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OBJECTIVE: We aimed to evaluate potential modifying effects of genetic susceptibility to obesity on the association of lifestyle factors with coronary artery disease (CAD) risk. METHODS: A total of 328,606 participants (54% women) were included using data from the UK Biobank. We evaluated the risk of developing CAD associated with obesity-related polygenic scores (PGSs) and healthy lifestyle scores (HLSs). HLSs were constructed using six lifestyle factors. Obesity PGSs were created using genetic variants identified by genome-wide association studies, including 941 variants for body mass index (BMI) and 457 for waist-to-hip ratio (WHR). Both HLSs and PGSs were categorized into three groups. RESULTS: During a 9-year median follow-up, 14,541 participants developed CAD. An unhealthy lifestyle was significantly associated with an increased CAD risk (hazard ratio [HR] = 2.24, 95% confidence interval [CI] = 2.09-2.40). High BMI and WHR PGSs were each significantly associated with an increased CAD risk (HRBMI = 1.23, 1.17-1.29; HRWHR = 1.15, 1.09-1.21). Lifestyle factors explained 41% (95% CI = 38%-45%) of CAD, while genetic variants for BMI explained only 10% (7%-14%). Risks of CAD were increased with poorer HLS independent of obesity-related PGSs. Individuals with the most unhealthy lifestyle and highest BMI PGS had the highest risk of CAD risk (HR = 2.59, 95% CI = 2.26-2.97), compared with participants with the healthiest lifestyle and lowest BMI PGS. CONCLUSIONS: While the observational nature of the study precludes the establishment of causality, our study provides supports for a causal association between obesity and CAD risk and the importance of lifestyle modification in the prevention of CAD.
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Doença da Artéria Coronariana , Humanos , Feminino , Masculino , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Fatores de Risco , Estudos de Coortes , Estudo de Associação Genômica Ampla , Bancos de Espécimes Biológicos , Biobanco do Reino Unido , Obesidade/genética , Estilo de Vida , Predisposição Genética para DoençaRESUMO
BACKGROUND: There are few prospective studies on the correlations between MRI features and whole RNA-sequencing data in breast cancer according to molecular subtypes. The purpose of our study was to explore the association between genetic profiles and MRI phenotypes of breast cancer and to identify imaging markers that influences the prognosis and treatment according to subtypes. METHODS: From June 2017 to August 2018, MRIs of 95 women with invasive breast cancer were prospectively analyzed, using the breast imaging-reporting and data system and texture analysis. Whole RNA obtained from surgical specimens was analyzed using next-generation sequencing. The association between MRI features and gene expression profiles was analyzed in the entire tumor and subtypes. Gene networks, enriched functions, and canonical pathways were analyzed using Ingenuity Pathway Analysis. The P value for differential expression was obtained using a parametric F test comparing nested linear models and adjusted for multiple testing by reporting Q value. RESULTS: In 95 participants (mean age, 53 years ± 11 [standard deviation]), mass lesion type was associated with upregulation of CCL3L1 (sevenfold) and irregular mass shape was associated with downregulation of MIR421 (sixfold). In estrogen receptor-positive cancer with mass lesion type, CCL3L1 (21-fold), SNHG12 (11-fold), and MIR206 (sevenfold) were upregulated, and MIR597 (265-fold), MIR126 (12-fold), and SOX17 (fivefold) were downregulated. In triple-negative breast cancer with increased standard deviation of texture analysis on precontrast T1-weighted imaging, CLEC3A (23-fold), SRGN (13-fold), HSPG2 (sevenfold), KMT2D (fivefold), and VMP1 (fivefold) were upregulated, and IGLC2 (73-fold) and PRDX4 (sevenfold) were downregulated (all, P < 0.05 and Q < 0.1). Gene network and functional analysis showed that mass type estrogen receptor-positive cancers were associated with cell growth, anti-estrogen resistance, and poor survival. CONCLUSION: MRI characteristics are associated with the different expressions of genes related to metastasis, anti-drug resistance, and prognosis, depending on the molecular subtypes of breast cancer.
