancer diagnosis in their lifetime. A rapid rise and then fall in prostate cancer incidence in the US and Europe corresponded to the implementation of widespread prostate specific antigen (PSA) testing in 1986 and then subsequent fall from favor due to high rates of false positives, overdiagnosis, and overtreatment (as many as 20-50% of men diagnosed could have remained asymptomatic in their lifetimes). Though few risk factors have been characterized, the best known include race (men of African descent are at higher risk), genetics (e.g., BRCA1/2 mutations), and obesity. The Gleason scoring system is used for histopathological staging and is combined with clinical staging for prognosis and treatment. National guidelines have grown more conservative over the past decades in management, recommending watchful waiting and observation in older men with low to intermediate risk disease. Among higher risk patients, prostatectomy (robotic is preferred) and/or external beam radiotherapy is the most common interventions, followed by ADT maintenance. Following progression on androgen deprivation therapy (ADT) (known as castration-resistance), next generation endocrine therapies like enzalutamide, often in combination with cytotoxic agent docetaxel, are standard of care. Other promising treatments include Radium-223 for bone metastases, pembrolizumab for programmed death ligand-1 (PDL1) and microsatellite instability (MSI) high disease, and poly ADP ribose polymerase (PARP) inhibitors for those with mutations in homologous recombination (most commonly BRCA2).
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Critically ill patients with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop respiratory failure and septic shock. Extracorporeal blood purification is proposed as an adjuvant therapy for sepsis and aims at controlling the dysregulated autoimmune system. We describe our experience in treating COVID-19 patients with the oXiris® hemofilter which adsorbs both cytokines and endotoxins, provides renal replacement therapy and has anti-thrombogenic properties. It was approved by the US Food and Drug Administration (FDA) under emergency use authorization for COVID-19 patients in April 2020. In our study, the use of the oXiris® filter decreased levels of inflammatory markers including interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), and improved clinical outcomes in two out of three patients.
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Obesity plays an essential role in the safety of pharmacologic drugs. There is paucity of data for direct oral anticoagulants (DOACs) in the obese, despite these agents becoming more widely used. The primary and secondary objectives of this study were to assess the safety and efficacy of DOACs in the overweight and obese populations when used for primary prophylaxis in the setting of non-valvular atrial fibrillation (NVAF) and for treatment of venous thromboembolisms (VTE). We conducted a retrospective cohort study in a large tertiary care center and obtained data through review of electronic health records. Among patients with NVAF and VTE on apixaban, there were no differences in rates of major bleeding (MB) and clinically relevant nonmajor bleeding (CRNMB) in the overweight and obese populations when compared to normal weight and underweight individuals. The multivariate adjusted analysis for rivaroxaban found that the odds of CRNMB for patients with BMI <25 was 5.37 (95% CI 1.50-19.32) times higher than that of BMI ≥25. Moreover, patients on medications that had known interactions with DOACs had 6.40 times higher odds of CRNMB than patients without such interactions (95% CI 1.49-27.57), which was not accounted for by the effects of aspirin and plavix alone. Efficacy was similar between all weight groups, for both apixaban and rivaroxaban. These results support previous analyses preformed in the large phase III trials and confirm that apixaban and rivaroxaban are safe in the overweight and obese.
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Spinal cord tumors are sporadic and account for around 2%-4% of central nervous system neoplasms. Ependymoma is one of the most common spinal cord neoplasms and can present with different neurological signs and symptoms. They commonly present with neck or back pain and associated neurological involvement, with sensory symptoms usually antedating the motor symptoms. We now present a rare case of spinal ependymoma in a 26-year-old female who presented with isolated neck pain and the absence of other neurological symptoms. Attention to peculiar characteristics like isolated neck pain might be an essential key to early diagnosis and better prognosis.
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Though renal cell carcinoma (RCC) accounts for 2% of global cancer diagnoses and deaths, it has more than doubled in incidence in the developed world over the past half-century, and today is the ninth most common neoplasm in the United States (US). While North America and Western Europe have the highest disease burden (with the Belarus highest in incidence), Latin America, Asia and Africa are projected to see an increase in incidence as nation's transition to a Western lifestyle. Most cases of RCC are discovered incidentally on imaging, and survival is highly dependent on the stage at diagnosis, with the metastatic disease having only a 12% 5-year survival rate. Two-thirds of RCC diagnoses are made in men, and the average age of diagnosis in the US is 64. Those with genetic predispositions, namely von Hippel-Lindau disease, tend to be diagnosed 20 years earlier. RCC has a greater incidence among Hispanics and Native Americans, and a lower survival rate among African Americans in the US. Modifiable risk factors for RCC include smoking, obesity, poorly-controlled hypertension, diet and alcohol, and occupational exposures. Prevention strategies aimed at improving survival and reducing disparities include addressing lifestyle factors and access to regular healthcare among underserved populations and in developing nations, as well as more rigorous imaging guidelines to detect RCC at an earlier stage. A stronger understanding of global RCC epidemiology can facilitate prevention efforts, especially in developing nations and underserved communities where disease burden is predicted to rise in the coming decades.
