Univariate Analysis Research Articles

Mohs micrographic surgery for the treatment of invasive melanoma: A systematic review with meta-analyses.

The use of Mohs micrographic surgery (MMS) in melanoma treatment has divided opinion and evidence-based guidelines are lacking. This systematic review aimed to analyse clinical outcomes for patients with invasive melanomas treated with Mohs rather than wide local excision (WLE). Embase, MEDLINE and Cochrane databases (to 30 August 2023) were searched for studies using Mohs to treat invasive melanoma. Outcomes of interest were local recurrence and death from melanoma. Thirty-five articles involving 41,499 patients with invasive melanoma treated with Mohs were identified. Sixteen studies compared Mohs with WLE and 19 were Mohs-only, non-comparative studies. Patients treated with Mohs differed significantly from those undergoing WLE, in particular Mohs patients were older and had thinner melanomas. Two comparative studies using the same data source reported adjusted hazard ratios for melanoma-specific death and both showed no significant difference between Mohs and WLE-treated patients; 0.87 (95% CI 0.55-1.35) and 1.20 (95% CI 0.71-20.36). There was also no statistically significant difference in local recurrence risk; the unadjusted risk ratio for patients treated with Mohs was 0.46 (95% CI 0.14-1.51 p = 0.20) with moderate heterogeneity (I2 = 62%). No studies reported multivariable analyses for risk of local recurrence. Many studies generated from relatively few and often overlapping data sets have reported the use of Mohs to treat patients with invasive melanoma. Fewer studies were comparative between Mohs and WLE and these reported substantially different baseline risks of recurrence and death from melanoma between the groups. Mohs has generally been used for thinner melanomas in older patients; therefore, comparisons based on univariable analyses are likely to have been misleading. On the basis of currently available data, it is not possible to reliably assess whether outcomes differ if invasive melanomas with comparable features are treated with Mohs or WLE, and randomized trial evidence will be required for reliable conclusions to be reached.

Nonanatomic femoral tunnel placement increases the risk of subsequent meniscal surgery after ACLR: Part II-Patients without recurrent ACL injury.

The purpose of this study was to identify risk factors for subsequent meniscal surgery following anterior cruciate ligament (ACL) reconstruction (ACLR) in patients without recurrent ACL injury. Patients aged ≥14 years who underwent primary ACLR with minimum 1-year follow-up and without recurrent ACL injury were retrospectively reviewed. Patient demographics and surgical data at the time of ACLR were collected. Postoperative radiographs were used to measure femoral and tibial tunnel position, and posterior tibial slope. Univariate and multivariate analyses were performed to identify risk factors for subsequent meniscal surgery. Of 629 ACLRs that fulfilled the inclusion criteria, subsequent meniscal surgery was performed in 65 [10.3%] patients. Multivariate analysis revealed that medial meniscal repair at the time of ACLR, younger age, anterior femoral tunnel position and distal femoral tunnel position were significantly associated with subsequent meniscal surgery (p < 0.001, p = 0.016, p = 0.015, p = 0.035, respectively). The frequency of femoral tunnel placement >10% outside of the literature-established anatomic position was significantly higher in those who underwent subsequent meniscal surgery compared to those who did not (38.3% vs. 20.3%, p = 0.006). Posterior tibial slope and ACL graft type were not significantly associated with subsequent meniscal surgery. Medial meniscal repair at the time of ACLR, younger age and nonanatomic femoral tunnel placement were risk factors for subsequent meniscal surgery in patients without recurrent ACL injury. Femoral tunnel placement <10% outside of the native anatomic position is important to reduce the risk of subsequent meniscal surgery. Level IV.

Standard-definition White-light, High-definition White-light versus Narrow-band Imaging Endoscopy for Detecting Colorectal Adenomas: A Multicenter Randomized Controlled Trial.

