Cerebral embolization associated with parenchymal seeding of the left atrial myxoma: Potential role of interleukin-6 and matrix metalloproteinases.

Systemic embolization has been reported in up to 40% of patients with left atrial myxoma, half of them with cerebral involvement. However, development of intracerebral embolization associated with parenchymal seeding of the myxoma emboli is an extremely rare complication, with only 36 histologically diagnosed cases reported in the published literature. We describe a 69-year-old woman who arrived at the emergency service with hemiparesis associated with drug-resistant epilepsy and a medical history of resection of a left atrial myxoma 10 months previously. Cranial computed tomography revealed multiple large lesions of heterogeneous density and cystic components in the occipital lobes and posterior fossa parenchyma. Histopathological analyses after stereotactic biopsy of the occipital lesion revealed infiltrative myxoma cells with benign histological findings and uniform expression of calretinin similar to that of the primary cardiac myxoma. Additional immunohistochemical studies confirmed brain parenchymal seeding of the myxoma cells with strong expression of interleukin-6 (IL-6) and focal expression of matrix metalloproteinases-2 (MMP-2). Here, we discuss the clinicopathological features of intracerebral embolization of left atrial myxomas associated with progressive parenchymal seeding of the tumor emboli and the potential pathogenic role of IL-6 and MMPs.

Clinicopathological Spectrum of Mitral Valve Myxoma.

Cardiac myxomas are the most common primary tumors of the heart. Although these tumors have been reported in all cardiac chambers, myxomas arising from heart valves are extremely rare. Here, the details are described of a patient with mitral valve myxoma, and a review is provided of 99 cases reported in the literature. Mitral valve myxomas most often occur in middle-aged patients, with a slight female predominance. Most of the tumors arise in an isolated fashion on the atrial side of the anterior mitral valve leaflet. Embolic events were the most frequent manifestation, followed by obstructive symptoms. Unlike atrial wall myxomas, these tumors have a lower incidence of constitutional manifestations. Tumor resection with valve preservation is the usual method of surgical treatment in isolated tumors, while most patients with multiple valve myxomas underwent valve replacement. Mitral valve myxomas should be considered in the differential diagnosis of mitral valve tumors, with an awareness of a relatively high risk of embolic events. This location should not raise suspicion for a heritable myxoma syndrome. Prompt surgical resection is warranted to reduce complications.

Congenital left ventricular diverticulum.

Congenital diverticulum of the left ventricle is a rare cardiac malformation usually associated with midline thoraco-abdominal defects and other congenital cardiac malformations.

Isolated cardiac valve involvement in smoldering adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive mature T-cell neoplasm caused by infection with the Human T-cell Lymphotropic Virus Type 1 (HTLV-1). Cardiac involvement in patients with ATLL is infrequent, and when it happens it is usually seen in aggressive ATLL subtypes. However, ATLL presenting as isolated cardiac valve involvement is extremely rare. To date, only three histologically proven cases of ATLL with isolated cardiac valve involvement have been reported. Herein, we describe a 61-year-old Peruvian man who presented heart failure symptoms secondary to progressive cardiac valve infiltration. The patient underwent mitral valve replacement with a mechanical prosthesis. Histopathological evaluation of the resected valve revealed leaflet thickening with a nodular appearance due to fibrous tissue containing atypical T-lymphocytes with Foxp3 expression, infiltrating all layers of the resected valve. Interestingly, tumor cells were distributed around an incidental venous malformation (i.e., cavernous hemangioma). Postoperative evaluation demonstrated positive serology for HTLV-1, and a diagnosis of ATLL was established. Postoperative positron emission tomography/computed tomography did not show lesions outside the heart and cell blood counts were within normal range with low level of circulating CD4+ CD25+ lymphoma cell counts (7%); therefore, patient's disease was considered as smoldering ATLL and a "watch and wait" strategy was pursued. Currently, the patient is alive with no progression of disease after 18 months from diagnosis. Isolated cardiac valve involvement by ATLL should be considered in the differential diagnosis of HTLV-1 carriers with progressive heart failure, even when systemic lymphoma involvement is absent or not apparent.

Evaluating three biomarkers as prognostic factors of in-hospital mortality and severity in heart failure: A prospective cohort.

