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BACKGROUND: People with human immunodeficiency virus (HIV) (PWH) have an increased risk of cardiovascular disease (CVD). Cardiac magnetic resonance (CMR) has documented higher myocardial fibrosis, inflammation, and steatosis in PWH, but studies have mostly relied on healthy volunteers as comparators and focused on men. METHODS: We investigated the associations of HIV and HIV-specific factors with CMR phenotypes in female participants enrolled in the Women's Interagency HIV Study's New York and San Francisco sites. Primary phenotypes included myocardial native (n) T1 (fibro-inflammation), extracellular volume fraction (fibrosis), and triglyceride content (steatosis). Associations were evaluated with multivariable linear regression, and results pooled or meta-analyzed across centers. RESULTS: Among 261 women with HIV (WWH, N = 362), 76.2% had undetectable viremia at CMR. For the 82.8% receiving continuous antiretroviral therapy (ART) in the preceding 5 years, adherence was 51.7%, and 69.4% failed to achieve persistent viral suppression (40.7% with peak viral load <200â cp/mL). Overall, WWH showed higher nT1 than women without HIV after full adjustment. This higher nT1 was more pronounced in those with antecedent or current viremia or nadir CD4+ count <200â cells/µL, with the latter also associated with higher extracellular volume fraction. WWH and current CD4+ count <200â cells/µL had less cardiomyocyte steatosis. Cumulative exposure to specific ART showed no associations. CONCLUSIONS: Compared with sociodemographically similar women without HIV, WWH on ART exhibit higher myocardial fibro-inflammation, which is more prominent with unsuppressed viremia or CD4+ lymphopenia. These findings support the importance of improved ART adherence strategies, along with better understanding of latent infection, to mitigate cardiac end-organ damage in this population.
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Infecções por HIV , Humanos , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Pessoa de Meia-Idade , Adulto , Cardiomiopatias , Carga Viral , Fatores de Risco , Imageamento por Ressonância Magnética , Miocárdio/patologiaRESUMO
OBJECTIVES: Stool characteristics may change depending on the endoscopic activity of ulcerative colitis (UC). We developed a deep learning model using stool photos of patients with UC (DLSUC) to predict endoscopic mucosal inflammation. METHODS: This was a prospective multicenter study conducted in six tertiary referral hospitals. Patients scheduled to undergo endoscopy for mucosal inflammation monitoring were asked to take photos of their stool using smartphones within 1 week before the day of endoscopy. DLSUC was developed using 2161 stool pictures from 306 patients and tested on 1047 stool images from 126 patients. The ulcerative colitis endoscopic index of severity (UCEIS) was used to define endoscopic activity. The performance of DLSUC in endoscopic activity prediction was compared with that of fecal calprotectin (Fcal). RESULTS: The area under the receiver operating characteristic curve (AUC) of DLSUC for predicting endoscopic activity was 0.801 (95% confidence interval [CI] 0.717-0.873), which was not statistically different from the AUC of Fcal (0.837 [95% CI, 0.767-0.899, DeLong's P=0.458]). When rectal sparing cases (23/126, 18.2%) were excluded, the AUC of DLSUC increased to 0.849 (95% CI, 0.760-0.919). The accuracy, sensitivity, and specificity of DLSUC in predicting endoscopic activity were 0.746, 0.662, and 0.877 in all patients and 0.845, 0.745, and 0.958 in patients without rectal sparing, respectively. Active patients classified by DLSUC were more likely to experience disease relapse during a median 8-month follow-up (log-rank test, P=0.002). CONCLUSIONS: DLSUC demonstrated a good discriminating power similar to that of Fcal in predicting endoscopic activity with improved accuracy in patients without rectal sparing. This study implies that stool photos are a useful monitoring tool for typical UC.
