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1.
Chem Rev ; 124(9): 5668-5694, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38635951

RESUMO

Faced with desiccation stress, many organisms deploy strategies to maintain the integrity of their cellular components. Amorphous glassy media composed of small molecular solutes or protein gels present general strategies for protecting against drying. We review these strategies and the proposed molecular mechanisms to explain protein protection in a vitreous matrix under conditions of low hydration. We also describe efforts to exploit similar strategies in technological applications for protecting proteins in dry or highly desiccated states. Finally, we outline open questions and possibilities for future explorations.


Assuntos
Dessecação , Géis , Proteínas , Proteínas/química , Proteínas/metabolismo , Géis/química , Vidro/química , Humanos , Água/química
2.
Ann Surg ; 280(1): 35-45, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38328975

RESUMO

OBJECTIVE: To evaluate the effect of nerve decompression on pain in patients with lower extremity painful diabetic peripheral neuropathy (DPN). BACKGROUND: Currently, no treatment provides lasting relief for patients with DPN. The benefits of nerve decompression remain inconclusive. METHODS: This double-blinded, observation and same-patient sham surgery-controlled randomized trial enrolled patients aged 18 to 80 years with lower extremity painful DPN who failed 1 year of medical treatment. Patients were randomized to nerve decompression or observation group (2:1). Decompression-group patients were further randomized and blinded to nerve decompression in either the right or left leg and sham surgery in the opposite leg. Pain (11-point Likert score) was compared between decompression and observation groups and between decompressed versus sham legs at 12 and 56 months. RESULTS: Of 2987 screened patients, 78 were randomized. At 12 months, compared with controls (n=37), both the right-decompression group (n=22) and left-decompression group (n=18) reported lower pain (mean difference for both: -4.46; 95% CI: -6.34 to -2.58 and -6.48 to -2.45, respectively; P < 0.0001). Decompressed and sham legs equally improved. At 56 months, compared with controls (n=m 14), pain was lower in both the right-decompression group (n=20; mean difference: -7.65; 95% CI: -9.87 to -5.44; P < 0.0001) and left-decompression group (n=16; mean difference: -7.26; 95% CI: -9.60 to -4.91; P < 0.0001). The mean pain score was lower in decompressed versus sham legs (mean difference: 1.57 95% CI: 0.46 to 2.67; P =0.0002). CONCLUSIONS: Although nerve decompression was associated with reduced pain, the benefit of surgical decompression needs further investigation as a placebo effect may be responsible for part or all of these effects.


Assuntos
Descompressão Cirúrgica , Neuropatias Diabéticas , Extremidade Inferior , Medição da Dor , Humanos , Descompressão Cirúrgica/métodos , Neuropatias Diabéticas/cirurgia , Neuropatias Diabéticas/complicações , Masculino , Pessoa de Meia-Idade , Feminino , Método Duplo-Cego , Idoso , Adulto , Resultado do Tratamento , Extremidade Inferior/inervação , Extremidade Inferior/cirurgia , Idoso de 80 Anos ou mais , Adolescente , Adulto Jovem
3.
J Am Chem Soc ; 145(42): 23308-23320, 2023 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-37845197

RESUMO

Solutes added to buffered solutions directly impact protein folding. Protein stabilization by cosolutes or crowders has been shown to be largely driven by protein-cosolute volume exclusion complemented by chemical and soft interactions. By contrast to previous studies that indicate the invariably destabilizing role of soft protein-sugar attractions, we show here that soft interactions with sugar cosolutes are protein-specific and can be stabilizing or destabilizing. We experimentally follow the folding of two model miniproteins that are only marginally stable but in the presence of sugars and polyols fold into representative and distinct secondary structures: ß-hairpin or α-helix. Our mean-field model reveals that while protein-sugar excluded volume interactions have a similar stabilizing effect on both proteins, the soft interactions add a destabilizing contribution to one miniprotein but further stabilize the other. Using molecular dynamics simulations, we link the soft protein-cosolute interactions to the weakening of direct protein-water hydrogen bonding due to the presence of sugars. Although these weakened hydrogen bonds destabilize both the native and denatured states of the two proteins, the resulting contribution to the folding free energy can be positive or negative depending on the amino acid sequence. This study indicates that the significant variation between proteins in their soft interactions with sugar determines the specific response of different proteins, even to the same sugar.