This study aimed to compare the performance of standard-definition white-light endoscopy (SD-WL), high-definition white-light endoscopy (HD-WL), and high-definition narrow-band imaging (HD-NBI) in detecting colorectal lesions in the Chinese population. This was a multicenter, single-blind, randomized, controlled trial with a non-inferiority design. Patients undergoing endoscopy for physical examination, screening, and surveillance were enrolled from July 2017 to December 2020. The primary outcome measure was the adenoma detection rate (ADR), defined as the proportion of patients with at least one adenoma detected. The associated factors for detecting adenomas were assessed using univariate and multivariate logistic regression. Out of 653 eligible patients enrolled, data from 596 patients were analyzed. The ADRs were 34.5% in the SD-WL group, 33.5% in the HD-WL group, and 37.5% in the HD-NBI group (P=0.72). The advanced neoplasm detection rates (ANDRs) in the three arms were 17.1%, 15.5%, and 10.4% (P=0.17). No significant differences were found between the SD group and HD group regarding ADR or ANDR (ADR: 34.5% vs. 35.6%, P=0.79; ANDR: 17.1% vs. 13.0%, P=0.16, respectively). Similar results were observed between the HD-WL group and HD-NBI group (ADR: 33.5% vs. 37.7%, P=0.45; ANDR: 15.5% vs. 10.4%, P=0.18, respectively). In the univariate and multivariate logistic regression analyses, neither HD-WL nor HD-NBI led to a significant difference in overall adenoma detection compared to SD-WL (HD-WL: OR 0.91, P=0.69; HD-NBI: OR 1.15, P=0.80). HD-NBI and HD-WL are comparable to SD-WL for overall adenoma detection among Chinese outpatients. It can be concluded that HD-NBI or HD-WL is not superior to SD-WL, but more effective instruction may be needed to guide the selection of different endoscopic methods in the future. Our study's conclusions may aid in the efficient allocation and utilization of limited colonoscopy resources, especially advanced imaging technologies.

Pregnancy Outcomes After Bariatric Surgery: Importance of Maternal Ferritin on Birth Weight.

The risks carried by pregnancy after bariatric surgery (BS) include small-for-gestational age (SGA) newborn and prematurity. However, the underlying mechanisms are not yet fully understood in pregnant women after BS. This single-center retrospective observational cohort study includes all women with a first and single pregnancy after BS who completed at least one clinical and biological nutritional assessment during pregnancy between 2010 and 2016. The quarterly biological assessment comprised blood count, ferritin, calcium, 25OH vitamin D, parathyroid hormone, fasting glucose, albumin, prealbumin, vitamin A, vitamin B12, folic acid, and zinc. Among 120 pregnancies analysed, two-thirds underwent gastric bypass (Roux-en-Y and one-anastomosis) and one-third a restrictive procedure (adjustable gastric band or sleeve gastrectomy). The median [Q1-Q3] preoperative BMI was 43.8 [41.1-47.7] kg/m2 and the mean age at pregnancy was 32.6 ± 5.3years. Weight loss and time from surgery to pregnancy were 35.1 ± 15.4kg and 2.9 [1.3-4.5] years, respectively. Ten women (8%) gave birth prematurely, and 22 newborns (19%) were SGA. Univariate analysis shows that ferritin was significantly higher in mothers with SGA than in those without SGA (35.5 [22.3-69.5] vs. 15 [10-32] ng/ml) at third trimester of pregnancy. Women who received pre-pregnancy nutritional assessment seemed less likely to give birth to a SGA newborn (32% vs. 54%, p = 0.07). Iron supplementation should be carefully prescribed and closely monitored during pregnancy in women who have undergone BS.

Development and validation of a social alienation predictive model for older maintenance hemodialysis patients based on latent profile analysis—a cross-sectional study

BackgroundSocial alienation refers to the state of feeling isolated, helpless, and unsatisfied due to maintaining distance from others or avoiding social interaction and activities. This phenomenon is caused by a lack of social skills, social anxiety, physical health problems, and other reasons. Older maintenance hemodialysis patients are exposed to a higher risk of social alienation. However, previous studies have been performed using the total score of the scale, which does not allow the identification of the characteristics of various patient groups with different levels of social alienation. In contrast, latent profile analysis can classify individuals into different categories based on continuous observational indicators, which improves accuracy and provides a more objective assessment by accounting for the uncertainty of variables. Given the concealed nature of social alienation and the differences in characteristics and treatment measures between different profiles, developing a predictive model for social alienation in older maintenance hemodialysis patients holds significance.ObjectiveTo explore the latent profile analysis of social alienation in older maintenance hemodialysis patients and to develop and validate a predictive model for social alienation in this population.MethodsA total of 350 older maintenance hemodialysis patients were selected as the study subjects using convenience sampling. A cross-sectional survey was conducted using a general information questionnaire, the Generalized Alienation Scale, and the Self-Perceived Burden Scale. Based on the results of the Generalized Alienation Scale, a latent profile analysis was performed, followed by univariate analysis and multinomial logistic regression to develop a predictive model. The effectiveness of the predictive model was evaluated in terms of its authenticity, reliability, and predictive ability.ResultsThree hundred nineteen valid questionnaires were collected. The social alienation of older maintenance hemodialysis patients based on latent profile analysis were divided into three profiles, which were named the low/medium/high-symptom groups, comprising 21%, 38.9%, and 40.1% of participants, respectively. Based on male, monthly social activity hours, Age-Adjusted Charlson Comorbidity Index, dialysis age, and Self-Perceived Burden Scale, a predictive model of social alienation for older maintenance hemodialysis patients was developed, and the Hosmer–Lemeshow tests showed no statistical significance (P > 0.05). The model has high predictive efficiency in authenticity, reliability and predictability.ConclusionOlder maintenance hemodialysis patients exhibited moderate to high levels of social alienation. The latent profile analysis based method was used to divide patients into low/medium/high-symptom profiles, and the predictive model demonstrates excellent authenticity, reliability, and predictability.