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PURPOSE: Liver T1 mapping techniques typically require long breath holds or long scan time in free-breathing, need correction for B 1 + inhomogeneities and process composite (water and fat) signals. The purpose of this work is to accelerate the multi-slice acquisition of liver water selective T1 (wT1) mapping in a single breath hold, improving the k-space sampling efficiency. METHODS: The proposed continuous inversion-recovery (IR) Look-Locker methodology combines a single-shot gradient echo spiral readout, Dixon processing and a dictionary-based analysis for liver wT1 mapping at 3 T. The sequence parameters were adapted to obtain short scan times. The influence of fat, B 1 + inhomogeneities and TE on the estimation of T1 was first assessed using simulations. The proposed method was then validated in a phantom and in 10 volunteers, comparing it with MRS and the modified Look-Locker inversion-recovery (MOLLI) method. Finally, the clinical feasibility was investigated by comparing wT1 maps with clinical scans in nine patients. RESULTS: The phantom results are in good agreement with MRS. The proposed method encodes the IR-curve for the liver wT1 estimation, is minimally sensitive to B 1 + inhomogeneities and acquires one slice in 1.2 s. The volunteer results confirmed the multi-slice capability of the proposed method, acquiring nine slices in a breath hold of 11 s. The present work shows robustness to B 1 + inhomogeneities ( wT 1 , No B 1 + = 1.07 wT 1 , B 1 + - 45.63 , R 2 = 0.99 ) , good repeatability ( wT 1 , 2 ° = 1 . 0 wT 1 , 1 ° - 2.14 , R 2 = 0.96 ) and is in better agreement with MRS ( wT 1 = 0.92 wT 1 MRS + 103.28 , R 2 = 0.38 ) than is MOLLI ( wT 1 MOLLI = 0.76 wT 1 MRS + 254.43 , R 2 = 0.44 ) . The wT1 maps in patients captured diverse lesions, thus showing their clinical feasibility. CONCLUSION: A single-shot spiral acquisition can be combined with a continuous IR Look-Locker method to perform rapid repeatable multi-slice liver water T1 mapping at a rate of 1.2 s per slice without a B 1 + map. The proposed method is suitable for nine-slice liver clinical applications acquired in a single breath hold of 11 s.
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Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Interpretação de Imagem Assistida por Computador/métodos , Fígado/diagnóstico por imagem , Abdome , Respiração , Imagens de Fantasmas , Reprodutibilidade dos Testes , CoraçãoRESUMO
Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed at investigating this regimen's efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age: 63 years). The overall response rate was 90% in responseevaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, highrisk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2 to 3 months prior to start of KRd treatment significantly decreased PFS and overall survival (OS) in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e.delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AEs) were observed in 56% of the patients, and non-fatal or fatal AE's that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM.
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This study aimed to determine the clinicopathological predictive factors of peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), and nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (nTFH, AI-type). In this single-centered, retrospective study, medical records of 59 patients who were diagnosed with PTCL, NOS, or nTFH, AI-type from March 2007 to September 2022 were reviewed. The clinicopathological variables, including immunohistochemistry(IHC) subgroups, distinguishing TBX21 from the GATA3 subgroups were analyzed. Overall, 28 patients (75.7%) in the TBX21 group were PTCL, NOS. There were 9 (24.3%) patients in the GATA3 group. In univariable analyses, lymphoma subtype, age, and performance status were associated with progression-free survival (PFS), and overall survival (OS). In multivariable analyses, lymphoma subtype, and performance status were related to PFS and OS (P = 0.012, P < 0.001, P = 0.006, and P < 0.001, respectively). The GATA3 subgroup tended to have a worse prognosis in univariable analyses; however, it became more insignificant in multivariable when lymphoma subtype and performance status were adjusted (P = 0.065, P = 0.180, P = 0.972, and P = 0.265, respectively). The double-positive group showed variable prognoses of better PFS and worse OS. PD-1 and PD-L1 were associated with the EBV in situ hybridization (P = 0.027, and P = 0.005), and PD-1 was associated with CD30 expression (P = 0.043). This study demonstrated the potential of IHC classification to predict prognosis for PTCL, NOS, as well as nTFH AI-type, although further validation is necessary. Treatments targeting CD30, PD-1, and PD-L1 appear promising for lymphoma treatment.
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Linfadenopatia Imunoblástica , Imunofenotipagem , Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/classificação , Linfoma de Células T Periférico/mortalidade , Linfoma de Células T Periférico/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Adulto , Linfadenopatia Imunoblástica/patologia , Linfadenopatia Imunoblástica/diagnóstico , Linfadenopatia Imunoblástica/mortalidade , Linfadenopatia Imunoblástica/classificação , Prognóstico , Idoso de 80 Anos ou mais , Proteínas com Domínio T/análise , Proteínas com Domínio T/metabolismo , Fator de Transcrição GATA3/análise , Células T Auxiliares Foliculares/imunologia , Taxa de SobrevidaRESUMO
Despite the efficacy of COVID-19 vaccines, patients with hematologic malignancy may still be fatal from COVID19. Therefore, we prospectively performed the analysis of administration of tixagevimab/cilgavimab in the real-world. In August 2022, 94 patients under active chemotherapy for lymphoma, multiple myeloma, or acute leukemia received a single dose AZD7442/Evusheld (two consecutive intramuscular injections of tixagevimab and cilgavimab, 300 mg each). Quantitative measurement of anti-SARS-CoV-2 spike protein (anti-S) and viral nucleocapsid (anti-N) titers were conducted before administration of tixagevimab/cilgavimab and at 1, 3, and 6 months after administration. Twenty-five patients (26.6%) had previously confirmed COVID-19 infection. Fifty-eight patients (61.7%) had previously received COVID-19 vaccinations, with a median of two doses (range, 1-5). The median anti-S Ab level increased from baseline (997.05 AU/mL) to 1 month (20,967.25 AU/mL), then decreased at 3 months (13,145.0 AU/mL), and 6 months (7123.0 AU/mL) (p < 0.001). There was no significant safety issue with tixagevimab/cilgavimab. With a median follow-up time of 6 months, thirteen patients (13.8%) had documented SARS-Cov-2 infection. A 20.2% rate of anti-N positivity was observed six months after the administration of tixagevimab/cilgavimab. The results of this study support the potential role of tixagevimab/cilgavimab for the prevention of symptomatic and severe COVID-19.Trial registration: KCT0007617; August 16, 2022.
