RESUMO
Calcium pyrophosphate deposition disease is not an uncommon cause of polyarthritis, especially in the elderly. This disease typically affects the appendicular skeleton but may rarely affect the axial skeleton as well. When the axial skeleton is involved, it can lead to numerous neurological signs and can be disabling. We describe a case in which a 68-year-old male presented with on-and-off myelopathy and was thought to have chronic inflammatory demyelinating polyneuropathy. Magnetic resonance imaging of the spine suggested an inflammatory or infectious lesion at the thoracic level. However, after a surgical biopsy, pathologists concluded that calcium pyrophosphate deposition, or pseudogout, was the cause of this patient's neurological symptoms. Pseudogout in the spine, especially the thoracic spine, is exceptionally rare. There are very few additional cases reported. In this report, we review the current literature on existing similar cases, radiological findings, risk factors, and treatments for this condition in hopes of increasing knowledge and awareness of this rare differential.
RESUMO
Pericardial disease is a rare complication after renal transplantation. We present a patient who developed high-output cardiac failure from a large arteriovenous (AV) fistula with recurrent pericardial effusion resulting in a constrictive hemodynamic pattern that was revealed during cardiac catheterization. Pericardiectomy was considered for recurrent effusive pericarditis, but per cardiac surgery recommendations, closure of the AV fistula dramatically cured the patient's heart failure, and no recurrence of pericardial effusion was seen during follow-up almost a year later.
Assuntos
Fístula , Insuficiência Cardíaca , Transplante de Rim , Derrame Pericárdico , Pericardite Constritiva , Fístula/complicações , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/etiologia , Humanos , Transplante de Rim/efeitos adversos , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/etiologia , Pericardite Constritiva/diagnóstico , Pericardite Constritiva/etiologia , Pericardite Constritiva/cirurgiaRESUMO
Lipoma of the interventricular septum involving the tricuspid valve is a rare entity. A 50-year-old woman presented with exertional dyspnea. She was found to have a large right interventricular septal mass in the initial transthoracic echocardiography. This mass was further investigated by transesophageal echocardiography, cardiac gated CT, and cardiac magnetic resonance imaging. It was found to be lipomatous and embedded into the septal leaflet of the tricuspid valve. The diagnosis was confirmed by biopsy. Surgical exploration revealed that the mass was deeply embedded in the interventricular septum and septal leaflet of the tricuspid valve. The mass was resected along with sections of the interventricular septum and tricuspid valve. She underwent bioprosthetic tricuspid valve placement and patch reconstruction of the interventricular septum. We also searched case reports from MEDLINE and studied pathological and epidemiological characteristics of the published cases of cardiac masses in the past year. Cardiac lipoma although a benign tumor can cause serious hemodynamic complications. Initial transthoracic echocardiography followed by multimodality imaging is the cornerstone of the diagnosis.
Assuntos
Neoplasias Cardíacas , Lipoma , Ecocardiografia/métodos , Ecocardiografia Transesofagiana , Feminino , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/cirurgia , Humanos , Lipoma/diagnóstico por imagem , Lipoma/cirurgia , Pessoa de Meia-Idade , Valva Tricúspide/diagnóstico por imagemRESUMO
Inflammatory pseudotumors of the liver are rare, non-neoplastic liver tumors. Due to the nonspecific clinical presentation, imaging features, and histopathological findings, they can mimic malignant tumors requiring invasive diagnostics. We present a case of a 61-year-old female patient with a history of type 2 diabetes mellitus, hypothyroidism, hyperlipidemia, and polymyalgia rheumatica who had initially presented with abdominal pain for 3 weeks. Further workup showed normal liver chemistries and tumor markers: AFP and CA 19-9. Magnetic resonance imaging (MRI) of the abdomen showed a segment 6 lesion measuring 4.1 × 4.0 × 3.7 cm. A liver biopsy then confirmed the diagnosis of an inflammatory pseudotumor of the liver with negative IgG4. On follow-up imaging, a rapid growth of this liver lesion was noted. Laparoscopy was done but did not show any distinct liver lesion. Follow-up imaging confirmed a decrease in the size of the mass. Interestingly, the patient had been on a higher dose of steroids for her polymyalgia rheumatic leading up to the follow-up imaging. This is the first case of an inflammatory pseudotumor of the liver in a patient with polymyalgia rheumatica. With this case, we would like to increase the awareness for inflammatory pseudotumors of the liver as a differential diagnosis of liver lesions in patients with underlying autoimmune disorders.