OBJECTIVE: To identify the relationship between red blood cell distribution width (RDW, %), interleukin-6 (IL-6) (pg/ml), high sensitivity-c-reactive protein (hs-CRP) (mg/l), in-hospital mortality and disease severity among patients with heart failure (HF). METHODS: Prospective cohort. We included adults diagnosed with acute non-ischemic HF in 2015. The dependent variables were in-hospital mortality (yes or no) and disease severity. The latter was assessed with the Get With The Guidelines-HF score. We used hierarchical regression models to describe the pattern of association between biomarkers, mortality, and severity. We used the Youden index to identify the best cut-off for mortality prediction. RESULTS: We included 167 patients; the mean age was 72.61 (SD: 11.06). The majority of patients presented with New York Heart Association classification II (40.12%) or III (43.11%). After adjusting for age and gender, all biomarkers were associated with mortality. After adding comorbidities, only IL-6 was associated. The final model with all clinical variables showed no effect from any biomarker. The best cut-off for RDW, hs-CRP and IL-6 for mortality were 14.8, 68.7 and 52.9, respectively. IL-6 presented the highest sensitivity (100%), specificity (75.35%) and area under the curve (0.91). CONCLUSIONS: No biomarker is independent from the most important clinical variables; therefore it should not be used for management modifications.

[Redo aortic valve reconstruction as saving surgery in a patient with severe rheumatoid cardiac disease]. / Reoperación utilizando reconstrucción valvular aórtica como cirugía de salvataje en paciente con carditis reumatoide extensa.

The combination of aortic regurgitation, rheumatoid aortitis, and subaortic stenosis is rare in patients with rheumatoid arthritis. Moreover, the surgical treatment of these entities can be challenging and with non-adequate results. We report a case of a patient with severe aortic regurgitation, inaccessible aortic root secondary to rheumatoid aortitis, and severe subaortic stenosis initially treated by aortic valve replacement. We reoperated the patient due to acute prosthetic valve failure by an aortic valve reconstruction using bovine pericardium and Ozaki technique with good outcomes.

When Frequent (Pandemic) Occurs in a Non-Frequent Disease: COVID-19 and Fabry Disease: Report of Two Cases.

Fabry disease (FD), like COVID-19, can affect multiple organs, including the lungs. Patients with FD are expected to develop severe COVID-19, due to involvement of not only the lungs but also the kidneys and the presence of other comorbidities. We present 2 cases of mild COVID-19 in patients with FD who were infected with the COVID-19 virus. Although it is unknown whether the X chromosome mutation in patients with FD affects the development of severe COVID-19, it is suggested that it may play a protective role against COVID-19 infection. Based on these cases, we suggest that FD is not a risk factor for severe COVID-19.

Clinicopathologic characteristics and survival of patients with primary effusion lymphoma.

Primary effusion lymphoma (PEL) is an aggressive B-cell lymphoma confined to body cavities and universally associated with human herpesvirus type 8 infection. The prognosis of this entity remains poor, with a median survival time of 6 to 9 months. To better understand the clinicopathologic features of the disease and identify possible prognostic factors, we performed a systematic review of the literature for cases of PEL, including 2 previously unreported cases from our institution. PEL was more prevalent in men (92%), with a median age at diagnosis of 55 years. The median overall survival for the entire series was 6 months. Peritoneal involvement (HR:1.62; 95% CI:1.06-2.48) and elevated serum lactate dehydrogenase (LDH) levels (HR:2.50; 95% CI:1.21-5.19) were associated with higher risk of death, while pericardial involvement (HR:0.43; 95% CI:0.20-0.94) was associated with lower risk of death. Therefore, effusion site and serum LDH levels are potential prognostic factors in patients with PEL.

TOCOSH FLOUR (Solanum tuberosum L.): A Toxicological Assessment of Traditional Peruvian Fermented Potatoes.

Potato tocosh is a naturally processed potato for nutritional and curative purposes from traditional Peruvian medicine. The aim of this study was to investigate the acute and sub-acute toxicity of tocosh flour (TF). For sub-acute toxicity, TF was administered orally to rats daily once a day for 28 days at doses of 1000 mg/kg body weight (BW). Animals were observed for general behaviors, mortality, body weight variations, and histological analysis. At the end of treatment, relative organ weights, histopathology, hematological and biochemical parameters were analyzed. For acute toxicity, TF was administered orally to mice at doses of 2000 and 5000 mg/kg BW at a single dose in both sexes. Body weight, mortality, and clinical signs were observed for 14 days after treatment. The results of acute toxicity showed that the median lethal dose (LD50) value of TF is higher than 2000 g/kg BW but less than 5000 mg/Kg BW in mice. Death and toxicological symptoms were not found during the treatment. For sub-acute toxicity, we found that no-observed-adverse-effect levels (NOAEL) of TF in rats up to 1000 g/kg BW. There were statistically significant differences in body weight, and relative organ weight in the stomach and brain. No differences in hematological and biochemical parameters were observed when compared with the control group. For sub-acute toxicity, histopathological studies revealed minor abnormalities in liver and kidney tissues at doses of 5000 mg/Kg. Based on these results, TF is a traditional Peruvian medicine with high safety at up to 1000 mg/kg BW for 28 days in rats.