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Anticorpos Monoclonais Humanizados , COVID-19 , Neoplasias Hematológicas , SARS-CoV-2 , Humanos , Pessoa de Meia-Idade , Feminino , Masculino , Idoso , COVID-19/prevenção & controle , COVID-19/epidemiologia , COVID-19/complicações , Neoplasias Hematológicas/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Antivirais/sangue , Idoso de 80 Anos ou mais , Estudos Prospectivos , Glicoproteína da Espícula de Coronavírus/imunologiaRESUMO
We studied the brain mechanisms underlying action selection in a social dilemma setting in which individuals' effortful gains are unfairly distributed among group members. A stable "worker-parasite" relationship developed when three individually operant-conditioned rats were placed together in a Skinner box equipped with response lever and food dispenser on opposite sides. Specifically, one rat, the "worker," engaged in lever-pressing while the other two "parasitic" rats profited from the worker's effort by crowding the feeder in anticipation of food. Anatomically, c-Fos expression in the anterior cingulate cortex (ACC) was significantly higher in worker rats than in parasite rats. Functionally, ACC inactivation suppressed the worker's lever-press behavior drastically under social, but only mildly under individual, settings. Transcriptionally, GABAA receptor- and potassium channel-related messenger RNA expressions were reliably lower in the worker's, relative to parasite's, ACC. These findings indicate the requirement of ACC activation for the expression of exploitable, effortful behavior, which could be mediated by molecular pathways involving GABAA receptor/potassium channel proteins.
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Comportamento de Escolha/fisiologia , Condicionamento Operante/fisiologia , Giro do Cíngulo/patologia , Tonsila do Cerebelo/metabolismo , Animais , Comportamento Animal , Tomada de Decisões/fisiologia , Masculino , Canais de Potássio/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Sprague-Dawley , Recompensa , Comportamento SocialRESUMO
BACKGROUND: End-stage kidney disease (ESKD) patients undergoing hemodialysis experience diverse neurological complications. This study investigated prefrontal cerebral blood volume (CBV) and cerebral blood flow (CBF) during hemodialysis using functional near-infrared spectroscopy (fNIRS) to analyze cerebral hemodynamic changes. METHODS: ESKD patients undergoing maintenance hemodialysis without a history of neurological disorders were enrolled prospectively. The fNIRS data were collected using a NIRSIT Lite device. The fNIRS values were recorded three times for each patient: before the start of hemodialysis (pre-HD), 1 h after the start of hemodialysis (mid-HD), and after the end of hemodialysis (post-HD). The average changes in oxy-hemoglobin (HbO2), deoxy-hemoglobin (HbR), total hemoglobin (HbT, calculated as HbO2 + HbR) concentrations, and in hemoglobin concentration difference (HbD, calculated as HbO2 - HbR) were analyzed. We then compared the differences in changes in HbO2, HbR, HbT, and HbD according to the hemodialysis period. RESULTS: Thirty hemodialysis patients were analyzed. The change in HbO2, HbT, and HbD levels showed significant differences according to the hemodialysis period. Between the pre-HD and post-HD periods, there were significant differences in changes in HbO2 (0.005 ± 0.001 µM vs. 0.015 ± 0.004 µM, p = .046) and HbT (0.006 ± 0.001 µM vs. 0.016 ± 0.008 µM, p = .029). Additionally, between pre-HD and post-HD periods, HbD tended to increase (0.005 ± 0.001 µM vs. 0.014 ± 0.004 µM, p = .094). CONCLUSIONS: We demonstrated that during one hemodialysis session, the relative change in prefrontal CBV increased post-HD compared with pre-HD. These results are expected to help understanding the mechanisms underlying the effects of hemodialysis on brain function.
