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1.
Artículo en Inglés | MEDLINE | ID: mdl-38876974

RESUMEN

OBJECTIVES: Integrating clinical and histological parameters into prognostic scores may enhance the prediction of progression to kidney failure in anti-neutrophil cytoplasm antibodies-associated vasculitis (AAV). This study aimed to evaluate the prognostic performance of histological classifications and scoring systems for kidney survival in AAV. METHODS: This retrospective cohort study included 101 AAV patients with kidney involvement diagnosed by biopsy and followed for ≥12 months. The main outcome was the time to kidney failure. The prognostic performance of each histological and prognostic score was evaluated using Harrell's C statistic and Akaike's Information Criteria. RESULTS: Among the 101 patients, 37 progressed to kidney failure over a median follow-up of 75 months (IQR 39-123). The Harrell's C statistic was 0.702 (0.620-0.784), 0.606 (0.473-0.738), 0.801 (0.736-0.867), 0.782 (0.706-0.858), and 0.817 (0.749-0.885) for the EUVAS/Berden classification, Mayo Clinic Chronicity Score, Percentage of ANCA Crescentic Score (PACS), ANCA renal risk score (ARRS), and the improved ANCA kidney risk score (AKRiS), respectively. The AKRiS best discriminated the risk of kidney failure progression among subgroups. The AKRiS performance decreased with longer follow-up intervals. Adding the peak estimated glomerular filtration rate attained post-therapy improved the AKRiS performance at all follow-up intervals. Kidney relapses precipitated kidney failure in 71% of cases that progressed after the first year of follow-up. CONCLUSION: The novel AKRiS enhances the prediction of kidney failure in AAV with kidney involvement. As the prognostic yield of AKRiS decreases over time, a second calculation of AKRiS, including post-therapy kidney function, may improve its long-term performance.

2.
Int Arch Otorhinolaryngol ; 28(1): e122-e128, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38322437

RESUMEN

Introduction Peripheral hearing loss, besides causing inadequate auditory input, can lead to distortions in the tonotopic auditory map and reorganization of neural networks. Therefore, the processing of temporal aspects of a sound stimulus and, consequently, the effectiveness of human communication can be negatively impacted. Objective To test the temporal ordering and auditory resolution of people with mild and moderate sensorineural hearing loss and to compare them with the those of people with normal hearing. Methods A total of 19 right-handed individuals aged 16 to 59 years with mild to moderate postlingually acquired symmetric bilateral sensorineural hearing loss participated in the study. They were submitted to frequency and duration pattern tests and a random gap detection test. Results The mean correct response rate in the frequency pattern test was of 66.3%, and, in the duration pattern test, 71.7%. The mean threshold in the random gap detection test was of 14.1 ms. A comparison with the criteria established for normal subjects without peripheral hearing loss revealed that more than half the subjects had abnormal results in the temporal ordering test, while a smaller fraction had reduced temporal resolution. Conclusions The performance of the subjects with acquired sensorineural hearing loss was poorer than that of the participants without peripheral hearing loss. Their results on the temporal ordering test were also poorer than in the temporal resolution test, demonstrating the importance of analyzing both these auditory skills in people with peripheral hearing loss.

3.
Sci Rep ; 14(1): 4314, 2024 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-38383742

RESUMEN

The Brazilian Organization for Crohn's Disease and Colitis (GEDIIB) established a national registry of inflammatory bowel disease (IBD). The aim of the study was to identify clinical factors associated with disease severity in IBD patients in Brazil. A population-based risk model aimed at stratifying the severity of IBD based on previous hospitalization, use of biologics, and need for surgery for ulcerative colitis (UC) and Crohn's Disease (CD) and on previous complications for CD. A total of 1179 patients (34.4 ± 14.7y; females 59%) were included: 46.6% with UC, 44.2% with CD, and 0.9% with unclassified IBD (IBD-U). The time from the beginning of the symptoms to diagnosis was 3.85y. In CD, 41.2% of patients presented with ileocolic disease, 32% inflammatory behavior, and 15.5% perianal disease. In UC, 46.3% presented with extensive colitis. Regarding treatment, 68.1%, 67%, and 47.6% received biological therapy, salicylates and immunosuppressors, respectively. Severe disease was associated with the presence of extensive colitis, EIM, male, comorbidities, and familial history of colorectal cancer in patients with UC. The presence of Montreal B2 and B3 behaviors, colonic location, and EIM were associated with CD severity. In conclusion, disease severity was associated with younger age, greater disease extent, and the presence of rheumatic EIM.


