RESUMO
OBJECTIVES: This study aimed to predict individual COVID-19 patient prognosis at hospital admission using artificial intelligence (AI)-based quantification of computed tomography (CT) pulmonary involvement. BACKGROUND: Assessing patient prognosis in COVID-19 pneumonia is crucial for patient management and hospital and ICU organization. METHODS: We retrospectively analyzed 559 patients with PCR-verified COVID-19 pneumonia referred to the hospital for a severe disease course. We correlated the CT extent of pulmonary involvement with patient outcome. We also attempted to define cut-off values of pulmonary involvement for predicting different outcomes. RESULTS: CT-based disease extent quantification is an independent predictor of patient morbidity and mortality, with the prognosis being impacted also by age and cardiovascular comorbidities. With the use of explored cut-off values, we divided patients into three groups based on their extent of disease: (1) less than 28 % (sensitivity 65.4 %; specificity 89.1 %), (2) ranging from 28 % (31 %) to 47 % (sensitivity 87.1 %; specificity 62.7 %), and (3) above 47 % (sensitivity 87.1 %; specificity, 62.7 %), representing low risk, risk for oxygen therapy and invasive pulmonary ventilation, and risk of death, respectively. CONCLUSION: CT quantification of pulmonary involvement using AI-based software helps predict COVID-19 patient outcomes (Tab. 4, Fig. 4, Ref. 38).
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COVID-19 , Pneumonia , Humanos , COVID-19/diagnóstico por imagem , Inteligência Artificial , SARS-CoV-2 , Estudos Retrospectivos , Pulmão/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodosRESUMO
During SARS-CoV-2 infection, the virus transforms the infected host cell into factories that produce new viral particles. As infection progresses, the infected cells undergo numerous changes in various pathways. One of these changes is the occurrence of a cytokine storm, which leads to severe symptoms. In this study, we examined the transcriptomic changes caused by COVID-19 by analyzing RNA-seq data obtained from COVID-19-positive patients as well as COVID-19-negative donors. RNA-seq data were collected for the purpose of identification of potential biomarkers associated with a different course of the disease. We analyzed the first datasets, consisting of 96 samples to validate our methods. The objective of this publication is to report the pilot results. To explore potential biomarkers related to disease severity, we conducted a differential expression analysis of human transcriptome, focusing on COVID-19 positivity and symptom severity. Given the large number of potential biomarkers we identified, we further performed pathway enrichment analysis with terms from Kyoto Encyclopedia of Genes and Genomics (KEGG) to obtain a more profound understanding of altered pathways. Our results indicate that pathways related to immune processes, response to infection, and multiple signaling pathways were affected. These findings align with several previous studies that also reported the influence of SARS-CoV-2 infection on these pathways.
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COVID-19 , Humanos , COVID-19/genética , SARS-CoV-2/genética , Perfilação da Expressão Gênica , Genômica , BiomarcadoresRESUMO
After the acute phase of COVID-19, some patients develop long COVID. This term is used for a variety of conditions with a complex, yet not fully elucidated etiology, likely including the prolonged persistence of the virus in the organism and progression to lung fibrosis. We present a unique autopsy case of a patient with severe COVID-19 with prolonged viral persistence who developed interstitial lung fibrosis complicated by a fatal combination of cytomegalovirus and Aspergillus infection. SARS-CoV-2 virus was detected at autopsy in the lungs more than two months after the acute infection, although tests from the nasopharynx were negative. Immune dysregulation after COVID-19 and the administration of corticoid therapy created favorable conditions for the cytomegalovirus and Aspergillus infection that were uncovered at autopsy. These pathogens may represent a risk for opportunistic infections, complicating not only the acute coronavirus infection but also long COVID, as was documented in the presented case.
