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1.
Brain ; 147(5): 1653-1666, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38380699

RESUMO

GRIN-related disorders are rare developmental encephalopathies with variable manifestations and limited therapeutic options. Here, we present the first non-randomized, open-label, single-arm trial (NCT04646447) designed to evaluate the tolerability and efficacy of L-serine in children with GRIN genetic variants leading to loss-of-function. In this phase 2A trial, patients aged 2-18 years with GRIN loss-of-function pathogenic variants received L-serine for 52 weeks. Primary end points included safety and efficacy by measuring changes in the Vineland Adaptive Behavior Scales, Bayley Scales, age-appropriate Wechsler Scales, Gross Motor Function-88, Sleep Disturbance Scale for Children, Pediatric Quality of Life Inventory, Child Behavior Checklist and the Caregiver-Teacher Report Form following 12 months of treatment. Secondary outcomes included seizure frequency and intensity reduction and EEG improvement. Assessments were performed 3 months and 1 day before starting treatment and 1, 3, 6 and 12 months after beginning the supplement. Twenty-four participants were enrolled (13 males/11 females, mean age 9.8 years, SD 4.8), 23 of whom completed the study. Patients had GRIN2B, GRIN1 and GRIN2A variants (12, 6 and 5 cases, respectively). Their clinical phenotypes showed 91% had intellectual disability (61% severe), 83% had behavioural problems, 78% had movement disorders and 58% had epilepsy. Based on the Vineland Adaptive Behavior Composite standard scores, nine children were classified as mildly impaired (cut-off score > 55), whereas 14 were assigned to the clinically severe group. An improvement was detected in the Daily Living Skills domain (P = 0035) from the Vineland Scales within the mild group. Expressive (P = 0.005), Personal (P = 0.003), Community (P = 0.009), Interpersonal (P = 0.005) and Fine Motor (P = 0.031) subdomains improved for the whole cohort, although improvement was mostly found in the mild group. The Growth Scale Values in the Cognitive subdomain of the Bayley-III Scale showed a significant improvement in the severe group (P = 0.016), with a mean increase of 21.6 points. L-serine treatment was associated with significant improvement in the median Gross Motor Function-88 total score (P = 0.002) and the mean Pediatric Quality of Life total score (P = 0.00068), regardless of severity. L-serine normalized the EEG pattern in five children and the frequency of seizures in one clinically affected child. One patient discontinued treatment due to irritability and insomnia. The trial provides evidence that L-serine is a safe treatment for children with GRIN loss-of-function variants, having the potential to improve adaptive behaviour, motor function and quality of life, with a better response to the treatment in mild phenotypes.


Assuntos
Receptores de N-Metil-D-Aspartato , Serina , Humanos , Feminino , Masculino , Criança , Pré-Escolar , Adolescente , Serina/uso terapêutico , Serina/genética , Receptores de N-Metil-D-Aspartato/genética , Encefalopatias/genética , Encefalopatias/tratamento farmacológico , Resultado do Tratamento , Qualidade de Vida
2.
Fish Shellfish Immunol ; 151: 109742, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38960109

RESUMO

Rainbow trout is an important fish species for Peruvian artisanal aquaculture, comprising over 60 % of the total aquaculture production. However, their industry has been highly affected by several bacterial agents such as Yersinia ruckeri. This pathogen is the causative agent of Enteric Redmouth Disease, and causes high mortality in fingerlings and chronic infection in adult rainbow trout. To date, the immune response of rainbow trout against Y. ruckeri has been well studied in laboratory-controlled infection studies (i.e. intraperitoneal infection, bath immersion), however, the immune response during natural infection has not been explored. To address this, in this study, 35 clinically healthy O. mykiss without evidence of lesions or changes in behavior and 32 rainbow trout naturally infected by Y. ruckeri, were collected from semi-intensive fish farms located in the Central Highlands of Peru. To evaluate the effect on the immune response, RT-qPCR, western blotting, and ELISA were conducted using head kidney, spleen, and skin tissues to evaluate the relative gene expression and protein levels. Our results show a significant increase in the expression of the pro-inflammatory cytokines il1b, tnfa, and il6, as well as ifng in all three tissues, as well as increases in IL-1ß and IFN-γ protein levels. The endogenous pathway of antigen presentation showed to play a key role in defense against Y. ruckeri, due to the upregulation of mhc-I, tapasin, and b2m transcripts, and the significant increase of Tapasin protein levels in infected rainbow trout. None of the genes associated with the exogenous pathway of antigen presentation showed a significant increase in infected fish, suggesting that this pathway is not involved in the response against this intracellular pathogen. Finally, the transcripts of immunoglobulins IgM and IgT did not show a modulation, nor were the protein levels evaluated in this study.