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MicroRNAs , Neoplasias de Mama Triplo Negativas , Feminino , Humanos , Estudos Prospectivos , Receptores de Estrogênio/genética , Imageamento por Ressonância Magnética , Radiografia , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/genética , Lectinas Tipo C , Proteínas de MembranaRESUMO
BACKGROUND: Page kidney (PK) is the occurrence of kidney hypoperfusion and ischemia due to pressure on the kidney by a subcapsular hematoma (SH), a mass, or fluid collection. SH after renal transplantation may result in kidney ischemia and graft loss. CASE PRESENTATION: We present a rare case of early spontaneous SH in an allograft kidney that led to a decrease in renal function. A 56-year-old male patient underwent deceased donor kidney transplantation. After declamping, appropriate renal perfusion and immediate diuresis were observed, with no evidence of SH. However, his urinary output abruptly decreased 6 h postoperatively. Abdominal ultrasonography showed 28 mm deep SH on transplant and the resistive index (RI) increased to 0.98-1 and diastolic flow reversal was observed. Surgical interventions were performed 2 days after transplantation, following a further decrease in urinary output. Serum creatinine decreased to 2.2 mg/dL, urinary output increased to an average of 200 cc per hour and the RI value was decreased to 0.7 on POD 7. CONCLUSION: In patients with abrupt decreased renal function after transplantation, SH should be suspected and the presence of PK should be determined using Doppler USG. In these cases, surgical intervention may avoid allograft dysfunction.
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Hipertensão Renal , Transplante de Rim , Nefroesclerose , Hematoma/diagnóstico por imagem , Hematoma/etiologia , Humanos , Hipertensão Renal/complicações , Isquemia/etiologia , Rim/diagnóstico por imagem , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-IdadeRESUMO
We evaluated whether the neutrophil-to-lymphocyte ratio (NLR) could aid dialysis decision-making in combination with the clinical presentation and biochemical findings. We retrospectively evaluated the medical records of 279 patients who commenced chronic maintenance hemodialysis. We compared the laboratory findings at 6 months before dialysis to those at dialysis initiation. NLR cutoffs and risk factors for each of six uremic symptoms were determined. Mean age was 60.7 years and mean estimated glomerular filtration rate (eGFR) was 5.7 ± 2.5 mL/min/1.73 m2 at the time of hemodialysis and 7.7 ± 3.8 mL/min/1.73 m2 6 months earlier (p < 0.001). The mean NLR increased significantly from 2.5 ± 1.0 to 4.9 ± 2.8 (p < 0.001). The NLR was positively correlated with the C-reactive protein level (r = 0.202, p = 0.009) and negatively correlated with those of albumin (r = -0.192, p = 0.001) and total CO2 (r = -0.134, p = 0.023). The NLR cutoffs for neurological and gastrointestinal symptoms as determined using receiver operator curve analysis were 2.4 (area under the curve [AUC] 0.976; 95% confidence interval [CI] 0.960-0.993; sensitivity 92.2%; specificity 94.7%) and 3.6 (AUC 0.671; 95% CI 0.588-0.755; sensitivity 68.1%; specificity 63.5%), respectively. On multiple linear regression analysis of neurological symptoms, the NLR was a significant predictor (ß = -0.218, p = 0.017), as was age (ß = 0.314, p = 0.037). In conclusion, the NLR may serve as a supplementary marker predicting uremic symptoms and a need for hemodialysis in stage 5 CKD patients.
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Linfócitos , Neutrófilos , Humanos , Contagem de Leucócitos , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Estudos RetrospectivosRESUMO
Genome-wide association studies (GWAS) have identified many genetic risk variants for cancers. The utility of these variants in assessing risk of esophageal, gastric and endometrial cancers, as well as melanoma, glioma, diffuse large B-cell lymphoma, follicular lymphoma, chronic lymphoid leukemia and multiple myeloma, has not been adequately investigated. We constructed a site-specific polygenic risk score (PRS) for each of these nine cancers using their GWAS-identified risk variants. Using data from 400 807 participants of European descent in the UK Biobank, a population-based cohort study, we estimated the hazard ratios of each cancer associated with its PRS using Cox proportional hazard models. During a median follow-up of 5.8 years, 3905 incident cases of these nine cancers were identified in the cohort. The area under the receiver operating characteristic curve ranged from 0.53 to 0.69 for these cancers. Except for esophageal cancer, significant dose-response associations were observed between PRS and cancer risk. Compared to individuals in the middle quintile (40%-60%) at an average risk, those among the highest 5% of the PRS had a twofold elevated risk of melanoma, glioma, follicular lymphoma or multiple myeloma, and a fourfold elevated risk of chronic lymphoid leukemia. Using PRS, 63.0% of the participants could be classified as having an over twofold elevated risk for at least one cancer. The PRS derived using risk variants identified to date by GWAS showed the potential in identifying individuals at a significantly elevated risk of cancer for prevention.