Real-time predictive model of extrauterine growth retardation in preterm infants with gestational age less than 32 weeks

The aim of this study was to develop a real-time risk prediction model for extrauterine growth retardation (EUGR). A total of 2514 very preterm infants were allocated into a training set and an external validation set. The most appropriate independent variables were screened using univariate analysis and Lasso regression with tenfold cross-validation, while the prediction model was designed using binary multivariate logistic regression. A visualization of the risk variables was created using a nomogram, while the calibration plot and receiver operating characteristic (ROC) curves were used to calibrate the prediction model. Clinical efficacy was assessed using the decision curve analysis (DCA) curves. Eight optimal predictors that namely birth weight, small for gestation age (SGA), hypertensive disease complicating pregnancy (HDCP), gestational diabetes mellitus (GDM), multiple births, cumulative duration of fasting, growth velocity and postnatal corticosteroids were introduced into the logistic regression equation to construct the EUGR prediction model. The area under the ROC curve of the training set and the external verification set was 83.1% and 84.6%, respectively. The calibration curve indicate that the model fits well. The DCA curve shows that the risk threshold for clinical application is 0–95% in both set. Introducing Birth weight, SGA, HDCP, GDM, Multiple births, Cumulative duration of fasting, Growth velocity and Postnatal corticosteroids into the nomogram increased its usefulness for predicting EUGR risk in very preterm infants.

Semi-physiological Pharmacokinetic Model of Clozapine and Norclozapine in Healthy, Non-smoking Volunteers: The Impact of Race and Genetics.

Healthy volunteers were recruited in a population pharmacokinetic study. Blood samples were collected at 30 min and 1, 2, 3, 5 and 8 h following a single flat dose of clozapine (12.5 mg). The clozapine and norclozapine concentrations were measured via high-performance liquid chromatography-ultraviolet method. A semi-physiological pharmacokinetic model of clozapine and norclozapine was developed using nonlinear mixed-effects modeling. Clinical and genetic predictors were evaluated, including CYP1A2 (rs762551) and ABCB1 (rs2032582), using restriction fragment length polymorphism. A total of 270 samples were collected from 33 participants. The data were best described using a two-compartment model for clozapine and a two-compartment model for norclozapine with first-order absorption and elimination and pre-systemic metabolism. The estimated (relative standard error) clearance of clozapine and norclozapine were 27 L h-1 (31.5 %) and 19.6 L h-1 (30%), respectively. Clozapine clearance was lower in sub-Saharan Africans (n = 4) and higher in Caucasians (n = 9) than Asians (n = 20). Participants with CYP1A2 (rs762551) (n = 18) and ABCB1 (rs2032582) (n = 12) mutant alleles had lower clozapine clearance in the univariate analysis. This is the first study to develop a semi-physiological pharmacokinetic model of clozapine and norclozapine accounting for the pre-systemic metabolism. Asians required lower doses of clozapine as compared with Caucasians, while clozapine pharmacokinetics in sub-Saharan Africans should be further investigated in larger trials.

Comprehensive analysis of the prognostic role of laboratory indices in advanced lung cancer patients.

