Abnormal expression of non-coding circular RNAs (circRNAs) have been reported in many types of tumors. circRNA have been suggested to be an ideal candidate biomarker for diagnostic and therapeutic ...implications in cancers. The aim of this study was to assess the circRNA expression profile of laryngeal squamous cell carcinomas (LSCC). The biopsy samples from patients with LSCC were obtained intra-operatively. The circRNA expression was performed using secondary sequencing. Among 10 patients with LSCC, 2 were well differentiated, 3 were moderately differentiated and 5 were adjunctive samples with normal and LSCC tissues. A total of 21,444 distinct circRNA candidates were detected. Among them, we defined the statistical criteria for selecting aberrant-expressed circRNA using a q-value of < 0.001 with a fold change of > 2.0 or < 0.5. A total of 29 circRNA were upregulated and 19 circRNA were downregulated significantly in the LSCC tissues. The intersection of these dysregulated circRNAs of normal-well differentiated set and normal-moderately differentiated set was then assessed to narrow the upregulated and downregulated circRNAs down to 18 and 5 respectively. Furthermore, an association of the circRNA-miRNA-mRNA was investigated, showing that 20 dysregulated circRNA successfully predicted an interaction with several cancer-related miRNAs. Finally, a further KEGG analysis showed that PPAR, Axon guidance, Wnt and Cell cycle signaling pathway were key putative pathways in the process of LSCC. hsa_circ:chr20:31876585-31,897,648 was found to be able to differentiate most of LSCC from the matching normal tissues. This observational study demonstrated dysregulation of circRNA in LSCC, which may have an impact on development of potential biomarkers in this disease. Validation of down-regulation of hsa_circ:chr20:31876585-31,897,648 in LSCC compared to each adjunctive tissue by Q-RT-PCR, indicating that hsa_circ:chr20:31876585-31,897,648 may be a novel promising tumor suppresser in LSCC.
Background: THSD7A is a new target antigen of idiopathic membranous nephropathy (IMN). Moreover, malignancies are also found in patients with THSD7A-positive membranous nephropathy. We aimed to ...systematically evaluate the prevalence of THSD7A in IMN patients and malignancies in THSD7A-positive patients.
Methods: We searched English and Chinese database to 31 December 2017 with the term 'THSD7A' or 'thrombospondin type 1 domain-containing 7A'. Meta-analysis was used to explore the positive rate of THSD7A in the IMN patients. Subgroup analysis was performed according to the race, sample size, and detecting method of THSD7A.
Results: Ten studies involving 4121 participants were eventually included. The prevalence of THSD7A was 3% (95% CI, 3%-4%) in all patients and 10% (95% CI, 6%-15%) in PLA2R-negative patients. 77 patients had positive circulating antibodies, and the prevalence of THSD7A was also low at 3% (95% CI, 2%-4%). Overall, 72 patients had positive THSD7A staining on renal biopsy, and the prevalence was 3% (95% CI 2%-4%). Subgroup analysis showed significant differences in the prevalence of THSD7A based on the study sample sizes, however, no significant differences were seen in different ethnic groups. Furthermore, among THSD7A-positive patients, 3/10 studies reported malignancies with the incidence varied from 6% to 25%.
Conclusions: The prevalence of THSD7A is more common in the PLA2R-negative patients than the IMN patients. Screening for malignancies in THSD7A-positive MN patients is recommended.
To highlight the impact of intimate partner violence (IPV), also known as domestic violence, on children and families and to provide a framework for pediatricians in managing IPV-affected families.
...Children living with a victim of IPV are at a much higher risk of being physically abused themselves. Exposure to IPV places children at high risk for multiple adverse childhood experiences, long-term health morbidity, and increased chance of intergenerational transmission of child abuse and future IPV. Exposure to a violent home environment alone is considered a form of child maltreatment. Furthermore, recent studies have proposed that maternal posttraumatic stress disorder and ineffective parenting styles by a victim of IPV mediate children's negative developmental outcomes, such as aggressive or internalizing behavior, mental health issues, and developmental delays. Trauma-informed care and a better understanding of the child abuse reporting process allow pediatricians to address specific needs of children and families exposed to IPV, to serve as mandated reporters with sensitivity and empathy, and to promote resiliency in families.
IPV is a public health issue that affects children in a variety of ways. Pediatricians can better manage this very serious and personal issue in their offices through an understanding of the unique healthcare needs of children and families impacted by IPV.
Both Genome-wide associations and our previous study have shown that single nucleotide polymorphisms (SNPs) of M-type phospholipase A2 receptor (PLA2R) and human leukocyte antigen complex class II ...HLA-DQα-chain 1 (HLA-DQA1) gene were identified to be associated with primary membranous nephropathy (PMN). However, whether these SNPs affect clinical manifestation and renal outcome for PMN patients is poorly defined. Here, we evaluated whether there is an association between these SNPs and clinical manifestations and renal outcomes of PMN in a western Chinese cohort.