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Neoplasias do Endométrio/epidemiologia , Neoplasias Esofágicas/epidemiologia , Glioma/epidemiologia , Neoplasias Hematológicas/epidemiologia , Melanoma/epidemiologia , Neoplasias Gástricas/epidemiologia , População Branca/genética , Estudos de Coortes , Neoplasias do Endométrio/genética , Neoplasias Esofágicas/genética , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Glioma/genética , Neoplasias Hematológicas/genética , Humanos , Masculino , Melanoma/genética , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/genética , Reino Unido/etnologiaRESUMO
BACKGROUND: Dynamic change in central venous pressure (CVP) was associated with fluid responsiveness. External jugular venous pressure (EJVP) may reliably estimate CVP and have the advantages of being less invasive. We investigated whether increase in EJVP induced by positive end-expiratory pressure (PEEP) could be a reliable predictor of fluid responsiveness in patients undergoing robot-assisted laparoscopic prostatectomy (RALP). METHODS: Fifty patients who underwent RALP with steep Trendelenburg position were enrolled. PEEP of 10 cmH2O was applied for 5 min and then 300 ml of colloid was administered. EJVP, stroke volume variation (SVV), and cardiac index calculated by pulse contour method were measured before and after the PEEP challenge and colloid administration. Increase in cardiac index > 10% was used to define the fluid responsiveness. RESULTS: Twenty-six patients were fluid responders. Neither the increase in EJVP after the initial PEEP nor SVV was significantly different between responders and non-responders. They were not significantly correlated with an increase in cardiac index. The areas under the receiver operating characteristic curve (AUC) of these two variables were not significantly greater than 0.5. However, a post hoc analysis revealed that AUC of a decrease in EJVP after removal of PEEP was significantly greater than 0.50. CONCLUSION: Our study results suggested that SVV and increase in EJVP after applying PEEP were not accurate predictors of fluid responsiveness during RALP. Further studies are required to find an adequate preload index in robot-assisted urologic surgery with steep Trendelenburg position.
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Hidratação/métodos , Laparoscopia/métodos , Respiração com Pressão Positiva , Prostatectomia/métodos , Idoso , Pressão Sanguínea/fisiologia , Pressão Venosa Central/fisiologia , Eletrocardiografia , Decúbito Inclinado com Rebaixamento da Cabeça/fisiologia , Hemodinâmica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Postura/fisiologia , Estudos Prospectivos , Curva ROC , Respiração Artificial/métodos , Estatísticas não Paramétricas , Volume Sistólico/fisiologia , Volume de Ventilação PulmonarRESUMO
BACKGROUND: Even with ultrasound guidance, arterial cannulation in children can be challenging. OBJECTIVE: To compare the short-axis/out-of-plane (SAX) with the long-axis/in-plane (LAX) technique for ultrasound-guided arterial cannulation in children. DESIGN: A randomised controlled trial. SETTING: A tertiary university hospital, from 5 January 2015 to 21 April 2015. PATIENTS: 101 children, American Society of Anesthesiologists' physical status 1 or 2 and younger than 5 years of age. INTERVENTIONS: All were randomised into one of four groups according to age and ultrasound guidance technique: infants with SAX technique (nâ=â25), infants with LAX technique (nâ=â25), children with SAX technique (nâ=â25) and children with LAX technique (nâ=â26). Ultrasound-guided arterial cannulation was performed under general anaesthesia via the radial or posterior tibial artery, depending on individual position and operative field. MAIN OUTCOME MEASURES: The primary outcome was the total time to successful cannulation. Secondary outcomes included diameter and depth of the artery, time variables (imaging time, time to first successful puncture and time between first successful puncture and cannulation), number of puncture attempts, success rates (first puncture and final cannulation), posterior wall puncture rate and complications. RESULTS: Ultrasound-guided arterial cannulation was successful in 97 children (96.0%). There were no significant differences in the total time to successful cannulation between the two groups. Ultrasound imaging time was significantly longer in the LAX group than in the SAX group (46.5â±â39.2 vs 16.0â±â17.6âs; 95% confidence interval of mean difference, -42.7 to -18.3; Pâ=â0.000). However, the posterior wall puncture rate was significantly higher in the SAX group than in the LAX group (95.7% vs 18.0%; Pâ=â0.000; odds ratio 0.01; 95% confidence interval, 0.002 to 0.048). There were no statistically significant differences in other secondary outcomes. CONCLUSION: Despite the longer imaging time with the LAX approach, there was no significant difference in the total time to successful cannulation between the two techniques. The posterior wall puncture rate was lower in the LAX group than in the SAX group. TRIAL REGISTRATION: Clinicaltrials.gov (identifier: NCT02333786).
