Deconvolution of B cell receptor repertoire in multiple sclerosis patients revealed a delay in tBreg maturation.

Background: B lymphocytes play a pivotal regulatory role in the development of the immune response. It was previously shown that deficiency in B regulatory cells (Bregs) or a decrease in their anti-inflammatory activity can lead to immunological dysfunctions. However, the exact mechanisms of Bregs development and functioning are only partially resolved. For instance, only a little is known about the structure of their B cell receptor (BCR) repertoires in autoimmune disorders, including multiple sclerosis (MS), a severe neuroinflammatory disease with a yet unknown etiology. Here, we elucidate specific properties of B regulatory cells in MS. Methods: We performed a prospective study of the transitional Breg (tBreg) subpopulations with the CD19+CD24highCD38high phenotype from MS patients and healthy donors by (i) measuring their content during two diverging courses of relapsing-remitting MS: benign multiple sclerosis (BMS) and highly active multiple sclerosis (HAMS); (ii) analyzing BCR repertoires of circulating B cells by high-throughput sequencing; and (iii) measuring the percentage of CD27+ cells in tBregs. Results: The tBregs from HAMS patients carry the heavy chain with a lower amount of hypermutations than tBregs from healthy donors. The percentage of transitional CD24highCD38high B cells is elevated, whereas the frequency of differentiated CD27+ cells in this transitional B cell subset was decreased in the MS patients as compared with healthy donors. Conclusions: Impaired maturation of regulatory B cells is associated with MS progression.

Molecular Profiling of the Cardiac Conduction System: the Dawn of a New Era.

PURPOSE OF REVIEW: Recent technological advances have led to an increased ability to define the gene expression profile of the cardiac conduction system (CCS). Here, we review the most salient studies to emerge in recent years and discuss existing gaps in our knowledge as well as future areas of investigation. RECENT FINDINGS: Molecular profiling of the CCS spans several decades. However, the advent of high-throughput sequencing strategies has allowed for the discovery of unique transcriptional programs of the many diverse CCS cell types. The CCS, a diverse structure with significant inter- and intra-component cellular heterogeneity, is essential to the normal function of the heart. Progress in transcriptomic profiling has improved the resolution and depth of characterization of these unique and clinically relevant CCS cell types. Future studies leveraging this big data will play a crucial role in improving our understanding of CCS development and function as well as translating these findings into tangible translational tools for the improved detection, prevention, and treatment of cardiac arrhythmias.

Ultra-rapid regrowth of urothelial cardiac metastasis after debulking surgery.

Cardiac metastases of urothelial carcinoma are a rare manifestation, and most of them are asymptomatic or autoptic findings. We report a case of a 64-year-old Caucasian man fully asymptomatic, who has been accidentally diagnosed with a right atrial mass during his routine follow up for previous urothelial cancer. Endomyocardial biopsy, and histological examination of the mass were crucial to reach a definitive diagnosis of urothelial metastasis. He underwent a debulking surgery of the mass to avoid cardiac life-threatening complications. Despite effective removal of the atrial metastasis, after 45 days the patient experienced an ultra-rapid regrowth of the mass in the same position. This case demonstrates how rapidly a urothelial cardiac metastasis can grow back, and that surgery does not avoid by itself early recurrence.

Human subpulmonary infundibulum has an endocardial network of specialized conducting cardiomyocytes.