Assuntos
Imunidade Adaptativa , Doenças dos Peixes , Imunidade Inata , Oncorhynchus mykiss , Yersiniose , Yersinia ruckeri , Animais , Oncorhynchus mykiss/imunologia , Yersinia ruckeri/fisiologia , Yersiniose/veterinária , Yersiniose/imunologia , Doenças dos Peixes/imunologia , Imunidade Inata/genética , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Peru
3.
Gastroenterol Hepatol ; 46(10): 764-773, 2023 Dec.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-36731726

RESUMO

BACKGROUND: Chronic hepatitis E virus (HEV) in persons with immune impairment has a progressive course leading to a rapid progression to liver cirrhosis. However, prospective data on chronic HEV is scarce. The aim of this study was to determine the prevalence and risk factors for chronic HEV infection in subjects with immune dysfunction and elevated liver enzymes. PATIENTS AND METHODS: CHES is a multicenter prospective study that included adults with elevated transaminases values for at least 6 months and any of these conditions: transplant recipients, HIV infection, haemodialysis, liver cirrhosis, and immunosuppressant therapy. Anti-HEV IgG/IgM (Wantai ELISA) and HEV-RNA by an automated highly sensitive assay (Roche diagnostics) were performed in all subjects. In addition, all participants answered an epidemiological survey. RESULTS: Three hundred and eighty-one patients were included: 131 transplant recipients, 115 cirrhosis, 51 HIV-infected subjects, 87 on immunosuppressants, 4 hemodialysis. Overall, 210 subjects were on immunosuppressants. Anti-HEV IgG was found in 94 (25.6%) subjects with similar rates regardless of the cause for immune impairment. HEV-RNA was positive in 6 (1.6%), all of them transplant recipients, yielding a rate of chronic HEV of 5.8% among solid-organ recipients. In the transplant population, only therapy with mTOR inhibitors was independently associated with risk of chronic HEV, whereas also ALT values impacted in the general model. CONCLUSIONS: Despite previous abnormal transaminases values, chronic HEV was only observed among solid-organ recipients. In this population, the rate of chronic HEV was 5.8% and only therapy with mTOR inhibitors was independently associated with chronic hepatitis E.


Assuntos
Hepatite E , Imunossupressores , Inibidores de MTOR , Adulto , Humanos , Anticorpos Anti-Hepatite/uso terapêutico , Hepatite E/epidemiologia , Hepatite Crônica/epidemiologia , Infecções por HIV , Imunoglobulina G , Imunossupressores/efeitos adversos , Cirrose Hepática/complicações , Inibidores de MTOR/efeitos adversos , Inibidores de MTOR/uso terapêutico , Estudos Prospectivos , Fatores de Risco , RNA Viral/análise , Transaminases
4.
Breast Cancer Res Treat ; 194(2): 327-335, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35699853

RESUMO

PURPOSE: Post-mastectomy breast reconstruction (PMBR) is an important component of breast cancer treatment, but disparities relative to insurance status persist despite legislation targeting the issue. We aimed to study this relationship in a large health system combining a safety-net hospital and a private academic center. METHODS: Data were collected on all patients who underwent mastectomy for breast cancer from 2011 to 2019 in a private academic center and an adjacent public safety-net hospital served by the same surgical teams. Multivariable logistic regression was used to assess the effect of insurance status on PMBR, controlling for covariates that included socioeconomic, demographic, and clinical factors. RESULTS: Of 1554 patients undergoing mastectomy for breast cancer, 753 (48.5%) underwent PMBR, of which 592 (79.9%) were privately insured, 50 (6.7%) Medicare, 68 (9.2%) Medicaid, and 31 (4.2%) uninsured. Multivariable logistic regression showed a significantly higher likelihood of not undergoing PMBR for uninsured (OR 6.0, 95% CI 3.7-9.8; p < 0.0001), Medicare (OR 1.9, (95% CI 1.2-3.0; p = 0.006), and Medicaid (OR 1.5, 95% CI 1.0-2.3; p = 0.04) patients compared with privately insured patients. Age, stage, race and ethnicity, and hospital type confounded this relationship. CONCLUSION: Patients without health insurance have dramatically reduced access to PMBR compared to those with private insurance. Expanding access to this important procedure is essential to achieve greater health equity for breast cancer patients.


