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BACKGROUND: Patients with antibody deficiency respond poorly to coronavirus disease 2019 (COVID-19) vaccination and are at risk of severe or prolonged infection. They are given long-term immunoglobulin replacement therapy (IRT) prepared from healthy donor plasma to confer passive immunity against infection. Following widespread COVID-19 vaccination alongside natural exposure, we hypothesized that immunoglobulin preparations will now contain neutralizing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibodies, which confer protection against COVID-19 disease and may help to treat chronic infection. METHODS: We evaluated anti-SARS-CoV-2 spike antibody in a cohort of patients before and after immunoglobulin infusion. Neutralizing capacity of patient samples and immunoglobulin products was assessed using in vitro pseudovirus and live-virus neutralization assays, the latter investigating multiple batches against current circulating Omicron variants. We describe the clinical course of 9 patients started on IRT during treatment of COVID-19. RESULTS: In 35 individuals with antibody deficiency established on IRT, median anti-spike antibody titer increased from 2123 to 10 600 U/mL postinfusion, with corresponding increase in pseudovirus neutralization titers to levels comparable to healthy donors. Testing immunoglobulin products directly in the live-virus assay confirmed neutralization, including of BQ1.1 and XBB variants, but with variation between immunoglobulin products and batches.Initiation of IRT alongside remdesivir in patients with antibody deficiency and prolonged COVID-19 infection (median 189 days, maximum >900 days with an ancestral viral strain) resulted in clearance of SARS-CoV-2 at a median of 20 days. CONCLUSIONS: Immunoglobulin preparations now contain neutralizing anti-SARS-CoV-2 antibodies that are transmitted to patients and help to treat COVID-19 in individuals with failure of humoral immunity.
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Anticorpos Neutralizantes , COVID-19 , Humanos , Glicoproteína da Espícula de Coronavírus , Vacinas contra COVID-19 , SARS-CoV-2 , Anticorpos AntiviraisRESUMO
BACKGROUND: Alterations in levels of circulating micro-RNAs might reflect within organ signaling or subclinical tissue injury that is linked to risk of diabetes and cardiovascular risk. We previously found that serum levels of miR-483-5p is correlated with cardiometabolic risk factors and incidence of cardiometabolic disease in a case-control sample from the populations-based Malmö Diet and Cancer Study Cardiovascular Cohort (MDC-CC). We here aimed at replicating these findings and to test for association with carotid atherosclerosis. METHODS: We measured miR-483-5p in fasting serum of 1223 healthy subjects from the baseline examination of the population-based, prospective cohort study Malmö Offspring Study (MOS) and correlated miR-483-5p to cardiometabolic risk factors and to incidence of diabetes mellitus and coronary artery disease (CAD) during 3.7 (± 1.3) years of follow-up using logistic regression. In both MOS and MDC-CC we related mir-483-5p to carotid atherosclerosis measured with ultrasound. RESULTS: In cross-sectional analysis miR-483-5p was correlated with BMI, waist circumference, HDL, and sex. After adjustment for age and sex, the association remained significant for all risk factors except for HDL. Logistic regression analysis showed significant associations between miR-483-5p and new-onset diabetes (OR = 1.94, 95% CI 1.06-3.56, p = 0.032) and cardiovascular disease (OR = 1.99, 95% CI 1.06-3.75, p = 0.033) during 3.7 (± 1.3) years of follow-up. Furthermore, miR-483-5p was significantly related with maximum intima-media thickness of the carotid bulb in MDC-CC (p = 0.001), but not in MOS, whereas it was associated with increasing number of plaques in MOS (p = 0.007). CONCLUSION: miR-483-5p is related to an unfavorable cardiometabolic risk factor profile and predicts diabetes and CAD, possibly through an effect on atherosclerosis. Our results encourage further studies of possible underlying mechanisms and means of modifying miR-483-5p as a possible interventional target in prevention of cardiometabolic disease.
