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1.
Semin Arthritis Rheum ; 66: 152441, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38657403

RESUMO

OBJECTIVE: To investigate the serum urate (SU) change among gout patients initiating SGLT2i, and to compare with sulfonylurea, the second-most widely used glucose-lowering medication after metformin. METHODS: We conducted a cohort study of patients with gout and baseline SU >6 mg/dL who had SU measured within 90 days before and after SGLT2i or sulfonylurea initiation. Using multivariable linear regression, we compared SU change among SGLT2i initiators between those with and without diabetes and then compared SU change between SGLT2i and sulfonylurea. RESULTS: We identified 28 patients with gout initiating SGLT2i (including 16 with diabetes) and 28 patients initiating sulfonylurea (all with diabetes). Among SGLT2i initiators, the mean within-group SU change was -1.8 (95 % CI, -2.4 to -1.1) mg/dL, including -1.2 (-1.8 to -0.6) mg/dL and -2.5 (-3.6 to -1.3) mg/dL among patients with and without diabetes, respectively, with an adjusted difference between those with and without diabetes of -1.4 (-2.4 to -0.5) mg/dL. The SU did not change after initiating sulfonylurea (+0.3 [-0.3 to 1.0] mg/dL). The adjusted SU change difference between SGLT2i vs. sulfonylurea initiation was -1.8 (-2.7 to -0.9) mg/dL in all patients. The SU reduction persisted regardless of urate-lowering therapy or diuretic use and the presence of diabetes, chronic kidney disease, or heart failure. CONCLUSION: Among patients with gout, SGLT2i was associated with a notable reduction in SU compared with sulfonylurea, with a larger reduction among patients without diabetes. With their proven cardiovascular-kidney-metabolic benefits, adding SGLT2i to current gout management could provide streamlined benefits for gout and its comorbidities.


Assuntos
Diabetes Mellitus Tipo 2 , Gota , Inibidores do Transportador 2 de Sódio-Glicose , Compostos de Sulfonilureia , Ácido Úrico , Humanos , Gota/tratamento farmacológico , Gota/sangue , Masculino , Feminino , Ácido Úrico/sangue , Pessoa de Meia-Idade , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Idoso , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Hipoglicemiantes/uso terapêutico , Resultado do Tratamento , Estudos de Coortes
2.
Acta Neuropathol Commun ; 11(1): 176, 2023 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-37932833

RESUMO

As the progression of low-grade diffuse astrocytomas into grade 4 tumors significantly impacts patient prognosis, a better understanding of this process is of paramount importance for improved patient care. In this project, we analyzed matched IDH-mutant astrocytomas before and after progression to grade 4 from six patients (discovery cohort) with genome-wide sequencing, 21 additional patients with targeted sequencing, and 33 patients from Glioma Longitudinal AnalySiS cohort for validation. The Cancer Genome Atlas data from 595 diffuse gliomas provided supportive information. All patients in our discovery cohort received radiation, all but one underwent chemotherapy, and no patient received temozolomide (TMZ) before progression to grade 4 disease. One case in the discovery cohort exhibited a hypermutation signature associated with the inactivation of the MSH2 and DNMT3A genes. In other patients, the number of chromosomal rearrangements and deletions increased in grade 4 tumors. The cell cycle checkpoint gene CDKN2A, or less frequently RB1, was most commonly inactivated after receiving both chemo- and radiotherapy when compared to other treatment groups. Concomitant activating PDGFRA/MET alterations were detected in tumors that acquired a homozygous CDKN2A deletion. NRG3 gene was significantly downregulated and recurrently altered in progressed tumors. Its decreased expression was associated with poorer overall survival in both univariate and multivariate analysis. We also detected progression-related alterations in RAD51B and other DNA repair pathway genes associated with the promotion of error-prone DNA repair, potentially facilitating tumor progression. In our retrospective analysis of patient treatment and survival timelines (n = 75), the combination of postoperative radiation and chemotherapy (mainly TMZ) outperformed radiation, especially in the grade 3 tumor cohort, in which it was typically given after primary surgery. Our results provide further insight into the contribution of treatment and genetic alterations in cell cycle, growth factor signaling, and DNA repair-related genes to tumor evolution and progression.