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Aspergilose , COVID-19 , Fibrose Pulmonar , Humanos , COVID-19/complicações , COVID-19/patologia , Citomegalovirus , Síndrome de COVID-19 Pós-Aguda , SARS-CoV-2 , Fibrose Pulmonar/patologia , Autopsia , Pulmão/patologia , Aspergilose/patologiaRESUMO
Endometrial cancer belongs to the most common gynecologic cancer types globally, with increasing incidence. There are numerous ways of classifying different cases. The most recent decade has brought advances in molecular classification, which show more accurate prognostic factors and the possibility of personalised adjuvant treatment. In addition, diagnostic approaches lag behind these advances, with methods causing patients discomfort while lacking the reproducibility of tissue sampling for biopsy. Minimally invasive liquid biopsies could therefore represent an alternative screening and diagnostic approach in patients with endometrial cancer. The method could potentially detect molecular changes in this cancer type and identify patients at early stages. In this pilot study, we tested such a detection method based on circulating tumour DNA isolated from the peripheral blood plasma of 21 Slovak endometrial cancer patients. We successfully detected oncomutations in the circulating DNA of every single patient, although the prognostic value of the detected mutations failed to offer certainty. Furthermore, we detected changes associated with clonal hematopoiesis, including DNMT3A mutations, which were present in the majority of circulating tumour DNA samples.
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DNA Tumoral Circulante , Neoplasias do Endométrio , Humanos , Feminino , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Projetos Piloto , Reprodutibilidade dos Testes , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Mutação , Biópsia Líquida/métodosRESUMO
BACKGROUND: COVID-19 caused by the SARS-CoV-2 infection may result in various disease symptoms and severity, ranging from asymptomatic, through mildly symptomatic, up to very severe and even fatal cases. Although environmental, clinical, and social factors play important roles in both susceptibility to the SARS-CoV-2 infection and progress of COVID-19 disease, it is becoming evident that both pathogen and host genetic factors are important too. In this study, we report findings from whole-exome sequencing (WES) of 27 individuals who died due to COVID-19, especially focusing on frequencies of DNA variants in genes previously associated with the SARS-CoV-2 infection and the severity of COVID-19. RESULTS: We selected the risk DNA variants/alleles or target genes using four different approaches: 1) aggregated GWAS results from the GWAS Catalog; 2) selected publications from PubMed; 3) the aggregated results of the Host Genetics Initiative database; and 4) a commercial DNA variant annotation/interpretation tool providing its own knowledgebase. We divided these variants/genes into those reported to influence the susceptibility to the SARS-CoV-2 infection and those influencing the severity of COVID-19. Based on the above, we compared the frequencies of alleles found in the fatal COVID-19 cases to the frequencies identified in two population control datasets (non-Finnish European population from the gnomAD database and genomic frequencies specific for the Slovak population from our own database). When compared to both control population datasets, our analyses indicated a trend of higher frequencies of severe COVID-19 associated risk alleles among fatal COVID-19 cases. This trend reached statistical significance specifically when using the HGI-derived variant list. We also analysed other approaches to WES data evaluation, demonstrating its utility as well as limitations. CONCLUSIONS: Although our results proved the likely involvement of host genetic factors pointed out by previous studies looking into severity of COVID-19 disease, careful considerations of the molecular-testing strategies and the evaluated genomic positions may have a strong impact on the utility of genomic testing.