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Cateterismo Periférico/métodos , Ultrassonografia de Intervenção/métodos , Anestesia Geral , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Artéria Radial/diagnóstico por imagem , Artérias da Tíbia/diagnóstico por imagem , Resultado do TratamentoRESUMO
Partial trisomy of 11q is characterized by pre/postnatal growth retardation, microcephaly, dysmorphic craniofacial features, cognitive disability, abnormal muscle tone, inguinal hernia, and possible congenital heart defects. Here, we describe a 17-year-old male with a 17.77 Mb-sized [arr 11q23.3-q25 (116,667,559 -134,434,130) ×3] partial trisomy resulting from the unbalanced translocation between chromosomes 11 and 22. The terminal translocation was detected using oligonucleotide array comparative genomic hybridization (CGH) with fluorescence in situ hybridization (FISH) confirmation. The partial trisomy was inherited from his mother who had the low-level (22.7%) mosaic unbalanced translocation and a normal phenotype. The patient showed most of the common features of partial trisomy 11q syndrome, with additional findings, including mesenteric fibromatosis.
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Cromossomos Humanos Par 11 , Mosaicismo , Translocação Genética , Trissomia , Adolescente , Hibridização Genômica Comparativa , Humanos , Hibridização in Situ Fluorescente , MasculinoRESUMO
BACKGROUND: The effect of the Mega Acer kit(@), a new heated and humidified breathing circuit (HHBC) containing a fluid-warming device, was investigated on intraoperative core temperature (T c). METHODS: A total of 102 patients undergoing elective craniotomies were randomly divided into three groups based on the breathing circuit used: a conventional breathing circuit (group C, n = 34), a Fisher & Paykel HHBC (group F, n = 34), and the Mega (group M, n = 34). From baseline to the end of the surgery, T c and infusion fluid temperature (T f) were recorded at 15-min intervals. If T c became lower than 35.5 °C, a forced-air warmer was used. RESULTS: Baseline temperatures were 36.7 ± 0.3, 36.6 ± 0.2, and 36.6 ± 0.2 °C in groups C, M, and F, respectively. T c at the end of surgery dropped from baseline values by 1.0 ± 0.4, 0.5 ± 0.5, and 0.8 ± 0.5 °C in groups C, M, and F, respectively. From 60 min of post-induction to the end of surgery, T c was higher in group M than group C (p < 0.05). From 105 min of post-induction to the end of surgery, T c was higher in group M than group F (p < 0.05). The number of patients receiving forced-air warmer and total forced-air warmer using time were significantly lower in group M than groups C and F (p < 0.05). T f was higher in group M than groups C and F throughout the study period (31.0 ± 1.0 vs. 23.5 ± 0.5 and 24.0 ± 0.4 °C; p < 0.01). CONCLUSIONS: The Mega significantly reduced the drop in intraoperative T c by delivering warm fluids, compared with the other breathing circuits tested. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01831843.