Assuntos
Astrocitoma , Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/genética , Estudos Retrospectivos , Glioma/genética , Astrocitoma/genética , Mutação , Temozolomida/uso terapêutico , Genômica , Isocitrato Desidrogenase/genética
3.
Cureus ; 15(7): e42350, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37621789

RESUMO

Giant cell arteritis (GCA), known as temporal arteritis, is a serious condition requiring immediate treatment to prevent complications. GCA can be difficult to diagnose, especially in emergency department (ED) settings where ophthalmology and rheumatology services may be unavailable. Temporal artery ultrasound (TAUS) is a valuable tool for diagnosing GCA. In the ED, TAUS can be used to quickly rule out GCA and avoid unindicated steroid treatment, which can cause serious morbidity in elderly patients. This article discusses the use of TAUS for evaluating patients with suspected GCA in the ED and its potential to expedite treatment and ensure appropriate, timely follow-up for patients with this potential vision and life-threatening condition.

4.
Arthritis Rheumatol ; 75(10): 1703-1713, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37494275

RESUMO

OBJECTIVE: Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic arthritis. The American College of Rheumatology (ACR) and EULAR have developed the first-ever validated classification criteria for symptomatic CPPD disease. METHODS: Supported by the ACR and EULAR, a multinational group of investigators followed established methodology to develop these disease classification criteria. The group generated lists of candidate items and refined their definitions, collected de-identified patient profiles, evaluated strengths of associations between candidate items and CPPD disease, developed a classification criteria framework, and used multi-criterion decision analysis to define criteria weights and a classification threshold score. The criteria were validated in an independent cohort. RESULTS: Among patients with joint pain, swelling, or tenderness (entry criterion) whose symptoms are not fully explained by an alternative disease (exclusion criterion), the presence of crowned dens syndrome or calcium pyrophosphate crystals in synovial fluid are sufficient to classify a patient as having CPPD disease. In the absence of these findings, a score >56 points using weighted criteria, comprising clinical features, associated metabolic disorders, and results of laboratory and imaging investigations, can be used to classify as CPPD disease. These criteria had a sensitivity of 92.2% and specificity of 87.9% in the derivation cohort (190 CPPD cases, 148 mimickers), whereas sensitivity was 99.2% and specificity was 92.5% in the validation cohort (251 CPPD cases, 162 mimickers). CONCLUSION: The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.


Assuntos
Calcinose , Pirofosfato de Cálcio , Condrocalcinose , Reumatologia , Humanos , Condrocalcinose/diagnóstico por imagem , Síndrome , Estados Unidos
5.
Ann Rheum Dis ; 82(10): 1248-1257, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37495237

RESUMO

OBJECTIVE: Calcium pyrophosphate deposition (CPPD) disease is prevalent and has diverse presentations, but there are no validated classification criteria for this symptomatic arthritis. The American College of Rheumatology (ACR) and EULAR have developed the first-ever validated classification criteria for symptomatic CPPD disease. METHODS: Supported by the ACR and EULAR, a multinational group of investigators followed established methodology to develop these disease classification criteria. The group generated lists of candidate items and refined their definitions, collected de-identified patient profiles, evaluated strengths of associations between candidate items and CPPD disease, developed a classification criteria framework, and used multi-criterion decision analysis to define criteria weights and a classification threshold score. The criteria were validated in an independent cohort. RESULTS: Among patients with joint pain, swelling, or tenderness (entry criterion) whose symptoms are not fully explained by an alternative disease (exclusion criterion), the presence of crowned dens syndrome or calcium pyrophosphate crystals in synovial fluid are sufficient to classify a patient as having CPPD disease. In the absence of these findings, a score>56 points using weighted criteria, comprising clinical features, associated metabolic disorders, and results of laboratory and imaging investigations, can be used to classify as CPPD disease. These criteria had a sensitivity of 92.2% and specificity of 87.9% in the derivation cohort (190 CPPD cases, 148 mimickers), whereas sensitivity was 99.2% and specificity was 92.5% in the validation cohort (251 CPPD cases, 162 mimickers). CONCLUSION: The 2023 ACR/EULAR CPPD disease classification criteria have excellent performance characteristics and will facilitate research in this field.


Assuntos
Calcinose , Condrocalcinose , Reumatologia , Humanos , Estados Unidos , Condrocalcinose/diagnóstico por imagem , Pirofosfato de Cálcio , Síndrome
6.
Ann Rheum Dis ; 82(4): 556-564, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36600183

RESUMO

OBJECTIVES: To develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties. METHODS: The OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima-media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24. RESULTS: Agreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72-0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from -1.19 to -2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corrcoeff 0.37-0.48). CONCLUSION: We developed a provisional OGUS for potential use in clinical trials.