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COVID-19 , Humanos , COVID-19/genética , SARS-CoV-2 , Sequenciamento do Exoma , Alelos , DNARESUMO
Innervation of cancerous tissue represents an important pathway enabling the nervous system to influence the processes associated with the initiation, progression, and metastasis of a neoplastic process. In the context of prostate cancer, several papers report the presence of innervation and its modulating effect on the cancer prognosis. However, most of the data are experimental, with limited information on human prostate cancer innervation. Morphometric analysis of archival prostate specimen immunohistochemistry with neural markers PGP9.5 and S100 showed a significant decrease of nerve density in the prostate cancer (n=44) compared to the normal prostate tissue (n=18) and benign prostatic hyperplasia (n=28). Sympathetic nerves were detected with TH, parasympathetic with VAChT, and sensory nerves with SP and CGRP protein detection. Dual immunofluorescence revealed numerous sympathetic nerves in normal prostate and benign prostatic hyperplasia, especially in the peripheral parts. Only a few parasympathetic nerves were found between the glands and in the peripheral parts of the prostate and benign hyperplasia. Sporadic positivity for sensory innervation was present only in approximately 1/10 of nerve fibers, especially in the larger nerves. The pattern of innervation in prostate cancer was analogous to that in normal prostate gland and benign prostatic hyperplasia but there was a significantly lower amount of all nerve types, especially in high-grade carcinoma cases. Although not significant, there was a tendency of decreasing innervation density with increasing Gleason score. Regarding the low density of nerves in prostate carcinoma, the significantly lower PCNA counts in nerves of the cancer specimens cannot be ascribed to lower proliferation activity. Our data confirmed the lower nerve density in the prostate cancer compared to the benign prostate tissue. We could not approve an increased nerve proliferation activity in prostate cancer. All nerve types, most the sympathetic, less the parasympathetic, and the sensory nerves, are present in prostate cancer. The highest nerve density at the periphery of the cancer tissue implies this to be the result of an expansive tumor growth. It is evident that the results of experimental prostate cancer models can be applied to human pathology only to a certain extent. The relation between the range of innervation and the biology of prostate cancer is very complex and will require more detailed information to be applied in therapeutic solutions.
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Carcinoma , Hiperplasia Prostática , Neoplasias da Próstata , Masculino , Humanos , PróstataRESUMO
BACKGROUND: Muscle-infiltrating urothelial carcinoma of the bladder is the most common genitourinary cancer. Immunotherapeutic agents targeting protein-1 programmed death or protein-1 programmed death ligand are currently considered the standard treatment in patients with either inoperable locally advanced or metastatic urothelial carcinoma (MUC) after platinum-based chemotherapy failure. CASE PRESENTATION: Here we report the case of a Caucasian male patient with metastatic urothelial carcinoma treated with second-line atezolizumab within a trial who achieved complete response by computed tomography (CT), but suddenly died due to cardiac tamponade resulting from malignant pericardial infiltration. Histopathology confirmed this as the only site of disease progression. CONCLUSIONS: Cardiovascular toxicity of atezolizumab was considered within differential diagnoses, however histopathological examination revealed progression of malignancy in the pericardium as the cause of the sudden death. This is the first published case report of a patient treated with second-line atezolizumab in whom the rare disease progression of pericardial infiltration was confirmed. Despite its rarity, the clinicians should always consider the possibility of pericardial metastases.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Anticorpos Monoclonais Humanizados , Antígeno B7-H1 , Carcinoma de Células de Transição/patologia , Morte Súbita , Progressão da Doença , Humanos , Masculino , Pericárdio/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias Urológicas/tratamento farmacológicoAssuntos
Meningite , Sinusite , Humanos , Meningite/complicações , Meningite/etiologia , Sinusite/complicaçõesRESUMO
BACKGROUND: SARS-CoV-2 infection in pregnant women can lead to placental damage and transplacental infection transfer, and intrauterine fetal demise is an unpredictable event. CASE STUDY: A 32-year-old patient in her 38th week of pregnancy reported loss of fetal movements. She overcame mild COVID-19 with positive PCR test 22 days before. A histology of the placenta showed deposition of intervillous fibrinoid, lympho-histiocytic infiltration, scant neutrophils, clumping of villi, and extant infarctions. Immunohistochemistry identified focal SARS-CoV-2 nucleocapsid and spike protein in the syncytiotrophoblast and isolated in situ hybridization of the virus' RNA. Low ACE2 and TMPRSS2 contrasted with strong basigin/CD147 and PDL-1 positivity in the trophoblast. An autopsy of the fetus showed no morphological abnormalities except for lung interstitial infiltrate, with prevalent CD8-positive T-lymphocytes and B-lymphocytes. Immunohistochemistry and in situ hybridization proved the presence of countless dispersed SARS-CoV-2-infected epithelial and endothelial cells in the lung tissue. The potential virus-receptor protein ACE2, TMPRSS2, and CD147 expression was too low to be detected. CONCLUSION: Over three weeks' persistence of trophoblast viral infection lead to extensive intervillous fibrinoid depositions and placental infarctions. High CD147 expression might serve as the dominant receptor for the virus, and PDL-1 could limit maternal immunity in placental tissue virus clearance. The presented case indicates that the SARS-CoV-2 infection-induced changes in the placenta lead to ischemia and consecutive demise of the fetus. The infection of the fetus was without significant impact on its death. This rare complication of pregnancy can appear independently to the severity of COVID-19's clinical course in the pregnant mother.