Lung cancer, the most common cause of cancer-related death, is diagnosed mostly in advanced stages, and 5-year survival is approximately 5.8%. It is critical to identify reliable prognostic factors to optimize treatment responses, guide therapeutic strategies and pave the way to new research. In this study, we aimed to investigate the strongest prognostic factors for advanced non-small cell lung cancer (NSCLC). We retrospectively analyzed 278 patients with NSCLC. We evaluated the association between potential prognostic factors and overall survival (OS) times using Kaplan-Meier analysis and Cox regression analysis. The median OS in all patients was 15.3 months. In univariate analysis, gender, histologic type, performance status, immunotherapy, radiotherapy, hemoglobin level, serum albumin, sodium-globulin ratio (SGR), neutrophil-lymphocyte ratio (NLR), systemic immune inflammation index (SII), hemoglobin-albumin-lymphocyte-plateletscore (HALP), and advanced lung cancer index (ALI) were associated with survival. Models were established for multivariate analyses. In the models, NLR, SGR, HALP, immunotherapy, radiotherapy, and Eastern Cooperative Oncology Group (ECOG) performance status showed independent prognostic features (p<0.001, p=0.003, p=0.002, p<0.001, p=0.010, and p=0.025, respectively). In addition, in the subgroup analysis, prognostic indexes (NLR, SGR, and HALP) were found to have a prognostic effect on survival in multiple subgroups. Pretreatment NLR, SGR, HALP, immunotherapy, radiotherapy, and ECOG performance status are independent prognostic factors for advanced NSCLC patients. These prognostic factors can be used in clinical practice as easily accessible, simple, and useful tools for clinicians.

Comparison of the effects of burn assessment mission game with feedback lecture on nursing students’ knowledge and skills in the burn patients’ assessment: a randomized clinical trial

BackgroundLearning of burn patient assessment is very important, but heart-breaking for nursing students. This study aimed to compare the effects of feedback lecture method with a serious game (BAM Game) on nursing students’ knowledge and skills in the assessment of burn patients.MethodIn this randomized controlled clinical trial, 42 nursing students in their 5th semester at Mashhad University of Medical Sciences School of Nursing and Midwifery, were randomly assigned to intervention (BAM game, available for two weeks) and control (feedback lecture method presented in two 90-minute sessions) groups. Two weeks after the intervention, all students were evaluated for their knowledge (using knowledge assessment test) and skills (using an Objective Structured Clinical Examination). Statistical analysis involved independent t-test, Fisher’s exact test, analysis of covariance (ANCOVA), and univariable and multivariable ordinal logistic regression models.ResultsFollowing the intervention, the skill scores were 16.4 (SD 2.2) for the intervention group and 11.8 (SD 3.8) for the control group. Similarly, the knowledge scores were 17.4 (SD 2.2) for the intervention group and 14.7 (SD 2.6) for the control group. Both differences were statistically significant (P < .001). These differences remained significant even after adjusting for various factors such as age, gender, marital status, residence, university entrance exam rank, and annual GPA (P < .05). Furthermore, the BAM game group showed significantly higher skills rank than the feedback lecture group across most stations (eight of ten) (P < .05) in the univariable analysis. Multivariable analysis also revealed a significantly higher skills score across most stations even after adjusting for the mentioned factors (P < .05). These results suggest that the BAM game group had higher skills scores over a range of 1.5 to 3.9 compared to the feedback lecture group.ConclusionsThis study demonstrated that nursing students who participated in the BAM game group exhibited superior performance in knowledge acquisition and skill development, compared to those in the control group. These results underscore a significant enhancement in educational outcomes for students involved with the BAM game, confirming its utility as a potent and effective pedagogical instrument within the realm of nursing education.Trial registrationIranian Registry of Clinical Trials: IRCT20220410054483N1, Registration date: 18/04/2022.

LINAS-Score: prognostic model for mortality assessment in patients with cirrhotic liver and infected ascites.

Patients with liver cirrhosis often face a grave threat from infected ascites (IA). However, a well-established prognostic model for this complication has not been established in routine clinical practice. Therefore, we aimed to assess mortality risk in patients with liver cirrhosis and IA. We conducted a retrospective study across three tertiary hospitals, enrolling 534 adult patients with cirrhotic liver and IA, comprising 465 with spontaneous bacterial peritonitis (SBP), 34 with bacterascites (BA), and 35 with secondary peritonitis (SP). To determine the attributable mortality risk linked to IA, these patients were matched with 122 patients with hydropic decompensated liver cirrhosis but without IA. Clinical, laboratory, and microbiological parameters were assessed for their relation to mortality using univariable analyses and a multivariable random forest model (RFM). Least absolute shrinkage and selection operator (Lasso) regression model was used to establish an easy-to-use mortality prediction score. The in-hospital mortality risk was highest for SP (39.0%), followed by SBP (26.0%) and BA (25.0%). Besides illness severity markers, microbiological parameters, such as Candida spp., were identified as the most significant indicators for mortality. The Lasso model determined 15 parameters with corresponding scores, yielding good discriminatory power (area under the receiver operating characteristics curve=0.89). Counting from 0 to 83, scores of 20, 40, 60, and 80 corresponded to in-hospital mortalities of 3.3%, 30.8%, 85.2%, and 98.7%, respectively. We developed a promising mortality prediction score for IA, highlighting the importance of microbiological parameters in conjunction with illness severity for assessing patient outcomes.

