Prediction of acute kidney injury incidence following acute type A aortic dissection surgery with novel biomarkers: a prospective observational study.

BACKGROUND: Acute kidney injury (AKI) is a prevalent complication following acute type A aortic dissection (ATAAD) surgery and is closely associated with unfavorable prognostic outcomes. Hence, the development of a robust and efficient diagnostic approach to identify high-risk patients is of paramount importance. METHODS: We conducted a prospective study involving 328 patients who underwent ATAAD surgery at our institution, comprising three distinct cohorts. In addition, 52 patients undergoing alternative cardiopulmonary surgeries and 37 healthy individuals were enrolled as control groups. Employing proteomic analysis, we initially identified plasma proteins potentially linked to AKI occurrence within the plasma proteomic cohort. Subsequent validation was performed in an independent cohort. Utilizing predictors derived from multivariate logistic regression analysis, a nomogram was meticulously formulated and its efficacy was validated in the model construction cohort. RESULTS: Proteomics revealed significant elevation of plasma levels of S100A8/A9, pentraxin 3 (PTX3), and chitinase 3-like 1 (CHI3L1) immediately post-surgery in patients who developed ATAAD surgery-associated AKI (ASA-AKI). Receiver operating characteristic (ROC) curves demonstrated impressive predictive performance of S100A8/A9, PTX3, and CHI3L1 at 0 h post-surgery, yielding area under the curve (AUC) values of 0.823, 0.786, and 0.803, respectively, for ASA-AKI prediction. Furthermore, our findings exhibited positive correlations between plasma levels of S100A8/A9, PTX3, CHI3L1, and urinary neutrophil gelatinase-associated lipocalin (NGAL) at 0 h post-surgery, along with correlations between plasma S100A8/A9, CHI3L1 levels, and the Cleveland Clinic score. A logistic regression model incorporating plasma S100A8/A9, PTX3, CHI3L1 levels, urinary NGAL levels, and the Cleveland Clinic score facilitated the construction of a predictive nomogram for ASA-AKI. This nomogram demonstrated robust discriminative ability, achieving an AUC of 0.963 in the model construction cohort. CONCLUSIONS: Our study underscored the augmentation of plasma S100A8/A9, PTX3, and CHI3L1 levels immediately post-surgery in patients developing ASA-AKI. The incorporation of these three biomarkers, in conjunction with the Cleveland Clinic score and NGAL, into a nomogram demonstrated commendable predictive efficacy. This presents a practical tool for identifying patients at an elevated risk of AKI following ATAAD surgery.

Functional Characterization of Renal Tubular Epithelial Cells in Optimized Coculture Systems.

BACKGROUND: Obtaining sufficient renal tubular epithelial cells (RTCs) and maintaining the functions of RTCs are vital for developing a bioartificial renal tubule-assisted device for continuous renal replacement therapy. METHODS: We established an optimal Transwell coculture system using human primary renal proximal tubule epithelial cells (RPTECs) and bone marrow mesenchymal stem cells at different cell ratios to investigate morphological and functional changes in RTCs. Changes in cell proliferation, megalin expression, cell cycle, apoptosis, and levels of insulin-like growth factor-1 (IGF-1) and bone morphogenetic protein-7 (BMP-7) after cell culture were investigated. RESULTS: RPTEC/BMMSC coculture at a cell ratio of 3:1 resulted in optimal morphology, function, and growth of RPTECs, in which, viability, proliferation, cytochrome P450 activity, and megalin expression in RPTECs were significantly increased compared to those in other cocultures or RPTECs alone. Additionally, IGF-1 and BMP-7 levels were significantly higher in the 3:1 RPTEC/BMMSC coculture than in the RPTECs alone. CONCLUSION: Our results demonstrate that coculture with RPTECs has great potential for use in renal replacement therapy, thereby providing fundamental information for manufacturing a bioartificial kidney.

Construction of a lactate-related prognostic signature for predicting prognosis after surgical repair for acute type a aortic dissection.