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Regulação da Temperatura Corporal/fisiologia , Temperatura Corporal/fisiologia , Procedimentos Cirúrgicos Eletivos/métodos , Adulto , Idoso , Procedimentos Cirúrgicos Eletivos/instrumentação , Feminino , Temperatura Alta , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Método Simples-Cego , Temperatura , Adulto JovemRESUMO
Overall, gastric adenocarcinoma (GC) incidence rates have declined in recent years, but racial/ethnic disparities persist. Individuals who identify as Hispanic/Spanish/Latino are diagnosed with GC at younger ages and have poorer outcomes than non-Hispanic individuals. However, our understanding of GC biology across racial/ethnic groups remains limited. We assessed tumor genomic patterns by race/ethnicity among 1019 patients with primary GC in the AACR Project GENIE Consortium. Hispanic individuals presented with significantly higher rates of ERBB2/HER2 amplification vs other racial/ethnic groups (Hispanic: 13.9% vs 9.8% non-Hispanic White, 8.1% non-Hispanic Asian, and 11.0% non-Hispanic Black; p < .001, FDR adjusted q < 0.001). Hispanic patients also had higher odds of an ERBB2 amplification vs non-Hispanic whites in adjusted models (OR = 2.52, 95%CI = 1.20-5.33, p = .015). These findings underscore the important role of genomic factors in GC disparities. Ensuring equitable access to genomic profiling and targeted therapies, such as trastuzumab for HER2-overexpressing GC, is a promising avenue to mitigate GC disparities and improve outcomes.
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BACKGROUND: Microsatellite instability (MSI) and tumor mutational burden (TMB) are predictive biomarkers for pan-cancer immunotherapy. The interrelationship between MSI-high (MSI-H) and TMB-high (TMB-H) in human cancers and their predictive value for immunotherapy in lung cancer remain unclear. METHODS: We analyzed somatic mutation data from the Genomics Evidence Neoplasia Information Exchange (n = 46,320) to determine the relationship between MSI-H and TMB-H in human cancers using adjusted multivariate regression models. Patient survival was examined using the Cox proportional hazards model. The association between MSI and genetic mutations was assessed. RESULTS: Patients (31-89%) with MSI-H had TMB-low phenotypes across 22 cancer types. Colorectal and stomach cancers showed the strongest association between TMB and MSI. TMB-H patients with lung cancer who received immunotherapy exhibited significantly higher overall survival [HR, 0.61; 95% confidence interval (CI), 0.44-0.86] and progression-free survival (HR, 0.65; 95% CI, 0.47-0.91) compared to the TMB-low group; no significant benefit was observed in the MSI-H group. Patients with TMB and MSI phenotypes showed further improvement in overall survival and PFS. We identified several mutated genes associated with MSI-H phenotypes, including known mismatch repair genes and novel mutated genes, such as ARID1A and ARID1B. CONCLUSIONS: Our results demonstrate that TMB-H and/or a combination of MSI-H can serve as biomarkers for immunotherapies in lung cancer. IMPACT: These findings suggest that distinct or combined biomarkers should be considered for immunotherapy in human cancers because notable discrepancies exist between MSI-H and TMB-H across different cancer types.
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Biomarcadores Tumorais , Instabilidade de Microssatélites , Mutação , Humanos , Feminino , Masculino , Biomarcadores Tumorais/genética , Neoplasias/genética , Neoplasias/mortalidade , Neoplasias/terapia , Genômica/métodos , Pessoa de Meia-Idade , IdosoRESUMO
Identifying risk protein targets and their therapeutic drugs is crucial for effective cancer prevention. Here, we conduct integrative and fine-mapping analyses of large genome-wide association studies data for breast, colorectal, lung, ovarian, pancreatic, and prostate cancers, and characterize 710 lead variants independently associated with cancer risk. Through mapping protein quantitative trait loci (pQTL) for these variants using plasma proteomics data from over 75,000 participants, we identify 365 proteins associated with cancer risk. Subsequent colocalization analysis identifies 101 proteins, including 74 not reported in previous studies. We further characterize 36 potential druggable proteins for cancers or other disease indications. Analyzing >3.5 million electronic health records, we uncover five drugs (Haloperidol, Trazodone, Tranexamic Acid, Haloperidol, and Captopril) associated with increased cancer risk and two drugs (Caffeine and Acetazolamide) linked to reduced colorectal cancer risk. This study offers novel insights into therapeutic drugs targeting risk proteins for cancer prevention and intervention.