Asunto(s)
Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Femenino , Humanos , Masculino , Enfermedad de Crohn/diagnóstico , Brasil/epidemiología , Datos de Salud Recolectados Rutinariamente , Enfermedades Inflamatorias del Intestino/epidemiología , Colitis Ulcerosa/epidemiología , Colitis Ulcerosa/diagnóstico
4.
Artículo en Inglés | MEDLINE | ID: mdl-37930870

RESUMEN

OBJECTIVES: To evaluate the effect of antimalarial drugs in response to therapy, incidence of LN flares, and progression of kidney disease in a large LN cohort. METHODS: We retrospectively studied 424 biopsy-proven LN patients followed for >3 years. We obtained demographic, clinical, laboratory, histopathological, and treatment variables. Antimalarial use was approached as 1) users versus no users, 2) according to prevalent vs incident use regarding the LN flare, and 3) according to the type of antimalarial. All outcomes were evaluated by time-to-event analyses. Adjusted hazard ratios were obtained by Cox regression. RESULTS: The cohort included 424 patients, median age of 29 years (IQR 23-37), 96% female, with a median eGFR of 81 ml/min/1.73m2 (IQR 48-118) and proteinuria of 3.4 g/g (IQR 1.9-5.5). Antimalarial use was associated with higher complete response (aHR 1.57, 1.08-2.27), lower incidence of kidney flares (aHR 0.63, 0.43-0.92), and lower progression to kidney failure (aHR 0.37, 0.23-0.53). The effect on these outcomes was modified by the presentation eGFR, histological class, and/or concomitant initial immunosuppressor. These protective effects were observed in patients with prevalent or incident use regarding the LN flare and patients using hydroxychloroquine. The incidence of toxic retinopathy was 1.7%, 5.7%, and 8.8% by 3-, 5-, and 7 years of continued antimalarial use. CONCLUSION: The use of antimalarial drugs is associated with increased response to therapy, lower incidence of kidney flares, and lower progression to kidney failure in LN patients. Conversely, this population is at high risk of toxic maculopathy, and yearly ophthalmologic examination is recommended.

5.
Crohns Colitis 360 ; 5(4): otad053, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37859629

RESUMEN

Background: In real-world experience, the number of patients using vedolizumab as first-line biological therapy was low. We aimed to evaluate the effectiveness and safety of vedolizumab in mild-to-moderate Crohn's disease (CD) biologic-naïve patients. Methods: We performed a retrospective multicentric cohort study with patients who had clinical activity scores (Harvey-Bradshaw Index [HBI]) measured at baseline and weeks 12, 26, 52, as well as at the last follow-up. Clinical response was defined as a reduction ≥3 in HBI, whereas clinical remission as HBI ≤4. Mucosal healing was defined as the complete absence of ulcers in control colonoscopies. Kaplan-Meier survival analysis was used to assess the persistence with vedolizumab. Results: From a total of 66 patients, 53% (35/66) reached clinical remission at week 12. This percentage increased to 69.7% (46/66) at week 26, and 78.8% (52/66) at week 52. Mucosal healing was achieved in 62.3% (33/53) of patients. Vedolizumab was well tolerated, and most adverse events were minor. During vedolizumab treatment, 3/66 patients underwent surgery. Conclusions: This study demonstrates the effectiveness and safety of vedolizumab as a first-line biological agent in patients with mild-to-moderate CD.