Related Clinical Factors of Platinum-Based Chemotherapy Resistance in Patients with Epithelial Ovarian Cancer.

Ovarian cancer is the second most common malignancy in women, but it is a fatal gynecological tumor. Although it has a standard treatment regimen, resistance to chemotherapy makes patients more prone to early recurrence, leading to poor survival rates. Therefore, this study investigated factors related to platinum resistance through a complete analysis of clinical data. Clinical data of patients with ovarian cancer were collected, and the patients were categorized into platinum-sensitive and platinum-resistant groups. By comparing the differences in clinical data between the groups, the key factors affecting platinum resistance were analyzed. We collected the clinical data of patients with epithelial ovarian cancer (EOC) who were admitted to the Department of Oncology of the General Hospital of Ningxia Medical University between January 1, 2019, and December 31, 2020. We conducted univariate and multivariate analyses and evaluated overall survival and progression-free survival using the Kaplan-Meier method. We enrolled 161 patients with EOC, of whom 124 demonstrated platinum sensitivity and 37 demonstrated platinum resistance after the initial platinum-based chemotherapy. Univariate analyses revealed that the International Federation of Gynecology and Obstetrics (FIGO) stage, neoadjuvant chemotherapy, and Fagotti score were associated with an increased risk of platinum resistance for the first recurrence. In multivariate logistic regression analysis, only Fagotti score and neoadjuvant chemotherapy were associated with an increased risk of platinum resistance (odds ratio: 0.372 and 0.328, 95% confidence interval: 0.160-0.863 and 0.141-0.762, p = 0.021 and 0.010, respectively). The sample size of this study was relatively small because of nonstandard treatment of some patients, the absence of clinical data, and failure of follow-up. Patients with EOC exhibiting platinum resistance had a very poor prognosis. The Fagotti score and neoadjuvant chemotherapy appeared to increase the risk of platinum resistance at first recurrence.

Machine learning survival prediction using tumor lipid metabolism genes for osteosarcoma

Osteosarcoma is a primary malignant tumor that commonly affects children and adolescents, with a poor prognosis. The existence of tumor heterogeneity leads to different molecular subtypes and survival outcomes. Recently, lipid metabolism has been identified as a critical characteristic of cancer. Therefore, our study aims to identify osteosarcoma's lipid metabolism molecular subtype and develop a signature for survival outcome prediction. Four multicenter cohorts—TARGET-OS, GSE21257, GSE39058, and GSE16091—were amalgamated into a unified Meta-Cohort. Through consensus clustering, novel molecular subtypes within Meta-Cohort patients were delineated. Subsequent feature selection processes, encompassing analyses of differentially expressed genes between subtypes, univariate Cox analysis, and StepAIC, were employed to pinpoint biomarkers related to lipid metabolism in TARGET-OS. We selected the most effective algorithm for constructing a Lipid Metabolism-Related Signature (LMRS) by utilizing four machine-learning algorithms reconfigured into ten unique combinations. This selection was based on achieving the highest concordance index (C-index) in the test cohort of GSE21257, GSE39058, and GSE16091. We identified two distinct lipid metabolism molecular subtypes in osteosarcoma patients, C1 and C2, with significantly different survival rates. C1 is characterized by increased cholesterol, fatty acid synthesis, and ketone metabolism. In contrast, C2 focuses on steroid hormone biosynthesis, arachidonic acid, and glycerolipid and linoleic acid metabolism. Feature selection in the TARGET-OS identified 12 lipid metabolism genes, leading to a model predicting osteosarcoma patient survival. The LMRS, based on the 12 identified genes, consistently accurately predicted prognosis across TARGET-OS, testing cohorts, and Meta-Cohort. Incorporating 12 published signatures, LMRS showed robust and significantly superior predictive capability. Our results offer a promising tool to enhance the clinical management of osteosarcoma, potentially leading to improved clinical outcomes.