Background: Serum lactate is commonly measured in the perioperative period in patients who have undergone surgery for an acute type A aortic dissection (ATAAD). However, conflicting data has been reported as to whether lactate elevation is associated with short-term prognosis. The aim of the current study was to determine the association between perioperative arterial lactate levels and postoperative 30-day mortality. Methods: Patients who underwent repair of a ATAAD at our institution were retrospectively screened and those with comprehensive measurements of serum lactate before surgery and at 0, 1, 3, 6, 12, and 24 h after surgery in the intensive care unit (ICU) were selected for the analysis. Patients' demographic features and outcomes were reviewed to determine risk factors associated with 30-day mortality using logistic regression modeling. The association between serum lactate levels at different time points and 30-day mortality were analyzed by receiver-operating characteristic curves. Results: 513 patients were identified and retrospectively analyzed for this study including 66 patients (12.9%) who died within 30 days after surgery. Patients who died within 30 days after surgery had elevated lactate levels measured before surgery and at 0, 1, 3, 6, 12, and 24 h after their ICU stay. Lactate measured at 24 h post ICU admission (odds ratio, 2.131; 95% confidence interval, 1.346-3.374; p = 0.001) was a predictor of 30-day mortality. The area under the curve (AUC) for 30-day mortality with lactate levels at 12 h and 24 h post ICU stay were 0.820 and 0.805, respectively. Conclusion: Early elevation of lactate level is correlated with increased 30-day mortality in patients who received ATAAD surgical repair.

Clinical characteristics and in silico analysis of congenital pseudarthrosis of the tibia combined with neurofibromatosis type 1 caused by a novel NF1 mutation.

Congenital pseudarthrosis of the tibia (CPT) is a rare congenital bone malformation, which has a strong relationship with Neurofibromatosis type 1 (NF1). NF1 is an autosomal dominant disease leading to multisystem disorders. Here, we presented the genotypic and phenotypic characteristics of one unique case of a five-generation Chinese family. The proband was CPT accompanied with NF1 due to NF1 mutation. The proband developed severe early-onset CPT combined with NF1 after birth. Appearance photos and X-ray images of the left limb of the proband showed significant bone malformation. Slit-lamp examination showed Lisch nodules in both eyes of the proband. Whole-exome sequencing (WES) and Sanger sequencing confirmed the truncation variant of NF1 (c.871G>T, p. E291*). Sequence conservative and evolutionary conservation analysis indicated that the novel mutation (p.E291*) was highly conserved. The truncated mutation led to the loss of functional domains, including CSRD, GRD, TBD, SEC14-PH, CTD, and NLS. It may explain why the mutation led to a severe clinical feature. Our report expands the genotypic spectrum of NF1 mutations and the phenotypic spectrum of CPT combined with NF1.

Hyperbilirubinemia after surgical repair for acute type a aortic dissection: A propensity score-matched analysis.

Background: Inflammation and oxidative stress are known to participate in the pathogenesis of hyperbilirubinemia. It has been known that acute type A aortic dissection (ATAAD) surgical repair often associates with complications which might affect the long-term prognosis. However, the clinical significance of postoperative hyperbilirubinemia (PH) has not been evaluated. Here in this study, we examined the incidence, risk factors, and prognosis of PH after ATAAD surgery. Methods: This retrospective study enrolled a total of 970 patients who received ATAAD surgical repair from January 2014 to December 2019. PH was defined as serum total bilirubin >3.0 mg/dl within the first week after the surgery. Propensity score matching was used to reduce selection bias and eliminate potential confounding factors. Kaplan-Meier survival and Cox proportional hazards regression analyses were conducted to explore the association between PH and postoperative long-term survival. Results: Development of PH (183 patients) was associated with a higher 30-Day mortality (20.8% vs. 9.0%, p < 0.001). Advanced age [odds ratio (OR) 1.538, p = 0.006], higher baseline total bilirubin level (OR 1.735, p = 0.026), preoperative pericardial tamponade (OR 3.192, p = 0.024), prolonged cardiopulmonary bypass (CPB) duration (OR 2.008, p = 0.005), and elevated postoperative central venous pressure (CVP) level (OR 2.183, p < 0.001) were associated with PH. The Kaplan-Meier analysis showed patients who developed PH were associated with poor long-term survival (p = 0.044). Cox analysis showed that the presence of PH (hazard ratio 2.006, p = 0.003) was an independent risk factor for increased mortality. Conclusion: PH is a common complication in patients undergoing ATAAD surgical repair that associates with worse short- and long-term prognosis. Our data indicated that age, preoperative total bilirubin level, pericardial tamponade, CPB duration, and postoperative CVP level were risk factors for the development of PH.