BACKGROUND: The right ventricular outflow tract is the most common source of ventricular arrhythmias in nonstructural heart disease. Most of these arrhythmias are of endocardial origin, but their morphologic substrate is mostly unknown. OBJECTIVE: The purpose of this study was to identify potential morphologic substrates for such arrhythmias originating within the right ventricular outflow tract. METHODS: Three adult human hearts that had been fixed in 4% formaldehyde were examined. In 2 of the hearts, which were obtained subsequent to necropsies, the base of the anterior papillary muscle of the tricuspid valve was removed at the site of its fusion with the moderator band. The block of removed myocardium was submitted to routine histologic processing and sectioned at 5-µm thickness. The free-standing subpulmonary infundibulum also was removed as a series of macroscopic preparations, which were sectioned in their short axis at 5-µm thickness. The third heart was assessed using microcomputed tomography after it had been stained with 7.5% I2KI contrast agent for 14 days, with the contrast agent refreshed on the seventh day. RESULTS: Specialized conducting cardiomyocytes from the base of the anterior papillary muscle to the supraventricular crest and subpulmonary infundibulum were identified and tracked using histology in 2 hearts and microcomputed tomography in the other. Transitional cells were also found at these sites. CONCLUSION: The existence of such specialized cardiomyocytes within the infundibulum is of clinical significance because they could be the morphologic substrate for arrhythmias known to originate from these sites.

Standardization of the apparent diffusion coefficient value of bladder cancer across different centers: Applicability in predicting aggressive pathologic phenotypes.

PURPOSE: We investigated whether the standardized apparent diffusion coefficient (ADC) value reflects bladder cancer characteristics across different centers. METHODS: Ninety-eight bladder cancer patients underwent MRI at two institutions. Standardized tumor ADC (sT-ADC) was calculated by dividing absolute tumor ADC (aT-ADC) by that of gluteus maximus. We compared ADCs between MRI protocols according to grade and T-stage. RESULTS: The differences in aT-ADC between MRI protocols were negated by sT-ADC. The best sT-ADC cut-offs to predict cancer aggressiveness in the development cohort worked in the validation cohort compared to the development cohort. CONCLUSION: Standardized ADC overcomes the incompatibility between different MRI protocols.

Pathologic Changes of the Peripheral Vestibular System Secondary to Chronic Otitis Media.

OBJECTIVE: To evaluate the histopathologic changes of dark, transitional, and hair cells of the vestibular system in human temporal bones from patients with chronic otitis media. STUDY DESIGN: Comparative human temporal bone study. SETTING: Otopathology laboratory. SUBJECTS AND METHODS: To compare the density of vestibular dark, transitional, and hair cells in temporal bones with and without chronic otitis media, we used differential interference contrast microscopy. RESULTS: In the chronic otitis media group (as compared with the age-matched control group), the density of type I and type II hair cells was significantly decreased in the lateral semicircular canal, saccule, and utricle (P < .05). The density of type I cells was also significantly decreased in the chronic otitis media group in the posterior semicircular canal (P = .005), but that of type II cells was not (P = .168). The mean number of dark cells was significantly decreased in the chronic otitis media group in the lateral semicircular canal (P = .014) and in the posterior semicircular canal (P = .002). We observed no statistically significant difference in the density of transitional cells between the 2 groups (P > .1). CONCLUSION: The findings of our study suggest that the decrease in the number of vestibular sensory cells and dark cells could be the cause of the clinical symptoms of imbalance of some patients with chronic otitis media.

Tumor de Brenner maligno: caso clínico / Malignant Brenner tumor: clinical case

El tumor de Brenner es una neoplasia rara, que representa el 1-2 por ciento de las neoplasias de ovario. La mayoría son benignas, pero existe un pequeño porcentaje de casos de tumor de Brenner maligno, entre ellos el caso que se presenta. Se trata de una mujer de 41 años que presentó una tumoración ovárica cuyo resultado anatomopatológico fue de carcinoma pobremente diferenciado, con asociación de tumor tipo Brenner maligno. A pesar de ser diagnosticado en estadio precoz, este caso destaca por su mal pronóstico.

Brenner tumor is a rare neoplasia, accounting for 1-2 percent of ovarian cancer. Most of them are benign, but there are a small percentage of malignant Brenner tumors, including the case presented. This is a 41-year-old woman who presented an ovarian tumor. Definitive histological result showed a poorly differentiated carcinoma, with association of malignant Brenner tumor. Despite being diagnosed in early stages, this case stands out for its poor prognosis.