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Volume Sanguíneo Cerebral , Circulação Cerebrovascular , Falência Renal Crônica , Córtex Pré-Frontal , Diálise Renal , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Masculino , Feminino , Falência Renal Crônica/terapia , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/complicações , Falência Renal Crônica/sangue , Pessoa de Meia-Idade , Circulação Cerebrovascular/fisiologia , Estudos Prospectivos , Idoso , Córtex Pré-Frontal/irrigação sanguínea , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiopatologia , Adulto , Hemoglobinas/análise , Hemoglobinas/metabolismo , HemodinâmicaRESUMO
BACKGROUND: Mechanisms underlying persistent cardiopulmonary symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (postacute sequelae of coronavirus disease 2019 [COVID-19; PASC] or "long COVID") remain unclear. This study sought to elucidate mechanisms of cardiopulmonary symptoms and reduced exercise capacity. METHODS: We conducted cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring among adults >1 year after SARS-CoV-2 infection, compared those with and those without symptoms, and correlated findings with previously measured biomarkers. RESULTS: Sixty participants (median age, 53 years; 42% female; 87% nonhospitalized; median 17.6 months after infection) were studied. At CPET, 18/37 (49%) with symptoms had reduced exercise capacity (<85% predicted), compared with 3/19 (16%) without symptoms (P = .02). The adjusted peak oxygen consumption (VO2) was 5.2 mL/kg/min lower (95% confidence interval, 2.1-8.3; P = .001) or 16.9% lower percent predicted (4.3%-29.6%; P = .02) among those with symptoms. Chronotropic incompetence was common. Inflammatory markers and antibody levels early in PASC were negatively correlated with peak VO2. Late-gadolinium enhancement on CMR and arrhythmias were absent. CONCLUSIONS: Cardiopulmonary symptoms >1 year after COVID-19 were associated with reduced exercise capacity, which was associated with earlier inflammatory markers. Chronotropic incompetence may explain exercise intolerance among some with "long COVID."
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COVID-19 , Tolerância ao Exercício , Feminino , Masculino , Humanos , Meios de Contraste , Frequência Cardíaca , SARS-CoV-2 , Gadolínio , Inflamação , FenótipoRESUMO
Materials that undergo reversible changes in form typically require top-down processing to program the microstructure of the material. As a result, it is difficult to program microscale, 3D shape-morphing materials that undergo non-uniaxial deformations. Here, a simple bottom-up fabrication approach to prepare bending microactuators is described. Spontaneous self-assembly of liquid crystal (LC) monomers with controlled chirality within 3D micromold results in a change in molecular orientation across thickness of the microstructure. As a result, heating induces bending in these microactuators. The concentration of chiral dopant is varied to adjust the chirality of the monomer mixture. Liquid crystal elastomer (LCE) microactuators doped with 0.05 wt% of chiral dopant produce needle-shaped actuators that bend from flat to an angle of 27.2 ± 11.3° at 180 °C. Higher concentrations of chiral dopant lead to actuators with reduced bending, and lower concentrations of chiral dopant lead to actuators with poorly controlled bending. Asymmetric molecular alignment inside 3D structure is confirmed by sectioning actuators. Arrays of microactuators that all bend in the same direction can be fabricated if symmetry of geometry of the microstructure is broken. It is envisioned that the new platform to synthesize microstructures can further be applied in soft robotics and biomedical devices.