Assuntos
Açúcares , Água , Ligação de Hidrogênio , Proteínas , Sequência de Aminoácidos , Dobramento de Proteína , Termodinâmica
4.
Eur J Neurol ; 30(5): 1417-1424, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36779862

RESUMO

BACKGROUND AND PURPOSE: Data on maintenance therapy with subcutaneous immunoglobulin (SCIg) in myasthenia gravis (MG) are limited. We report on transitioning acetylcholine receptor (AChR) antibody-positive (Ab+) MG patients on stable intravenous immunoglobulin (IVIg) regimens as part of routine clinical care to SCIg 1:1.2. METHODS: This multicenter North American open-label prospective investigator-initiated study had two components: the IVIg Stabilization Period (ISP) enrolling patients already on IVIg as part of routine clinical care (Weeks -10 to -1), followed by transition of stable MG subjects to SCIg in the Experimental Treatment Period (ETP; Weeks 0 to 12). We hypothesized that >65% of patients entering the ETP would have a stable Quantitative Myasthenia Gravis (QMG) score from Week 0 to Week 12. Secondary outcome measures included other efficacy measures, safety, tolerability, IgG levels, and treatment satisfaction. RESULTS: We recruited 23 patients in the ISP, and 22 entered the ETP. A total of 12 subjects (54.5%) were female, and 18 (81.8%) were White, with mean age 51.4 ± 17 years. We obtained Week 12 ETP QMG data on 19 of 22; one subject withdrew from ETP owing to clinical deterioration, and two subjects withdrew due to dislike of needles. On primary analysis, 19 of 22 participants (86.4%, 95% confidence interval = 0.72-1.00) were treatment successes using last observation carried forward (p = 0.018). Secondary efficacy measures supported MG stability. SCIg was safe and well tolerated, and IgG levels were stable. Treatment satisfaction was comparable between ISP and ETP. CONCLUSIONS: MG patients on IVIg as part of their routine clinical care remained stable on monthly IVIg dosage, and most maintained similar disease stability on SCIg.


Assuntos
Imunoglobulinas Intravenosas , Miastenia Gravis , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Imunoglobulinas Intravenosas/uso terapêutico , Estudos Prospectivos , Miastenia Gravis/tratamento farmacológico , Receptores Colinérgicos , Autoanticorpos
5.
Neth Heart J ; 30(6): 328-334, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34910278

RESUMO

INTRODUCTION: Sex disparities exist in coronary artery disease (CAD) in terms of risk profile, clinical management and outcome. It is unclear if differences are also present in coronary aneurysms, a rare variant of CAD. METHODS: Patients were selected from the international Coronary Artery Aneurysm Registry (CAAR; ClinicalTrials.gov: NCT02563626), and differences between groups were analysed according to sex. The CAAR database is a prospective multicentre registry of 1565 patients with coronary aneurysms (336 females). Kaplan-Meier method was used for event-free survival analysis for death, major adverse cardiac events (MACE: composite endpoint of death, heart failure and acute coronary syndrome) and bleeding. RESULTS: Female patients were older, were more often hypertensive and less frequently smoker. They were treated conservatively more often compared to male patients and received significantly less frequently aspirin (92% vs 88%, p = 0.002) or dual antiplatelet therapy (DAPT) (67% vs 58%, p = 0.001) at discharge. Median DAPT duration was also shorter (3 vs 9 months, p = 0.001). Kaplan-Meier analysis revealed no sex differences in death, MACE or bleeding during a median follow-up duration of 37 months, although male patients did experience acute coronary syndrome (ACS) more often during follow-up (15% vs 10%, p = 0.015). CONCLUSIONS: These CAAR findings showed a comparable high-risk cardiovascular risk profile for both sexes. Female patients were treated conservatively more often and received DAPT less often at discharge, with a shorter DAPT duration. ACS was more prevalent among male patients; however, overall clinical outcome was not different between male and female patients during follow-up.