Early dynamic behavior of lactate in predicting continuous renal replacement therapy after surgery for acute type A aortic dissection.

Background: It has been well known that hyperlactatemia is an independent risk factor for postoperative mortality in patients who received acute type A aortic dissection (ATAAD) surgery. Some patients may require the assistance of continuous renal replacement therapy (CRRT) for acute postoperative renal deficiency and often associate with increased mortality rate. This study aimed to examine the association between the early dynamic change of lactate levels and postoperative CRRT in ATAAD patients who received surgical repairment. Methods: This retrospective study included 503 patients who received ATAAD surgeries. Serum lactate levels were measured before operation and at 0, 1, 3, 6, 12, 24 h post intensive care unit (ICU) admission. We examined the association between dynamic changes of lactate and CRRT. Results: Among all patients, 19.9% (100 patients) required CRRT. Our data showed that the lactate levels were higher in the CRRT group at all timepoints compared to the non-CRRT group. In a multivariate model, lactate levels at 12 h post ICU admission [odds ratio (OR), 1.362; p = 0.007] was identified as an independent predictor for requiring CRRT. Unsurprisingly, 30-day mortality in the CRRT group (41%) was 8.2 times higher than in the non-CRRT group (5%). To better understand the associations between CRRT and lactate levels, patients in the CRRT group were further stratified into the non-survivor group (n = 41) and survivor group (n = 59) based on the 30-day mortality. Elevated lactate levels measured upon ICU admission (OR, 1.284; p = 0.001) and decreased 24 h lactate clearance (OR, 0.237; p = 0.039) were independent risk factors for 30-day mortality in patients who received CRRT. The area under the curve to predict requirement for CRRT at 6 and 12 h post CICU admission were 0.714 and 0.722, respectively, corresponding to lactate cut-off levels of 4.15 and 2.45 mmol/L. Conclusion: The CRRT is commonly required in patients who received ATAAD surgery and often associated with worse mortality. Early dynamic changes of lactate levels can be used to predict the requirement of postoperative CRRT.

WNT1 expression influences the development of dysplasia of the hip via regulating RBPMS2/NOG-BMP2/4-GDF5- WISP2 pathway.

OBJECTIVE: To explore the role of WNT family member 1 (WNT1) in the development of dysplasia of the hip (DDH) and the molecular mechanism involved in this process. Methods: Si-WNT1, pcDNA3.1-WNT1 or corresponding negative controls were transfected into human osteoblast hFOB1.19 and human chondrocyte C28/I2, respectively. The proliferation of cells was measured by EdU assay. The relative expressions of human noggin gene (NOG), growth differentiating factor 5 (GDF5), WNT1, and WNT1-inducible-signaling pathway protein 2 (WISP2) were determined by immunofluorescence analysis. The protein expressions of RNA-binding protein of multiple splice forms 2 (RBPMS2), NOG, bone morphogenetic protein 2 (BMP2), BMP4, WNT1 and WISP2 were determined by western blot. Animal experiment was also performed and the morphological development of hip joint was observed. Results: Overexpression of WNT1 promoted osteoblast proliferation and inhibited chondrocyte proliferation, while knockdown of WNT1 inhibited osteoblast proliferation. In chondrocytes, knockdown of WNT1 upregulated NOG expression, while overexpression of WNT1 downregulated its expression. In osteoblasts and chondrocytes, overexpression of WNT1 increased BMP2, BMP4, WNT1, and WISP2 expression. RBPMS2 and NOG were slightly expressed in each group. Conclusion: Overexpression of WNT1 promoted osteoblast proliferation, inhibited chondrocyte proliferation, and increased the expressions of BMP2, BMP4, WNT1, and WISP2. Therefore, WNT1 may be a new therapeutic target for DDH.

Risk factors for re-dislocation after closed reduction in children with developmental dysplasia of the hip.