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Choledochoduodenal fistula (CDF) is an abnormal communication between the common bile duct and the duodenum. It accounts for about 5% to 25% of the total biliary fistulas and is usually due to a perforated duodenal ulcer, choledocholithiasis, and complications secondary to tuberculosis or could be iatrogenic. Primary intrabilliary tumors usually cause obstructive jaundice and rarely biliary metastasis arising from other organs like colon, breast, and lungs can cause obstructive jaundice. There has been a case report of metastasis from ovarian cancer to the major papilla of the duodenum but no reported cases of it causing a CDF. We report a rare case of an 83-year-old female with ovarian cancer who developed a metastatic lesion to the duodenum eventually resulting in a CDF.
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Fístula Biliar/etiología , Neoplasias Duodenales/secundario , Fístula Intestinal/etiología , Neoplasias Ováricas/patología , Anciano de 80 o más Años , Ampolla Hepatopancreática/patología , Colangiopancreatografia Retrógrada Endoscópica , Pancreatocolangiografía por Resonancia Magnética , Conducto Colédoco/patología , Neoplasias Duodenales/fisiopatología , Endoscopía del Sistema Digestivo , Femenino , Humanos , Tomografía Computarizada por Rayos XRESUMEN
Nocardia transvalensis is a rare species of Nocardia and is known to be a drug-resistant organism. Multiple cases have been reported of Nocardia species causing opportunistic infections in immunocompromised hosts. To our knowledge, we report the first case of successfully treated drug-resistant Nocardia transvalensis causing pulmonary nocardiosis in a renal transplant patient. Our case validates the importance of prompt identification of Nocardia species and their drug sensitivities to improve clinical outcomes and reduce mortality.
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Trasplante de Riñón , Nocardiosis/microbiología , Nocardia/aislamiento & purificación , Infecciones Oportunistas/complicaciones , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple , Humanos , Huésped Inmunocomprometido , Nocardiosis/tratamiento farmacológicoRESUMEN
We report a rare complication of the use of an intrarectal catheter. An 18-year-old female with T-cell acute lymphoblastic leukemia post-matched unrelated donor allogeneic stem cell transplantation (auto-SCT) developed hepatic encephalopathy secondary to hepatic sinusoidal obstructive disease. A fecal management system was used to contain and divert fecal matter in this immobilized patient. Approximately 1 month after placement of an intrarectal catheter, stool was noted in the vaginal vault. Speculum examination confirmed development of a rectovaginal fistula.
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Catéteres/efectos adversos , Fístula Rectovaginal/etiología , Recto , Adolescente , Cateterismo/efectos adversos , Resultado Fatal , Femenino , Rechazo de Injerto/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/terapia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapiaRESUMEN
Anticoagulation-related nephropathy (ARN) is an uncommon diagnosis that should be considered in patients presenting with unexplained acute kidney injury (AKI) and coagulopathy. In this article, we present the case of a 70-year-old male with a history of cirrhosis and portal vein thrombosis on Coumadin who presented to the hospital with gross hematuria. The patient was diagnosed with AKI on chronic kidney disease (CKD) secondary to ARN superimposed on sclerosing IgA nephropathy. ARN, also known as warfarin-associated nephropathy, is an uncommon condition in which AKI from glomerular hemorrhage develops in a patient with an international normalized ratio greater than 3. The most common risk factor for development of ARN is CKD. AKI in our patient unearthed preexisting CKD due to IgA nephropathy as evidenced by the biopsy.
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Lesión Renal Aguda/etiología , Anticoagulantes/efectos adversos , Glomerulonefritis por IGA/complicaciones , Glomérulos Renales/patología , Warfarina/efectos adversos , Lesión Renal Aguda/patología , Anciano , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/patología , Hematuria/etiología , Humanos , Relación Normalizada Internacional , Riñón/irrigación sanguínea , Glomérulos Renales/efectos de los fármacos , Masculino , Insuficiencia Renal Crónica/inducido químicamente , Insuficiencia Renal Crónica/fisiopatología , Factores de RiesgoRESUMEN
Hepatitis C viral infection is recognized worldwide as a leading cause of cirrhosis and hepatocellular carcinoma. The goal of hepatitis C viral antiviral therapy is the permanent eradication of hepatitis C viral RNA, commonly referred to as a sustained virologic response - defined as "undetectable" RNA at 12 weeks following the completion of therapy. Hepatitis C viral treatment has dramatically advanced with the FDA approval of several new agents known as direct-acting antivirals. These drugs target specific nonstructural proteins of the virus, which disrupt viral replication, and therefore halt infection. However, recently, there has been a concern for increased risk of recurrence of treated hepatocellular carcinoma or denovo occurrence of hepatocellular carcinoma after treatment with direct-acting antivirals. We are now reporting three cases of intrahepatic cholangiocarcinoma that developed after sustained virologic response following hepatitis C viral treatment with direct-acting antivirals.