Assuntos
COVID-19/complicações , Placenta/patologia , Complicações Infecciosas na Gravidez , Natimorto , Adulto , Enzima de Conversão de Angiotensina 2 , Linfócitos B , Linfócitos T CD8-Positivos , COVID-19/diagnóstico , Células Endoteliais/patologia , Feminino , Feto/patologia , Humanos , Transmissão Vertical de Doenças Infecciosas , Placenta/virologia , Doenças Placentárias/patologia , Doenças Placentárias/virologia , Gravidez , Complicações Infecciosas na Gravidez/patologia , Complicações Infecciosas na Gravidez/virologia , SARS-CoV-2 , Serina Endopeptidases , Glicoproteína da Espícula de Coronavírus , TrofoblastosRESUMO
BACKGROUND: Chemotherapy remains a standard treatment option for breast cancer despite its toxic effects to normal tissues. However, the long-lasting effects of chemotherapy on non-malignant cells may influence tumor cell behavior and response to treatment. Here, we have analyzed the effects of doxorubicin (DOX) and paclitaxel (PAC), commonly used chemotherapeutic agents, on the survival and cellular functions of mesenchymal stromal cells (MSC), which comprise an important part of breast tumor microenvironment. METHODS: Chemotherapy-exposed MSC (DOX-MSC, PAC-MSC) were co-cultured with three breast cancer cell (BCC) lines differing in molecular characteristics to study chemotherapy-triggered changes in stromal compartment of the breast tissue and its relevance to tumor progression in vitro and in vivo. Conditioned media from co-cultured cells were used to determine the cytokine content. Mixture of BCC and exposed or unexposed MSC were subcutaneously injected into the immunodeficient SCID/Beige mice to analyze invasion into the surrounding tissue and possible metastases. The same mixtures of cells were applied on the chorioallantoic membrane to study angiogenic potential. RESULTS: Therapy-educated MSC differed in cytokine production compared to un-exposed MSC and influenced proliferation and secretory phenotype of tumor cells in co-culture. Histochemical tumor xenograft analysis revealed increased invasive potential of tumor cells co-injected with DOX-MSC or PAC-MSC and also the presence of nerve fiber infiltration in tumors. Chemotherapy-exposed MSC have also influenced angiogenic potential in the model of chorioallantoic membrane. CONCLUSIONS: Data presented in this study suggest that neoadjuvant chemotherapy could possibly alter otherwise healthy stroma in breast tissue into a hostile tumor-promoting and metastasis favoring niche. Understanding of the tumor microenvironment and its complex net of signals brings us closer to the ability to recognize the mechanisms that prevent failure of standard therapy and accomplish the curative purpose.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Transformação Celular Neoplásica/patologia , Células-Tronco Mesenquimais/patologia , Animais , Apoptose , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células , Transformação Celular Neoplásica/induzido quimicamente , Doxorrubicina/administração & dosagem , Feminino , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Camundongos SCID , Invasividade Neoplásica , Paclitaxel/administração & dosagem , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Rheumatoid arthritis (RA) is a chronic multisystem disease, therapy of which remains a challenge for basic research. The present work examined the effect of unconjugated bilirubin (UCB) administration in adjuvant-induced arthritis (AIA)-an experimental model, in which oxidative stress (OS), inflammation and inadequate immune response are often similar to RA. Male Lewis rats were randomized into groups: CO-control, AIA-untreated adjuvant-induced arthritis, AIA-BIL-adjuvant-induced arthritis administrated UCB, CO-BIL-control with administrated UCB. UCB was administered intraperitoneally 200 mg/kg of body weight daily from 14th day of the experiment, when clinical signs of the disease are fully manifested, to 28th