6.
Acta Neurol Scand ; 144(5): 546-552, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34131909

RESUMO

OBJECTIVES: The aim of this study was to achieve the translation and cross-cultural adaptation of the MG-QOL15R questionnaire into Spanish and the analysis of its psychometric properties. MATERIALS AND METHODS: We recruited patients with MG, ≥18 years old, whose mother tongue was Spanish. After the translation and cross-cultural adaptation of the MG-QOL15-R, the following tests were performed: internal consistency using the Cronbach-α coefficient and corrected item-total correlations; reproducibility with a test-retest analysis using intraclass correlation coefficients; and concurrent validity using Spearman's correlation coefficient of the Spanish language MG-QOL15R-S, Myasthenia Gravis Activity of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores. As an approximation to construct validity, the nonparametric Mann-Whitney U test was performed between MG-QOL15R-S scores according to the Myasthenia Gravis Foundation of America classification. RESULTS: A total of 83 MG patients were enrolled, mean age 48.19 ± 17.25 years; 58 (69.9%) were women. The mean MG-QOL15R-S score was 11.3 ± 7.1. Cronbach-α coefficient was 0.92. Item-total correlation ranged between 0.43 and 0.75. Intraclass correlation coefficient was 0.80. The Spearman correlation coefficient was 0.637 (p-value < .001) for MG-ADL and 0.487 (p-value < .001) for QMG. Mann-Whitney U tests of the mean MG-QOL15R-S scores were significantly different according to the clinical severity (p-value < .001). CONCLUSIONS: The Spanish version of the MG-QOL15R is a valid and reliable instrument and potentially useful for measuring health-related quality of life in Spanish-speaking MG patients.


Assuntos
Miastenia Gravis , Qualidade de Vida , Adolescente , Adulto , Idoso , Feminino , Humanos , Idioma , Pessoa de Meia-Idade , Miastenia Gravis/diagnóstico , Reprodutibilidade dos Testes , Inquéritos e Questionários
7.
Molecules ; 26(3)2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33494502

RESUMO

Recently, the use of alternative vessels to oak barrels during winemaking has become increasingly popular, but little is known about their impact on the chemical composition of the resulting wines. To address this issue, a Sauvignon Blanc wine was elaborated from the same grape juice by using cylindrical stainless-steel tanks, oval-shaped concrete vessels, oval-shaped polyethylene vessels, and clay jars in triplicate. Each vessel was used for alcoholic fermentation and the aging of wines over its own lees. Wines elaborated in concrete vessels showed the highest pH and the lowest titratable acidity, most likely related to the observed release of inorganic compounds from the concrete walls. Little effect of the vessels was seen on the wine color and phenolic composition. Wines elaborated in clay jars showed the highest turbidity and the highest content of soluble polysaccharides, while those made using cylindrical stainless-steel tanks showed the highest content of volatile compounds. Despite the observed differences, all of the vessels tested seem suitable for white wine production since every wine showed chemical features that corresponded with the quality standards of Sauvignon Blanc wines.


Assuntos
Quercus , Compostos Orgânicos Voláteis/análise , Vinho
8.
Muscle Nerve ; 62(2): 261-266, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32369631

RESUMO

INTRODUCTION: Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis Activities of Daily Living (MG-ADL) scales were compared using the data from the Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy (MGTX) study. METHODS: Correlation between QMG and MG-ADL raw and change-from-baseline scores was calculated every 3 months for 60 months based on treatment groups and minimal manifestation status (MMS). RESULTS: QMG and MG-ADL change-from-baseline scores correlated significantly, with increasing strength of correlation over time, in both treatment groups. QMG and MG-ADL raw scores correlated significantly in both treatment groups, with increasing correlation only in the prednisone-alone group. Correlation between raw scores was weaker in patients who were in MMS, demonstrating a "floor effect" on the MG-ADL scale. Raw QMG scores could be modeled assuming a normal distribution, whereas raw MG-ADL scores could not be modeled this way. DISCUSSION: The floor effect and skewed distribution of the MG-ADL measure should be taken into account in the design of myasthenia gravis clinical trials.