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Antivirales/uso terapéutico , Neoplasias de los Conductos Biliares/diagnóstico , Colangiocarcinoma/diagnóstico , Hepatitis C/tratamiento farmacológico , Anciano , Carcinoma Hepatocelular/virología , Femenino , Humanos , Cirrosis Hepática/virología , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Recurrencia Local de NeoplasiaRESUMEN
Bevacizumab (Avastin) is a recombinant humanized monoclonal antibody used for the management of various solid malignancies including colorectal, lung, brain, renal, and ovarian cancers as well as age-related macular degeneration of the eye. It is a vascular endothelial growth factor inhibitor which exhibits its action by blocking the growth of blood vessels in cancerous tissue. Common side effects include hypertension, fatigue, headaches, and increased risk of infections. Atypical hemolytic uremic syndrome is a serious side effect associated with bevacizumab due to its anti-angiogenic effect. It encompasses the clinical triad of thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure, without any association with Shiga toxins. Eculizumab is a terminal complement inhibitor used in the treatment of atypical hemolytic uremic syndrome. Herein, we present three cases of bevacizumab-induced atypical hemolytic syndrome treated successfully with eculizumab.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversos , Síndrome Hemolítico Urémico Atípico/inducido químicamente , Síndrome Hemolítico Urémico Atípico/tratamiento farmacológico , Bevacizumab/efectos adversos , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Anciano , Femenino , Humanos , Persona de Mediana EdadRESUMEN
Acquired hemophilia A poses a clinical and diagnostic challenge. Although rare, it is still the most common acquired factor deficiency. We present a case of acquired hemophilia A diagnosed in a 71-year-old female who presented with a right thigh hematoma of acute onset. The diagnosis was established based on the coagulation profile along with factor VIII levels, mixing studies, and inhibitor levels. The patient received multiple lines of therapy including steroids, factor VIIa, Obizur (porcine-derived recombinant factor VIII), followed by multiple cycles of chemotherapy including cyclophosphamide and rituximab.
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Factor VIII/uso terapéutico , Factor VIIa/uso terapéutico , Hematoma/sangre , Hemofilia A/sangre , Anciano , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Ciclofosfamida , Quimioterapia Combinada , Femenino , Hematoma/complicaciones , Hemofilia A/complicaciones , Hemofilia A/tratamiento farmacológico , Humanos , Tiempo de Tromboplastina Parcial , RituximabRESUMEN
Ifosfamide, an alkylating agent used in cancer treatments, can cause neurotoxicity. The clinical presentation can range from mild symptoms such as acute confusion to non-convulsive seizures, severe irreversible coma, and death. The benefit of methylene blue use in treating ifosfamide-induced metabolic encephalopathy is not well established. In this article, we present 2 cases of ifosfamide-induced metabolic encephalopathy responsive to methylene blue treatment.
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May-Thurner syndrome (MTS) is a rarely diagnosed vascular abnormality that typically presents in young adults. The anomaly arises from compression of the left common iliac vein between the right iliac artery anteriorly and the lumbar vertebral body posteriorly, resulting in lower extremity venous outflow obstruction and recurrent deep vein thromboses (DVTs). We report the case of a 24-year-old female with a long history of recurrent DVTs and pulmonary emboli (PE) despite full anticoagulation. A computed tomography (CT) scan revealed findings consistent with MTS, and a left common iliac vein stent was placed. However, the patient continued to have DVTs while trialing several anticoagulation therapies, including rivaroxaban, enoxaparin, and warfarin. Eventually, the patient developed arterial thrombi resulting in critical limb ischemia, necessitating a right below knee amputation (BKA). One month status-post BKA, the patient was admitted for severe BKA stump pain secondary to infection and necrosis. She underwent BKA revision, but continued to experience pain post-operatively and was found to have new right common iliac artery, external iliac artery, and common femoral artery thrombosis in the setting of continued inpatient anticoagulation therapy with enoxaparin and aspirin. The patient returned to the operating room for emergent Fogarty thrombectomy, however, this was complicated by rupture of the balloon catheter secondary to migration of the left common iliac vein stent into the right common iliac artery lumen. A stent was placed in the right common iliac artery to shift the rogue vein stent, but the patient continued to have poor distal circulation of the BKA stump and eventually underwent an above knee amputation. Dual anti-platelet therapy (DAPT) with aspirin and clopidogrel in combination with enoxaparin were used to prevent in-stent thrombosis and future formation of arterial and venous thrombi. After the initiation of DAPT and enoxaparin, her clinical course was free of any further thromboembolic events. Clinicians should consider MTS in the differential diagnosis of younger adults presenting with recurrent DVTs or other unprovoked thromboembolic events. A two-pronged strategy of DAPT and anticoagulation was employed for successful prevention of thrombotic events.
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Hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome. It is categorized as familial or acquired, most commonly caused by infections, malignancies, rheumatologic and immunodeficiency disorders. Irrespective of the etiology, the age at the onset is the strongest prognostic factor, hence it is extremely important to have a high suspicion for HLH, diagnose it promptly and initiate treatment without any delay. We encountered a 70-year-old female patient who initially presented with left-sided facial weakness and pancytopenia, secondary to diffuse stage IV B diffuse large B-cell lymphoma with isolated bone marrow involvement with secondary HLH.