Assuntos
Arterite de Células Gigantes , Humanos , Arterite de Células Gigantes/diagnóstico por imagem , Espessura Intima-Media Carotídea , Reprodutibilidade dos Testes , Estudos Prospectivos , Artérias Temporais/diagnóstico por imagem , Ultrassonografia/métodos
7.
Arthritis Care Res (Hoboken) ; 75(4): 825-834, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35439343

RESUMO

OBJECTIVE: To develop definitions for imaging features being considered as potential classification criteria for calcium pyrophosphate deposition (CPPD) disease, additional to clinical and laboratory criteria, and to compile example images of CPPD on different imaging modalities. METHODS: The American College of Rheumatology and European Alliance of Associations for Rheumatology CPPD classification criteria Imaging Advisory Group (IAG) and Steering Committee drafted definitions of imaging features that are characteristic of CPPD on conventional radiography (CR), conventional computed tomography (CT), dual-energy CT (DECT), and magnetic resonance imaging (MRI). An anonymous expert survey was undertaken by a 35-member Combined Expert Committee, including all IAG members. The IAG and 5 external musculoskeletal radiologists with expertise in CPPD convened virtually to further refine item definitions and voted on example images illustrating CR, CT, and DECT item definitions, with ≥90% agreement required to deem them acceptable. RESULTS: The Combined Expert Committee survey indicated consensus on all CR definitions. The IAG and external radiologists reached consensus on CT and DECT item definitions, which specify that calcium pyrophosphate deposits appear less dense than cortical bone. The group developed an MRI definition and acknowledged limitations of this modality for CPPD. Ten example images for CPPD were voted acceptable (4 CR, 4 CT, and 2 DECT), and 3 images of basic calcium phosphate deposition were voted acceptable to serve as contrast against imaging features of CPPD. CONCLUSION: An international group of rheumatologists and musculoskeletal radiologists defined imaging features characteristic of CPPD on CR, CT, and DECT and assembled a set of example images as a reference for future clinical research studies.


Assuntos
Calcinose , Condrocalcinose , Humanos , Condrocalcinose/diagnóstico por imagem , Pirofosfato de Cálcio , Consenso , Radiografia
8.
Rheumatology (Oxford) ; 62(6): 2247-2251, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36218483

RESUMO

OBJECTIVES: Gout prevalence is reportedly ∼20% higher in US Black adults than Whites, but racial differences in emergency department (ED) visits and hospitalizations for gout are unknown. We evaluated the latest US national utilization datasets according to racial/ethnic groups. METHODS: Using 2019 US National Emergency Department Sample and National Inpatient Sample databases, we compared racial/ethnic differences in annual population rates of ED visits and hospitalizations for gout (primary discharge diagnosis) per 100 000 US adults (using 2019 age- and sex-specific US census data). We also examined rates of ED visits and hospitalizations for gout among all US ED visits/hospitalizations and mean costs for each gout encounter. RESULTS: Compared with White patients, the per capita age- and sex-adjusted rate ratio (RR) of gout primary ED visits for Black patients was 5.01 (95% CI 4.96, 5.06), for Asian patients 1.29 (1.26, 1.31) and for Hispanic patients 1.12 (1.10, 1.13). RRs for gout primary hospitalizations were 4.07 (95% CI 3.90, 4.24), 1.46 (1.34, 1.58) and 1.06 (0.99, 1.13), respectively. Corresponding RRs among total US hospitalizations were 3.17 (95% CI 2.86, 3.50), 3.23 (2.71, 3.85) and 1.43 (1.21, 1.68) and among total ED visits were 2.66 (95% CI, 2.50, 2.82), 3.28 (2.64, 4.08), and 1.14 (1.05, 1.24), respectively. RRs were largest among Black women. Costs for ED visits and hospitalizations experienced by race/ethnicity showed similar disparities. CONCLUSIONS: These first nationwide data found a substantial excess in both gout primary ED visits and hospitalizations experienced by all underserved racial/ethnic groups, particularly by Black women, revealing an urgent need for improved care to eliminate inequities in gout outcomes.