Avaliação da sobrevida livre de doença em pacientes com carcinoma epidermoide de laringe submetidos à tratamento radioterápico exclusivo ou associado à quimioterapia / Assessment of disease-free survival in patients with laryngeal squamous cell carcinoma treated with radiotherapy associated or not with chemotherapy

No carcinoma epidermoide de laringe em estádios clínicos precoces (I e II), tanto a cirurgia quanto a radioterapia resultam em controle loco-regional significativo. Nos tumores avançados (III e IV), a radioterapia exclusiva tem índices de 32-43 por cento de controle loco-regional. OBJETIVO: É avaliar a sobrevida livre de doença dos pacientes com CEC de laringe submetidos à radioterapia exclusiva e/ou associada à quimioterapia. CASUÍSTICA E MÉTODOS: Estudo retrospectivo de 84 casos de CEC de laringe tratados com radioterapia ou quimioterapia concomitante à radioterapia. Cinquenta e três casos foram tratados com intenção curativa e 31 por irressecabilidade da doença. Quanto ao estádio clínico (EC), 12 eram de EC I, 15 II, 21 III e 5 IV. No segundo grupo, 11 casos eram EC III e 20 IV. RESULTADOS: Idade média foi de 60 anos, sendo 84,5 por cento homens. Cinquenta e oito (69,1 por cento) casos tiveram resposta completa e 26 (30,9 por cento) apresentavam doença persistente ou residual. A sobrevida livre de doença há cinco anos foi de 42,5 por cento, sendo de 62,5 por cento nos pacientes com indicação de preservação de órgãos e 9,75 no grupo de doença irressecável. CONCLUSÃO: A sobrevida livre de doença a cinco anos dos pacientes submetidos à radioterapia por CEC de laringe foi de 62,5 por cento.

In early stage (I and II) laryngeal squamous cell carcinoma, both surgery and radiotherapy results in significant local and regional control. In advanced tumors (III and IV), radiotherapy alone has local-regional control rates of 32-43 percent. AIM: To assess disease-free survival in SCC laryngeal carcinoma patients submitted to radiotherapy alone and/or associated with chemotherapy. MATERIALS AND METHODS: Retrospective study involving 84 cases of laryngeal SCC treated with radiotherapy or chemotherapy together with radiotherapy. Fifty-three cases were treated with intension to cure and 31 because of impossibility to resect the disease. As to clinical stage (CS), 12 were CS I, 15 II, 21 III and 5 IV. In the second group, 11 cases were EC III and 20 IV. RESULTS: Mean age was 60 years, 84.5 percent were men. Fifty-eight (69.1 percent) cases had complete response and 26 (30.9 percent) had persistent or residual disease. Five-year disease-free survival was of 42.5 percent; 62.5 percent of the patients with organ preservation indication and 9.75 in the group of irressecable disease. CONCLUSION: disease-free survival of those patients submitted to radiotherapy because of laryngeal SCC was of 62.5 percent

Tumor de Brenner bilateral benigno / Bilateral benign Brenner tumor

El tumor de Brenner es un tumor raro que representa aproximadamente el 1,5 por ciento de los tumores de ovario. Se define como un tumor de células transicionales compuesto por células uroteliales dispuestas en agregados sólidos o quísticos embebidos en un estroma fibroso. Se clasifica en tumor de Brenner benigno (95 por ciento), borderline (3-4 por ciento) y maligno (1 por ciento). Presentamos el caso clínico de una paciente de 91 años intervenida por una tumoración anexial gigante en la que el estudio anatomopatológico reveló la presencia de un tumor de Brenner bilateral benigno asociado a dos cistoadenomas serosos de ovario derecho.

Brenner's tumor is a rare tumor that represents approximately 1.5 percent of the tumors of ovary. It is defined as a tumor of transitional cells composed by cells uroteliales arranged in solid or cystic acccumulations absorbed in a fibrous estroma. It qualifies in tumor of benign Brenner (95 percent), borderline (3-4 percent) and malignantly (1 percent). We present the clinical case of a 91-year-old patient controlled by a giant anexial mass in whom the pathology study (biopsy) revealed the presence of a tumor of bilateral benign Brenner associated with two cistoadenomas serous of right ovary.