[Intravascular leiomyomatosis with intracardiac extension]. / Leiomiomatosis intravascular con extensión intracardiaca.

Intravascular leiomyomatosis is a rare condition characterized by histologically benign smooth muscle cell growth within the uterine veins and inferior vena cava and, rarely, into the right chambers of the heart. A 39-year-old female with a history of hysterectomy for uterine leiomyoma was admitted for lower limb oedema and progressive dyspnea of 5 months' duration. Transthoracic echocardiography and contrast-enhanced computed tomography showed a large mass extending through the inferior vena cava into the right chambers of the heart. As there was a suspicion of an intravenous thrombus, the patient underwent surgical resection. The histopathology of the resected mass led to a diagnosis of Intravascular leiomyomatosis with intracardiac extension.

[Pathology of heart transplantation in peru: experience with 61 cases in a national reference center]. / Patología del trasplante cardiaco en el Perú: Experiencia con 61 casos en un centro de referencia nacional.

OBJETIVE.: To describe the histopathological characteristics of explanted hearts and post-transplant biopsy specimens at a national reference center in Peru. MATERIALS AND METHODS.: A case series study of patients who underwent heart transplantation between March 2010 and February 2018. RESULTS.: Sixty-one (61) transplanted patients with a mean age of 40.1 years (range: 9-66 years). Five cases (8.2%) initially diagnosed as dilated cardiomyopathy were reclassified after the histopathological study. The three leading causes of primary disease after transplantation were: idiopathic dilated cardiomyopathy (50.8%), ischemic cardiomyopathy (16.4%), and valvular cardiomyopathy (6.6%). The mean follow-up was 2.8 years. The post-transplant survival rate was 85.1% at 1 year and 82.8% at 5 years. Moderate/severe acute cellular rejection occurred in 12 patients (21.1%) and antibody-mediated rejection occurred in 3 patients (5.3%). CONCLUSIONS.: Routine histopathological evaluation of the explanted heart is essential to confirm the etiology of heart failure, especially in cases clinically diagnosed as dilated cardiomyopathy. In addition, routine follow-up through endomyocardial biopsies shows that acute cellular rejection is still a frequent complication after a heart transplant, especially within the first year, and that antibody-mediated rejection has a low incidence in our population.

OBJETIVOS: Describir las características histopatológicas de los explantes cardiacos y las biopsias endomiocárdicas postrasplante realizadas en un centro de referencia nacional del Perú. MATERIALES Y MÉTODOS.: Estudio de una serie de casos de pacientes sometidos a trasplante cardiaco entre marzo de 2010 y febrero de 2018. RESULTADOS.: Los 61 pacientes trasplantados, tuvieron un promedio de edad de 40,1 (rango: 9-66 años). Cinco casos (8,2%) diagnosticados inicialmente como miocardiopatía dilatada fueron reclasificados después del estudio histopatológico. Las tres primeras causas de enfermedad primaria previa al trasplante fueron: miocardiopatía dilatada idiopática (50,8%), cardiopatía isquémica (16,4%), y cardiopatía valvular (6,6%). El seguimiento promedio fue de 2,8 años. La tasa de supervivencia después del trasplante fue del 85,1% al año y del 82,8% a los cinco años. El rechazo celular agudo moderado/severo ocurrió en 12 pacientes (21,1%) y el rechazo mediado por anticuerpos ocurrió en tres pacientes (5,3%). CONCLUSIONES.: La evaluación histopatológica rutinaria del explante cardiaco es esencial para confirmar la etiología de la insuficiencia cardíaca, especialmente en los casos diagnosticados clínicamente como miocardiopatía dilatada. Asimismo, el seguimiento rutinario mediante biopsias endomiocárdicas muestra que el rechazo celular agudo continúa siendo una complicación frecuente durante el primer año de trasplante, y que el rechazo mediado por anticuerpos tiene una baja frecuencia en nuestra población.