Assuntos
Neoplasias da Mama , Mamoplastia , Idoso , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/cirurgia , Feminino , Disparidades em Assistência à Saúde , Humanos , Cobertura do Seguro , Seguro Saúde , Mastectomia , Medicaid , Medicare , Estados Unidos/epidemiologia
5.
BMC Med ; 20(1): 129, 2022 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-35351135

RESUMO

BACKGROUND: SARS-CoV-2 infection portends a broad range of outcomes, from a majority of asymptomatic cases to a lethal disease. Robust correlates of severe COVID-19 include old age, male sex, poverty, and co-morbidities such as obesity, diabetes, and cardiovascular disease. A precise knowledge of the molecular and biological mechanisms that may explain the association of severe disease with male sex is still lacking. Here, we analyzed the relationship of serum testosterone levels and the immune cell skewing with disease severity in male COVID-19 patients. METHODS: Biochemical and hematological parameters of admission samples in 497 hospitalized male and female COVID-19 patients, analyzed for associations with outcome and sex. Longitudinal (in-hospital course) analyses of a subcohort of 114 male patients were analyzed for associations with outcome. Longitudinal analyses of immune populations by flow cytometry in 24 male patients were studied for associations with outcome. RESULTS: We have found quantitative differences in biochemical predictors of disease outcome in male vs. female patients. Longitudinal analyses in a subcohort of male COVID-19 patients identified serum testosterone trajectories as the strongest predictor of survival (AUC of ROC = 92.8%, p < 0.0001) in these patients among all biochemical parameters studied, including single-point admission serum testosterone values. In lethal cases, longitudinal determinations of serum luteinizing hormone (LH) and androstenedione levels did not follow physiological feedback patterns. Failure to reinstate physiological testosterone levels was associated with evidence of impaired T helper differentiation and augmented circulating classical monocytes. CONCLUSIONS: Recovery or failure to reinstate testosterone levels is strongly associated with survival or death, respectively, from COVID-19 in male patients. Our data suggest an early inhibition of the central LH-androgen biosynthesis axis in a majority of patients, followed by full recovery in survivors or a peripheral failure in lethal cases. These observations are suggestive of a significant role of testosterone status in the immune responses to COVID-19 and warrant future experimental explorations of mechanistic relationships between testosterone status and SARS-CoV-2 infection outcomes, with potential prophylactic or therapeutic implications.


Assuntos
COVID-19 , Androgênios , Feminino , Humanos , Hormônio Luteinizante/metabolismo , Masculino , SARS-CoV-2 , Testosterona
6.
Mult Scler ; 28(7): 1138-1145, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35475363

RESUMO

BACKGROUND: The effect of disease-modifying therapies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine response is unclear. OBJECTIVES: We aim to determine the immunological responses to SARS-CoV-2 in multiple sclerosis (MS) and anti-CD20-treated patients with other autoimmune diseases (AID). METHODS: Humoral and cellular responses we determined before and 30-90 days after vaccination in patients with MS and anti-CD20-treated patients with other AID in two Catalan centers. RESULTS: 457 patients were enrolled. Findings showed that humoral response decreased under anti-CD20s or sphingosine 1-phosphate receptor modulators (S1PRM) and with longer treatment duration and increased after 4.5 months from the last anti-CD20 infusion. Cellular response decreased in S1PRM-treated. Patients on anti-CD20 can present cellular responses even in the absence of antibodies. CONCLUSION: Anti-CD20s and S1PRM modify the immunological responses to SARS-CoV-2 vaccines.


Assuntos
COVID-19 , Esclerose Múltipla , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Esclerose Múltipla/tratamento farmacológico , SARS-CoV-2 , Vacinação
7.
Clin Exp Rheumatol ; 40 Suppl 134(5): 71-80, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35238758

RESUMO

Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a chronic, clinically heterogenous fibroinflammatory condition, characterised by an accumulation of IgG4 secreting plasma cells in affected tissues and associated with increased serum IgG4 concentrations. Despite a growing recognition of the disease among clinicians from different specialties worldwide, its indolent nature, lack of a single diagnostic test and ability to mimic other malignant, infective and inflammatory conditions, makes the diagnosis challenging. As treatment options evolve, biomarkers correlating with disease activity, predicting prognosis and response to treatment are deemed required. A multidisciplinary panel of experts from the European Reference Network for Rare and Complex Connective tissue diseases (ERN ReCONNET) and affiliated international partners have performed a narrative literature search and reviewed the current evidence of biomarkers in IgG4-RD, including immunoglobulins, cytokines, chemokines and other soluble immune mediators, and cellular components of the immune system. The aim of this paper is to provide useful information for clinicians as to the utility of biomarkers for diagnosing and monitoring IgG4-RD in clinical routine and sets out recommendations for clinical decision making.