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BACKGROUND: Abdominal aortic aneurysms (AAAs) may rupture before reaching maximum diameter (Dmax ) thresholds for repair. Aortic wall microvasculature has been associated with elastin content and rupture sites in specimens, but its relation to progression is unknown. PURPOSE: To investigate whether dynamic contrast-enhanced (DCE) MRI of AAA is associated with Dmax or growth. STUDY TYPE: Prospective. POPULATION: A total of 27 male patients with infrarenal AAA (mean age ± standard deviation = 75 ± 5 years) under surveillance with DCE MRI and 2 years of prior follow-up intervals with computed tomography (CT) or MRI. FIELD STRENGTH/SEQUENCE: A 3-T, dynamic three-dimensional (3D) fast gradient-echo stack-of-stars volumetric interpolated breath-hold examination (Star-VIBE). ASSESSMENT: Wall voxels were manually segmented in two consecutive slices at the level of Dmax . We measured slope to 1-minute and area under the curve (AUC) to 1 minute and 4 minutes of the signal intensity change postcontrast relative to that precontrast arrival, and, Ktrans , a measure of microvascular permeability, using the Patlak model. These were averaged over all wall voxels for association to Dmax and growth rate, and, over left/right and anterior/posterior quadrants for testing circumferential homogeneity. Dmax was measured orthogonal to the aortic centerline and growth rate was calculated by linear fit of Dmax measurements. STATISTICAL TESTS: Pearson correlation and linear mixed effects models. A P value <0.05 was considered statistically significant. RESULTS: In 44 DCE MRIs, mean Dmax was 45 ± 7 mm and growth rate in 1.5 ± 0.4 years of prior follow-up was 1.7 ± 1.2 mm per year. DCE measurements correlated with each other (Pearson r = 0.39-0.99) and significantly differed between anterior/posterior versus left/right quadrants. DCE measurements were not significantly associated with Dmax (P = 0.084, 0.289, 0.054 and 0.255 for slope, AUC at 1 minute and 4 minutes, and Ktrans , respectively). Slope and 4 minutes AUC significantly associated with growth rate after controlling for Dmax . CONCLUSION: Contrast uptake may be increased in lateral aspects of the AAA. Contrast enhancement 1-minute slope and 4-minutes AUC may be associated with a period of recent AAA growth that is independent of Dmax . EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.
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Aneurisma da Aorta Abdominal , Humanos , Masculino , Estudos Prospectivos , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/complicações , Aorta , Progressão da Doença , Imageamento por Ressonância Magnética/métodosRESUMO
OBJECTIVES: Allogeneic hematopoietic stem-cell transplantation (HCT) is the only curative option for most hematologic malignancies. However, HSCT can cause early menopause and various complications in premenopausal women. Therefore, we aimed to investigate risk factors predicting early menopause and its clinical implications among survivors post HCT. METHODS: We retrospectively analyzed 30 adult women who had received HCT at premenopausal status between 2015 and 2018. We excluded patients who had received autologous stem cell transplantation, had relapsed, or died of any cause within 2 years of HCT. RESULTS: The median age at HCT was 41.6 years (range, 22-53). Post-HCT menopause was identified in 90% of myeloablative conditioning (MAC) HCT and 55% of reduced-intensity conditioning (RIC) HCT (p = .101). In the multivariate analysis, the post-HCT menopausal risk was 21 times higher in a MAC regimen containing 4 days of busulfan (p = .016) and 9.3 times higher in RIC regimens containing 2-3 days of busulfan (p = .033) than that of non-busulfan-based conditioning regimens. CONCLUSIONS: Higher busulfan dose in conditioning regimens is the most significant risk factor affecting post-HCT early menopause. Considering our data, we need to decide on conditioning regimens and individualized fertility counseling before HCT for premenopausal women.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Adulto , Feminino , Adulto Jovem , Pessoa de Meia-Idade , Doença Enxerto-Hospedeiro/etiologia , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante Homólogo , Transplante Autólogo , Fatores de Risco , Menopausa , Condicionamento Pré-Transplante/efeitos adversosRESUMO
BACKGROUND: We aimed to compare trough infliximab levels and the development of antidrug antibody (ADA) for 1 year between Crohn's disease (CD) and ulcerative colitis (UC) patients who were biologic-naive, and to evaluate their impact on clinical outcomes. METHODS: This was a prospective, multicenter, observational study. Biologic-naive patients with moderate to severe CD or UC who started CT-P13, an infliximab biosimilar, therapy were enrolled. Trough drug and ADA levels were measured periodically for 1 year after CT-P13 initiation. RESULTS: A total of 267 patients who received CT-P13 treatment were included (CD 168, UC 99). The rates of clinical remission (72% vs. 32.3%, P <0.001) at week 54 were significantly higher in CD than in UC. The median trough drug level (µg/mL) was significantly higher in CD than in UC up to week 14 (week 2, 18.7 vs. 14.7, P <0.001; week 6, 12.5 vs. 8.6, P <0.001; week 14, 3.4 vs. 2.5, P =0.001). The median ADA level (AU/mL) was significantly lower in CD than in UC at week 2 (6.3 vs. 6.5, P =0.046), week 30 (7.9 vs. 11.8, P =0.007), and week 54 (9.3 vs. 12.3, P =0.032). Development of ADA at week 2 [adjusted odds ratio (aOR)=0.15, P =0.026], initial C-reactive protein level (aOR=0.87, P =0.032), and CD over UC (aOR=1.92, P <0.001) were independent predictors of clinical remission at week 54. CONCLUSION: Infliximab shows more favorable pharmacokinetics, including high drug trough and low ADA levels, in CD than in UC, which might result in better clinical outcomes for 1-year infliximab treatment in CD patients.