DNA Methylation Dynamics Regulate the Formation of a Regenerative Wound Epithelium during Axolotl Limb Regeneration.

The formation of a blastema during regeneration of an axolotl limb involves important changes in the behavior and function of cells at the site of injury. One of the earliest events is the formation of the wound epithelium and subsequently the apical epidermal cap, which involves in vivo dedifferentiation that is controlled by signaling from the nerve. We have investigated the role of epigenetic modifications to the genome as a possible mechanism for regulating changes in gene expression patterns of keratinocytes of the wound and blastema epithelium that are involved in regeneration. We report a modulation of the expression DNMT3a, a de novo DNA methyltransferase, within the first 72 hours post injury that is dependent on nerve signaling. Treatment of skin wounds on the upper forelimb with decitabine, a DNA methyltransferase inhibitor, induced changes in gene expression and cellular behavior associated with a regenerative response. Furthermore, decitabine-treated wounds were able to participate in regeneration while untreated wounds inhibited a regenerative response. Elucidation of the specific epigenetic modifications that mediate cellular dedifferentiation likely will lead to insights for initiating a regenerative response in organisms that lack this ability.

Large B-cell lymphoma arising in cardiac myxoma or intracardiac fibrinous mass: a localized lymphoma usually associated with Epstein-Barr virus?

Primary cardiac neoplasms are rare. However, among them, cardiac myxoma is the most common tumor. In contrast, primary cardiac lymphoma within a cardiac myxoma is extremely rare and might be difficult to diagnose because of non-specific clinical manifestations. We report the case of a previously healthy 52-year-old man who presented with acute onset of transient dysarthria and left hemiplegia. A transthoracic echocardiography showed a 6×2.5-cm solid mass in the left atrium, which was subsequently resected. Histological, immunohistochemical, and molecular analyses revealed an EBV-associated CD30-positive large B-cell lymphoma with anaplastic morphology within a cardiac myxoma and fibrinous material. Staging studies showed no evidence of lymphoma elsewhere. The patient achieved complete remission and is alive 42 months after diagnosis, and did not receive chemotherapy. We discuss the clinical and pathologic features of lymphoma arising in cardiac myxoma or in intra-atrial fibrinoid mass and the potential role of IL-6 in its pathogenesis.

Gain-of-function assays in the axolotl (Ambystoma mexicanum) to identify signaling pathways that induce and regulate limb regeneration.

The adult salamander has been studied as a model for regeneration of complex tissues for many decades. Only recently with the development of gain-of-function assays for regeneration, has it been possible to screen for and assay the function of the multitude of signaling factors that have been identified in studies of embryonic development and tumorigenesis. Given the conservation of function of these regulatory pathways controlling growth and pattern formation, it is now possible to use the functional assays in the salamander to test the ability of endogenous as well as small-molecule signaling factors to induce a regenerative response.

A primary cardiac osteosarcoma: Case report and review of the literature.

Primary cardiac osteosarcoma is a rare and aggressive neoplasm that can be difficult to diagnose. We report a case of a previously healthy 49-year-old woman who presented with dyspnea, atrial flutter, and heart failure. A mass was visualized in her left atrium by echocardiography and cardiac computed tomography, and the diagnosis of cardiac myxoma was raised. The patient subsequently underwent surgical resection of the mass and atrial reconstruction. Surprisingly, histological and immunohistological analyses revealed the mass to be an osteosarcoma. The patient received chemotherapy and radiotherapy. Eight months later, she has shown evidence of local recurrence. We briefly discuss primary osteosarcomas in the cardiac cavity and their management. .

Leiomyosarcoma of the splenic vein.

Leiomyosarcomas arising from the wall of blood vessels are rare and aggressive neoplasm. We report a case of a previously healthy 66-year-old woman who presented with intermittent abdominal pain, progressive constipation, and weight loss. Abdominal computed tomography showed a 12 cm solid heterogeneous tumor in the tail of the pancreas. The patient subsequently underwent surgical resection of the pancreatic mass. Surprisingly, histological and immunohistochemical analyses revealed leiomyosarcoma arising from the smooth muscle of the splenic vein. After surgery, she received adjuvant chemotherapy. One year later, there was no evidence of local recurrence. In this paper, we discuss the available information about leiomyosarcomas of splenic vein and its management.