Assuntos
Doenças Autoimunes , Doença Relacionada a Imunoglobulina G4 , Doenças Autoimunes/diagnóstico , Biomarcadores , Quimiocinas , Humanos , Imunoglobulina G , Doença Relacionada a Imunoglobulina G4/diagnóstico , Plasmócitos/patologia
8.
Appl Environ Microbiol ; 87(23): e0174821, 2021 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-34550760

RESUMO

Sulfate-reducing bacteria (SRBs) are one of the main sources of biogenic H2S generation in oil reservoirs. Excess H2S production in these systems leads to oil biosouring, which causes operational risks and health hazards and can increase the cost of refining crude oil. Nitrate salts are often added to the system to suppress sulfidogenesis. Because SRB populations can persist in biofilms even after nitrate treatment, identifying shifts in the sessile community is crucial for successful mitigation. However, sampling the sessile community is hampered by its inaccessibility. Here, we use the results of a long-term (148 days) ex situ experiment to identify particular sessile community members from observations of the sample waste stream. Microbial community structure was determined for 731 samples across 20 bioreactors using 16S rRNA gene sequencing. By associating microbial community structure with specific steps in the mitigation process, we could distinguish between taxa associated with H2S production and mitigation. After initiation of nitrate treatment, certain SRB populations increased in the planktonic community during critical time points, indicating the dissociation of SRBs from the biofilm. Predicted relative abundances of the dissimilatory sulfate reduction pathway also increased during the critical time points. Here, by analyzing the planktonic community structure, we describe a general method that uses high-throughput amplicon sequencing, metabolic inferences, and cell abundance data to identify successful biofilm mitigation. We anticipate that our approach is also applicable to other systems where biofilms must be mitigated but cannot be sampled easily. IMPORTANCE Microbial biofilms are commonly present in many industrial processes and can negatively impact performance and safety. Within the oil industry, subterranean biofilms cause biosouring with implications for oil quality, cost, occupational health, and the environment. Because these biofilms cannot be sampled directly, methods are needed to indirectly assess the success of mitigation measures. This study demonstrates how the planktonic microbial community can be used to assess the dissociation of sulfate-reducing bacterium (SRB)-containing biofilms. We found that an increase in the abundance of a specific SRB population in the effluent after nitrate treatment can be used as a potential indicator for the successful mitigation of biofilm-forming SRBs. Moreover, a method for determining critical time points for detecting potential indicators is suggested. This study expands our knowledge of improving mitigation strategies for biosouring and could have broader implications in other systems where biofilms lead to adverse consequences.


Assuntos
Nitratos , Sulfatos/metabolismo , Bactérias Redutoras de Enxofre/isolamento & purificação , Biofilmes , Indústria de Petróleo e Gás , RNA Ribossômico 16S/genética , Sulfetos , Bactérias Redutoras de Enxofre/classificação
9.
Rheumatology (Oxford) ; 60(12): 5647-5658, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33620072

RESUMO

OBJECTIVE: To assess the potential diagnostic utility of advanced lymphocyte profiling to differentiate between primary Sjögren's Syndrome (pSS) and non-Sjögren Sicca syndrome. METHODS: Distribution of peripheral lymphocyte subpopulations was analysed by flow cytometry in 68 patients with pSS, 26 patients with sicca syndrome and 23 healthy controls. The ability to discriminate between pSS and sicca syndrome was analysed using the area under the curve (AUC) of the receiver operating characteristic curve of the different lymphocyte subsets. RESULTS: The ratio between naïve/memory B cell proportions showed an AUC of 0.742 to differentiate pSS and sicca syndrome, with a sensitivity of 76.6% and a specificity of 72% for a cut-off value of 3.4. The ratio of non-switched memory B cells to activated CD4+ T cells percentage (BNSM/CD4ACT) presented the highest AUC (0.840) with a sensitivity of 83.3% and specificity of 81.7% for a cut-off value <4.1. To differentiate seronegative pSS patients from sicca patients, the BNSM/CD4ACT ratio exhibited an AUC of 0.742 (sensitivity 75%, specificity 66.7%, cut-off value <4.4), and the number of naïve CD4 T cells had an AUC of 0.821 (sensitivity 76.9%, specificity 88.9%, cut-off value <312/mm3). CONCLUSION: Patients with pSS show a profound imbalance in the distribution of circulating T and B lymphocyte subsets. The ratio BNSM/CD4ACT is useful to discriminate between pSS and sicca syndrome.