Seven SNPs within PLA2R and one SNP in HLA-DQA1 were selected in our study. Clinical data from 314 patients with PMN were collected and the relationship between the genotype and phenotype was evaluated. A total of 186 patients had follow-up data. We assessed the treatment responses and renal outcomes between patients with these gene polymorphisms after a median follow-up of 18.6 months.
Eight SNPs were not associated with clinical manifestations of PMN patients (Pc < 0.05). rs3828323 T allele was marginally significantly associated with hypertension (P = 0.008, Pc = 0.064, OR = 1.821). After treatment for PMN, the SR group (including CR and PR) had lower serum creatinine level (68.4 ± 18.8 μmol/L vs. 122.8 ± 126.6 μmol/L, P < 0.001), urea (5.5 ± 1.9 mmol/L vs. 8.0 ± 4.0 mmol/L, P < 0.001), uric acid (358.5 ± 95.1 μmol/L vs. 392.8 ± 118.1 μmol/L, P = 0.037) and urinary protein (0.23 (0.76,1.05) g/d vs. 3.01 (2.06,7.95) g/d, P < 0.001), higher eGFR (100.0 ± 20.1 ml/min/1.73m
vs. 77.1 ± 35.3 ml/min/1.73m
, P < 0.001) and albumin (41.1 ± 5.1 g/L vs.30.4 ± 8.2 g/L, P < 0.001). We also identified that PMN patients with CT/TT genotype for rs3828323 achieved higher cumulative survival rate than patients with CC genotype.
Rs3828323 may influence hypertension and renal outcome in patients with PMN. Further research is needed to explore the mechanism for this genotype-disease phenotype association.
The worldwide prevalence of obesity is increasing. Obesity is associated with a variety of chronic diseases, including chronic kidney disease. Several studies suggested that body mass index (BMI) ...could be an independent risk factor for progression of IgA nephropathy (IgAN). However, whether high BMI is associated with progression of IgAN remains uncertain.
This retrospective study included patients with biopsy proven IgAN from 2006 to 2017 in Sichuan Provincial People's Hospital. BMI was categorized according to the WHO Asian guideline: underweight (< 18.5 kg/m
), normal weight (18.5-25 kg/m
), overweight (25-28 kg/m
) and obese (≥28 kg/m
). The main outcome was development of end-stage renal disease (ESRD) or a decline in eGFR by at least 30%. The association of BMI and IgAN progression was determined by propensity-score-matched cohort analysis.
Four hundred eighty one patients with IgAN were finally enrolled in this study. The mean age was 37 ± 11 years and 40.3% were men. There was no significant difference in clinical and pathological characteristics among the four-group patients categorized by BMI. After matching with propensity scores, no significant correlation between BMI and renal outcomes was seen. However, compared with the reference group (18.5≦BMI≦25 kg/m
), being overweight (odd ratio OR, 2.28; 95%CI: 1.06-4.88; P = 0.034) and obese (OR, 3.43; 95%CI: 1.06-11.04; P = 0.039) was associated with a high risk of interstitial fibrosis. In the cross figure demonstrating the association of BMI subgroup and interstitial fibrosis on renal outcomes, ORs of interstitial fibrosis groups were higher than those of no interstitial fibrosis. Compared with other BMI subgroups, patients with 18.5-25 kg/m
had lowest ORs.
High BMI and interstitial fibrosis were associated with progression of IgAN. Interstitial fibrosis appears to be common in IgAN patients with elevated BMI.
Aims:
We aim to perform a systematic review and meta-analysis examining randomized controlled trials assessing the efficacy and safety of sacubitril/valsartan in patients on renal outcomes, in ...comparison with the renin–angiotensin–aldosterone system inhibitor (RAASi).
Methods:
Eligible studies were retrieved on MEDLINE, EMBASE, and Cochrane until September 2021. The primary outcome was the incidence of renal impairment, which was defined as the composite of increases in serum creatinine by >0.3 mg/dl and/or a reduction in eGFR ≥25%, development of ESRD, or renal death. We pooled relative risks (RRs) with 95% confidence intervals (CIs) or the mean difference with 95% CIs for the variables.