Assuntos
Atividades Cotidianas , Miastenia Gravis/fisiopatologia , Avaliação de Resultados em Cuidados de Saúde , Terapia Combinada , Glucocorticoides/uso terapêutico , Humanos , Miastenia Gravis/terapia , Prednisona/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Timectomia
9.
Molecules ; 25(24)2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33302548

RESUMO

The aim of this study was to determine the volatile profiles of new seedless table grape cultivars Timco™, Magenta™, Krissy™ and Arra15™ and compare them with the traditional table grape variety Crimson seedless. The volatile profiles were extracted employing solid-phase microextraction and analyzed with gas chromatography coupled with mass spectrometry. Terpenes were present in very different proportions, with the Magenta, Krissy, and Arra15 varieties showing much higher quantities than Crimson and Timco. ß-Ionone and octanal, important indicators in the aromatic flavor quality of table grapes, were present in higher levels in Crimson and Arra15, and this might be responsible for driving consumer preference. These compounds significantly increased during ripening, except in Crimson, and gradually decreased from harvest to the end of the storage in all the cultivars. Evolution during ripening was different depending on the variety but the general tendency terpenes was to increase from veraison to harvest. A postharvest study revealed that Crimson could have a better conservation of the volatile components during postharvest storage compared with Timco and Krissy. These results could help in plant breeding programs and to make decisions for new planting according to needs for storing fresh table grapes given distances to consumer markets.


Assuntos
Frutas/química , Vitis/química , Compostos Orgânicos Voláteis/química , Fenômenos Químicos , Conservação de Alimentos , Compostos Fitoquímicos/química , Fatores de Tempo
10.
N Engl J Med ; 375(6): 511-22, 2016 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-27509100

RESUMO

BACKGROUND: Thymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone. METHODS: We compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednisone over a 3-year period. RESULTS: A total of 126 patients underwent randomization between 2006 and 2012 at 36 sites. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, P<0.001); patients in the thymectomy group also had a lower average requirement for alternate-day prednisone (44 mg vs. 60 mg, P<0.001). Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine (17% vs. 48%, P<0.001) or were hospitalized for exacerbations (9% vs. 37%, P<0.001). The number of patients with treatment-associated complications did not differ significantly between groups (P=0.73), but patients in the thymectomy group had fewer treatment-associated symptoms related to immunosuppressive medications (P<0.001) and lower distress levels related to symptoms (P=0.003). CONCLUSIONS: Thymectomy improved clinical outcomes over a 3-year period in patients with nonthymomatous myasthenia gravis. (Funded by the National Institute of Neurological Disorders and Stroke and others; MGTX ClinicalTrials.gov number, NCT00294658.).


Assuntos
Glucocorticoides/administração & dosagem , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/cirurgia , Prednisona/administração & dosagem , Timectomia , Adolescente , Adulto , Idoso , Terapia Combinada , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/classificação , Índice de Gravidade de Doença , Método Simples-Cego , Resultado do Tratamento , Adulto Jovem
11.
Environ Res ; 158: 768-772, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28755561

RESUMO

In this paper, the level of exposure to broadband radiofrequency electromagnetic field in a mid-size European city was evaluated in accordance with the International Commission on Non-ionizing Radiation Protection guidelines from 1998. With the aim to analyse all the potential electromagnetic waves present in the city up to 18GHz, a total of 271 locations distributed along Terrassa (Spain) have been measured. To show the results in an easy-to-interpret way by the citizen, the results have been represented in a set of raster maps. The measurement results obtained showed that the electromagnetic wave measured in all broadband frequency range along the city is much lower than the safety level according to the international regulations for both public and occupational sectors.


Assuntos
Exposição à Radiação , Monitoramento de Radiação , Ondas de Rádio , Cidades , Humanos , Espanha
12.
Muscle Nerve ; 53(3): 363-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26179124

RESUMO

INTRODUCTION: In this study we evaluated the safety, tolerability, and efficacy of prednisone in patients with ocular myasthenia gravis (OMG) concurrently treated with pyridostigmine. METHODS: This investigation was a randomized, double-blind, placebo-controlled trial. Participants whose symptoms failed to remit on pyridostigmine were randomized to receive placebo or prednisone, initiated at 10 mg every other day, and titrated to a maximum of 40 mg/day over 16 weeks. The primary outcome measure was treatment failure. RESULTS: Fewer subjects were randomized than the 88 planned. Of the 11 randomized, 9 completed 16 weeks of double-blind therapy. Treatment failure incidence was 100% (95% CI 48%-100%) in the placebo group (n = 5) vs. 17% (95% CI 0%-64%) in the prednisone group, P = 0.02 (n = 6). Median time to sustained minimal manifestation status (MMS) was 14 weeks, requiring an average prednisone dose of 15 mg/day. Adverse events were infrequent and generally mild in both groups. CONCLUSIONS: A strategy of low-dose prednisone with gradual escalation appears to be safe, well-tolerated, and effective in treating OMG.