Assuntos
Ceratoconjuntivite Seca/diagnóstico , Subpopulações de Linfócitos/patologia , Síndrome de Sjogren/diagnóstico , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Citometria de Fluxo , Seguimentos , Humanos , Ceratoconjuntivite Seca/imunologia , Subpopulações de Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Síndrome de Sjogren/imunologia
10.
Rheumatology (Oxford) ; 60(1): 217-223, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-32658963

RESUMO

OBJECTIVES: Several IgG4-related disease (IgG4-RD) phenotypes have been proposed and the first set of classification criteria have been recently created. Our objectives were to assess the phenotype distribution and the performance of the classification criteria in Spanish patients as genetic and geographical differences may exist. METHODS: We performed a cross-sectional multicentre study (Registro Español de Enfermedad Relacionada con la IgG4, REERIGG4) with nine participating centres from Spain. Patients were recruited from November 2013 to December 2018. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria (AECC) were used. RESULTS: We included 105 patients; 88% had Caucasian ethnicity. On diagnosis, 86% met the international pathology consensus while 92% met the Japanese comprehensive criteria. The phenotype distribution was head and neck 25%, Mikulicz and systemic (MS) 20%, pancreato-hepato-biliary (PHB) 13%, retroperitoneal and aorta (RA) 26%. Sixteen per cent had an undefined phenotype. Seventy-seven per cent of the cases met the AECC. From the 24 patients not meeting the AECC, 33% met exclusion criteria, and 67% did not get a score ≥20 points. Incomplete pathology reports were associated to failure to meet the AECC. CONCLUSIONS: The PHB phenotype was rare among Spanish IgG4-RD patients. The MS phenotype was less frequent and the RA phenotype was more prevalent than in other, Asian patient series. An undefined phenotype should be considered as some patients do not fall into any of the categories. Three quarters of the cases met the 2019 AECC. Incomplete pathology reports were the leading causes of failure to meet the criteria.


Assuntos
Doença Relacionada a Imunoglobulina G4/classificação , Imunoglobulina G , Fenótipo , Sistema de Registros , Fatores Etários , Estudos Transversais , Bases de Dados Factuais , Feminino , Humanos , Imunoglobulina G/sangue , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/etnologia , Doença Relacionada a Imunoglobulina G4/patologia , Masculino , Pessoa de Meia-Idade , Proibitinas , Fatores Sexuais , Espanha , População Branca/estatística & dados numéricos
11.
Clin Exp Rheumatol ; 39 Suppl 133(6): 131-139, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34919042

RESUMO

OBJECTIVES: To investigate the utility of serum BAFF, IL-17, IL-18, IL-21, IL-22, CXCL13, TNF-R2 and PD-L2 as biomarkers of disease activity in primary Sjögren's syndrome (pSS), their relationship with lymphocyte subpopulations and their accuracy to discriminate pSS from Sicca syndrome. METHODS: We conducted an observational study on 66 pSS patients and 48 controls (25 with Sicca syndrome and 23 healthy volunteers). Serum levels of BAFF, IL-17 A/F, IL-18, IL-21, IL-22, CXCL13, TNF-R2 and PD-L2 were measured using a multiplex immunoassay. Lymphocyte subpopulations were analysed by flow cytometry. Disease activity of pSS was assessed with ESSDAI at study inclusion. RESULTS: Patients with pSS presented higher serum CXCL13 (364.7 vs. 205.2 pg/mL), IL-21 (43.2 vs. 0 pg/mL) and BAFF (1646 vs. 1369 pg/mL), and lower PD-L2 levels (1950.8 vs. 2792.3 pg/mL) than controls. ESSDAI was associated with BAFF, IL-18 and IL-22. Patients with ESSDAI >0 exhibited higher CXCL13, IL-21, IL-22 and TNFR2 concentrations. IL-21 levels correlated with lower memory B-cell and higher naïve B-cell percentages and IL-22 levels correlated with increased circulating activated CD4+ T-cells. The combination of serum CXCL13, BAFF and PDL2 levels using the formula [ln(CXCL13)+ln(BAFF)]/ln(PDL2) exhibit an AUC of 0.854 (95% CI: 0.750-0.919) to discriminate between pSS and Sicca syndrome (sensitivity 77.2% and specificity 86.4% using a cut-off of 1.7). CONCLUSIONS: CXCL13, BAFF, IL-21, and IL-22 are potential biomarkers of pSS activity and IL-21 and IL-22 are associated with disturbances of lymphocyte subpopulations in pSS. The combination of serum CXCL13, BAFF, and PD-L2 levels allows discrimination between pSS and Sicca syndrome.