OBJECTIVE: To investigate the risk factors for re-dislocation after the closed reduction in children with developmental dysplasia of the hip (DDH). METHODS: The clinical data of 88 children aged ≤ 18 months with DDH (103 hips) who were treated with adductor muscle relaxation + closed reduction + plaster fixation at the Children's Hospital, Zhejiang University School of Medicine from January 2015 to December 2017, were retrospectively analyzed. According to the diagnostic criteria of hip dislocation, patients were divided into two groups: reduction group and re-dislocation group. The univariate and multivariate logistic regression analysis were applied to identify the risk factors for the re-dislocation of children. RESULTS: Eighty-six patients (99 hips) successively underwent the treatment. 69 hips were fixed at the first intention, 9 hips at the second intention, and a total of 78 hips with no re-dislocation occurred till the last follow-up with a rate of 78.8%. The univariate analysis showed that preoperative acetabular index (AI), International Hip Dysplasia Institute (IHDI) grade, intraoperative hip flexion angle, and intraoperative head-socket spacing were significantly related to the occurrence of re-dislocation after closed-reduction. The multivariate logistic regression analysis showed that preoperative AI > 40.5° ( OR=5.57, P<0.01), flexion angle < 80.5° ( OR=4.93, P<0.01) and head-socket distance > 6.95 mm ( OR=8.42, P<0.01) were risk factors for the re-dislocation. The area under the receiver operator characteristic curve was 0.91 when preoperative AI > 40.5°, flexion angle < 80.5°, head-socket distance > 6.95 mm, and IHDI grade were used to predict the occurrence of re-dislocation, and the sensitivity and specificity were 0.72 and 0.87, respectively. CONCLUSIONS: Preoperative AI > 40.5°, intraoperative hip flexion angle < 80.5°, and head-socket distance > 6.95 mm are risk factors for postoperative re-dislocation in children with DDH. These risk factors combining with the IHDI grade would be better to predict the occurrence of re-dislocation.

Monteggia equivalent lesion in children: a narrative review.

Background: Monteggia equivalent lesion represents a group of injury or combined injury patterns that resemble the Monteggia lesion in its presentations and mechanisms. Unlike Monteggia lesions, the equivalent ones, which share vague definitions and mostly occur as sporadic single case reports in the literature, have not been thoroughly reviewed since Bado first proposed the term, especially in the pediatric population. The objective of this review was to elucidate the definition by elaborating on its clinical styles and thus analyzing the mechanism, diagnosis, and management through related literature. Data sources: Based on the terms of 'Monteggia equivalent', 'radial neck fracture' and 'pediatric', all of the related literature was searched on the PubMed and Google Scholar search engine. Results: The advance of the definitions for pediatric Monteggia equivalent lesion (PMEL) was reviewed. The functional roles of the ulnar and the related mechanism theories in this injury were analyzed. The status of the radiocapitellar joint in this injury was emphasized. According to the previous statements, a new classification model was proposed and proper diagnosis and treatment approaches were suggested. Conclusions: PMEL should be defined as an ulnar fracture at any level combined with a proximal radial fracture. According to the status of the radiocapitellar joint, it could be divided into three groups. The occult ulnar bowing and delayed radial head dislocation should be a serious concern of orthopedists. Surgical need is usually warranted. Maintaining the ulnar length and securing the radiocapitellar joint are highly recommended.

Microsurgical anatomical study of the frontotemporal-zygomatic arch approach to the superior petroclival region.

The aim of this study was to explore the microsurgical anatomy of the superior petroclival region, and thus provide an anatomical basis for operative approaches. The frontotemporal-orbitozygomatic approach was performed on 20 sides of 10 adult cadaver heads. In comparison to the range of the exposure with the removal of the anterior clinoid process, posterior clinoid process and part of the tip of the petrous bone, we measured the neurovascular course and their relation to the superior petroclival region. We found that the trochlear nerve goes through the edge of the tentorial marginal branch, taking 5.42 mm (4.26-6.96) away from the ophthalmic nerve. Exposing the arteria basilaris, above the middle piece the length of exposure is 15.52 mm (14.22-16.70), resulting in the posterior cerebral artery and the front part of the midbrain being completely exposed. There is little exposure on the front part of the pons and midbrain with a length of 5.6 mm (4.38-6.82). Removing the partial petrosal bones, the inferior segment of the basal artery is exposed, while 4 other nerves cab also be observed: Cranial, abducens, facial and vestibulocochlear. The frontotemporal-zygomatic arch approach can clearly expose the superior petroclival region. Obtaining more information on the relationship between the location of these structures, is therefore helpful in improving the safety and success of surgery in this region.