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Síndrome Metabólica/sangue , Síndrome Metabólica/prevenção & controle , MicroRNAs/sangue , Adulto , Idoso , Biomarcadores/sangue , Fatores de Risco Cardiometabólico , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/genética , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Estudos Transversais , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/genética , Feminino , Humanos , Incidência , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/genética , MicroRNAs/genética , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Suécia , Fatores de TempoRESUMO
Combination therapy with parathyroid hormone (PTH) analogs and antiresorptive agents may be more effective than monotherapy for the treatment of osteoporosis. This study aimed to estimate the effectiveness and safety of this combination therapy for osteoporosis. MEDLINE, EMBASE, and Cochrane Library were searched from inception to May 1, 2018, including randomized controlled trials (RCTs) with a duration of at least 6 months on adults with osteoporosis treated with combination therapy versus monotherapy. Outcomes included fractures, bone mineral density (BMD) changes, and adverse events. A meta-analysis was performed using a random-effect model, to estimate risk ratios (RRs) for fractures, and mean differences (MDs) for BMD changes. A total of 19 RCTs and 2177 patients were included. Compared with monotherapy, combination therapy had an advantage of 36% (RR, 0.64; 95% confidence interval (CI), 0.42-0.98) regarding fracture risk reduction. It also appears to improve lumbar spine BMD by 4.06% (95%CI = 2.60-5.53) and total hip BMD by 1.89% (95%CI = 1.25-2.53). No RCT reported an increased risk of serious adverse events. Among patients with osteoporosis, combination therapy was superior to monotherapy regarding improvement of the lumbar spine and total hip BMD, without risk of serious adverse events. Combination therapy also had an advantage over monotherapy on fracture risk reduction. However, owing to the limited sample size, additional larger studies are required to confirm this benefit.
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Conservadores da Densidade Óssea/uso terapêutico , Osteoporose/tratamento farmacológico , Hormônio Paratireóideo/análogos & derivados , Densidade Óssea/efeitos dos fármacos , Quimioterapia Combinada , Articulação do Quadril/fisiopatologia , Humanos , Vértebras Lombares/fisiopatologia , Osteoporose/fisiopatologia , Fraturas por Osteoporose/prevenção & controle , Hormônio Paratireóideo/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
PURPOSE: Osteoporotic vertebral compression fractures (OVCFs) are common in the elderly population and are often treated using percutaneous vertebroplasty (PVP). However, the effectiveness of PVP reported by various randomized controlled trials (RCTs) is inconclusive. This study aimed to analyze, from published literature, the efficacy and safety of PVP for OVCFs. METHODS: A search was conducted in Medline, EMBASE, and Cochrane Libraries since their respective inception on January 1, 2019, for RCTs of OVCFs treated with PVP compared with non-operative treatment. The primary outcomes were pain relief at 1 to 2 weeks, 1 to 3 months, and 6 to 12 months. The secondary outcome was the rate of occurrence of new vertebral fractures. Meta-analysis was performed using a random effect model. RESULTS: A total of 13 RCTs comprising 1624 patients were included. For the blinded studies, statistical differences were found between PVP and the sham injection group for the 3 primary outcomes in the subgroup of the Vertebroplasty for Acute Painful Osteoporotic fractURes (VAPOUR) trial. Although pain scores were similar between the PVP group and the sham injection group for the VAPOUR trial at each period, the effect size of PVP increased over time. For the open-label studies, PVP significantly reduced pain at all time points. The risk of new vertebral fractures was similar between the PVP groups and control groups. CONCLUSIONS: Application of PVP was effective and safe only in patients with acute OVCFs having persistent and severe pain. No benefits were recorded, among patients with older fractures or those bearing non-severe symptoms.
