Proposal for the applicability of modified Breslow (measured from the basal membrane) as a predictor of survival and sentinel lymph node outcome in patients with cutaneous melanoma.

BACKGROUND: Cutaneous melanoma is a neoplasm with a high mortality rate and risk of metastases to distant organs. The Breslow micrometric measurement is considered the most important factor for evaluating prognosis and management, measured from the granular layer to the deepest portion of the neoplasm. Despite its widespread use, the Breslow thickness measurement has some inaccuracies, such as not considering variations in the thickness of the epidermis in different body locations or when there is ulceration. OBJECTIVE: To evaluate the applicability of a modified Breslow measurement, measured from the basal membrane instead of from the granular layer, in an attempt to predict sentinel lymph node examination outcome and survival of patients with melanoma. METHODS: A retrospective and cross-sectional analysis was carried out based on the evaluation of slides stained with hematoxylin & eosin from 275 cases of melanoma that underwent sentinel lymph node biopsy from 2008 to 2021 at a reference center in Brazil. RESULTS: Analysis of the Cox model to evaluate the impact of the Breslow measurement and the modified Breslow measurement on survival showed that both methods are statistically significant. Logistic regression revealed a significant association between both measurements and the presence of metastasis in sentinel lymph nodes. CONCLUSION: Measuring melanoma depth from the basal membrane (modified Breslow measurement) is capable of predicting survival time and sentinel lymph node outcome, as well as the conventional Breslow measurement.

Macroscopic tumor dimension, sentinel lymph node outcome, and survival analysis among cutaneous melanoma.

BACKGROUND: Cutaneous melanoma is characterized by a high risk of metastasis to distant organs and a substantial mortality rate. For planning treatment and assessing outcomes, the Breslow micrometric measurement is critical. The tumor macroscopic dimension is not considered a prognostic parameter in cutaneous melanoma, although there are studies showing that tumor size is an independent prognostic factor for melanoma-specific survival. Therefore, this study aimed to evaluate the macroscopic dimension of melanoma and other known prognostic factors (i.e., Breslow index, mitoses, regression, and ulceration) as predictors of sentinel lymph node outcome and survival outcome. METHODS: We performed a retrospective cross-sectional study of 227 melanoma lesions subjected to sentinel lymph node biopsy at two Brazilian referral centers. RESULTS: On univariate analysis, there was a statistically significant correlation between the largest macroscopic tumor dimension and the sentinel lymph node result (P = 0.001); however, on multivariate analysis considering all evaluated parameters, there was no significant difference between the sentinel lymph node result and the tumor macroscopic dimension (P = 0.2689). Regarding melanoma-specific survival, the macroscopic dimension showed no significant correlation (P = 0.4632) in contrast to Breslow's dimension (P < 0.0001). CONCLUSION: The Breslow thickness was the only significant factor related to both the sentinel lymph node outcome and melanoma specific survival among the evaluated variables.

Malignant lung PEComa (clear cell tumor): rare case report and literature review.

Clear cell tumors of the lung (CCTL), or "sugar tumors" of lung, are very uncommon lesions and are mostly benign perivascular epithelioid cell (PEC) tumors with no specific morphologic features. Fewer than 100 cases have been reported; the aggressive nature demonstrated in sporadic reports has rarely been described in the literature. Although the course is generally described as benign, eight reported cases showed malignant behavior. We report a case of a PEC with a malignant presentation in a young man, correlating the main characteristics of the tumor with other cases reported in the literature to better elucidate this rare presentation. We also performed a literature review of reports on benign and malignant CCTL cases, with a focus on clinical, imaging, and immunohistochemical differentiation. CCTLs are rare tumors that require histopathological and immunohistochemical confirmation; to date, criteria that can predict malignant evolution are lacking.

Evaluation of Biointegration and Inflammatory Response to Blood Vessels Produced by Tissue Engineering-Experimental Model in Rabbits.

Peripheral arterial disease (PAD) is the main cause of mortality in the western population and requires surgical intervention with the use of vascular substitutes, such as autologous veins or Dacron or PTFE prostheses. When this is not possible, it progresses to limb amputation. For cases where there is no autologous vascular substitute, tissue engineering with the production of neovessels may be a promising option. Previous experimental studies have shown in vitro that rabbit vena cava can be decellularized and serve as a scaffold for receiving mesenchymal stem cells (MSC), with subsequent differentiation into endothelial cells. The current study aimed to evaluate the behavior of a 3D product structure based on decellularized rabbit inferior vena cava (IVC) scaffolds seeded with adipose-tissue-derived stem cells (ASCs) and implanted in rabbits dorsally subcutaneously. We evaluated the induction of the inflammatory response in the animal. We found that stem cells were positive in reducing the inflammatory response induced by the decellularized scaffolds.