Assuntos
Serviço Hospitalar de Emergência , Utilização de Instalações e Serviços , Gota , Disparidades em Assistência à Saúde , Hospitalização , Adulto , Feminino , Humanos , Masculino , Serviço Hospitalar de Emergência/estatística & dados numéricos , Etnicidade , Gota/epidemiologia , Gota/etnologia , Gota/terapia , Hispânico ou Latino/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Estados Unidos/epidemiologia , Disparidades em Assistência à Saúde/etnologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Utilização de Instalações e Serviços/estatística & dados numéricos , Negro ou Afro-Americano/estatística & dados numéricos , Brancos/estatística & dados numéricos , Asiático
9.
Sci Rep ; 12(1): 14083, 2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-35982066

RESUMO

Oligodendrogliomas are typically associated with the most favorable prognosis among diffuse gliomas. However, many of the tumors progress, eventually leading to patient death. To characterize the changes associated with oligodendroglioma recurrence and progression, we analyzed two recurrent oligodendroglioma tumors upon diagnosis and after tumor relapse based on whole-genome and RNA sequencing. Relapsed tumors were diagnosed as glioblastomas with an oligodendroglioma component before the World Health Organization classification update in 2016. Both patients died within 12 months after relapse. One patient carried an inactivating POLE mutation leading to a clearly hypermutated progressed tumor. Strikingly, both relapsed tumors carried focal chromosomal rearrangements in PTPRD and CNTNAP2 genes with associated decreased gene expression. TP53 mutation was also detected in both patients after tumor relapse. In The Cancer Genome Atlas (TCGA) diffuse glioma cohort, PTPRD and CNTNAP2 expression decreased by tumor grade in oligodendrogliomas and PTPRD expression also in IDH-mutant astrocytomas. Low expression of the genes was associated with poor overall survival. Our analysis provides information about aggressive oligodendrogliomas with worse prognosis and suggests that PTPRD and CNTNAP2 expression could represent an informative marker for their stratification.


Assuntos
Astrocitoma , Neoplasias Encefálicas , Glioma , Oligodendroglioma , Astrocitoma/patologia , Biomarcadores , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/patologia , Glioma/patologia , Humanos , Isocitrato Desidrogenase/genética , Proteínas de Membrana/genética , Mutação , Recidiva Local de Neoplasia , Proteínas do Tecido Nervoso/genética , Oligodendroglioma/patologia , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/genética
10.
Pain Physician ; 25(2): E319-E329, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35322987

RESUMO

BACKGROUND: Medial knee pain is a common complaint in the adult population. When conservative measures fail, intraarticular knee corticosteroid injections are often offered through the superolateral approach into the suprapatellar recess to provide short-term relief. However, some patients fail to respond and require alternative approaches. The anteromedial joint line (AMJL) approach, which targets the medial compartment, may be more effective when pain-generating pathologies such as synovitis are located in the medial compartment. To date, there have been no dedicated studies evaluating ultrasound-guided (USg) corticosteroid injections through the AMJL approach to reduce medial knee pain. OBJECTIVES: The current study aims to assess the clinical characteristics, ultrasound findings, and clinical outcomes for patients with medial knee pain who received USg corticosteroid injections via the AMJL approach. STUDY DESIGN: Retrospective study. SETTING: This study took place at one academic musculoskeletal ultrasound clinic at an urban tertiary care center. METHODS: Sixty-five patients (76 knees; 11 patients with bilateral injections) with medial knee pain who had received USg-AMJL corticosteroid injections from January 2016 through  March 2020 were reviewed for inclusion. Baseline demographic information and clinical characteristics from one year prior to 6 months following USg-AMJL injection were analyzed for each patient. Responders were defined as those who reported pain relief, decreased usage of analgesic medications, or increased physical activity. Nonresponders  were defined as those not meeting any of the responder endpoints. RESULTS: Within one year prior to receiving a USg-AMJL injection, 51.3% (39/76 knees) had attempted superolateral knee injections without relief. Immediately following a USg-AMJL injection, 98.7% (75/76) experienced symptomatic relief. Follow-up visits took place on average at 11 weeks postinjection with 92.3% (60/65 patients) responding positively. In comparison to the responder group, the nonresponder group had a significantly older mean age (P = 0.009), lower mean body mass index (P = 0.007), and higher burden of morbidities as measured by the Charlson Comorbidity Index (P = 0.044). One patient reported a steroid flare within one week of injection. The most common diagnoses contributing to medial knee pain for these patients were osteoarthritis, medial meniscal injury, crystal arthropathy, and medial collateral ligament injury, which were supported by point-of-care ultrasound findings. LIMITATIONS: This study was limited by its sample size and retrospective observational design. CONCLUSIONS: USg AMJL injection is a safe and effective procedure for targeting medial knee pain, particularly in the settings of obesity and prior failed superolateral and suprapatellar knee injections. Further investigation is required to assess long-term clinical outcomes of this injection approach.