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Medicamentos Biossimilares , Colite Ulcerativa , Doença de Crohn , Humanos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Doença de Crohn/tratamento farmacológico , Infliximab/uso terapêutico , Estudos Prospectivos , Fármacos Gastrointestinais/uso terapêutico , Resultado do Tratamento , Indução de Remissão , Medicamentos Biossimilares/uso terapêuticoRESUMO
BACKGROUND AND AIMS: Perforation is a life-threatening adverse event of colonoscopy that often requires hospitalization and surgery. We aimed to prospectively assess the incidence of colonoscopy-related perforation in a multicenter registry and to analyze the clinical factors associated with poor clinical outcomes. METHODS: This prospective observational study was conducted at six tertiary referral hospitals between 2017 and 2020, and included patients with colonic perforation after colonoscopy. Poor clinical outcomes were defined as mortality, surgery, and prolonged hospitalization (> 13 days). Logistic regression was used to identify factors associated with poor clinical outcomes. RESULTS: Among 84,673 patients undergoing colonoscopy, 56 had colon perforation (0.66/1000, 95% confidence interval [CI] 0.51-0.86). Perforation occurred in 12 of 63,602 diagnostic colonoscopies (0.19/1000, 95% CI 0.11-0.33) and 44 of 21,071 therapeutic colonoscopies (2.09/1000, 95% CI 1.55-2.81). Of these, 15 (26.8%) patients underwent surgery, and 25 (44.6%) patients had a prolonged hospital stay. One patient (1.8%) died after perforation from a diagnostic colonoscopy. In the multivariate analysis, diagnostic colonoscopy (adjusted odds ratio [aOR] 196.43, p = 0.025) and abdominal rebound tenderness (aOR 17.82, p = 0.012) were independent risk factors for surgical treatment. The location of the sigmoid colon (aOR 18.57, p = 0.048), delayed recognition (aOR 187.71, p = 0.008), and abdominal tenderness (aOR 63.20, p = 0.017) were independent risk factors for prolonged hospitalization. CONCLUSIONS: This prospective study demonstrated that the incidence of colonoscopy-related perforation was 0.66/1000. The incidence rate was higher in therapeutic colonoscopy, whereas the risk for undergoing surgery was higher in patients undergoing diagnostic colonoscopy. Colonoscopy indication (diagnostic vs. therapeutic), physical signs, the location of the sigmoid perforation, and delayed recognition were independent risk factors for poor clinical outcomes in colonoscopy-related perforation.
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Doenças do Colo , Perfuração Intestinal , Humanos , Estudos Prospectivos , Incidência , Colonoscopia/efeitos adversos , Fatores de Risco , Doenças do Colo/epidemiologia , Doenças do Colo/etiologia , Doenças do Colo/cirurgia , Sistema de Registros , Perfuração Intestinal/epidemiologia , Perfuração Intestinal/etiologia , Perfuração Intestinal/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: The Helicobacter pylori eradication rate with standard triple therapy (STT) is continuously decreasing due to clarithromycin resistance. This study aimed to investigate the eradication rate of empirical and tailored therapy and explore various factors affecting this eradication rate using clarithromycin resistance test data for the last 4 years at a single institution in Daegu. METHODS: From August 2018 to July 2021, a total of 1,395 patients diagnosed with H. pylori infection based on rapid urea testing and histology at Keimyung University Dongsan Hospital were retrospectively examined. Participants were classified into the empirical and tailored therapy groups according to the results of the clarithromycin resistance test using the polymerase chain reaction. RESULTS: The overall eradication rate of empirical STT was 72.8%, and the eradication rate by year was 71.6% in 2018, 77.4% in 2019, 70.3% in 2020, and 70.6% in 2021; the differences were not statistically significant (p = 0.173). No significant difference was noted in the eradication rate according to gender, age, type of proton pump inhibitors, and use of probiotics. Significant differences were noted in the eradication rate according to the treat-ment period: 69.7% in the 7-day, 67.3% in the 10-day, and 81.4% in the 14-day group (p = 0.001). The eradication rate with STT was 87.4% in the non-resistant group. In the case of clarithromycin resistance, treatment was mainly with bismuth quadruple therapy (BQT), and the eradication rate was 86.1%. The eradication rate was higher with administration of BQT for 10 days or 14 days than for administration of BQT for 7 days, but with no statistical significance (p = 0.364). CONCLUSIONS: Extending the treatment period of STT helped in improving the eradication rate, and tailored therapy through clarithromycin resistance testing showed superior results when compared to empirical therapy.