Assuntos
Diabetes Mellitus Tipo 2 , Arterite de Células Gigantes , Granuloma de Células Plasmáticas , Polimialgia Reumática , Diabetes Mellitus Tipo 2/complicações , Feminino , Granuloma de Células Plasmáticas/complicações , Granuloma de Células Plasmáticas/diagnóstico , Humanos , Fígado , Pessoa de Meia-Idade , Polimialgia Reumática/complicações , Polimialgia Reumática/diagnósticoRESUMO
Regulatory T cells (Tregs) play an important role in controlling autoimmunity and limiting tissue damage and inflammation. IL2-inducible T cell kinase (Itk) is part of the Tec family of tyrosine kinases and is a critical component of T cell receptor mediated signaling. Here, we showed that either genetic ablation of Itk signaling or inhibition of Itk signaling pathways resulted in increased frequency of "noncanonical" CD4+ CD25- FOXP3+ Tregs (ncTregs), as well as of "canonical" CD4+ CD25+ FOXP3+ Tregs (canTregs). Using in vivo models, we showed that ncTregs can avert the formation of acute graft-versus-host disease (GVHD), in part by reducing conventional T cell proliferation, proinflammatory cytokine production, and tissue damage. This reduction in GVHD occurred without disruption of graft-versus-leukaemia (GVL) effects. RNA sequencing revealed that a number of effector, cell adhesion, and migration molecules were upregulated in Itk-/- ncTregs. Furthermore, disrupting the SLP76: ITK interaction using a specific peptide inhibitor led to enhanced Treg development in both mouse and primary human cells. This peptide inhibitor also significantly reduced inflammatory cytokine production in primary GVHD patient samples and mouse T cells without causing cell death or apoptosis. We provide evidence that specifically targeting Itk signaling could be a therapeutic strategy to treat autoimmune disorders.
Assuntos
Interleucina-2/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/estatística & dados numéricos , Eritrócitos/metabolismo , Interleucina-2/metabolismo , Camundongos , Camundongos Endogâmicos C57BL/genética , Camundongos Endogâmicos C57BL/metabolismo , Transdução de Sinais/efeitos dos fármacos , Linfócitos T Reguladores/fisiologiaRESUMO
A 67-year-old female patient presented asymptomatically for further evaluation of a chest mass. Other than significant smoking history, the patient had been healthy with a recently treated case of uncomplicated pneumonia. The mass originated in the aortopulmonary window of the left mediastinum and invaded proximally into the left superior pulmonary vein and subsequently into the left atrium. The mass protrusion into the mitral valve occupied 50% of the left atrium space but showed no clinical symptoms of a valvular blockade. Poorly differentiated squamous cell carcinoma was identified upon biopsy. These findings of a primary lung tumor with atrial extension in an asymptomatic patient point to the importance of age-appropriate screening and standardization treatment modalities.
RESUMO
Gout is a common inflammatory arthritis that has a high prevalence worldwide. It is characterized by monosodium urate deposition, usually affecting the joints and soft tissue of the lower extremities. Urate deposition in the axial skeleton resulting in spinal gout is rare. However, it seems to be more prevalent than usually thought, largely because it is underdiagnosed. Imaging findings are, for the most part, nonspecific and often mimic infectious etiologies. Definitive diagnosis requires pathological examination. Thus, it can be easily missed. We present a 41-year-old male with a seven-year history of untreated gout who came in with severe back pain, fevers, and radiculopathy. He was initially diagnosed with vertebral osteomyelitis. However, after a biopsy, spinal gout was confirmed. Spinal gout can be misdiagnosed as vertebral osteomyelitis given the similarities in presentation and imaging findings. This case report highlights the importance of keeping spinal gout as a differential of vertebral osteomyelitis, especially in patients with long-standing or uncontrolled gout with tophi.
RESUMO
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most widely applied forms of adoptive immunotherapy for the treatment of hematological malignancies. Detrimental graft-versus-host disease (GVHD), but also beneficial graft-versus-leukemia (GVL) effects occurring after allo-HSCT are largely mediated by alloantigen-reactive donor T cells in the graft. Separating GVHD from GVL effects is a formidable challenge, and a greater understanding of donor T cell biology is required to accomplish the uncoupling of GVHD from GVL. Here, we evaluated the role of ß-catenin in this process. Using a unique mouse model of transgenic overexpression of human ß-catenin (Cat-Tg) in an allo-HSCT model, we show here that T cells from Cat-Tg mice did not cause GVHD, and surprisingly, Cat-Tg T cells maintained the GVL effect. Donor T cells from Cat-Tg mice exhibited significantly lower inflammatory cytokine production and reduced donor T cell proliferation, while upregulating cytotoxic mediators that resulted in enhanced cytotoxicity. RNA sequencing revealed changes in the expression of 1169 genes for CD4, and 1006 genes for CD8+ T cells involved in essential aspects of immune response and GVHD pathophysiology. Altogether, our data suggest that ß-catenin is a druggable target for developing therapeutic strategies to reduce GVHD while preserving the beneficial GVL effects following allo-HSCT treatment.
RESUMO
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for hematological malignancies, due to graft-versus-leukemia (GVL) activity mediated by alloreactive donor T cells. However, graft-versus-host disease (GVHD) is also mediated by these cells. Here, we assessed the effect of attenuating TCR-mediated SLP76:ITK interaction in GVL vs. GVHD effects after allo-HSCT. CD8+ and CD4+ donor T cells from mice expressing a Y145F mutation in SLP-76 did not cause GVHD but preserved GVL effects against B-ALL cells. SLP76Y145FKI CD8+ and CD4+ donor T cells also showed less inflammatory cytokine production and migration to GVHD target organs. We developed a novel peptide to specifically inhibit SLP76:ITK interactions, resulting in decreased phosphorylation of PLCγ1 and ERK, decreased cytokine production in human T cells, and separation of GVHD from GVL effects. Altogether, our data suggest that inhibiting SLP76:ITK interaction could be a therapeutic strategy to separate GVHD from GVL effects after allo-HSCT treatment.