Assuntos
Inibidores da Colinesterase/uso terapêutico , Miastenia Gravis/tratamento farmacológico , Brometo de Piridostigmina/uso terapêutico , Resultado do Tratamento , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença
13.
Eur J Clin Microbiol Infect Dis ; 34(9): 1879-84, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26115631

RESUMO

The aim of this study was to assess the efficacy of and the risk of major bleeding during pegylated interferon (peg-IFN)/ribavirin (RBV) treatment among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients according to the pretreatment platelet count. Two hundred and seventy-four HCV/HIV-coinfected, previously naïve individuals with compensated cirrhosis enrolled in one Spanish prospective cohort who received peg-IFN/RBV were included in this study. The frequency of severe bleeding and sustained virological response (SVR) rate were compared between patients with a pretreatment platelet count ≤70,000/mm(3) and >70,000/mm(3), respectively. Sixty-one (22 %) patients had a baseline platelet count ≤70,000/mm(3). The median (Q1-Q3) pretreatment platelet count was 58,000 (49,000-65,000) cells/mm(3) in the platelet ≤70,000 group and 129,000 (102,500-166,000) cells/mm(3) in the platelet >70,000 group (p < 0.0001). Seventeen (28 %) subjects of the platelet ≤70,000 group and 71 (33 %) patients of the platelet >70,000 group achieved SVR (p = 0.4). Only 2 (3.2 %) patients in the platelet ≤70,000 group developed a severe hemorrhagic event, specifically esophageal variceal bleeding. The efficacy of therapy with peg-IFN/RBV in HIV/HCV-coinfected patients with low pretreatment platelet counts is comparable to that found in the overall subset of subjects with compensated cirrhosis. The frequency of severe hemorrhagic events related with this therapy is low in this population.


Assuntos
Hemorragia Gastrointestinal/patologia , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Trombocitopenia/complicações , Adulto , Antivirais/uso terapêutico , Estudos de Coortes , Coinfecção/virologia , Quimioterapia Combinada , Varizes Esofágicas e Gástricas/patologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Prospectivos , Proteínas Recombinantes/uso terapêutico , Risco , Espanha , Resultado do Tratamento , Carga Viral
14.
J Eur Acad Dermatol Venereol ; 29(1): 56-60, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24629001

RESUMO

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic skin disease which causes a great impact in the quality of life. Multiple therapeutic options have been proposed, and recently the potential use of biological drugs in severe cases has been postulated. MATERIAL AND METHODS: A retrospective study from seven tertiary Spanish centers reviewing the charts of patients with HS treated with biological drugs was performed. Retrieved information included epidemiological data, clinical features, pain intensity, Hurley stage, laboratory data and therapeutic outcomes. RESULTS: Nineteen patients were included in the study; 10 men (52.6%) and 9 women. Eight patients (42%) showed a Hurley severity stage II and 11 a stage III (57.8%). Adalimumab was prescribed as the first biological treatment in nine out of 19 cases (47.3%), whereas infliximab was prescribed in seven cases (36.8%), ustekinumab in two cases (10.5%) and etanercept in one (5.2%). A complete response was observed in three patients (two cases with infliximab and one case with ustekinumab), a partial improvement in 10 patients and in six patients no clinical improvement was noted. One patient referred worsening of the skin symptoms. In 6 cases, a second biological treatment was prescribed. In three of such cases, a partial improvement was noted, whereas in three cases no clinical improvement was observed. In two cases a switch to a third biological drug was indicated, with a partial improvement in one case. DISCUSSION AND CONCLUSIONS: Biological drugs could be a potential and effective therapeutic option for patients with severe HS. Complete and persistent clinical responses are rarely obtained (15%) and partial responses are achieved in approximately 50% of patients. No specific markers for a therapeutic response have been identified. No definitive conclusions regarding the most effective biological drug for HS could be drawn. Higher dosage schedules seem to be associated with higher response rates. The lack of response of one particular drug does not preclude a potential efficacy to another biological treatment.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Terapia Biológica , Hidradenite Supurativa/tratamento farmacológico , Imunoglobulina G/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Adalimumab , Adolescente , Adulto , Substituição de Medicamentos , Etanercepte , Feminino , Humanos , Infliximab , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Ustekinumab , Adulto Jovem
16.
Handb Clin Neurol ; 203: 185-203, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39174248