6.
Virol J ; 20(1): 204, 2023 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-37661255

RESUMEN

BACKGROUND: Dengue virus (DENV) is a Flaviviridae member classified into four antigenically distinct serotypes (DENV 1, 2, 3, and 4) and further subdivided genotypes. DENV3 is subdivided into four or five genotypes, depending on the classification adopted. Despite their high genetic proximity, as revealed by phylogenetic complete polyprotein analysis, DENV3 MG-20 and DENV3 PV_BR showed different neurovirulence in mice models. Our group identified six amino acid mutations in protein E, including the E62K and E123Q, which may affect interactions of hydrophobic clusters on domain II, thus leading to the observed differences in the studied viruses. METHODS: Human glioblastoma cells (U251) derived from a malignant glioblastoma tumor by explant technique were infected by the DENV3 GIL1 isolates DENV3 MG-20 and DENV3 PV_BR and analyzed by plaque assays and titration, optical, immunofluorescence, and transmission electronic microscopy. RESULTS: The two isolates showed different cytopathic effects (CPE) and fusogenic patterns, further confirmed by indirect immunofluorescence. Transmission electron microscopy revealed intense cytopathic effects in DENV3 MG-20 infected U251 cells, displaying endoplasmic reticulum hypertrophy and turgid vesicles with proteins and multiple viruses, distinct from DENV3 PV_BR infected cells. It is hypothesized that the different amino acids in the DENV3 MG-20 isolate are related to an increased membrane fusion ability in viral infection, thus facilitating immune system evasion and increased chances of central nervous system cell infection. CONCLUSION: These results emphasize the biological differences between the isolates, which could be a critical factor in host-virus interaction and severe dengue development. Our study presents comparative results of highly similar isolates with the potential to generate more subsidies for a deeper understanding of the DENV pathogenesis. The neurotropism of the isolate DENV3 MG-20 (belonging to the DENV3 GI L1 genotype) showing infection of nervous system cells (U251) could contribute to understanding neurological dengue disease.


Asunto(s)
Virus del Dengue , Glioblastoma , Humanos , Animales , Ratones , Virus del Dengue/genética , Filogenia , Aminoácidos , Genotipo , Células Gigantes
7.
J Virol Methods ; 317: 114742, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37116586

RESUMEN

The pandemic caused by COVID-19 and the emergence of new variants of SARS-CoV-2 have generated clinical and epidemiological impacts on a global scale. The use of strategies for monitoring viral circulation and identifying mutations in genomic regions involved in host interaction are important measures to mitigate viral dissemination and reduce its likely complications on population health. In this context, the objective of this work was to explore the potential of high-resolution melting (HRM) analysis combined with one-step real-time reverse transcription PCR in a closed-tube system, as a fast and convenient method of screening for SARS-CoV-2 mutations with possible implications on host-pathogen interactions. The HRM analyses allowed the distinction of the Gamma, Zeta, Alpha, Delta, and Omicron variants against the predecessors (B.1.1.28, B.1.1.33) of occurrence in Brazil. It is concluded that the molecular tool standardized here has the potential to optimize the genomic surveillance of SARS-CoV-2, and could be adapted for genomic surveillance of other pathogens, due to its ability to detect, prior to sequencing, samples suggestive of new variants, selecting them more assertively and earlier for whole genome sequencing when compared to random screening.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Genómica , Reacción en Cadena en Tiempo Real de la Polimerasa , Mutación
8.
Arq Gastroenterol ; 59(suppl 1): 51-84, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36995889

RESUMEN

BACKGROUND: Inflammatory bowel diseases are immune-mediated disorders that include Crohn's disease (CD) and ulcerative colitis (UC). UC is a progressive disease that affects the colorectal mucosa causing debilitating symptoms leading to high morbidity and work disability. As a consequence of chronic colonic inflammation, UC is also associated with an increased risk of colorectal cancer. OBJECTIVE: This consensus aims to provide guidance on the most effective medical management of adult patients with UC. METHODS: A consensus statement was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's Disease and Colitis [GEDIIB]). A systematic review including the most recent evidence was conducted to support the recommendations and statements. All recommendations/statements were endorsed using a modified Delphi Panel by the stakeholders/experts in inflammatory bowel disease with at least 80% or greater consensus. RESULTS AND CONCLUSION: The medical recommendations (pharmacological and non-pharmacological) were mapped according to the stage of treatment and severity of the disease onto three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus targeted general practitioners, gastroenterologists and surgeons who manage patients with UC, and supports decision-making processes by health insurance companies, regulatory agencies, health institutional leaders, and administrators.