Short-term effects of bowel function on global health quality of life after radical cystectomy.

Radical cystectomy (RC) shows an important impact on quality of life (QoL), for various clinical aspects. The aim of our study was to evaluate the short-term bowel function in patients that underwent RC. Two hundred and six patients with MIBC underwent RC with ONB or IC urinary diversion. QoL was measured using the EORTC QLQ C30 and the Short-Form SF-36 questionnaires before surgery and at 12 months postoperatively. Baseline characteristics, including demographic profile, BMI, Charlson Comorbidity Index (CCI), modified Frailty Index (m-FI), pathological tumor stage, Clavien-Dindo grade, and neo-adjuvant chemotherapy were recorded and compared. The uni-variate and multivariate analysis (OR) were performed for constipation, diarrhea and m-FI of patients underwent RC for localized MIBC according to global health status score (poor/good vs very good). Multivariate analysis showed that constipation medium/high was significant associated with global health status poor/good (OR=2.39; 95% CI: 1.22-4.71; P=0.01); Diarrhea medium/high was associated with global health status poor/good (OR=2.85; 95% CI:1.18-6.92; P=0.02), and m-FI ≥2 score (OR=2.13; 95% CI: 0.99-4.57; P=0.05). Diarrhea and constipation are associated with a lower QoL in cystectomized patients, both with ONB or IC urinary diversion; such association is especially significant in more fragile patients (Frailty Index ≥2).

An evaluation model of hepatic steatosis based on CT value and serum uric acid/HDL cholesterol ratio can predict intrahepatic recurrence of colorectal cancer liver metastasis.

Intrahepatic recurrence is one of the main causes of treatment failure in patients with colorectal cancer liver metastasis (CRLM). Hepatic steatosis was reported to provide fertile soil for metastasis. The effect of irinotecan-inducted hepatic steatosis on the progression of liver metastasis remains to be verified. Therefore, we aim to clarify the effect of hepatic steatosis on postoperative intrahepatic recurrence in CRLM and whether it is relevant to irinotecan-based chemotherapy. Data for a total of 284 patients undergoing curative surgical treatment for CRLMs were retrospectively reviewed between March 2007 and June 2018. Hepatic steatosis score (HSS) was established by combining Liver to Spleen CT ratio (LSR) and Uric acid to HDL-cholesterol ratio (UHR) to detect the presence of hepatic steatosis. The evaluation model is consistent with pathological results and has high prediction ability and clinical application value. Patients with HSS high risk (HSS-HR) had significantly worse prognosis than those with HSS low risk (HSS-LR) (3-year intrahepatic RFS: 42.7% vs. 29.4%, P = 0.003; 5-year OS: 45.7% vs. 26.5%, P = 0.002). Univariate and multivariate analysis confirmed its essential role in the prediction of intrahepatic RFS. Besides, patients treated with preoperative irinotecan chemotherapy were more likely to end up with HSS-HR than those with non-irinotecan chemotherapy (63.3% vs. 21.8%, P < 0.001). Furthermore, irinotecan chemotherapy is relevant to worse prognosis in baseline HSS-HR patients. In summary, patients with HSS-HR had significantly worse 5-year OS and 3-year intrahepatic RFS. Irinotecan chemotherapy is more likely to lead to HSS-HR and pre-existing hepatic steatosis may be a worse prognostic factor limiting patients underwent IRI-based chemotherapy.

ZEB family is a prognostic biomarker and correlates with anoikis and immune infiltration in kidney renal clear cell carcinoma

BackgroundZinc finger E-box binding homEeobox 1 (ZEB1) and ZEB2 are two anoikis-related transcription factors. The mRNA expressions of these two genes are significantly increased in kidney renal clear cell carcinoma (KIRC), which are associated with poor survival. Meanwhile, the mechanisms and clinical significance of ZEB1 and ZEB2 upregulation in KIRC remain unknown.MethodsThrough the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, expression profiles, prognostic value and receiver operating characteristic curves (ROCs) of ZEB1 and ZEB2 were evaluated. The correlations of ZEB1 and ZEB2 with anoikis were further assessed in TCGA-KIRC database. Next, miRTarBase, miRDB, and TargetScan were used to predict microRNAs targeting ZEB1 and ZEB2, and TCGA-KIRC database was utilized to discern differences in microRNAs and establish the association between microRNAs and ZEBs. TCGA, TIMER, TISIDB, and TISCH were used to analyze tumor immune infiltration.ResultsIt was found that ZEB1 and ZEB2 expression were related with histologic grade in KIRC patient. Kaplan-Meier survival analyses showed that KIRC patients with low ZEB1 or ZEB2 levels had a significantly lower survival rate. Meanwhile, ZEB1 and ZEB2 are closely related to anoikis and are regulated by microRNAs. We constructed a risk model using univariate Cox and LASSO regression analyses to identify two microRNAs (hsa-miR-130b-3p and hsa-miR-138-5p). Furthermore, ZEB1 and ZEB2 regulate immune cell invasion in KIRC tumor microenvironments.ConclusionsAnoikis, cytotoxic immune cell infiltration, and patient survival outcomes were correlated with ZEB1 and ZEB2 mRNA upregulation in KIRC. ZEB1 and ZEB2 are regulated by microRNAs.