Results:
Our search yielded 10 randomized controlled trials with a total of 18,362 patients. Compared with RAASi treatment, patients treated with sacubitril/valsartan had lower incidence of composite renal impairment (10 studies, 18,362 patients, RR 0.84; 95% CI 0.72–0.96,
p
= 0.01;
I
2
= 22%), ESRD development (3 studies, 13,609 patients, RR 0.53; 95% CI 0.30–0.96,
p
= 0.03;
I
2
= 0%), drug discontinuation due to renal events (4 studies, 9,995 patients, RR 0.58; 95% CI 0.40–0.83,
p
= 0.003;
I
2
= 47%), severe hyperkalemia (6 studies, 16,653 patients, RR 0.80; 95% CI 0.68–0.93,
p
= 0.01;
I
2
= 25%) and a slower eGFR decline (4 studies, 13,608 patients, WMD 0.56; 95% CI 0.36–0.76,
p
< 0.00001;
I
2
= 65%). Subgroup analysis demonstrated that sacubitril/valsartan was associated with a lower incidence of renal impairment in patients with heart failure and preserved ejection fraction (HFpEF), but not in those with heart failure and reduced ejection fraction (HFrEF). The superior renal function preservation of sacubitril/valsartan treatment was not associated with different baseline eGFR levels and follow-up duration. There was a smaller increase in the change in the urine albumin-to-creatinine ratio (UACR) (3 studies, 9,114 patients, SMD 0.06; 95% CI 0.02–0.10,
p
= 0.003;
I
2
= 14%) with sacubitril/valsartan treatment. However, patients with heart failure appeared to have increased microalbuminuria, not patients without HF (
p
= 0.80 for interaction).
Conclusion:
Sacubitril/valsartan was associated with a lower incidence of composite renal impairment especially in patients with HFpEF, but higher microalbuminuria in patients with heart failure (both HFrEF and HFpEF) compared with RAASi. The lower incidence of severe hyperkalemia and drug discontinuation due to renal events in patients with sacubitril/valsartan treatment demonstrated its superior safety compared with RAASi.
Acute kidney injury (AKI) is independently associated with morbidity and mortality in a wide range of surgical settings. Nowadays, with the increasing use of electronic health records (EHR), advances ...in patient information retrieval, and cost reduction in clinical informatics, artificial intelligence is increasingly being used to improve early recognition and management for perioperative AKI. However, there is no quantitative synthesis of the performance of these methods. We conducted this systematic review and meta-analysis to estimate the sensitivity and specificity of artificial intelligence for the prediction of acute kidney injury during the perioperative period.
Pubmed, Embase, and Cochrane Library were searched to 2nd October 2021. Studies presenting diagnostic performance of artificial intelligence in the early detection of perioperative acute kidney injury were included. True positives, false positives, true negatives and false negatives were pooled to collate specificity and sensitivity with 95% CIs and results were portrayed in forest plots. The risk of bias of eligible studies was assessed using the PROBAST tool.
Nineteen studies involving 304,076 patients were included. Quantitative random-effects meta-analysis using the Rutter and Gatsonis hierarchical summary receiver operating characteristics (HSROC) model revealed pooled sensitivity, specificity, and diagnostic odds ratio of 0.77 (95% CI: 0.73 to 0.81),0.75 (95% CI: 0.71 to 0.80), and 10.7 (95% CI 8.5 to 13.5), respectively. Threshold effect was found to be the only source of heterogeneity, and there was no evidence of publication bias.
Our review demonstrates the promising performance of artificial intelligence for early prediction of perioperative AKI. The limitations of lacking external validation performance and being conducted only at a single center should be overcome.
This study was not registered with PROSPERO.
Background Whether convective modalities of dialysis, including hemofiltration (HF) and hemodiafiltration (HDF), improve cardiovascular outcomes and mortality is unclear. Study Design Systematic ...review and meta-analysis. Setting & Population Patients receiving HDF, HF, or standard hemodialysis (HD). Selection Criteria for Studies Randomized controlled trials. Intervention Convective modalities of dialysis (HDF and HF) versus standard HD. Outcomes The primary outcome was clinical cardiovascular outcomes. Secondary outcomes were all-cause mortality, episodes of symptomatic hypotension, dialysis adequacy, and β2 -microglobulin level. Relative risks (RRs) or weighted mean differences with 95% CIs for individual trials were pooled using random-effects models. Results The search yielded 16 trials including 3,220 patients. Therapies assessed were convective modalities (HDF or HF) compared with standard HD. Compared with HD, convective modalities did not significantly reduce the risk of cardiovascular events (RR, 0.85; 95% CI, 0.66-1.10) or all-cause mortality (RR, 0.83; 95% CI, 0.65-1.05). Convective modalities reduced symptomatic hypotension (RR, 0.49; 95% CI, 0.30-0.81) and improved serum β2 -microglobulin levels (−5.95 mg/L; 95% CI, −10.27 to −1.64), but had no impact on small-molecule clearance (weighted mean difference in Kt/V, 0.04; 95% CI, −0.04 to 0.12). There was a nonsignificant trend to a greater likelihood of receiving a kidney transplant for participants allocated to filtration therapies (RR, 1.19; 95% CI, 0.99-1.42). Limitations The trials were predominantly of suboptimal quality and underpowered, with imbalance in some prognostic variables at baseline. Intention-to-treat analysis was not used in some trials. Our analysis was limited to published outcomes. Conclusions The potential benefits of convective modalities over standard HD for cardiovascular outcomes and mortality remain unproved. Further high-quality randomized trials are needed to define the impact of these modalities on clinically important outcomes.
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