Asunto(s)
Colitis Ulcerosa , Neoplasias Colorrectales , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Humanos , Adulto , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/terapia , Enfermedad de Crohn/diagnóstico , Brasil , Enfermedades Inflamatorias del Intestino/complicaciones , Inflamación , Neoplasias Colorrectales/complicaciones
9.
Arq Gastroenterol ; 59(suppl 1): 20-50, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36995888

RESUMEN

BACKGROUND: Inflammatory bowel disease (IBD) is an immune-mediated disorder that includes Crohn's disease (CD) and ulcerative colitis. CD is characterized by a transmural intestinal involvement from the mouth to the anus with recurrent and remitting symptoms that can lead to progressive bowel damage and disability over time. OBJECTIVE: To guide the safest and effective medical treatments of adults with CD. METHODS: This consensus was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's disease and Colitis (GEDIIB)). A systematic review of the most recent evidence was conducted to support the recommendations/statements. All included recommendations and statements were endorsed in a modified Delphi panel by the stakeholders and experts in IBD with an agreement of at least 80% or greater consensus rate. RESULTS AND CONCLUSION: The medical recommendations (pharmacological and non-pharmacological interventions) were mapped according to the stage of treatment and severity of the disease in three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus is targeted towards general practitioners, gastroenterologists, and surgeons interested in treating and managing adults with CD and supports the decision-making of health insurance companies, regulatory agencies, and health institutional leaders or administrators.


Asunto(s)
Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Adulto , Humanos , Enfermedad de Crohn/terapia , Enfermedad de Crohn/tratamiento farmacológico , Consenso , Brasil , Colitis Ulcerosa/tratamiento farmacológico
10.
Crohns Colitis 360 ; 5(1): otac050, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36777366

RESUMEN

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease which affects the colorectal mucosa with a relapsing-remitting pattern. The therapeutic options currently available for the medical management of UC include many options. Tofacitinib is an oral small molecule, Janus kinase (JAK) inhibitor, more selective for JAK1 and JAK3, which reduces the inflammatory process involved in the pathogenesis of UC. Methods: Retrospective observational multicentric study of patients with UC who used tofacitinib in any phase of their treatment. Clinical remission and response (according to Mayo score), mucosal healing, primary and secondary loss of response, discontinuation of the drug with possible causes, and the need for dose optimization or switching to biologicals, need for surgery and adverse events were evaluated. Results: From a total of 56 included patients, clinical remission was observed in 43.6% at week 12, 54.5% at week 26, 57.9% at week 52, and 40% at the last follow-up visit. Clinical response was observed in 71.4%, 81.8%, 89.5%, and 61.8% at the same time periods, respectively. Mucosal healing rates were 50% and 17.8% needed colectomy. Conclusions: Tofacitinib was effective in induction and maintenance of clinical response and remission rates, compatible to other international real-word studies and meta-analyses.

11.
Acta Otolaryngol ; 143(1): 31-36, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36661392

RESUMEN

BACKGROUND: Zika virus (ZIKV) infection can result in hearing loss in babies, consequently, audiological monitoring is necessary. AIMS: This study aimed to evaluate the frequency of hearing impairment in neonates and children exposed to ZIKV during the intrauterine period. MATERIALS AND METHODS: A cohort of 30 children born to mothers infected with ZIKV during pregnancy (March 2016-January 2017) underwent repeated hearing assessments performed 48 h after birth. Universal Newborn Hearing Screening revealed normal results in all children at 6, 13, 24, and 36 months. Children were divided into two subgroups based on real-time polymerase chain reaction: RT-PCR(+) and RT-PCR(-). RESULTS: At 24 months, the cumulative incidence of hearing alteration was 57.1%. There was no significant difference in the detection of hearing alteration between RT-PCR(+) and (-) groups. None of the children had sensorineural hearing loss. CONCLUSIONS AND SIGNIFICANCE: None of the children had sensorineural hearing loss. Total incidence conductive type (per 1000 live births), RT-PCR ZIKV (-) 2.2, prevalence 20% and RT-PCR ZIKV 3.1, prevalence 35.7%.The incidence of hearing alteration was highest at 24 months of age (57.1%, n = 8; only conductive type).