Preoperative Quantitative Flow Ratio, Intraoperative Transit Time Flow Measurement Parameters, and Their Predictive Value for Short-Term Graft Failure After Coronary Artery Bypass Grafting.

Studies on the relationship between the preoperative quantitative flow ratio (QFR) and parameters of intraoperative transit time flow measurement (TTFM) are extremely rare. In addition, the predictive value of QFR and TTFM parameters for early internal mammary artery (IMA) failure after coronary artery bypass grafting still needs to be validated.Methods and Results: We retrospectively collected data from 510 patients who underwent in situ IMA grafting to the left anterior descending (LAD) artery at Fuwai Hospital. Spearman correlation coefficients between preoperative QFR of the LAD artery and intraoperative TTFM parameters of the IMA were -0.13 (P=0.004) for mean graft flow (Qm) and 0.14 (P=0.002) for the pulsatility index (PI). QFR and TTFM exhibited similar and good predictive value for early IMA failure (5.7% at 1 year), and they were better than percentage diameter stenosis (area under the curve 0.749 for QFR, 0.733 for Qm, 0.688 for PI, and 0.524 for percentage diameter stenosis). The optimal cut-off value of QFR was 0.765. Both univariate and multivariable regression analyses revealed that QFR >0.765, Qm ≤15 mL/min, and PI >3.0 independently contributed to early IMA failure. There were statistically significant correlations between preoperative QFR of the LAD artery and intraoperative TTFM parameters (Qm, PI) of the IMA. Preoperative QFR and intraoperative Qm and PI exhibited excellent predictive value for early IMA failure.

Neurological abnormalities in individuals with Marfan syndrome: results from a genetically confirmed Italian cohort.

Neurological abnormalities have been frequently reported in individuals with Marfan Syndrome (MFS). However, available data relies solely on retrospective studies predating current diagnostic criteria. Cross-sectional study comprehensively investigating neurological abnormalities within a prospective cohort of adults (≥ 18years) with genetically confirmed MFS referred to an Italian hub center for heritable connective tissue diseases (Jan. 1st - Nov. 15th, 2021). We included a total of 38 individuals (53% female). The commonest neurological symptom was migraine (58%), usually without aura (73%). Neuropsychological testing was generally unremarkable, whilst anxiety and depression were highly prevalent within our cohort (42% and 34%, respectively). The most frequent brain parenchymal abnormality was the presence of cortico-subcortical hypointense spots on brain MRI T2* Gradient-Echo sequences (39%), which were found only in patients with a prior history of aortic surgery. Migraineurs had a higher frequency of brain vessels tortuosity vs. individuals without migraine (73% vs. 31%; p = 0.027) and showed higher average and maximum tortuosity indexes in both anterior and posterior circulation brain vessels (all p < 0.05). At univariate regression analysis, the presence of brain vessels tortuosity was significantly associated with a higher risk of migraine (OR 5.87, CI 95% 1.42-24.11; p = 0.014). Our study confirms that neurological abnormalities are frequent in individuals with MFS. While migraine appears to be associated with brain vessels tortuosity, brain parenchymal abnormalities are typical of individuals with a prior history of aortic surgery. Larger prospective studies are needed to understand the relationship between parenchymal abnormalities and long-term cognitive outcomes.

Pressure-dimension index and left ventricular sphericity index following HeartMate II and HeartMate 3 implantation.