day, the end of the experiment. AIA was induced by a single intradermal immunization at the base of the tail with suspension of Mycobacterium butyricum in incomplete Freund's adjuvant. Clinical, hematologic, biochemical and histologic examinations were performed. UCB administration to animals with AIA lead to a significant decrease in hind paws volume, plasma levels of C-reactive protein (CRP) and ceruloplasmin, drop of leukocytes, lymphocytes, erythrocytes, hemoglobin and an increase in platelet count. UCB administration caused significantly lowered oxidative damage to DNA in arthritic animals, whereas in healthy controls it induced considerable oxidative damage to DNA. UCB administration also induced atrophy of the spleen and thymus in AIA and CO animals comparing to untreated animals. Histological signs of joint damage assessed by neutrophils infiltration and deposition of fibrin were significantly reduced by UCB administration. The effects of exogenously administered UCB to the animals with adjuvant-induced arthritis might be identified as therapeutic, in contrast to the effects of UCB administration in healthy animals rather classified as toxic.
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Anti-Inflamatórios/administração & dosagem , Artrite Experimental/tratamento farmacológico , Bilirrubina/administração & dosagem , Adjuvante de Freund/efeitos adversos , Lipídeos/efeitos adversos , Mycobacterium/imunologia , Animais , Anti-Inflamatórios/farmacologia , Artrite Experimental/induzido quimicamente , Artrite Experimental/metabolismo , Bilirrubina/farmacologia , Proteína C-Reativa , Ceruloplasmina/metabolismo , Injeções Intraperitoneais , Masculino , Estresse Oxidativo/efeitos dos fármacos , Fragmentos de Peptídeos/sangue , Distribuição Aleatória , Ratos , Ratos Endogâmicos Lew , Resultado do TratamentoRESUMO
The goal of this manuscript is to provide an overview of the significance of immunohistochemical methods in diagnosing endometrial carcinoma. The main points discussed include: the use of immunohistochemistry in the differential diagnosis of the main histological types of endometrial carcinoma, the difference between primary serous endometrial carcinoma and the involvement with high grade serous carcinoma of another primary source, the diagnosis of undifferentiated/dedifferentiated endometrial carcinoma, and diagnosing tumours with neuroendocrine differentiation. The role of p53 expression evaluation is also emphasized as a special area of interest, not only in the context of differential diagnosis, but also from the point of view of the prognosis and prediction of endometrial carcinoma as an ancillary marker for subtypization of these tumours.
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Carcinoma Endometrioide , Neoplasias do Endométrio , Biomarcadores Tumorais , Carcinoma Endometrioide/diagnóstico , Diagnóstico Diferencial , Neoplasias do Endométrio/diagnóstico , Feminino , Humanos , Imuno-HistoquímicaRESUMO
Hereditary tumor syndromes with a possible manifestation in the female internal genital tract represent a heterogeneous group of diseases. The two most common entities are the hereditary breast and ovarian cancer syndrome, and the Lynch syndrome. The less common syndromes include the rhabdoid tumor predisposition syndrome, Cowden syndrome, tuberous sclerosis complex, DICER1 syndrome, nevoid basal cell carcinoma syndrome, Peutz-Jeghers syndrome, von Hippel-Lindau disease, and hereditary leiomyomatosis and renal cell cancer syndrome. The goal of this manuscript is to provide a comprehensive overview of those hereditary tumor syndromes which can manifest in the area of the female genital system, with an emphasis on their summary, the characteristics of the tumors which can develop in association with these syndromes, and the approach to the processing of prophylactically removed tissues and organs. The issue of Lynch syndrome screening is also discussed.