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Fraturas por Compressão/cirurgia , Fraturas por Osteoporose/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Vertebroplastia/métodos , Dor nas Costas/etiologia , Dor nas Costas/cirurgia , Fraturas por Compressão/complicações , Humanos , Fraturas por Osteoporose/complicações , Manejo da Dor/métodos , Medição da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Fraturas da Coluna Vertebral/complicações , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the performance of high-resolution chromosomal microarray (CMA) as the standard diagnostic approach for genomic imbalances in pregnancies with increased risk based on combined first-trimester screening (cFTS). METHODS: This was a retrospective study of genomic findings in a cohort of 575 consecutive pregnancies undergoing invasive testing because of a cFTS risk ≥ 1:300 on a publicly funded population-based screening program in the Central and Northern Regions of Denmark, between September 2015 and September 2016. Women with fetal nuchal translucency thickness ≥ 3.5 mm or opting for non-invasive prenatal testing (NIPT) were excluded. Comparative genomic hybridization was performed using a 180-K oligonucleotide array on DNA extracted directly from chorionic villus/amniocentesis samples. Genomic outcomes were reported in relation to cFTS findings. RESULTS: Of the 575 pregnancies that underwent invasive testing, CMA detected 22 (3.8% (95% CI, 2.5-5.7%)) cases of trisomies 21, 18 and 13, 14 (2.4% (95% CI, 1.4-4.0%)) cases of other types of aneuploidy and 15 (2.6% (95% CI, 1.5-4.3%)) cases with a pathogenic or probably pathogenic copy number variant (CNV). Of the 15 CNVs, three were > 10 Mb and would probably have been detected by chromosomal analysis, but the other 12 would most probably not have been detected using conventional cytogenetic techniques; therefore, the overall detection rate of CMA (8.9% (95% CI, 6.8-11.5%)) was significantly higher than that estimated for conventional cytogenetic analysis (6.8% (95% CI, 5.0-9.1%)) (P = 0.0049). Reducing the cFTS risk threshold for invasive diagnostic testing to 1 in 100 or 1 in 50 would have led, respectively, to 60% or 100% of the pathogenic CNVs being missed. CONCLUSIONS: CMA is a valuable diagnostic technique that can identify an increased number of genomic aberrations in pregnancies at increased risk on cFTS. Limiting diagnostic testing to pregnancies with a risk above 1 in 100 or 1 in 50, as proposed in contingent NIPT/invasive testing models, would lead to a significant proportion of pathogenic CNVs being missed at first-trimester screening. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
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Variações do Número de Cópias de DNA/genética , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Análise de Sequência com Séries de Oligonucleotídeos/estatística & dados numéricos , Adulto , Amniocentese/estatística & dados numéricos , Amostra da Vilosidade Coriônica/estatística & dados numéricos , Síndrome de Down/epidemiologia , Feminino , Humanos , Programas de Rastreamento/estatística & dados numéricos , Testes para Triagem do Soro Materno , Pessoa de Meia-Idade , Medição da Translucência Nucal/estatística & dados numéricos , Valor Preditivo dos Testes , Gravidez , Primeiro Trimestre da Gravidez , Estudos Retrospectivos , Medição de Risco , Adulto JovemRESUMO
OBJECTIVE: MicroRNA (miRNA) processing genes play important roles in the craniofacial development. The aim of this study was to explore the associations between single nucleotide polymorphisms (SNPs) of miRNA processing genes with the risk of non-syndromic orofacial clefts (NSOC). METHODS: We genotyped 12 potentially functional SNPs from seven miRNA processing genes (GEMIN3, DROSHA, DGCR8, GEMIN4, PIWIL1, XPO5, and DICER) in a case-control study of 602 NSOC cases and 605 controls. RESULTS: Two SNPs were associated with the susceptibility of CL/P: rs10719 in DROSHA led to an increased risk of cleft lip with or without palate (CL/P) (GA/AA: p = .024, OR = 1.33, 95% CI = [1.04, 1.70]; GG + GA/AA: p = .037, OR = 1.29, 95% CI = [1.02, 1.63]), while rs493760 in DROSHA (CC/TT: p = .049, OR = 0.58, 95% CI = [0.34, 0.99]) could reduce the risk of CL/P. In addition, rs10719 (A)-rs493760 (C) haplotype contributed to a decreased risk of CL/P (OR = 0.77, 95% CI = [0.63, 0.94]), whereas the rs10719 (G)-rs493760 (C) haplotype contributed to the increased risk of cleft palate only (CPO) (OR = 2.70, 95% CI = [1.15, 6.35]). However, there was no difference observed in these SNPs after the Bonferroni correction. CONCLUSION: Taken together, our results provided the potential evidence that rs10719 and rs493760 might contribute to the risk of CL/P and suggested potential genetic basis and mechanisms of CL/P. The lack of association between these SNPs and CPO might be due to the limited sample size of CPO subgroup.