Clinical, radiological, and transbronchial biopsy findings in patients with long COVID-19: a case series.

This brief communication demonstrates the correlation of persistent respiratory symptoms with functional, tomographic, and transbronchial pulmonary biopsy findings in patients with COVID-19 who had a long follow-up period. We report a series of six COVID-19 patients with pulmonary involvement who presented with persistent dyspnea within 4-15 months of discharge. We performed transbronchial biopsies, and the histopathological pattern consistently demonstrated peribronchial remodeling with interstitial pulmonary fibrosis. Therefore, lung biopsy may be useful in the approach of patients with long COVID-19, although the type of procedure, its precise indication, and the moment to perform it are yet to be clarified. (Brazilian Registry of Clinical Trials-ReBEC; identifier: RBR-8j9kqy [http://www.ensaiosclinicos.gov.br]).

Clinical, radiological, and transbronchial biopsy findings in patients with long COVID-19: a case series / Achados clínicos, radiológicos e de biópsia transbrônquica em pacientes com COVID-19 prolongada: série de casos

ABSTRACT This brief communication demonstrates the correlation of persistent respiratory symptoms with functional, tomographic, and transbronchial pulmonary biopsy findings in patients with COVID-19 who had a long follow-up period. We report a series of six COVID-19 patients with pulmonary involvement who presented with persistent dyspnea within 4-15 months of discharge. We performed transbronchial biopsies, and the histopathological pattern consistently demonstrated peribronchial remodeling with interstitial pulmonary fibrosis. Therefore, lung biopsy may be useful in the approach of patients with long COVID-19, although the type of procedure, its precise indication, and the moment to perform it are yet to be clarified. (Brazilian Registry of Clinical Trials-ReBEC; identifier: RBR-8j9kqy [http://www.ensaiosclinicos.gov.br])

RESUMO Esta comunicação breve demonstra a correlação de sintomas respiratórios persistentes com achados funcionais, tomográficos e de biópsia pulmonar transbrônquica em pacientes com COVID-19 que tiveram um longo período de acompanhamento. Relatamos uma série de seis pacientes com COVID-19 com acometimento pulmonar que apresentavam dispneia persistente após 4-15 meses da alta. Realizamos biópsias transbrônquicas, e o padrão histopatológico consistentemente demonstrou remodelação peribrônquica com fibrose pulmonar intersticial. Portanto, a biópsia pulmonar pode ser útil na abordagem de pacientes com COVID-19 prolongada, embora o tipo de procedimento, suas indicações precisas e o momento de sua realização ainda não estejam esclarecidos. (Registro Brasileiro de Ensaios Clínicos - ReBEC; número de identificação: RBR-8j9kqy [http://www.ensaiosclinicos.gov.br])

Quantification of adhesion of mesenchymal stem cells spread on decellularized vein scaffold.

PURPOSE: To evaluate methods that improve adipose-derived stem cells (ASCs) population in decellularized biological venous scaffold for tissue engineering in blood vessels, a model in rabbits. METHODS: The ASC was expanded until the third passage. Inferior vena cava (IVC) was submitted to the decellularization process using 1% sodium dodecyl sulfate (SDS) or 2% sodium deoxycholate (SD) to compose 12 study groups (G): pure SD or SDS, exposed or not to 1% TritonX-100 (TX-100) and exposed or not to poly-l'lysine and laminin (PL). Scaffolds were covered with 1 × 105 or 1 × 106 ASCs diluted in 10 µL Puramatrix™. The histological analysis was done by cell counting in hematoxylin and eosin (HE) and nuclei count in immunofluorescence (IF) with 4',6-Diamidine-2'-phenylindole dihydrochloride (DAPI). RESULTS: The study of groups in HE and IF showed similar results. For both analyses,IVC-SD-1 × 106 ASC and IVC-SD-PL-1 × 106 ASC provided the best results. The IF technique showed better sensitivity than HE, with a weak agreement between them. CONCLUSIONS: Decellularizing agent and the number of ASC influence scaffolds cellularization response and the best protocols as those ones using SD with or without the addition of PL.

SNPs in genes encoding for IL-10, TNF-α, and NFκB p105/p50 are associated with clinical prognostic factors for patients with Hodgkin lymphoma.