Asunto(s)
Pérdida Auditiva Sensorineural , Complicaciones Infecciosas del Embarazo , Infección por el Virus Zika , Virus Zika , Lactante , Recién Nacido , Embarazo , Femenino , Humanos , Niño , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/epidemiología , Estudios Longitudinales , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/epidemiología , Estudios de Cohortes , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/epidemiología , Pérdida Auditiva Sensorineural/etiología , Audición
12.
AIDS Res Hum Retroviruses ; 39(1): 38-43, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36301928

RESUMEN

Medication adherence can be challenging for persons with difficulty swallowing tablets. We investigated the bioequivalence of a dissolved tablet when compared with that of a whole tablet of the fixed-dose combination elvitegravir (EVG)/cobicistat (COBI)/emtricitabine (FTC)/tenofovir (TFV) alafenamide fumarate (TAF). A within-subject fixed-order two-period open-label study was conducted in 12 HIV-negative research participants after obtaining informed consent. Participants took a single dose each of the whole tablet and dissolved tablet under direct observation, separated by a 14-day washout period. The dissolved tablet was prepared by adding one whole EVG/COBI/FTC/TAF tablet to 120 mL tap water and stirring. Both dosage types were taken with a standardized meal. Plasma samples were obtained for 72 h postdose. Plasma EVG, FTC, TAF, and TFV were analyzed with liquid chromatographic-tandem mass spectrometric methods. Peak plasma concentration (Cmax) and the area under the concentration-time curve extrapolated to infinity (AUC0-∞) were estimated using WinNonlin software (v.8.3). The primary outcome was bioequivalence consistent with FDA guidance using the 90% confidence interval or the geometric mean ratio. Of 12 participants, 7 were black (58%) and 5 were white (42%), 4 were women (33%), 8 were men (67%), and the mean age was 43.6 years (23-54). There were no complaints about taste with the dissolved tablet. Bioequivalence was established only for FTC. EVG Cmax and AUC0-∞ were higher by 18% and 12%, respectively, when taking the dissolved compared with the whole tablet. TAF AUC0-∞ and Cmax were both 8% lower, whereas TFV Cmax and AUC0-∞ were 8% and 5% lower, respectively, when taken after dissolution. EVG/COBI/FTC/TAF dissolved rapidly in water and had no unpleasant taste. Increases in EVG and decreases in TAF and TFV concentrations were observed when taking dissolved EVG/COBI/FTC/TAF. These changes were judged to be clinically insignificant. Dissolving EVG/COBI/FTC/TAF in water may be suitable for those with pill swallowing challenges. The trial was registered on (//clinicaltrials.gov NCT03717129).


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Adulto , Femenino , Humanos , Masculino , Adenina , Fármacos Anti-VIH/uso terapéutico , Cobicistat/uso terapéutico , Combinación de Medicamentos , Emtricitabina/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Comprimidos , Tenofovir/uso terapéutico , Equivalencia Terapéutica
13.
Sci Total Environ ; 864: 161025, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36584950

RESUMEN

The presence of microplastics (MPs) in marine environments has been extensively documented. However, studies of terrestrial species are scarce. Fecal samples (105) of lagomorphs were collected at sites with different levels of urbanization in the Baja California Chaparral and analyzed to quantify and characterize MPs found in the feces. The lagomorph species recorded in the study area are the desert cottontail rabbit (Sylvilagus audubonii), brush rabbit (Sylvilagus bachmani), and black-tailed jackrabbit (Lepus californicus), which play important roles in the food web of the chaparral ecosystem. Microplastics were identified using attenuated total reflectance Fourier transform infrared spectroscopy. Microplastics were detected in 49 % of the samples, with fibers being the dominant shape found (72 %). Most (75 %) of the MPs were <1 mm in size, with a mean length of 0.93 ± 0.99 mm (median 0.60 mm, range 0.02 - <5 mm). Polyamide was the dominant polymer (54 %), indicating that MPs are likely derived from textiles; polyethylene was also abundant (27 %). A difference was also observed in the abundance of MPs in feces from sites with different levels of urbanization, with the highest abundance in feces from the urban sites.