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Fenda Labial/genética , Fissura Palatina/genética , MicroRNAs/metabolismo , Processamento Pós-Transcricional do RNA/genética , Ribonuclease III/genética , Proteínas Argonautas/genética , Estudos de Casos e Controles , Criança , Pré-Escolar , Proteína DEAD-box 20/genética , RNA Helicases DEAD-box/genética , Feminino , Haplótipos , Humanos , Lactente , Recém-Nascido , Carioferinas/genética , Masculino , MicroRNAs/genética , Antígenos de Histocompatibilidade Menor/genética , Polimorfismo de Nucleotídeo Único , Proteínas de Ligação a RNA/genética , Ribonucleoproteínas Nucleares Pequenas/genéticaRESUMO
Variation in ecological selection pressures has been implicated to explain variation in brain size and architecture in fishes, birds and mammals, but little is known in this respect about amphibians. Likewise, the relative importance of constraint vs. mosaic hypotheses of brain evolution in explaining variation in brain size and architecture remains contentious. Using phylogenetic comparative methods, we studied interspecific variation in brain size and size of different brain parts among 43 Chinese anuran frogs and explored how much of this variation was explainable by variation in ecological factors (viz. habitat type, diet and predation risk). We also evaluated which of the two above-mentioned hypotheses best explains the observed patterns. Although variation in brain size explained on average 80.5% of the variation in size of different brain parts (supporting the constraint hypothesis), none of the three ecological factors were found to explain variation in overall brain size. However, habitat and diet type explained a significant amount of variation in telencephalon size, as well in three composite measures of brain architecture. Likewise, predation risk explained a significant amount of variation in bulbus olfactorius and optic tecta size. Our results show that evolution of anuran brain accommodates features compatible with both constraint (viz. strong allometry among brain parts) and mosaic (viz. independent size changes in response to ecological factors in certain brain parts) models of brain size evolution.
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Anuros/anatomia & histologia , Anuros/genética , Encéfalo/anatomia & histologia , Ecossistema , Filogenia , Animais , Especificidade da EspécieRESUMO
Leaching of phosphorus (P) mobilizes edaphic and applied sources of P and is a primary pathway of concern in agricultural soils of the Delmarva Peninsula, which defines the eastern boundary of the eutrophic Chesapeake Bay. We evaluated P leaching before and after poultry litter application from intact soil columns (30 cm diameter × 50 cm depth) obtained from low- and high-P members of four dominant Delmarva Peninsula soils. Surface soil textures ranged from fine sand to silt loam, and Mehlich-3 soil P ranged from 64 to 628 mg kg. Irrigation of soil columns before litter application pointed to surface soil P controls on dissolved P in leachate (with soil P sorption saturation providing a stronger relationship than Mehlich-3 P); however, strong relationships between P in the subsoil (45-50 cm) and leachate P concentrations were also observed ( = 0.61-0.73). After poultry litter application (4.5 Mg ha), leachate P concentrations and loads increased significantly for the finest-textured soils, consistent with observations that well-structured soils have the greatest propensity to transmit applied P. Phosphorus derived from poultry litter appeared to contribute 41 and 76% of total P loss in leachate from the two soils with the finest textures. Results point to soil P, including P sorption saturation, as a sound metric of P loss potential in leachate when manure is not an acute source of P but highlight the need to factor in macropore transport potential to predict leaching losses from applied P sources.