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RATIONALE: Only 1 case of IgA nephropathy (IgAN) with minimal change disease (MCD) associated with primary Sjögren's syndrome (SS) has been reported. We additionally describe IgAN with MCD associated with primary SS. PATIENT CONCERNS: A 80-year-old woman visited our hospital complaining of generalized edema that had started 4 weeks prior. She reported a sense of thirst and dry eye for the last 5 years. DIAGNOSES: Her initial laboratory findings were compatible with nephrotic syndrome; both the antinuclear antibody (1:80) and anti-SS-A (Ro) antibody (200 U/mL) tests were positive. A salivary gland scan revealed markedly decreased uptake for both the parotid and submandibular glands. The Schirmer test was positive. The random urine protein/creatinine ratio was 10 mg/mg. Renal biopsy was compatible with IgAN with superimposed MCD. INTERVENTIONS: Furosemide was intravenously administered with intermittent albumin infusion for her edema control. She was started on prednisone 40mg daily for 6 weeks, which was tapered to 5 mg for another 6 months after starting prednisolone. OUTCOMES: Over the next 6 months, her edema improved and the proteinuria decreased significantly. LESSONS: Physician should suspect IgA with MCD when patient with SS clinically showed nephrotic syndrome, and perform renal biopsy for pathologically diagnosis and appropriate treatment.
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Glomerulonefrite por IGA , Nefrose Lipoide , Síndrome Nefrótica , Síndrome de Sjogren , Humanos , Feminino , Idoso de 80 Anos ou mais , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/tratamento farmacológico , Síndrome Nefrótica/complicações , Nefrose Lipoide/complicações , Nefrose Lipoide/diagnóstico , Nefrose Lipoide/tratamento farmacológico , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/tratamento farmacológico , Edema/diagnósticoRESUMO
BACKGROUND: This study is the protocol to evaluate the clinical evidence for external treatments using herbal medicine (ETHM) with tuina as a congenital muscular treatment (CMT) in pediatrics. METHODS: Eleven databases will be searched until June 2022, without any language restrictions: four English databases (MEDLINE, Pubmed, EMBASE, and The Cochrane Central Register of Database of Controlled Trials), three Chinese databases (China National Knowledge Infrastructure, Chinese Scientific Journal Database, and Wan Fang Database), and four Korean electronic databases (Oriental Medicine Advanced Searching Integrated System, Korean Studies Information Service System, National Digital Science Links, and Research Information Sharing Service). This review will include randomized clinical trials (RCTs) of ETHM with tuina as an intervention versus the same tuina. All published RCTs for any ETHM for CMT will be included. Non-RCTs, RCT protocol, animal studies, case reports, reviews, and surveys will be excluded. The methodological quality assessment will be performed using the Cochrane risk of bias (ROBs). Review Manager version 5.4. will be used for the data synthesis and quantitative analysis. RESULTS AND DISCUSSIONS: The systematic review and meta-analysis will provide evidence for ETHM as a treatment of CMT. The evidence can help clinicians and patients recognize more effective therapeutic and safe inventions. INPLASY REGISTRATION NUMBER: INPLASY202210017.
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Medicina Tradicional Chinesa , Plantas Medicinais , Criança , Medicina Herbária , Humanos , Medicina Tradicional Chinesa/métodos , Metanálise como Assunto , Projetos de Pesquisa , Literatura de Revisão como Assunto , Revisões Sistemáticas como Assunto , Torcicolo/congênitoRESUMO
BACKGROUND: Congenital muscular torticollis (CMT) is the third most common musculoskeletal disease in children. With no standardized treatment method hence, so it is necessary to find an effective treatment method that can be received comfortably by children. This review assessed the efficacy of an external treatment of herbal medicine (ETHM) with tuina for CMT in children. METHODS: This study searched the English, Chinese, and Korean databases (total of 10) until June 7 2022, without any language restrictions. All included studies were randomized clinical trials (RCTs) of ETHM with tuina as an intervention comparted to the same tuina alone according to the inclusion and exclusion criteria. The mean differences (MD), standardized mean differences (SMD), risk ratio (RR) with the 95% confidence interval (CI), and risk of bias (ROBs) were calculated using Review Manager Version 5.4 software. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) rating system was used to assess the quality of evidence. The publication bias was evaluated using a funnel plot, the Egger test, the fail-safe N test, and the Duval and Tweedle's trim and fill method using Review Manager Version 5.4 software, the software R Version 4.1.1 and R studio Version 1.4.1106 program. RESULTS: Nineteen RCTs with 1710 patients were included in the meta-analysis. ETHM plus tuina improved the outcomes of the total effective rate (TER) [RR 1.21, 95% CI:1.15 to 1.26, Pâ <â .001], sternocleidomastoid (SCM) muscle thickness [MD: -1.82, 95% CI: -2.23 to -1.41, Pâ <â .001], cervical rotation range [MD: 13.43, 95% CI: 10.41-16.45, Pâ <â .001] and lateral flexion range [MD: 8.50, 95% CI: 6.15-10.85, Pâ <â .001], tissue elasticity grade [SMD: -0.46; 95% CI: -0.71 to -0.22, Pâ =â .0002], muscle elasticity scores [RR: 1.56; 95% CI: 1.04 to 2.34, Pâ =â .03], and clinical symptom and sign scores [SMD: -0.78; 95% CI: -1.09 to -0.47, Pâ <â .001]. CONCLUSIONS: ETHM plus tuina have a combined effect on CMT children. However, further studies with high-quality clinical trials are needed to obtain more robust clinical evidence.