Patología del trasplante cardiaco en el Perú: Experiencia con 61 casos en un centro de referencia nacional / Pathology of heart transplantation in peru: experience with 61 cases in a national reference center

RESUMEN. Objetivos Describir las características histopatológicas de los explantes cardiacos y las biopsias endomiocárdicas postrasplante realizadas en un centro de referencia nacional del Perú. Materiales y métodos. Estudio de una serie de casos de pacientes sometidos a trasplante cardiaco entre marzo de 2010 y febrero de 2018. Resultados. Los 61 pacientes trasplantados, tuvieron un promedio de edad de 40,1 (rango: 9-66 años). Cinco casos (8,2%) diagnosticados inicialmente como miocardiopatía dilatada fueron reclasificados después del estudio histopatológico. Las tres primeras causas de enfermedad primaria previa al trasplante fueron: miocardiopatía dilatada idiopática (50,8%), cardiopatía isquémica (16,4%), y cardiopatía valvular (6,6%). El seguimiento promedio fue de 2,8 años. La tasa de supervivencia después del trasplante fue del 85,1% al año y del 82,8% a los cinco años. El rechazo celular agudo moderado/severo ocurrió en 12 pacientes (21,1%) y el rechazo mediado por anticuerpos ocurrió en tres pacientes (5,3%). Conclusiones. La evaluación histopatológica rutinaria del explante cardiaco es esencial para confirmar la etiología de la insuficiencia cardíaca, especialmente en los casos diagnosticados clínicamente como miocardiopatía dilatada. Asimismo, el seguimiento rutinario mediante biopsias endomiocárdicas muestra que el rechazo celular agudo continúa siendo una complicación frecuente durante el primer año de trasplante, y que el rechazo mediado por anticuerpos tiene una baja frecuencia en nuestra población.

ABSTRACT Objetive. To describe the histopathological characteristics of explanted hearts and post-transplant biopsy specimens at a national reference center in Peru. Materials and Methods. A case series study of patients who underwent heart transplantation between March 2010 and February 2018. Results. Sixty-one (61) transplanted patients with a mean age of 40.1 years (range: 9-66 years). Five cases (8.2%) initially diagnosed as dilated cardiomyopathy were reclassified after the histopathological study. The three leading causes of primary disease after transplantation were: idiopathic dilated cardiomyopathy (50.8%), ischemic cardiomyopathy (16.4%), and valvular cardiomyopathy (6.6%). The mean follow-up was 2.8 years. The post-transplant survival rate was 85.1% at 1 year and 82.8% at 5 years. Moderate/severe acute cellular rejection occurred in 12 patients (21.1%) and antibody-mediated rejection occurred in 3 patients (5.3%). Conclusions. Routine histopathological evaluation of the explanted heart is essential to confirm the etiology of heart failure, especially in cases clinically diagnosed as dilated cardiomyopathy. In addition, routine follow-up through endomyocardial biopsies shows that acute cellular rejection is still a frequent complication after a heart transplant, especially within the first year, and that antibody-mediated rejection has a low incidence in our population.

[Effects of spironolactone administration on the podocytes loss and progression of experimental diabetic nephropathy]. / Efecto de la administración de espironolactona sobre la pérdida de podocitos y la progresión de la nefropatía diabética experimental.

OBJECTIVES: Evaluate the effect of spironolactone (SPL) on the loss of podocytes during the progression of experimental diabetic nephropathy (DN). MATERIALS AND METHODS: A group of male Holtzman rats randomly received streptozotocin (diabetic group) or a buffer citrate (control group). Diabetic rats were treated with SPL (50 mg/kg/day). The glomerular area and the cellularity were evaluated by histomorphometric methods. The injury and loss of podocytes was assessed by desmin expression and Wt-1, respectively. The gene expression of TGF-ß1 was assessed by RT-PCR. RESULTS: Glucose levels, the glomerular area, the mesangial expansion and collagen content increased significantly in diabetic rats. The administration of SPL prevented these changes without changing glucose levels. Immunostain for Wt-1 decreased significantly while immunostain for desmin increased dramatically in diabetic rats. Treatment with SPL prevented the increase of desmin expression and the loss of Wt-1 expression. Furthermore, the administration of SPL prevented the increase of TGF-ß1 mRNA expression in diabetic rats. CONCLUSIONS: Treatment with SPL, through independent glucose effects, reduces the loss of podocytes and the progression of DN morphological changes. These results suggest that these effects are mediated, at least in part, by the inhibition of TGF-ß1 mRNA expression.