Classical Hodgkin lymphoma (cHL) is a B-cell-derived malignant neoplasia that has a unique histological distribution, in which the scarce malignant Hodgkin and Reed-Sternberg cells are surrounded by nonmalignant inflammatory cells. The interactions between the malignant and inflammatory cells are mediated by aberrantly produced cytokines, which play an important role in tumor immunopathogenesis. Single nucleotide polymorphisms (SNPs) in genes encoding cytokines and their regulatory proteins may influence the peripheral levels of these molecules and affect disease's pathobiology. In this study, we evaluate SNPs in the promoter regions of the genes encoding for two key cytokines in Hodgkin lymphoma: IL-10 (SNP/pIL10-592, rs1800872; and SNP/pIL10-1082, rs1800896) and TNF-α (SNP/pTNF -238, rs361525; and SNP/pTNF -862, rs1800630), as well as an SNP in the intronic region of the NFκB1 gene (SNP/iNFKB1, rs1585215), an important regulator of cytokine gene expression. We then look to their possible association with clinical and laboratory features in cHL patients. Seventy-three patients with cHL are genotyped by qPCR-high resolution melting. The SNPs' genotypes are analyzed individually for each SNP, and when more than two allelic combinations are identified, the genotypes are also divided into two groups according to proposed biological relevance. By univariate analysis, patients harboring SNP/pTNF -238 AG genotype more frequently have EBV-associated cHL compared to homozygous GG, whereas the presence of mediastinal disease (bulky and nonbulky) is more common in the pIL10-592 AC/CC group compared to the AA homozygous group. Patients with SNP/iNFKB1 AA genotype more frequently have stage IV and extranodal disease at diagnosis. These results indicate that some SNPs' genotypes for IL-10 and TNF-α genes are associated with prognostic parameters in cHL. For the first time, the SNP/iNFKB1 is described in association with clinical features of the disease.

Quantification of adhesion of mesenchymal stem cells spread on decellularized vein scaffold

ABSTRACT Purpose: To evaluate methods that improve adipose-derived stem cells (ASCs) population in decellularized biological venous scaffold for tissue engineering in blood vessels, a model in rabbits. Methods: The ASC was expanded until the third passage. Inferior vena cava (IVC) was submitted to the decellularization process using 1% sodium dodecyl sulfate (SDS) or 2% sodium deoxycholate (SD) to compose 12 study groups (G): pure SD or SDS, exposed or not to 1% TritonX-100 (TX-100) and exposed or not to poly-l'lysine and laminin (PL). Scaffolds were covered with 1 × 105 or 1 × 106 ASCs diluted in 10 μL Puramatrix™. The histological analysis was done by cell counting in hematoxylin and eosin (HE) and nuclei count in immunofluorescence (IF) with 4',6-Diamidine-2'-phenylindole dihydrochloride (DAPI). Results: The study of groups in HE and IF showed similar results. For both analyses,IVC-SD-1 × 106 ASC and IVC-SD-PL-1 × 106 ASC provided the best results. The IF technique showed better sensitivity than HE, with a weak agreement between them. Conclusions: Decellularizing agent and the number of ASC influence scaffolds cellularization response and the best protocols as those ones using SD with or without the addition of PL.

Effect of Albendazole Treatment in an Experimental Model of Neurocysticercosis-Induced Hydrocephalus

Hydrocephalus is a major concern in neurocysticercosis (NCC), and its management is more challenging than that of hydrocephalus caused by other etiologies. Even though albendazole is a well-established drug for the treatment of NCC, the death of the parasites may worsen the clinical symptoms and eventually, deteriorate the course of hydrocephalus. The aim of this study was to analyze the effects of treatment with albendazole on the course of hydrocephalus as well as on animal behavior in a ratmodel of NCC-induced hydrocephalus in order to verify whether the course of hydrocephalus and the animal behavior were changed. Ventricle volumes before and after treatment showed a slight but non-statistically significant difference (168.11 mm3 versus 184.98 mm3, p » 0.45). The distribution and location of the cysts were unaffected. In addition, the behavioral patterns before and after the treatment were not significantly different, as assessed by the open field test. On histologic assessment, mononuclear leukocyte infiltration was present in diverse sites, such as the perivascular and peri-ependymal regions, choroid plexus, and meningeal membranes. A positive correlation was found between the degree of ventricle enlargement and tissue damage. Further studies with long-term comparisons are required.

Should Serum Protein Electrophoresis Be a Surrogate for Liver Biopsy in Some Cases of Alpha1 Antitrypsin Deficiency?

Most patients with alpha1 antitrypsin deficiency do not receive this diagnosis until developing severe complications, in particular when respiratory symptoms are absent. This is a reason for making alpha1 antitrypsin deficiency a possible diagnosis among patients with cryptogenic cirrhosis or other conditions of liver disease without a clear etiology. In this report, a case of cryptogenic cirrhosis is presented, showing the role of serum protein electrophoresis in the diagnosis, which was made before liver biopsy. Therefore, the possibility of using a typical pattern of serum protein electrophoresis as a surrogate for liver biopsy in alpha1 antitrypsin deficiency is discussed.