RESUMO

Myasthenia gravis (MG) is a rare neuromuscular junction disorder that is characterized by fatigable weakness of muscles. People with MG experience various clinical manifestations based on the muscles involved. MG can be autoimmune, paraneoplastic, congenital, medication-related, or transient in the neonatal period due to the passive placental transfer of antibodies from mothers with MG. Acetylcholine receptor antibodies are seen in the majority of patients with MG. However, other antibodies have been discovered in the last 20 years, including muscle-specific tyrosine kinase (MuSK) and lipoprotein-related peptide 4 (LRP4), and are now available through commercial testing. More recently, a handful of other antibodies have been associated with MG; however, they are not presently available for routine testing. A disease classification system has been developed by the Myasthenia Gravis Foundation of America (MGFA) and is commonly used worldwide. A number of objective and subjective outcome measures have been developed and validated over the years and have been proven useful for both clinical and research purposes, serving as primary and secondary outcome measures in most clinical trials. A growing number of therapies are available for both acute and chronic management of MG, with several new mechanistic approaches under investigation. An international consensus guidance for the management of MG was first published in 2016 and updated in 2020.


Assuntos
Miastenia Gravis , Miastenia Gravis/diagnóstico , Miastenia Gravis/terapia , Humanos , Autoanticorpos/imunologia , Receptores Colinérgicos/imunologia
17.
J Neurol Sci ; 463: 123135, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39068745

RESUMO

BACKGROUND: The Myasthenia Gravis-Activities of Daily Living scale (MG-ADL) is an 8-item outcome measure to assess symptoms and functional limitations in myasthenia gravis (MG) patients. The MG-ADL score is an equally weighted level sum score that is used as primary outcome measures in clinical trials, in clinical practice, and as an end-point in health economic evaluation. This data analysis aims to obtain detailed knowledge of measurement properties of MG-ADL items and the MG-ADL score. METHODS: Cross-sectional data from a real-world prospective study (MRW) were combined with longitudinal data from the ADAPT trial. Outcome measures included were MG-ADL, Quantitative Myasthenia Gravis score (QMG), MG 15-item Quality of Life (MG-QOL15r) and EQ-5D-5L. Patients were categorized by their Myasthenia Gravis Foundation of America (MGFA) clinical classification. The following measurement properties were assessed: distributional characteristics, inter-item correlation, convergent, known groups and construct validity and internal factor structure. RESULTS: Correlations of items within MG-ADL dimensions were moderate, while MG-ADL correlations between comparable MG-QOL15r and QMG items were mixed. Known groups validity for the MG-ADL score was demonstrated for MGFA class. Mean MG-ADL item level scores by MGFA class demonstrated construct validity. PCA, including all four outcome measures, resulted in a nine factor solution. DISCUSSION: Psychometric properties of individual MG-ADL items were moderate to good. This study showed that the MG-ADL adequately captures the multidimensional heterogeneous nature of MG. This is, however, accompanied by mixed psychometric performance of the MG-ADL score, which may complicate health economic modelling. REGISTRATION: MyRealWorld-MG was registered on November 25, 2019, with registration numberNCT04176211. The ADAPT randomized clinical trial is registered atClinicalTrials.gov(NCT03669588).


Assuntos
Atividades Cotidianas , Miastenia Gravis , Psicometria , Humanos , Psicometria/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Miastenia Gravis/psicologia , Miastenia Gravis/diagnóstico , Idoso , Estudos Prospectivos , Qualidade de Vida/psicologia , Reprodutibilidade dos Testes , Estudos Longitudinais , Adulto , Avaliação de Resultados em Cuidados de Saúde
18.
Neurol Clin Pract ; 14(5): e200335, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38919930