Assuntos
Fator Ativador de Células B/sangue , Quimiocina CXCL13/sangue , Interleucinas/sangue , Síndrome de Sjogren , Humanos , Linfócitos , Síndrome de Sjogren/sangue , Síndrome de Sjogren/diagnóstico , Interleucina 22
12.
Liver Int ; 40(8): 1906-1916, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32329119

RESUMO

BACKGROUND & AIMS: Check point inhibitors (CPI) have improved survival of oncology patients but adverse effects that mimic autoimmune disorders have been reported. Our aim was describe the characteristics of immune-related hepatitis (irH) and prognosis, and compared them to those of patients with autoimmune hepatitis (AIH). METHODS: This is a retrospective study including all grade ≥ 3 (severe) irH diagnosed among 414 patients treated with CPI from 2016 to 2018. RESULTS: Twenty-eight cases of severe irH were recorded: 10 on anti-CTLA-4 ± anti-PD1/PD-L1 and 18 on anti-PD1/PD-L1. Half were female, age 63 years, median time on CPI three cycles. Four (14.3%) presented acute liver injury or failure and one (3.6%) died as consequence. 94% presented normal immunoglobulin G (IgG). Six (21.4%) patients were retreated with CPI and none presented relapse or new immune-related adverse events after a median cycles of 11 (range 6-36). Subjects with irH were older and had lower IgG values than a cohort of AIH (N = 38). Presentation tended to be more severe in AIH. Twenty-five percent of irH and 84% AIH presented ANAs ≥ 1:80 (P = .001). In irH Initial dose of corticosteroids was higher (60 vs 30 mg, P < .001) but duration shorter (2.3 vs 7 months, P < .001) and frequently in monotherapy (41.7% vs 91.3%, P < .001). CONCLUSIONS: Immune-related hepatitis can lead to acute liver failure, with absence of increased values of IgG and ANAs. In contrast to autoimmune hepatitis, initial corticosteroids dose were higher, duration shorter with few requiring additional immunosuppression. Retreatment with CPI was not associated with recurrence.


Assuntos
Hepatite Autoimune , Inibidores de Checkpoint Imunológico , Feminino , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
13.
Eur J Nucl Med Mol Imaging ; 46(8): 1626-1632, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31081519

RESUMO

PURPOSE: To analyse the risk of ischaemic events in patients with newly diagnosed giant cell arteritis (GCA) according to PET/CT findings. METHODS: PET/CT was performed during the first 10 days of steroid therapy. Clinical manifestations at diagnosis, and physical examination and PET/CT findings were recorded and compared according to the presence or absence of ischaemic symptoms at disease onset. Analysed territories included the ascending aorta, aortic arch, descending aorta, abdominal aorta, carotid arteries, brachiocephalic trunk, vertebral arteries, subclavian arteries and axillary arteries. RESULTS: The study group comprised 30 patients with a median age of 80.8 years. Of these patients, 21 (70%) reported ischaemic symptoms at diagnosis, and 13 (43.3%) had permanent visual loss. Of the 30 patients, 77.8% showed large vessel vasculitis (including aortic and vertebral artery involvement) on PET/CT, and 60% had isolated involvement of the vertebral territory. Vertebral arteries were more frequently involved in patients with ischaemic symptoms (OR 5.0, 95% CI 0.99-24.86, p = 0.051). The presence of vertebral artery involvement in the absence of aortic involvement was associated with the presence of ischaemic manifestations (Fisher's exact test, p = 0.001). The presence of aortitis was found to protect against the development of permanent visual loss (OR 19.0, 95% CI 2.79-127.97, p = 0.001). CONCLUSION: Our findings suggest an association between the vascular pattern on PET/CT at the time of GCA diagnosis and the risk of ischaemic events.