Assuntos
Osteoartrite do Joelho , Dor , Corticosteroides/uso terapêutico , Adulto , Humanos , Injeções Intra-Articulares , Articulação do Joelho , Osteoartrite do Joelho/tratamento farmacológico , Dor/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Ultrassonografia de Intervenção/métodos
13.
Arthritis Care Res (Hoboken) ; 74(10): 1649-1658, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-33973414

RESUMO

OBJECTIVE: Classification criteria for calcium pyrophosphate deposition (CPPD) disease will facilitate clinical research on this common crystalline arthritis. Our objective was to report on the first 2 phases of a 4-phase process for developing CPPD classification criteria. METHODS: CPPD classification criteria development is overseen by a 12-member steering committee. Item generation (phase I) included a scoping literature review of 5 literature databases and contributions from a 35-member combined expert committee and 2 patient research partners. Item reduction and refinement (phase II) involved a combined expert committee meeting, discussions among clinical, imaging, and laboratory advisory groups, and an item-rating exercise to assess the influence of individual items toward classification. The steering committee reviewed the modal rating score for each item (range -3 [strongly pushes away from CPPD] to +3 [strongly pushes toward CPPD]) to determine items to retain for future phases of criteria development. RESULTS: Item generation yielded 420 items (312 from the literature, 108 from experts/patients). The advisory groups eliminated items that they agreed were unlikely to distinguish between CPPD and other forms of arthritis, yielding 127 items for the item-rating exercise. Fifty-six items, most of which had a modal rating of +/- 2 or 3, were retained for future phases. As numerous imaging items were rated +3, the steering committee recommended focusing on imaging of the knee and wrist and 1 additional affected joint for calcification suggestive of CPP crystal deposition. CONCLUSION: A data- and expert-driven process is underway to develop CPPD classification criteria. Candidate items comprise clinical, imaging, and laboratory features.


Assuntos
Condrocalcinose , Artropatias por Cristais , Pirofosfato de Cálcio , Condrocalcinose/diagnóstico , Humanos , Articulação do Joelho , Articulação do Punho
14.
J Immunother Cancer ; 9(9)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34544895

RESUMO

BACKGROUND: In 2017, Massachusetts General Hospital implemented the Severe Immunotherapy Complications (SIC) Service, a multidisciplinary care team for patients hospitalized with immune-related adverse events (irAEs), a unique spectrum of toxicities associated with immune checkpoint inhibitors (ICIs). This study's objectives were to evaluate the intervention's (1) effect on patient outcomes and healthcare utilization, and (2) ability to collect biological samples via a central infrastructure, in order to study the mechanisms responsible for irAEs. METHODS: A hospital database was used to identify patients who received ICIs for a malignancy and were hospitalized with severe irAEs, before (April 2, 2016-October 3, 2017) and after (October 3, 2017-October 24, 2018) SIC Service initiation. The primary outcome was readmission rate after index hospitalization. Secondary outcomes included length of stay (LOS) for admissions, corticosteroid and non-steroidal second-line immunosuppression use, ICI discontinuation, and inpatient mortality. RESULTS: In the pre-SIC period, 127 of 1169 patients treated with ICIs were hospitalized for irAEs; in the post-SIC period, 122 of 1159. After SIC service initiation, reductions were observed in irAE readmission rate (14.8% post-SIC vs 25.9% pre-SIC; OR 0.46; 95% CI 0.22 to 0.95; p=0.036) and readmission LOS (median 6 days post-SIC vs 7 days pre-SIC; 95% CI -16.03 to -0.14; p=0.046). No significant pre-initiation and post-initiation differences were detected in corticosteroid use, second-line immunosuppression, ICI discontinuation, or inpatient mortality rates. The SIC Service collected 789 blood and tissue samples from 234 patients with suspected irAEs. CONCLUSIONS: This is the first study to report that establishing a highly subspecialized care team focused on irAEs is associated with improved patient outcomes and reduced healthcare utilization. Furthermore, the SIC Service successfully integrated blood and tissue collection safety into routine care.