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Leaching of nutrients through agricultural soils is a priority water quality concern on the Atlantic Coastal Plain. This study evaluated the effect of tillage and urea application on leaching of phosphorus (P) and nitrogen (N) from soils of the Delmarva Peninsula that had previously been under no-till management. Intact soil columns (30 cm wide × 50 cm deep) were irrigated for 6 wk to establish a baseline of leaching response. After 2 wk of drying, a subset of soil columns was subjected to simulated tillage (0-20 cm) in an attempt to curtail leaching of surface nutrients, especially P. Urea (145 kg N ha) was then broadcast on all soils (tilled and untilled), and the columns were irrigated for another 8 wk. Comparison of leachate recoveries representing rapid and slow flows confirmed the potential to manipulate flow fractions with tillage, albeit with mixed results across soils. Leachate trends in the finer-textured soil suggest that tillage impeded macropore flow and forced greater matrix flow. Despite significant vertical stratification of soil P that suggested tillage could prevent leaching of P via macropores from the surface to the subsoil, tillage had no significant impact on P leaching losses. Relatively high levels of soil P below 20 cm may have served as the source of P enrichment in leachate waters. However, tillage did lower losses of applied urea in leachate from two of the three soils, partially confirming the study's premise that tillage would destroy macropore pathways transmitting surface constituents to the subsoil.
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OBJECTIVE: Blood and crystalloid cardioplegia are the main myocardial protective solutions used in pediatric cardiac surgery. However, the effectiveness of these two solutions on myocardial metabolism, reperfusion injury and clinical outcomes in pediatric patients is still under debate. The purpose of this meta-analysis was to compare the efficacy of these two cardioplegia solutions in pediatric cardiac surgery. METHODS: Keyword searches were performed on PUBMED, EMBASE and The Cochrane Library for randomized, controlled, clinical studies which were primarily comparing blood and crystalloid cardioplegia in pediatric cardiac surgery and provided data of postoperative cardiac troponin I (cTnI), lactate, mechanical ventilation time, length of intensive care unit (ICU) stay and inotropic support. Databases were searched from 1966 to June 2013 and were restricted to peer-reviewed English language publications of human subjects. We summarized the combined results of the data as mean difference (MD, when outcome measurements were made on the same scale) or standard mean difference (SMD, when the studies assess the same outcome with different scales), with 95% confidence intervals. RESULTS: Five studies were identified, with a total of 323 patients. Lactate level after cardiopulmonary bypass (CPB) was significantly lower after blood cardioplegia compared with crystalloid cardioplegia (SMD 1.09, 95%CI 0.12 to 2.06, p=0.03); cTnI release postoperatively at 4-6 h (MD 0.92 ng/ml, 95%CI -0.13 to 1.97, p=0.09), 12 h (MD 0.2 ng/ml, 95% CI -0.43 to 0.84, p=0.53) and 24 h (MD 0.98 ng/ml, 95%CI -0.26 to 2.22, p=0.12) was not significantly different between the groups; ventilation duration (MD 5.15 hours, 95%CI -7.51 to 17.81, p=0.42) and length of ICU stay (SMD -0.3, 95%CI -0.80 to 0.21, p=0.25) were not significantly different between the groups either. CONCLUSION: Myocardial metabolism was better in the blood cardioplegia group compared with the crystalloid cardioplegia group. However, there was no evidence of improvement in myocardial damage or clinical outcome for either cardioplegia solution.