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Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Renais , Leiomiomatose , Síndromes Neoplásicas Hereditárias , Neoplasias Colorretais Hereditárias sem Polipose/genética , RNA Helicases DEAD-box , Feminino , Predisposição Genética para Doença , Humanos , Síndromes Neoplásicas Hereditárias/genética , Ribonuclease IIIRESUMO
Desmoid-type fibromatosis is locally aggressive tumor rare in general population, although commonly present in patients with familial adenomatous polyposis, significantly contributing to the morbidity and mortality of patients. To optimize and individualize the management of patients it is necessary to better understand the biology of these tumors. Immunohistochemical analysis of ß-catenin, VEGF, hormone receptors ERß, ERα and PR, COX-2, APC protein, EGFR, c-kit (CD117), bcl-2 and HER2 expression, potential therapeutic targets, was carried out on 15 archival biopsy samples together with APC gene mutational screening. ß-catenin expression was found in all samples, with over 73% showing high range positivity, however with no prognostic significance. Non-specific cytoplasmic localization of ß-catenin was observed FAP-associated cases lacking CTNNB1 mutations. Hormone receptor status demonstrated expression of ERß in 93% of lesions, without detectable ERα or PR. Distinct COX-2 expression of variable intensity was present in all but one desmoid-type fibromatosis case. All lesions demonstrated intense VEGF positivity. Immunoreactivity for the APC protein was found only in 4 cases associated with FAP. No EGFR, HER2, bcl-2 or c-kit expression was detected in any sample. Expression of ß-catenin, VEGF, ERß, COX-2 in high number of cases suggests a potential as future therapeutic targets in desmoid-type fibromatosis.
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Polipose Adenomatosa do Colo , Fibromatose Agressiva , Polipose Adenomatosa do Colo/genética , Humanos , Mutação , Prognóstico , beta Catenina/genéticaRESUMO
BACKGROUND: Primary squamous cell carcinomas (SCC) of the colon are extremely rare and occur predominantly in the fifth decade of life, with a slight prevalence in men. The most common anatomical sites are the rectum and the proximal colon. Clinical signs and common dia-gnostic methods cannot clearly distinguish SCC from adenocarcinoma. METHODS: In this case report, we present a case of a 68-year-old patient with SCC of the cecum and colon ascendens, who was treated with resection and systemic gemcitabine- and cisplatin-based chemotherapy. RESULTS: A 68-year-old patient underwent right-sided hemicolectomy for cecal and colon ascendens tumor, histologically poorly differentiated epidermoid carcinoma, grade 3 with an initial stage of pT4aN1aM0. Due to local recurrence at the resection site with suspected infiltration of straight and oblique abdominal muscles, he was treated with systemic gemcitabine and cisplatin based chemotherapy with partial remission. Subsequently, the postchemotherapeutic residual tumor was radically resected, achieving complete remission of the disease, which persists for 10 months after the surgery. CONCLUSION: The case emphasizes the need for a multidisciplinary treatment approach of this rare disease. Early surgery plays a key role. Although the standard chemotherapy regimen is not well defined, the use of a combination of cisplatin and gemcitabine resulted in partial remission in our patient, which in turn allowed a radical resection of the relapse and subsequently achieved complete remission of the disease.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/cirurgia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Idoso , Carcinoma de Células Escamosas/patologia , Cisplatino/administração & dosagem , Neoplasias do Colo/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Humanos , Masculino , GencitabinaRESUMO
Hypertension-induced renal injury is characterized by structural kidney alterations and function deterioration. Therapeutics for kidney protection are limited, thus novel renoprotectives in hypertension are being continuously sought out. Ivabradine, an inhibitor of the If current in the sinoatrial node reducing heart rate (HR), was shown to be of benefit in various cardiovascular pathologies. Yet, data regarding potential renoprotection by ivabradine in hypertension are sparse. Thirty-six adult male Wistar rats were divided into non-diseased controls and rats with NG-nitro-L-arginine methyl ester (L-NAME)-induced hypertension to assess ivabradine's site-specific effect on kidney fibrosis. After 4 weeks of