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Infecções por Helicobacter , Helicobacter pylori , Humanos , Claritromicina/uso terapêutico , Claritromicina/farmacologia , Antibacterianos/uso terapêutico , Estudos Retrospectivos , Quimioterapia Combinada , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Bismuto/uso terapêutico , Resultado do TratamentoRESUMO
PURPOSE: The purpose of this study was to examine differences in functional connectivity between patients with end-stage renal disease (ESRD) with and without restless legs syndrome (RLS). In addition, the study aimed to identify any potential associations between RLS severity and functional connectivity. METHODS: We enrolled patients with ESRD who had been undergoing hemodialysis. Patients with and without RLS were separated into two groups. Using functional near-infrared spectroscopy (fNIRS) and a graph theory approach, we determined the functional connectivity of patients with ESRD. The data were collected during a 300-s resting state evaluation performed in the dialysis room prior to dialysis. RESULTS: Eighteen of 48 patients with ESRD were diagnosed with RLS, whereas 30 patients did not exhibit RLS symptoms. Notably, functional connectivity metrics differed significantly between patients with and without RLS. Specifically, patients with ESRD and RLS displayed higher values for mean clustering coefficient (0.474 vs. 0.352, p = 0.001), global efficiency (0.520 vs. 0.414, p = 0.001), strength (6.538 vs. 4.783, p = 0.001), and transitivity (0.714 vs. 0.521, p = 0.001), while values for diameter (5.451 vs. 7.338, p = 0.002), eccentricity (4.598 vs. 5.985, p = 0.004), and characteristic path length (2.520 vs. 3.271, p = 0.002) were lower in patients with ESRD and RLS compared to those without RLS. In addition, there were correlations between the RLS severity score and the assortative coefficient (r = 0.479, p = 0.044), the small-worldness index (r = -0.475, p = 0.046), and transitivity (r = 0.500, p = 0.034). CONCLUSIONS: We demonstrated differences in functional connectivity between patients with ESRD with and without RLS, which may shed light on the pathophysiology of RLS. Notably, a number of functional connectivity metrics demonstrated strong associations with RLS severity. Our study also confirmed the applicability of fNIRS as a tool for investigating functional connectivity in patients with RLS.
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INTRODUCTION: The aims of this study were to evaluate 1) glymphatic system function in patients with end-stage kidney disease (ESKD) before initiating dialysis compared to healthy controls, and 2) changes in the glymphatic system function after kidney replacement therapy including dialysis in patients with ESKD using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) method. MATERIALS AND METHODS: This study was prospectively conducted at a single hospital. We enrolled 14 neurologically asymptomatic patients who first initiated hemodialysis or peritoneal dialysis for ESKD and 17 healthy controls. Patients had magnetic resonance imaging scans before initiating dialysis and again 3 months after initiating dialysis and the DTI-ALPS index was calculated. We compared the DTI-ALPS index before and after the initiation of dialysis and compared the DTI-ALPS index between the patients with ESKD and healthy control. RESULTS: There were differences in the DTI-ALPS index between ESKD patients before initiating dialysis and healthy controls (1.342 vs. 1.633, p = 0.003). DTI-ALPS index between ESKD patients before initiating dialysis and those after dialysis were not different (1.342 vs. 1.262, p = 0.386). There was a positive correlation between DTI-ALPS index and phosphate (r = 0.610, p = 0.020) in patients with ESKD. CONCLUSION: We confirmed the presence of glymphatic dysfunction in patients with ESKD. However, there was no difference in the glymphatic system before and after dialysis initiation. This finding may be related to uremic toxins that are not removed by dialysis in patients with ESKD. This study can be used for the development of pathophysiology of patients with ESKD.