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Transfusão de Sangue/métodos , Ponte Cardiopulmonar/métodos , Parada Cardíaca Induzida/métodos , Compostos de Potássio/uso terapêutico , Adolescente , Ponte Cardiopulmonar/efeitos adversos , Criança , Pré-Escolar , Feminino , Parada Cardíaca Induzida/efeitos adversos , Humanos , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Compostos de Potássio/efeitos adversos , Reação TransfusionalRESUMO
Keratocystic odontogenic tumour (KOT or KCOT) is defined by the WHO to be 'a benign uni- or multicystic, intraosseous tumour of odontogenic origin'. In 2005, the World Health Organization renamed the lesion; previously known as an odontogenic keratocyst (OKC) as the KCOT. WHO recommends the term KCOT as it reflects its neoplastic nature. In this case report, a 21-year-old female with a histologically proven large parakeratinised KCOT of the right mandible underwent treatment that involved a 14-month period of decompression, followed by enucleation (with Carnoys application) of the residual cyst. During the period of decompression, a custom made removable mandibular chrome-cobalt appliance was used to hold the decompression tube in the oral cavity.
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Descompressão Cirúrgica/instrumentação , Neoplasias Mandibulares/diagnóstico por imagem , Neoplasias Mandibulares/cirurgia , Tumores Odontogênicos/diagnóstico por imagem , Tumores Odontogênicos/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
BACKGROUND: Breast cancer metastasis suppressor 1 (BRMS1) is a potent metastasis suppressor of various types of malignancies, including melanoma and ovarian cancer. Unfortunately, the clinical data regarding its role as a true metastatic suppressor and its efficacy as a prognostic marker and therapeutic target remain controversial. This study was designed to investigate the effect of BRMS1 on the invasion and metastasis of human ovarian cancer cells and its potential underlying mechanisms. MATERIALS AND METHODS: BRMS1 small interfering RNAs (siRNAs) or control siRNAs were transfected into the OVCAR3 human ovarian cancer cell line. Invasion and migration activities were assessed using the Transwell invasion and migration assay. Protein levels of nuclear factor-kappaB (NF-kappaB) subunit p65, osteopontin (OPN) and urokinase-type plasminogen activator (uPA) were evaluated by Western blot, immunofluorescence and immunocytochemistry methods. RESULTS: Successful knockdown of BRMS1 was verified by quantitative real-time RT-PCR and Western blot. The invasion and migration capacities of OVCAR3 cells were significantly enhanced in the BRMS1-silenced group, compared to controls (p < 0.05). Silencing of BRMS 1 significantly induced the expression of NF-kappaB subunit, p65, uPA, and OPN proteins. CONCLUSIONS: BRMS1 inhibits expression of p65, uPA and OPN protein. In turn, this leads to inhibition of ovarian cancer cell invasion and metastasis. This study unveils a potential novel mechanism by which BRMS1 inhibits metastasis of ovarian cancer cells.
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Proteínas de Neoplasias/fisiologia , Osteopontina/antagonistas & inibidores , Neoplasias Ovarianas/patologia , Fator de Transcrição RelA/antagonistas & inibidores , Ativador de Plasminogênio Tipo Uroquinase/antagonistas & inibidores , Linhagem Celular Tumoral , Movimento Celular , Feminino , Humanos , Invasividade Neoplásica , Metástase Neoplásica , Proteínas de Neoplasias/genética , Osteopontina/genética , RNA Interferente Pequeno/genética , Proteínas Repressoras , Fator de Transcrição RelA/genética , Ativador de Plasminogênio Tipo Uroquinase/genéticaRESUMO