Assuntos
Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Neoplasias/tratamento farmacológico , Ciência Translacional Biomédica/métodos , Feminino , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
15.
Oncologist ; 26(6): 514-522, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33655682

RESUMO

BACKGROUND: The aim of this study was to characterize severe immune-related adverse events (irAEs) seen among hospitalized patients and to examine risk factors for irAE admissions and clinically relevant outcomes, including length of stay, immune checkpoint inhibitor (ICI) discontinuation, readmission, and death. METHODS: Patients who received ICI therapy (ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, avelumab, or any ICI combination) at Massachusetts General Hospital (MGH) and were hospitalized at MGH following ICI initiation between January 1, 2011, and October 24, 2018, were identified using pharmacy and hospital admission databases. Medical records of all irAE admissions were reviewed, and specialist review with defined criteria was performed. Demographic data, relevant clinical history (malignancy type and most recent ICI regimen), and key admission characteristics, including dates of admission and discharge, immunosuppressive management, ICI discontinuation, readmission, and death, were collected. RESULTS: In total, 450 admissions were classified as irAE admissions and represent the study's cohort. Alongside the increasing use of ICIs at our institution, the number of patients admitted to MGH for irAEs has gradually increased every year from 9 in 2011 to 92 in 2018. The hospitalization rate per ICI recipient has declined over that same time period (25.0% in 2011 to 8.5% in 2018). The most common toxicities leading to hospitalization in our cohort were gastrointestinal (30.7%; n = 138), pulmonary (15.8%; n = 71), hepatic (14.2%; n = 64), endocrine (12.2%; n = 55), neurologic (8.4%; n = 38), cardiac (6.7%; n = 30), and dermatologic (4.4%; n = 20). Multivariable logistic regression revealed statistically significant increases in irAE admission risk for CTLA-4 monotherapy recipients (odds ratio [OR], 2.02; p < .001) and CTLA-4 plus PD-1 combination therapy recipients (OR, 1.88; p < .001), relative to PD-1/PD-L1 monotherapy recipients, and patients with multiple toxicity had a 5-fold increase in inpatient mortality. CONCLUSION: This study illustrates that cancer centers must be prepared to manage a wide variety of irAE types and that CTLA-4 and combination ICI regimens are more likely to cause irAE admissions, and earlier. In addition, admissions for patients with multi-organ involvement is common and those patients are at highest risk of inpatient mortality. IMPLICATIONS FOR PRACTICE: The number of patients admitted to Massachusetts General Hospital for immune-related adverse events (irAEs) has gradually increased every year and the most common admissions are for gastrointestinal (30.7%), pulmonary (15/8%), and hepatic (14.2%) events. Readmission rates are high (29% at 30 days, 49% at 180 days) and 64.2% have to permanently discontinue immune checkpoint inhibitor therapy. Importantly, multiple concurrent toxicities were seen in 21.6% (97/450) of irAE admissions and these patients have a fivefold increased risk of inpatient death.


Assuntos
Antineoplásicos Imunológicos , Neoplasias/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/efeitos adversos , Estudos de Coortes , Feminino , Hospitalização , Humanos , Pacientes Internados , Masculino , Massachusetts , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
Pathog Glob Health ; 115(3): 135-136, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33475047

RESUMO

The coronavirus pandemic has exposed not only the lack of preparation to combat the deadly disease, but also the nature of response by governments worldwide. This article analyses how some governments suppress science reporting in the Asia Pacific region during the pandemic. It also highlights how the political interference in science undermines liability and openness leading to the lack of freedom to express facts honestly.