treatment, L-NAME increased the average systolic blood pressure (SBP) (by 27%), decreased glomerular density (by 28%) and increased glomerular tuft area (by 44%). Moreover, L-NAME induced glomerular, tubulointerstitial, and vascular/perivascular fibrosis by enhancing type I collagen volume (16-, 19- and 25-fold, respectively). L-NAME also increased the glomerular type IV collagen volume and the tubular injury score (3- and 8-fold, respectively). Ivabradine decreased average SBP and HR (by 8 and 12%, respectively), increased glomerular density (by 57%) and reduced glomerular tuft area (by 30%). Importantly, ivabradine decreased type I collagen volume at all three of the investigated sites (by 33, 38, and 72%, respectively) and enhanced vascular/perivascular type III collagen volume (by 67%). Furthermore, ivabradine decreased the glomerular type IV collagen volume and the tubular injury score (by 63 and 34%, respectively). We conclude that ivabradine attenuated the alterations of glomerular density and tuft area and modified renal fibrosis in a site-specific manner in L-NAME-hypertension. It is suggested that ivabradine may be renoprotective in hypertensive kidney disease.
RESUMO
BACKGROUND: Metastatic pancreatic carcinoma is an aggressive disease with adverse prognosis. Despite slight advances in chemotherapy, complete remission of the disease is extremely rare. CASE: In this article we present a case of a patient with initially metastatic pancreatic adenocarcinoma, associated with double heterozygous germline mutation in BRCA2 and CHEK2 genes, with the description of clinical, radiological and histomorphological characteristics of the disease as well as the dia-gnostic and therapeutic procedure. RESULTS: The patient with initially metastatic pancreatic adenocarcinoma with multiple liver involvement achieved complete remission following first-line FOLFIRINOX chemotherapy. The treatment lasted for 12 months but due to increased neurotoxicity since the 9th cycle, oxaliplatin was excluded from the regimen. Given the family history of several malignancies (prostate cancer, seminoma), genetic testing was performed, which confirmed heterozygous germline mutations in BRCA2 and CHEK2 genes. Since the treatment has been completed, the patient remains in complete remission at 30 months. CONCLUSION: Given the low incidence of complete remissions in patients with metastatic pancreatic cancer, the further therapeutic approach is not clearly established, an individual treatment is important. Universal genetic testing is recommended in patients with pancreatic cancer as it may affect the treatment strategy.
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Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Proteína BRCA2/genética , Quinase do Ponto de Checagem 2/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Genes BRCA2 , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oxaliplatina/uso terapêutico , Linhagem , Neoplasias PancreáticasRESUMO
PURPOSE: The aim of the present study was (i) to evaluate the safety and efficacy of aspiration thrombectomy in patients with M2 occlusions and (ii) to compare outcome of treatment of occlusion of different M2 segments. MATERIALS AND METHODS: Between March 2016 and June 2019, 82 patients with acute ischemic stroke and isolated M2 occlusions were treated in cerebrovascular stroke center with aspiration thrombectomy as the first-line treatment. Functional outcomes of patients with different types of M2 occlusions were statistically compared. Multivariable logistic regression analysis was performed to determine the factors associated with good clinical outcome. RESULTS: The mean age was 71.9 ± 13.4 years, 47.6% were men. Aspiration thrombectomy alone was utilized in 72.5% of patients, with 27.5% of patients being treated with a combination of aspiration thrombectomy and stent retriever. At the three-month follow-up, there was no statistically significant difference in functional outcome between different types of M2 occlusions (p = 0.662), however in the underpowered analysis because of the small sample size of patients, with good clinical outcome mRS 0-2 in 50% of all treated patients. Symptomatic intracranial hemorrhage was found in 6.1% of patients. Lower age (OR 0.932, 95% CI 0.878-0.988) and lower NIHSS score upon admission (OR 0.893, 95% CI 0.805-0.991) were independent predictors of good clinical outcome. CONCLUSION: Aspiration thrombectomy appeared to be a safe and effective first-line treatment option for patients with M2 occlusion, being the first-line option for almost three-quarters of patients.