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Extratos Vegetais , Criança , HumanosRESUMO
BACKGROUND: Kawasaki disease (KD) is a major cause of coronary artery lesions (CALs) in children. Approximately 10% to 20% of children treated with intravenous immunoglobulin are intravenous immunoglobulin-resistant. This study evaluated the efficacy and safety of adding herbal medicine to conventional western medicines versus conventional western medicines alone for CALs in children with KD. METHODS: This study searched 9 electronic databases until August 31, 2021. The inclusion criteria were the randomized controlled trials (RCTs) that assessed the CALs in children with KD and compared integrative treatment with conventional western treatments. Two authors searched independently for RCTs, including eligible articles that fulfilled the inclusion criteria, extracted data, and assessed the methodological quality using the Cochrane risk of bias tool. Meta-analysis was conducted using Cochrane Collaboration's Review Manager 5.4 software. The effect size was presented as the risk ratio (RR), and the fixed-effect models were used to pool the results. RESULTS: The finally selected 12 studies included a total of 1030 KD patients. According to a meta-analysis, the integrative treatment showed better results than the conventional treatment in the CAL prevalence rate (RRâ=â2.00; 95% confidence interval [CI], 1.49-2.71; Pâ<â.00001), CAL recovery rate (RRâ=â1.27; 95% CI, 1.05-1.54; Pâ=â.02), and total effective rate (RRâ=â1.17; 95% CI, 1.11-1.23; Pâ<â.00001). Only 2 studies referred to the safety of the treatment. The asymmetrical funnel plot of the CAL prevalence rate indicated the possibility of potential publication bias. CONCLUSIONS: This review found the integrative treatment to be more effective in reducing the CAL prevalence rate and increasing the CAL recovery rate and total effective rate in KD patients than conventional western treatment. However, additional well-designed RCTs will be needed further to compensate restrictions of insufficient trials on safety, methodological quality, and publication bias.
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Síndrome de Linfonodos Mucocutâneos , Plantas Medicinais , Criança , Vasos Coronários , Medicina Herbária , Humanos , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , FitoterapiaRESUMO
Tissue clearing for 3-dimensional (3D) imaging is increasingly utilized in many biomedical applications, including the pathological examination of human biopsy specimens. Although many protocols offer rapid and efficient tissue clearing (>1 d), immunofluorescence labeling of thick specimens is a highly time-consuming process. The use of low molecular weight chemical dyes has potential benefits in terms of speed and quality of 3D labeling. Accordingly, we tested several chemical dyes to assess their potential applications in 3D imaging. The combination of SYTO 16 and eosin (S&E) was found to be a potential fluorescent version of the hematoxylin-eosin (H&E) stain. Furthermore, picrosirius red (for collagen), Congo red (for senile plaques), and fluorescent Nissl (for neurons in the normal brain or blood vessels in the injured brain) stains can be used alone or in combination with antibody labeling. As chemical labeling requires a relatively short incubation time (<1 d), fluorescent chemical dyes could expedite the 3D imaging process.