BACKGROUND: POD1UM-203, an open-label, multicenter, phase II study, evaluated retifanlimab, a humanized monoclonal antibody targeting programmed cell death protein-1 (PD-1) in patients with selected solid tumors where immune checkpoint inhibitor therapies have previously shown efficacy. PATIENTS AND METHODS: Eligible patients (≥18 years) had measurable disease and included unresectable or metastatic melanoma, treatment-naive metastatic non-small-cell lung cancer (NSCLC) with high programmed death-ligand 1 (PD-L1) expression (tumor proportion score ≥50%), cisplatin-ineligible locally advanced/metastatic urothelial carcinoma (UC) with PD-L1 expression (combined positive score ≥10%), or treatment-naive locally advanced/metastatic clear-cell renal cell carcinoma (RCC). Retifanlimab 500 mg was administered intravenously every 4 weeks as a 30-min infusion. The primary endpoint was investigator-assessed overall response rate. RESULTS: Overall, 121 patients (35 melanoma, 23 NSCLC, 29 UC, 34 RCC) were enrolled and treated. The overall response rate [95% confidence interval (CI)] was 40.0% (23.9-57.9) in the melanoma cohort, 34.8% (16.4-57.3) in the NSCLC cohort, 37.9% (20.7-57.7) in the UC cohort, and 23.5% (10.7-41.2) in the RCC cohort. Median duration of response was 11.5 months (95% CI 2.2-not reached) in the UC cohort, and was not reached in the other cohorts. Retifanlimab safety was consistent with previous experience for PD-(L)1 inhibitors. CONCLUSIONS: Retifanlimab demonstrated durable antitumor activity in patients with melanoma, NSCLC, UC, or RCC. The efficacy and safety of retifanlimab were as expected for a PD-(L)1 inhibitor. These data support further study of retifanlimab in solid tumors.
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Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Renais , Carcinoma de Células de Transição , Neoplasias Pulmonares , Melanoma , Neoplasias da Bexiga Urinária , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Renais/tratamento farmacológico , Antígeno B7-H1 , Melanoma/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêuticoRESUMO
Wu et al. report that patients with hematologic malignancies have reduced immunity against SARS-CoV-2 Omicron subvariants and Sotrovimab retains neutralizing capacity against all tested Omicron subvariants.
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COVID-19 , Neoplasias Hematológicas , Neoplasias , Humanos , SARS-CoV-2 , Neoplasias Hematológicas/tratamento farmacológicoRESUMO
BACKGROUND: Renal cell carcinoma (RCC) is the most common cancer of the kidney. Despite advances in treatment, 5-year survival rate for metastatic RCC is estimated to be less than 10%. Thus, new therapeutic options for RCC are urgently needed. AIM: In this study, our objective here was to identify a set of discriminating genes in RCC and normal kidney tissue, and predict their underlying molecular pathway in response to RCC using graph-clustering approach and gene ontology (GO) term analysis. MATERIALS AND METHODS: The GSE6344 expression profile was used in this study and the tissues used were either de-identified or were archival tissues. Through Statistical analysis, Network analyses, graph clustering and Pathway enrichment analysis to predict underlying molecular pathway. RESULTS: The results indicated the genes in cluster 1 and cluster 6 were involved in metabolism pathways, such as PPAR (peroxisome proliferator activated receptor) signaling pathway and Glycolysis pathway, etc. The genes in cluster 2, 3, 5, and 7 were associated with RCC progression through adhesion pathways, such as Focal adhesion, Cell adhesion molecules, and Gap junction. Besides, cluster 4 participated in MAPK (mitogen activated protein kinases) signaling pathway. CONCLUSIONS: These results suggested these pathways play an important role in RCC progression. Further study may pay more attention to confirm the unidentified genes, explore their prognosis for RCC, and novel chemotherapeutic targets.