Asunto(s)
Lagomorpha , Contaminantes Químicos del Agua , Animales , Conejos , Microplásticos , Plásticos , Ecosistema , Urbanización , México , Contaminantes Químicos del Agua/análisis , Heces/química , Monitoreo del Ambiente
14.
Arq Gastroenterol ; 59(4): 462-477, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36515338

RESUMEN

Crohn's disease (CD) is a relapse-remitting inflammatory bowel disease that can affect any part of the digestive system. This heterogeneous disease has multiple factors that contribute to an abnormal immune response to intestinal microorganisms. Treatment is based on the use of anti-inflammatories, corticosteroids, immunosuppressants and biologic biologic agents either alone or in combination. Surgical treatment is usual and, ten years after diagnosis, more than 80% of patients report having undergone surgical procedures related to the disease. Unfortunately, none of the treatments described offer a cure, and many cases become refractory or without therapeutic options. In this scenario, hematopoietic stem cell transplantation has been suggested because clinical remission was obtained in patients who had CD associated with malignant hematological diseases and an alternative since the first reports in 2010. In this report, the Transplantation Committee of the Brazilian Group for the Study of Inflammatory Bowel Diseases reviews the history and results of the procedure in patients with CD, detailing and discussing the various relevant points that permeate hematopoietic stem cell transplantation and cell therapy in this disease.


Asunto(s)
Enfermedad de Crohn , Trasplante de Células Madre Hematopoyéticas , Enfermedades Inflamatorias del Intestino , Humanos , Enfermedad de Crohn/cirugía , Enfermedad de Crohn/complicaciones , Trasplante de Células Madre Hematopoyéticas/métodos , Inmunosupresores/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico
15.
Arq. gastroenterol ; 59(4): 462-477, Out,-Dec. 2022. tab
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1420214

RESUMEN

ABSTRACT Crohn's disease (CD) is a relapse-remitting inflammatory bowel disease that can affect any part of the digestive system. This heterogeneous disease has multiple factors that contribute to an abnormal immune response to intestinal microorganisms. Treatment is based on the use of anti-inflammatories, corticosteroids, immunosuppressants and biologic biologic agents either alone or in combination. Surgical treatment is usual and, ten years after diagnosis, more than 80% of patients report having undergone surgical procedures related to the disease. Unfortunately, none of the treatments described offer a cure, and many cases become refractory or without therapeutic options. In this scenario, hematopoietic stem cell transplantation has been suggested because clinical remission was obtained in patients who had CD associated with malignant hematological diseases and an alternative since the first reports in 2010. In this report, the Transplantation Committee of the Brazilian Group for the Study of Inflammatory Bowel Diseases reviews the history and results of the procedure in patients with CD, detailing and discussing the various relevant points that permeate hematopoietic stem cell transplantation and cell therapy in this disease.


RESUMO A doença de Crohn (DC) é uma doença inflamatória intestinal (DII) recidivante recorrente que pode afetar qualquer parte do sistema digestivo. É doença heterogênea e possui múltiplos fatores que contribuem para uma resposta imune anormal aos microrganismos intestinais. O tratamento baseia-se no uso de anti-inflamatórios, corticosteroides e imunossupressores e imunobiológicos que são utilizados isoladamente ou em combinação. O tratamento cirúrgico é frequente e 10 anos após o diagnóstico, mais de 50% dos pacientes relatam terem sido submetidos a procedimentos cirúrgicos relacionados à doença. Infelizmente, nenhum dos tratamentos descritos oferece cura, e inúmeros casos tornam-se refratários ou sem opções terapêuticas. Nesse cenário, o transplante de células-tronco hematopoéticas (TCTH) em decorrência da remissão clínica de pacientes que apresentavam DC associada a doenças hematológicas malignas, passou a ser alternativa desde os primeiros resultados em 2010. Neste relato, a Comissão de Transplantes do Grupo Brasileiro de Estudo das Doenças Inflamatórias Intestinais revisa a história e os resultados do procedimento em pacientes com DC, detalhando e discutindo os diversos pontos relevantes que permeiam o TCTH e a terapia celular no tratamento da moléstia.