RESUMO

Background and Objectives: In 2016, a randomized controlled trial demonstrated the clinical efficacy of trans-sternal thymectomy for patients with non-thymomatous myasthenia gravis (MG). Whether large-scale changes occurred in clinical practice after this trial is unknown. Methods: We performed a retrospective longitudinal cross-sectional analysis using National Inpatient Sample (NIS) data from 2012 to 2019. Our study included hospitalized adults at least 18 years of age diagnosed with MG without an associated thymoma. We used joinpoint regression to analyze annual trends in thymectomy volume and surgical approach (minimally invasive vs trans-sternal) from 2012 to 2019. Using logistic regression models, we examined patient and hospital-level factors that may have influenced whether thymectomy was performed, such as age, sex, race, insurance payor, hospital size and teaching status, and Elixhauser Comorbidity Index. Sampling weights were applied to account for the complex survey design of NIS. Results: The total number of thymectomy procedures increased by 69.8% per year (95% CI 40.1-105.8) between 2012 and 2019. Trans-sternal thymectomies increased by 62.8% per year (95% CI 35.8-95.2) and minimally invasive thymectomies by 83.7% per year (95% CI 38.1-144.3). Thymectomies were significantly more likely to occur in 2017-2019 compared with 2012-2016 (OR 1.93, 95% CI 1.62-2.31). In a multivariable regression model, several factors decreased the odds of patients with MG having a thymectomy: older age, Black race (OR 0.62, 95% CI 0.49-0.77), female (OR 0.73, 95% CI 0.63-0.86), and higher Elixhauser Comorbidity Index. Patients in medium (OR 1.82, 95% CI 1.30-2.55) or large (OR 2.81, 95% CI 2.07-3.82) size and urban teaching hospitals (OR 6.09, 95% CI 2.65-13.97) were more likely to undergo thymectomy. Discussion: Thymectomy is being performed more frequently for non-thymomatous MG, especially after 2016 after publication of a positive phase III clinical trial. There are several disparities in thymectomy utilization that warrant further attention.

19.
Neurology ; 102(12): e209482, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38781559

RESUMO

The role of immunosenescence, particularly the natural process of thymic involution during aging, is increasingly acknowledged as a factor contributing to the development of autoimmune diseases and cancer. Recently, a concern has been raised about deleterious consequences of the surgical removal of thymic tissue, including for patients who undergo thymectomy for myasthenia gravis (MG) or resection of a thymoma. This review adopts a multidisciplinary approach to scrutinize the evidence concerning the long-term risks of cancer and autoimmunity postthymectomy. We conclude that for patients with acetylcholine receptor antibody-positive MG and those diagnosed with thymoma, the removal of the thymus offers prominent benefits that well outweigh the potential risks. However, incidental removal of thymic tissue during other thoracic surgeries should be minimized whenever feasible.


Assuntos
Miastenia Gravis , Timectomia , Timoma , Timo , Neoplasias do Timo , Humanos , Timectomia/efeitos adversos , Timectomia/métodos , Miastenia Gravis/cirurgia , Timo/cirurgia , Neoplasias do Timo/cirurgia , Neoplasias do Timo/complicações , Timoma/cirurgia , Timoma/complicações , Complicações Pós-Operatórias/etiologia , Doenças Autoimunes/cirurgia
20.
J Healthc Qual Res ; 39(1): 50-54, 2024.
Artigo em Espanhol | MEDLINE | ID: mdl-37891094

RESUMO

INTRODUCTION: The implementation of the Critical Care Outreach Teams can influence the time of admission of patients to the Intensive Care Unit (ICU). MATERIAL AND METHODS: Retrospective, descriptive, quasi-experimental "before-after" cohort study. All patients admitted to the unit urgently from Monday to Friday for two periods (between February 1, 2022 and June 30 and between February 1, 2023 and June 30, 2023) are included. The patients were divided into regular shift admissions (08-15h) and on-call (15-08h). The secondary objective was to assess whether there were differences in mortality between the two periods. RESULTS: During the first period of the study, 239 patients were admitted. 29.29% entered the ordinary shift and 70.71% on duty shift. During the second period, 211 patients were included with 43.13% of admissions in the ordinary shift. The comparison between the two periods observed a significant increase in the percentage of admissions in the morning hours in the second period (P=.0031). Mortality in the first period was 13.80% and in the second period 9.95%. The comparison between the two periods did not reveal significant differences. CONCLUSIONS: The start-up of the Critical Care Outreach Teams is associated with an increase in the proportion of ICU admissions in the morning period without any observed changes in mortality.


Assuntos
Cuidados Críticos , Unidades de Terapia Intensiva , Humanos , Estudos de Coortes , Estudos Retrospectivos , Mortalidade Hospitalar
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