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AVC Isquêmico/cirurgia , Artéria Cerebral Média , Trombectomia/métodos , Idoso , Angiografia Cerebral , Angiografia por Tomografia Computadorizada , Feminino , Humanos , AVC Isquêmico/diagnóstico por imagem , Masculino , Estudos RetrospectivosRESUMO
PURPOSE: To evaluate the patient and the neurointerventionalist radiation dose levels during endovascular treatment of acute ischemic stroke, and to analyze factors affecting doses. MATERIALS AND METHODS: From October 2017 to January 2019, we prospectively collected patient radiation data and neurointerventionalist data from real-time dosimetry from all consecutive thrombectomies. Multivariate analysis was performed to analyze patient total dose area product (DAP) and neurointerventionalist dose variability in terms of clinical characteristics and the technical parameters of thrombectomies. Local dose reference levels (RL) were derived as the 75th percentile of the patient dose distributions. RESULTS: A total of 179 patients were treated during the study period and included in this study. Local dose RL for thrombectomy was derived for total DAP to 34 Gy cm2, cumulative air kerma of 242 mGy and fluoroscopy time of 12 min. The mean neurointerventionalist dose for thrombectomy was 7.7 ± 7.4 µSv. Height (P = 0.018), weight (P = 0.004), body mass index (P = 0.015), puncture to recanalisation (P < 0.001), fluoro time (P < 0.001), number of passes (P < 0.001), thrombolysis in cerebral infarction 2b/3 recanalisation (P = 0.034) and aspiration thrombectomy (P < 0.001) were independent factors affecting patient total DAP, whereas baseline National Institutes of Health Stroke Scale (P = 0.043), puncture to recanalisation (P = 0.003), fluoroscopy time (P = 0.009) and number of passes (P = 0.009) were factors affecting the neurointerventionalist dose. CONCLUSION: New reference patient doses lower than those in previously published studies were defined. However, the operator's doses were higher than those in the only available study reporting on operator's dose during cerebral interventions.
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Isquemia Encefálica/cirurgia , Procedimentos Endovasculares/métodos , Doses de Radiação , Radiografia Intervencionista/métodos , Acidente Vascular Cerebral/cirurgia , Trombectomia , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Feminino , Fluoroscopia , Humanos , Masculino , Estudos Prospectivos , Radiometria , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagemRESUMO
Sclerotic fibroma (storiform collagenoma) is a rare benign skin tumor. A solitary tumor, as well as multifocal lesions, are found either sporadically, or associated with Cowden syndrome. The tumor usually presents as clinically asymptomatic, slowly growing papule or nodule on the skin of the head, neck, and upper extremities. Microscopically the lesion is sharply demarcated, composed of hyalinized bands of collagen with low cellularity and a distinctive irregularly whorled or storiform pattern. We describe a case of a unique variant of this tumor in the scalp of a 33-year-old male. The tumor was microscopically composed of concentrically arranged collagen bundles with prevailing type III collagen, which resembled an enlarged Vater-Pacini corpuscle, with low density of CD34-positive and glucose transporter 1-negative spindle shaped cells. The specific microscopic appearance is suggestive of the term "Pacinian collagenoma" for this unique benign tumor.