Assuntos
Arteriopatias Oclusivas/epidemiologia , Arterite de Células Gigantes/complicações , Isquemia/epidemiologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Idoso , Idoso de 80 Anos ou mais , Arteriopatias Oclusivas/complicações , Arteriopatias Oclusivas/diagnóstico por imagem , Feminino , Arterite de Células Gigantes/diagnóstico por imagem , Humanos , Isquemia/complicações , Isquemia/diagnóstico por imagem , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/normas
14.
Ann Hepatol ; 18(1): 215-219, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31113593

RESUMO

IgG4-related disease is a recently-described fibro-inflammatory condition with characteristic histopathological findings in the organs involved. The most commonly affected organs are pancreas, lymph nodes, and retroperitoneum. Liver disease usually involves bile structures and therefore IgG4-related disease is considered a cause of secondary sclerosing cholangitis. One out of three patients with IgG4 sclerosing cholangitis also presents autoimmune pancreatitis, although it can be associated with manifestations in other organs. One of the main features of IgG4-related disease is its good prognosis due to the great response to glucocorticoid therapy. However, relapse of the disease is not uncommon, especially when steroid therapy is decreased or stopped. Rituximab seems to be an effective treatment to achieve remission of the disease. We report the case of a 74 year-old man diagnosed with IgG4-related disease based on increase of serum IgG4 levels, imaging and histopathological findings, with systemic involvement including sclerosing cholangitis. Despite the absence of liver fibrosis at onset, the early use of glucocorticoids and rituximab therapy, the patient presented clinical and analytical deterioration, leading to secondary biliary cirrhosis. In conclusion, this clinical case highlights the importance of prompt diagnosis and therapeutics for sclerosing cholangitis secondary to IgG4-related disease in order to avoid progression of the disease and development of liver cirrhosis, as well as the refractory, aggressive nature of the disease in some cases as this one.


Assuntos
Colangite Esclerosante/diagnóstico , Doença Relacionada a Imunoglobulina G4/diagnóstico , Imunoglobulina G/sangue , Fígado/diagnóstico por imagem , Rituximab/uso terapêutico , Idoso , Biópsia , Colangiopancreatografia por Ressonância Magnética , Colangite Esclerosante/tratamento farmacológico , Colangite Esclerosante/imunologia , Diagnóstico Diferencial , Humanos , Imunoglobulina G/imunologia , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Doença Relacionada a Imunoglobulina G4/imunologia , Fatores Imunológicos/uso terapêutico , Masculino , Tomografia por Emissão de Pósitrons
16.
Gac Med Mex ; 153(2): 255-272, 2017.
Artigo em Espanhol | MEDLINE | ID: mdl-28474712

RESUMO

This Symposium highlights the recognition that this year reaches half a century of the Medical Movement (1964-1965), and 27 years of publishing the book titled, "Documental Memories and Reflections" ("Crónica Documental y Reflexiones") edited by the Faculty of Medicine of the UNAM, at that time directed by the prestigious Dr. Fernando Cano Valle. Our President Dr. Graue indicated that Dr. Alejandro Treviño-Becerra assumed the coordination of this session with the commitment to be published in the Medical Gazette of Mexico for current and future generations. The Academic participants were: Norberto Treviño García-Manzo, president of the Academy in 1988. Dr. Felipe Mota Hernández was the Recording Secretary of the Mexican Medical Alliance ("Alianza de Médicos Mexicanos"). Now he is the Dean of the Children's Hospital of Mexico "Federico Gómez". Dr. Cesar Gutiérrez Samperio, surgeon at IMSS and professor at Medicine School, University of Queretaro until a year ago. Dr. Fernando Cano Valle, former Head of the Medical Faculty, UNAM, presently a researcher in Medicine and Human Rights in the Institute for Juridical Research, UNAM. I quote the Academic Treviño Zapata: "I believe that it will be difficult to bring again the conditions and circumstances that made possible the vigorous realization of the Medical Movement, the enthusiastic and hopeful creation of the Mexican Medical Alliance, and the promising start and progress of the integration of the national medical union."