Assuntos
COVID-19/epidemiologia , Notificação de Doenças , Ásia , COVID-19/psicologia , Surtos de Doenças/estatística & dados numéricos , Saúde Global , Governo , Humanos , Pandemias , Política , Revelação da Verdade
17.
Clin Rheumatol ; 40(1): 321-330, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32506316

RESUMO

INTRODUCTION/OBJECTIVES: Musculoskeletal ultrasound (MSUS) has been extensively studied by rheumatologists in Europe and the Americas, but less is known about MSUS use in Asia. Our hypothesis is that MSUS use is less prevalent in China as compared with its Western counterparts. This study reports the most up-to-date recommendations for MSUS use in rheumatology globally and is also the first study to characterize the current practices, training, and perceptions regarding MSUS of rheumatologists in China. METHOD: A 43-question survey was designed and distributed via mobile application to members of the Chinese Rheumatology Association, primarily to investigate the current prevalence and utilization of MSUS in China. Statistical analyses included the use of chi-square tests and independent-samples t tests, with p values less than 0.05 considered statistically significant. RESULTS: The results showed low rates of MSUS training (129/528, 24%) and current MSUS use (89/524, 17%) in China. However, there was a high level of interest in learning MSUS, especially among younger respondents. Lack of access to training programs and user variability in skill were seen as significant barriers to the uptake of MSUS. CONCLUSIONS: Despite low rates of MSUS training and utilization, the vast majority of respondents believe that MSUS should become a standard clinical tool in rheumatology, and there was great interest in undergoing training. Importantly, lack of access to MSUS training programs and user variability in skill were seen as significant obstacles to the more widespread use of MSUS, which suggests a need for more standardized, high-quality MSUS training in China. Key Points • A low percentage of Chinese rheumatologists (17%) currently use MSUS. • Chinese rheumatologists expressed a high level of interest in obtaining MSUS training. • The greatest perceived obstacle to more widespread MSUS use is the lack of training programs.


Assuntos
Doenças Musculoesqueléticas , Reumatologia , Ásia , China , Competência Clínica , Europa (Continente) , Humanos , Reumatologistas , Reumatologia/educação , Ultrassonografia
19.
Artigo em Inglês | MEDLINE | ID: mdl-33104967

RESUMO

In response to the coronavirus pandemic, several countries have imposed curfews, quarantines, and lockdowns to restrict the spread of the infection among people. India had initiated a nationwide lockdown to combat the pandemic starting from the last week of March until the end of May 2020. But, the lockdown had continued subsequently in several red zones across parts of the country for few months. However, scientists have criticized the government's abrupt lockdown since it prevented people from preparing for the worst aftermath. Besides, the curfews have blocked millions of impoverished migrant workers from leaving cities to return to their homes in distant rural villages. As a result, the destitute workers have endured enormous hardship and outright discrimination desolately leading to their added physical and mental distress, pain, suffering, and death. Most of the victims of the lockdown have belonged to the economically distressed lower social classes of the Indian caste hierarchy. This article outlines their sufferings triggered by the long drawn-out lockdown episode.


Assuntos
COVID-19/prevenção & controle , Pobreza , Quarentena , COVID-19/epidemiologia , Disparidades nos Níveis de Saúde , Humanos , Índia/epidemiologia , Preconceito , Migrantes/psicologia , Migrantes/estatística & dados numéricos
20.
ACR Open Rheumatol ; 2(7): 438-448, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32597564

RESUMO

OBJECTIVE: This study sought to develop and employ a comprehensive and standardized ultrasound (US) protocol and scoring atlas for the evaluation of features relevant to knee osteoarthritis (KOA) in a community-based cohort in the United States, with the goals of demonstrating feasibility, reliability, and validity. METHODS: We utilized data from the fourth follow-up (2016-2018) of the Johnston County OA Project, which includes individuals with (~50%) and without radiographic KOA. All participants underwent standardized knee radiography and completed standard questionnaires including the Knee Injury and Osteoarthritis Outcome Score (KOOS). Bilateral knee US images were obtained by a trained sonographer using a standardized protocol and scored by trained rheumatologists using an atlas developed for this study. A total of 396 knees were each scored by two readers according to the atlas. Associations between US features, radiographic findings (graded by an expert radiologist), and KOOS scores were assessed. RESULTS: Overall interreader reliability for US scoring was fair to moderate. The strongest correlations between US and radiographic features were seen for osteophytes, and similarly strong correlations were seen between US osteophytes and overall radiographic Kellgren-Lawrence Grade, demonstrating criterion validity. Features of effusion/synovitis and osteophytes were most associated with KOOS pain and impaired function. CONCLUSION: US is a feasible, reliable, and valid method to assess features relevant to KOA in clinical and research settings. The protocol and atlas developed in this study can be utilized to evaluate KOA in a standardized fashion in future clinical studies, enabling greater utilization of this valuable modality in osteoarthritis.

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