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Carcinoma de Células Renais/metabolismo , Perfilação da Expressão Gênica , Neoplasias Renais/metabolismo , Análise por Conglomerados , Conexinas/genética , Fosfatases de Especificidade Dupla/genética , Humanos , Sistema de Sinalização das MAP Quinases , Fosfatases da Proteína Quinase Ativada por Mitógeno/genética , PPAR gama/genética , Proteína beta-1 de Junções ComunicantesRESUMO
OBJECTIVES: To investigate whether starch-based colloid may impact differently on blood glucose than a gelatin-based colloid in adult patients receiving open heart surgery. METHODS: 70 adult patients scheduled for elective first-time cardiac surgery were enrolled and randomized into two groups. The circuits were primed with either 6% HES 130/0.4 or 4% gelatin. The peak glucose level, incidence of hyperglycemia, glucose variation and glucose level at different time points during operation were compared between the two groups. A p-value ≤ 0.05 was accepted as significant. RESULTS: The peak glucose (150±30mg/dl vs 142±27, p=0.236) and glucose variation demonstrated by standard deviation (26±12mg/dl vs 23±11mg/dl, p=0.202) were comparable between the two groups. Repeated measurement ANOVA revealed that the main effect for artificial colloid was not significant (p=0.349). CONCLUSIONS: With the data available, we could not prove that starch-based colloid (HES130) had a different impact on intra-operative blood glucose than a gelatin-based colloid in adult patients receiving open heart surgery.
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Glicemia/metabolismo , Gelatina/uso terapêutico , Derivados de Hidroxietil Amido/uso terapêutico , Substitutos do Plasma/uso terapêutico , Cirurgia Torácica , Adulto , Análise de Variância , Ponte Cardiopulmonar , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Land application of manure, while beneficial to soil health and plant growth, can lead to an overabundance of nutrients and introduction of emerging contaminants into agricultural fields. Compared with surface application of manure, subsurface injection has been shown to reduce nutrients and antibiotics in surface runoff. However, less is known about the influence of subsurface injection on the transport and persistence of antibiotic-resistant microorganisms. We simulated rainfall to field plots at two sites (one in Virginia and one in Pennsylvania) 1 or 7 d after liquid dairy manure surface and subsurface application (56 Mg ha-1 ) and monitored the abundance of culturable antibiotic-resistant fecal coliform bacteria (ARFCB) in surface runoff and soils for 45 d. We performed these tests at both sites in spring 2018 and repeated the test at the Virginia site in fall 2019. Manure subsurface injection, compared with surface application, resulted in less ARFCB in surface runoff, and this reduction was greater at Day 1 after application compared with Day 7. The reductions of ARFCB in surface runoff because of manure subsurface injection were 2.5-593 times at the Virginia site in spring 2018 and fall 2019 and 4-5 times at the Pennsylvania site in spring 2018. The ARFCB were only detectable in the 0-to-5-cm soil depth within 14 d of manure surface application but remained detectable in the injection slits of manure subsurface-injected plots even at Day 45. This study demonstrated that subsurface injection can significantly reduce surface runoff of ARFCB from manure-applied fields.
Assuntos
Esterco , Solo , Antibacterianos , Bactérias , Esterco/microbiologia , Pennsylvania , FósforoRESUMO
The application of poultry litter to soils is a water quality concern on the Delmarva Peninsula, as runoff contributes P to the eutrophic Chesapeake Bay. This study compared a new subsurface applicator for poultry litter with conventional surface application and tillage incorporation of litter on a Coastal Plain soil under no-till management. Monolith lysimeters (61 cm by 61 cm by 61 cm) were collected immediately after litter application and subjected to rainfall simulation (61 mm h(-1) 1 h) 15 and 42 d later. In the first rainfall event, subsurface application of litter significantly lowered total P losses in runoff (1.90 kg ha(-1)) compared with surface application (4.78 kg ha(-1)). Losses of P with subsurface application were not significantly different from disked litter or an unamended control. By the second event, total P losses did not differ significantly between surface and subsurface litter treatments but were at least twofold greater than losses from the disked and control treatments. A rising water table in the second event likely mobilized dissolved forms of P in subsurface-applied litter to the soil surface, enriching runoff water with P. Across both events, subsurface application of litter did not significantly decrease cumulative losses of P relative to surface-applied litter, whereas disking the litter into the soil did. Results confirm the short-term reduction of runoff P losses with subsurface litter application observed elsewhere but highlight the modifying effect of soil hydrology on this technology's ability to minimize P loss in runoff.