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Sistema Glinfático , Falência Renal Crônica , Diálise Peritoneal , Humanos , Diálise Renal/efeitos adversos , Sistema Glinfático/diagnóstico por imagem , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Processamento de Imagem Assistida por ComputadorRESUMO
BACKGROUND: Severe graft versus host disease (GVHD) is the main reason for non-relapse mortality following allogeneic hematopoietic cell transplantation (HCT). We investigated the serum protein profiles of patients who had undergone HCT to identify predictive biomarkers of severe acute GVHD (aGVHD). METHODS: Serum samples were collected for 30 patients from day - 7 to day + 14 of HCT. The serum levels of plasma beta2-microglobulin (ß2-MG), soluble vascular cell adhesion molecule-1 (sVCAM-1), platelet factor 4, and TNFSF-14 were measured by ELISA as potential biomarkers following 310 cytokine profiling array. RESULTS: The median age of the study patients was 53.5 years (range, 19-69). All grade and grade 2-4 aGVHD developed in 21 (70.0%) and 17 (56.7%) patients, respectively. Compared with their baseline levels on day - 7, ß2-MG and sVCAM-1 were significantly increased on day + 14 of the HCT procedure (P = 0.028 and P < 0.001, respectively). Patients with a grade 2-4 severe aGVHD showed a significantly higher sVCAM-1 level at baseline (day-7) and at day + 14, compared with the other group with a grade 1 aGVHD or no aGVHD (P = 0.028 and P = 0.035, respectively). CONCLUSION: Higher sVCAM- levels at baseline and on day + 14 in HCT patients could be a significant predictive biomarker of severe aGVHD.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adulto , Idoso , Biomarcadores , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Pessoa de Meia-Idade , Fator Plaquetário 4 , Molécula 1 de Adesão de Célula Vascular , Adulto JovemRESUMO
BACKGROUND: Endoscopic assessment of disease activity is a key parameter in the management of ulcerative colitis. Whether sigmoidoscopy alone is sufficient to evaluate the disease activity in ulcerative colitis lacks studies. METHODS: We retrospectively analyzed the medical records and endoscopic results of patients with ulcerative colitis followed by colonoscopy in seven tertiary hospitals between January 2012 and December 2018. Endoscopic disease activity was scored using the Mayo endoscopic subscore (MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) for each segment from the colonoscopy images. Concordance was evaluated by comparing the highest MES and UCEIS in the rectosigmoid and proximal regions to confirm the usefulness of sigmoidoscopy. RESULTS: A total of 500 colonoscopic examinations from 333 patients were enrolled. Only in 7.6% [k(kappa): 0.893, r(Spearman): 0.906, p < 0.001] and 8.6% [k(kappa): 0.890, r(Spearman): 0.914; p < 0.001] of cases, MES and UCEIS scored more severely in the proximal colon. Comparison of active disease (MES ≥ 2) in the rectosigmoid area and the entire colon showed a high concordance rate [k(kappa): 0.899, r(Spearman): 0.904, p < 0.001]. Endoscopic healing (MES = 0) also showed a high concordance rate [k(kappa): 0.882, r(Spearman): 0.887, p < 0.001]. In 38 cases (7.6%) of patients with a higher MES in the proximal area, it was significantly higher in patients with previous extensive colitis. CONCLUSIONS: Sigmoidoscopy and colonoscopy showed a high concordance rate. Therefore, sigmoidoscopy is considered a sufficient substitute for colonoscopy. However, colonoscopy should be considered in patients with previous extensive colitis.
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Colite Ulcerativa , Sigmoidoscopia , Colite Ulcerativa/diagnóstico por imagem , Colonoscopia/métodos , Humanos , Estudos Retrospectivos , Índice de Gravidade de Doença , Sigmoidoscopia/métodosRESUMO
BACKGROUND: Colectomy risk after acute severe ulcerative colitis (ASUC) has not been compared between Eastern and Western countries. We compared the 1-year colectomy risk after ASUC between Korea and the USA. METHODS: Data on patients admitted for ASUC to five tertiary referral hospitals in Korea and Mount Sinai Hospital, New York, the USA, between January 2015 and January 2019 were reviewed retrospectively. For comparability between groups, a 1:1 propensity score matching (PSM) was performed. The primary outcome was colectomy, and secondary outcomes were mortality, readmission, and venous thromboembolism (VTE) within 1-year of the index admission for ASUC. The risk of each outcome was compared using Cox proportional hazards model in pre-matched cohort and Kaplan-Meier analysis with log-rank test in post-matched cohort. RESULTS: 290 ASUC patients were included in the study (121 Korea, 169 the USA). After PSM, 56 patients were selected in each group with no significant differences in baseline variables. At 1 year after ASUC, colectomy was less common in Korea than in the USA [3 (5.4%) vs. 24 (42.9%), p < 0.001]. The cumulative colectomy risk was significantly higher in the USA than in Korea in pre-matched cohort [adjusted hazard ratio 7.89, 95% confidence interval 3.23 to 19.22] and in post-matched cohort (log-rank p < 0.001), while there was no difference in cumulative risk of mortality, readmission, and VTE. CONCLUSION: Colectomy risk within 1 year of ASUC is significantly higher in the USA than in Korea. We observed no differences in mortality, readmission, and VTE between the two groups.