Assuntos
História da Medicina , Aniversários e Eventos Especiais , História do Século XX , México
17.
Int Ophthalmol ; 36(2): 185-94, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26220873

RESUMO

Our aim was to identify the potential risk factors for developing post-traumatic endophthalmitis (PTE) and the possible measures of prevention. Retrospective case-control study, with 15 cases of PTE and 2 matched controls. We reviewed the medical records of the cases and their respective controls during the period 1996-2008 at a Spanish Hospital. We collected demographic data and information about the type of trauma, the potential risk factors, comorbidities, microbial isolations, antimicrobial susceptibility, administered treatments, and the visual outcome. The independent predictor factors identified for PTE were intraocular foreign body (IOFB) (OR 5.48; CI 95 % 1.05-28.7), dirty wound (OR 4.91; CI 95 % 0.96-25.3), and wound closure delays of 24 h or more (OR 5.48; CI 95 % 1.05-28.7). The probability of endophthalmitis in patients without these risk factors was 5.9 %, but ascended to 65.3 % and 90.3 %, in those patients with two and three risk factors, respectively. Infected patients presented a complication rate of 80 %, with an evisceration rate of 53 %; both were significantly associated with infection. The visual outcome was poor and related to the presence of IOFB and virulent microorganisms (Bacillus sp., filamentous fungus), visual acuity at presentation, and retinal detachment. Patients who presented an IOFB, dirty wound, and delayed wound closure were 15 times more likely to develop infection, and when infected, patients fared much worse than those non-infected. We thus recommend aggressive prophylactic measures in patients with these risk factors, adding antifungal prophylaxis when the injury is contaminated with vegetable matter.


Assuntos
Endoftalmite/etiologia , Infecções Oculares/etiologia , Ferimentos Oculares Penetrantes/complicações , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Estudos de Casos e Controles , Criança , Endoftalmite/microbiologia , Endoftalmite/prevenção & controle , Corpos Estranhos no Olho/complicações , Infecções Oculares/microbiologia , Infecções Oculares/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Espanha , Acuidade Visual , Adulto Jovem
19.
Retina ; 35(9): 1836-43, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25946689

RESUMO

PURPOSE: To investigate the long-term safety and efficacy of microincisional 23-gauge pars plana vitrectomy with internal limiting membrane (ILM) peeling and gas tamponade in the treatment of myopic traction maculopathy. METHODS: A prospective nonrandomized multicenter study was designed. Patients with myopic traction maculopathy without macular hole and retinal detachment were included in the study between January 2009 and May 2012. All patients underwent microincisional 23-gauge pars plana vitrectomy with ILM peeling and 12% C3F8 gas tamponade. In all cases, brilliant blue G staining of the ILM was performed. All patients were prospectively evaluated. The evolution of best-corrected visual acuity (BCVA) and macular thickness were recorded. RESULTS: Myopic traction maculopathy resolved in 28 of the 30 patients (93%) included. Mean follow-up was 33.8 ± 13 months (range, 24-60 months). Mean time of myopic traction maculopathy resolution after surgery was 2.65 ± 1.4 months. At 1 month after surgery, one patient developed a macular hole and another one a rhegmatogenous retinal detachment. After 2 years, another patient developed a retinal detachment. Statistically significant improvements in macular thickness compared with baseline were found at all follow-up visits (P < 0.001, Student's t-test). At final visit, BCVA improved significantly compared with baseline (P = 0.044, Wilcoxon's test). However, a statistically significant improvement in visual acuity was achieved only in eyes with a preoperative Snellen visual acuity ≥ 20/63 (P = 0.027). In contrast, the final BCVA of eyes with worse preoperative visual acuity (<20/63) did not improve significantly (P = 0.41, Wilcoxon's test). CONCLUSION: Microincisional 23-gauge pars plana vitrectomy with ILM peeling and gas tamponade is effective in the treatment of myopic traction maculopathy, with low postoperative complications. Globally, both BCVA and macular thickness improved significantly during the follow-up period. However, greater visual acuity improvements were only seen in eyes with preoperative BCVA equal to or better than 20/63 Snellen equivalent. Some concerns remain about the risk of macular hole formation after ILM peeling. Further studies are necessary to investigate this issue.


Assuntos
Tamponamento Interno , Membrana Epirretiniana/cirurgia , Fluorocarbonos/administração & dosagem , Miopia Degenerativa/cirurgia , Retinosquise/cirurgia , Vitrectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Membrana Basal/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Microcirurgia/métodos , Pessoa de Meia-Idade , Miopia Degenerativa/diagnóstico , Miopia Degenerativa/fisiopatologia , Complicações Pós-Operatórias , Estudos Prospectivos , Retinosquise/diagnóstico , Retinosquise/fisiopatologia , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia
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