16.
Int J Mol Sci ; 23(22)2022 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-36430237

RESUMEN

Group VIA phospholipase A2 (iPLA2ß) play diverse biological functions in epithelial cells and macrophages. Global deletion in iPLA2ß-null (KO) mice leads to protection against hepatic steatosis in non-alcoholic fatty liver disease, in part, due to the replenishment of the loss of hepatocellular phospholipids. As the loss of phospholipids also occurs in hepatocellular carcinoma (HCC), we hypothesized that global deletion in KO mice may lead to protection against HCC. Here, HCC induced by diethylnitrosamine (DEN) was chosen because DEN causes direct injury to the hepatocytes. Male wild-type (WT) and KO mice at 3-5 weeks of age (12-13 mice/group) were subjected to a single intraperitoneal treatment with 10 mg/kg DEN, and mice were killed 12 months later. Analyses of histology, plasma cytokines, and gene expression were performed. Due to the low-dose DEN used, we observed a liver nodule in 3 of 13 WT and 2 of 12 KO mice. Only one DEN-treated WT mouse was confirmed to have HCC. DEN-treated KO mice did not show any HCC but showed suppressed hepatic expression of cell-cycle cyclinD2 and BCL2 as well as inflammatory markers IL-1ß, IL-10, and VCAM-1. Notably, DEN-treated KO mice showed increased hepatic necrosis and elevated levels of plasma lactate dehydrogenase suggesting an exacerbation of liver injury. Thus, global iPLA2ß deficiency in DEN-treated mice rendered HCC protection by an induction of cell-cycle arrest. Our results suggest the role of iPLA2ß inhibition in HCC treatment.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Masculino , Ratones , Animales , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Dietilnitrosamina/toxicidad , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Ratones Endogámicos C57BL , Ratones Noqueados , Puntos de Control del Ciclo Celular
17.
Clinics (Sao Paulo) ; 77: 100118, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36202032

RESUMEN

INTRODUCTION: Traumatic brain injury can impair the central auditory pathways and auditory cortex. Hence, individuals who suffered a traumatic brain injury may be at risk of central auditory processing disorders, which can be identified with behavioral tests that assess central auditory function. OBJECTIVE: To characterize and compare the performance of children and adolescents with and without a history of traumatic brain injury in behavioral tests that assess central auditory processing. METHOD: The sample comprised 8- to 18-year-old individuals of both sexes who suffered moderate or severe closed traumatic brain injury 3 to 24 months before their participation in the study and whose hearing thresholds were normal. These individuals were matched for sex and age with other subjects without a history of traumatic brain injury and submitted to behavioral assessment of the central auditory processing with special tests to assess hearing skills (namely, auditory closure, figure-ground, and temporal processing), selected according to their chronological age and response-ability. RESULTS: The study group performed statistically worse than the comparison group in auditory closure, figure-ground in verbal dichotic listening, and temporal ordering. The central auditory processing tests with abnormal results in the comparison group were different from those in the study group. CONCLUSION: Central auditory processing disorders were identified in all subjects of the study group, especially involving auditory closure and temporal processing skills, in comparison with subjects without a history of traumatic brain injury.


Asunto(s)
Trastornos de la Percepción Auditiva , Lesiones Traumáticas del Encéfalo , Adolescente , Vías Auditivas , Percepción Auditiva , Trastornos de la Percepción Auditiva/etiología , Lesiones Traumáticas del Encéfalo/complicaciones , Niño , Femenino , Pruebas Auditivas , Humanos , Masculino
18.
Sci Rep ; 12(1): 17976, 2022 10 26.
Artículo en Inglés | MEDLINE | ID: mdl-36289252

RESUMEN

Viscosupplementation (VS) of the temporomandibular joint (TMJ) aims to treat temporomandibular dysfunction (TMD) by stimulating synovial cells to improve intracapsular lubrication. The purpose of the present study was to assess a VS protocol planned with the aid of cone-beam computed tomography (CBCT) and checked by ultrasonography (US). The study was carried out in 3 stages. The first was to check the correspondence between the proposed facial reference points and the osseous components of the joint by means of CBCT. In the second stage, the upper and lower compartments of 20 TMJs of fresh frozen cadavers were injected with coloured liquids, and the accuracy of the technique was confirmed by dissecting the anatomical specimens. The third stage consisted of VS in 10 patients (20 TMJs), with real-time verification of the location of the needle tip by means of ultrasonography. CBCT confirmed the correct locations of the marked points used in the proposed VS protocol. The dissections showed that 13 of the 14 injections effectively reached the upper and lower compartments. The location of the needle tip was effectively verified by ultrasonography, confirming the correct access to both compartments. The proposed protocol was effective for accessing the upper and lower compartments of the TMJ. The evaluated protocol proved to be accurate, safe and clinically reproducible means of VS in the upper and lower compartments of the TMJ.