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Certain genetic variants are associated with risks of multiple cancers. We investigated breast cancer risk with overall genetic susceptibility to each of 16 other cancers. We constructed polygenic risk scores (PRS) for 16 cancers using risk variants identified by genome-wide association studies. We evaluated the associations of these PRSs with breast cancer risk (overall and by subtypes) using Breast Cancer Association Consortium data, including 106,278 cases and 91,477 controls of European ancestry. Odds ratios (OR) and 95% confidence intervals (CIs) were estimated to measure the association of each PRS with breast cancer risk. Data from the UK Biobank, including 4,337 cases and 209,983 non-cases, were used to replicate the findings. A 5%-8% significantly elevated risk of overall breast cancer was associated with per unit increase of the PRS for glioma and cancers of the corpus uteri, stomach, or colorectum. Analyses by subtype revealed that the PRS for corpus uteri cancer (OR = 1.09; 95% CI, 1.03-1.15) and stomach cancer (OR = 1.07; 95% CI, 1.03-1.12) were associated with estrogen receptor-positive breast cancer, while ovarian cancer PRS was associated with triple-negative breast cancer (OR = 1.25; 95% CI, 1.01-1.55). UK Biobank data supported the positive associations of overall breast cancer risk with PRS for melanoma and cancers of the stomach, colorectum, and ovary. Our study provides strong evidence for shared genetic susceptibility of breast cancer with several other cancers. Results from our study help uncover the genetic basis for breast and other cancers and identify individuals at high risk for multiple cancers.
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It is largely unknown whether genetic susceptibility contributes to tumor immune infiltration in common cancers. We systematically investigated the association between polygenic risk scores (PRSs) and tumor immune infiltration in common cancers. First, we constructed a PRS for common cancers using the risk variants identified in previous genome-wide association studies. Then, we analyzed 139 immune traits predicted by previous studies by examining gene expression data in tumor tissues from The Cancer Genome Atlas (TCGA). We applied regression analyses to evaluate the associations between PRS and immune traits for each cancer overall and stratified by stage, including 2160 pathologically confirmed cases of breast, colorectal, lung, ovarian, pancreatic, and prostate cancers in the White population. At a nominal (p < 0.05) significance level, we identified 31 significant associations between PRS and immune traits. In the analyses stratified by stage for breast, colorectal, lung adenocarcinoma, and lung squamous cell carcinoma, we identified 65 significant associations, including 56 associations that were undetected by the overall analysis. This study provides evidence for genetic risk factors affecting immune infiltration and provides novel insights into the role of genetic susceptibility in immune responses, underlying cancer development, prognosis, and the potential role of an early diagnostic or therapeutic targeting strategy.
RESUMO
BACKGROUND: Invasive fungal diseases (IFDs) increase the mortality rate of patients with neutropenia who receive chemotherapy or have previously undergone hematopoietic stem cell transplantation (HSCT). Micafungin is a broad-spectrum echinocandin with minimal toxicity and low drug interactions. We therefore investigated the efficacy and safety of prophylactic micafungin in pediatric and adolescent patients who underwent autologous HSCT. METHODS: This was a phase II, prospective, single-center, open-label, and single-arm study. From November 2011 to February 2017, 125 patients were screened from Seoul National University Children's Hospital, Korea, and 112 were enrolled. Micafungin was administered intravenously at a dose of 1 mg/kg/day (maximum 50 mg/day) from day 8 of autologous HSCT until neutrophil engraftment. Treatment success was defined as the absence of proven, probable, or possible IFD up to 4 weeks after therapy. RESULTS: The study protocol was achieved without premature interruption in 110 patients (98.2%). The reasons interrupting micafungin treatment included early death (n = 1) and patient refusal (n = 1). Treatment success was achieved in 109 patients (99.1%). Only one patient was diagnosed with probable IFD. No patients were diagnosed with possible or proven IFD. In the full analysis set, 21 patients (18.8%) experienced 22 adverse events (AEs); however, all AEs were classified as "unlikely" related to micafungin. No patient experienced grade IV AEs nor discontinued treatment, and none of the deaths were related to micafungin. CONCLUSIONS: Our study demonstrated that micafungin is a safe and effective option for antifungal prophylaxis in pediatric patients who underwent autologous HSCT, with promising efficacy without significant AEs.