Asunto(s)
Trastornos de la Articulación Temporomandibular , Viscosuplementación , Humanos , Trastornos de la Articulación Temporomandibular/diagnóstico por imagen , Trastornos de la Articulación Temporomandibular/tratamiento farmacológico , Articulación Temporomandibular/diagnóstico por imagen , Tomografía Computarizada de Haz Cónico/métodos , Ultrasonografía
19.
Audiol Res ; 12(5): 527-538, 2022 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-36285910

RESUMEN

OBJECTIVES: To characterize the results of the Short Form Health Survey-36 (SF-36), Abbreviated Profile of Hearing Aid Benefit (APHAB), and the Hearing Handicap Inventory for Adults (HHIA) questionnaires in individuals with mild to moderate sensorineural hearing loss and compare them with brainstem auditory evoked potentials (BAEPs). METHODS: There were 26 individuals with mild to moderate bilateral symmetrical sensorineural hearing loss who participated in the study. They were aged between 13 and 59 years old, right-hand preference, of both sexes, and were assigned to one of two groups according to the result of a BAEP test: normal (n = 16) or altered (n = 10). All subjects underwent a brief, cognitive screening battery and answered the SF-36, APHAB, and HHIA self-assessment questionnaires. For analysis of results, descriptive measures and inferential analysis were used. RESULTS: On the SF-36 questionnaire, scores below 80 points were found in both groups, signifying minimal impact in the domains of pain, general health, vitality, and mental health compared to the other domains. The results of the APHAB questionnaire showed worse scores on the environmental noise subscale, and evaluation with the HHIA revealed a perception of severe restriction in participation in daily life activities. In a comparison between the groups, normal or abnormal BAEPs, no significant differences were found for any of the questionnaires. CONCLUSIONS: The results of the self-assessment questionnaires indicate that individuals with hearing loss can experience reduced quality of life, with limitations and restrictions for participation in daily living. The use of BAEPs as a criterion for dividing the groups was not effective in isolating the central component in the results of the self-assessment questionnaires.

20.
São Paulo med. j ; 140(5): 636-641, Sept.-Oct. 2022. tab
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1410208

RESUMEN

ABSTRACT BACKGROUND: Maritime transportation is an activity of vital importance for societies. The Mar Grande-Salvador crossing is an intercity waterway transport line in Brazil that transports 3,500 passengers/day, including residents and tourists. In 2017, an accident on this crossing was considered to be the biggest maritime tragedy in Bahia in the last decade. OBJECTIVE: To describe the clinical and epidemiology characteristics of victims of this maritime accident, with analysis on bodily injuries, causes of death and means/instruments that caused the fatal injuries. DESIGN AND SETTING: Case-series study at the Forensic Medical Institute of Bahia, Brazil. METHODS: Reports on 73 victims who were examined for bodily injury or were necropsied by the Forensic Medical Institute were analyzed. This study was approved by the institution's Research Ethics Committee (protocol 04012218.1.0000.5032). RESULTS: The victims' mean age was 33.0 years [95% confidence interval, CI, 26.3-47.0]. The mean age of those who died was 43.0 years [95% CI, 30.5-53.5]. Bodily injuries were found in 74% of the victims. The most frequent bodily injuries were ecchymoses among females (69.7%) and abrasions among males (76.2%). Blunt instruments produced most bodily injuries (85.2%). Among the victims who died, 68.4% were female. Mechanical asphyxiation through drowning was the leading cause of death (89.4%). The overall lethality rate was 26%, and this was higher among females (28.2%). CONCLUSION: Women were the main victims of this maritime accident. Bodily injuries occurred more frequently than death, but these injuries proved to be quite significant, thus demonstrating the importance of measures to improve the safety of navigation.

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