This study aimed to compare the changes in the left ventricle (LV) and right ventricle (RV) geometry and performance after the implantation of HeartMate II (HMII) and HeartMate 3 (HM3). In addition, we investigated whether the echocardiographic parameters LV sphericity index (LVSI) and the novel pressure-dimension index (PDI) can predict post-operative right ventricular failure (RVF). Between 2012 and 2020, 46 patients [HMII (n=22) and HM3 (n=24)] met the study's criteria and had echocardiography tests pre-operatively, 6 and 12months post-operatively. The LVSI and PDI were calculated together with the standard LV and RV echocardiographic parameters. The mean follow-up was 24±7months. In both groups, the LV end-diastolic diameter (LVEDD) significantly decreased 12months post-operatively compared with the pre-operative values (HMII: 6.4±1.4cm vs. 5.7±0.9cm, P=0.040; HM3: 6.7±1.3cm vs. 5.5±0.9cm, P<0.01, respectively). RV function 12months post-operatively was better in the HM3 group than in the HMII group, as indicated by a significantly higher RV fractional area change (RVFAC) in the HM3 group than in the HMII group 12months post-operatively (35±12% vs. 26±16%, P=0.039), significantly higher tricuspid annular plane systolic excursion (TAPSE) in the HM3 group 12months post-operatively compared with the HMII group (13.9±1.9mm vs. 12.0±2.1mm, P=0.002), and the tissue Doppler estimated tricuspid annular systolic velocity (TASV) was also significantly higher in the HM3 group 12months post-operatively compared with the HMII group (11.5±2.7mm/s vs. 9.9±1.5mm/s, P=0.020). The LVSI value was significantly higher 12months post-operatively in the HMII group than in the HM3 group (1.2±0.4 vs. 0.8±0.2, P=0.001, respectively), indicating worse geometric changes. The PDI decreased 12months post-operatively in the HM3-group compared with the baseline (3.4±1.4mmHg/cm2 vs. 2.0±0.8mmHg/cm2, P<0.001). In the univariate and multivariate analyses, only the pre-operative PDI was a predictor of post-operative RVF [odds ratio: 3.84 (95% CI: 1.53-18.16, P=0.022)]. The area under the curve for pre-operative PDI was 0.912. The 2year survival was significantly better in the HM3 group (log-rank, P=0.042). The design of HM3 offered better geometrical preservation of the LV and enabled normal PDI values, leading to improved RV function, as indicated by better RVFAC, TAPSE, and TASV values. The use of pre-operative PDI as an additional tool for established risk scores might offer a better pre-operative predictor of RVF.

Left Atrial Reservoir Strain and Recurrence of Atrial Fibrillation Following De-Novo Pulmonary Vein Isolation - Results of the ASTRA-AF Pilot Study.

Achieving early rhythm control and maintaining sinus rhythm are associated with improved outcomes in patients with atrial fibrillation (AF). Pulmonary vein isolation (PVI) is a validated alternative to medical rhythm control. This study determined associations between left atrial strain reservoir (LASR) and AF recurrence after PVI.Methods and Results: In all, 132 patients (88 with paroxysmal AF [PAF], 44 with persisting AF [PersAF]) who presented in sinus rhythm for de novo PVI of AF between December 2017 and January 2019 were included in the study. All patients underwent preprocedural echocardiography. After 12 months, all patients underwent 24-h Holter electrocardiogram monitoring to screen for AF recurrence. Kaplan-Meier curve analysis revealed an association between decreasing LASRand increased AF recurrence, with a cut-off at 31.4%. In univariable Cox regression analysis, LASRdemonstrated an association with AF recurrence, with hazard ratios (HR) of 0.83 (95% confidence interval [CI] 073-0.93; P=0.001) per 5% increase in univariable models and 0.83 (95% CI 073-0.95; P=0.005) in multivariable analysis. When clinical variables with age, sex and type of AF (PAF/PersAF) were included in the multivariable analysis, LASRremained relevant in a model with age (HR 0.86; 95% CI 073-1.00; P=0.046). In patients undergoing de novo PVI for AF, LASRcould be of use in risk stratification regarding AF recurrence.

Genetic polymorphisms of inflammatory and bone metabolism related proteins in a population with dental implants of the Basque Country. A case-control study

BackgroundPeri-implantitis (PI) is a frequent inflammatory disorder characterised by progressive loss of the supporting bone. Not all patients with recognised risk factors develop PI. The aim of this study is to evaluate the presence of single nucleotide polymorphisms (SNP) of inflammatory and bone metabolism related proteins in a population treated with dental implants from the Basque Country (Spain).MethodsWe included 80 patients with diagnosis of PI and 81 patients without PI, 91 women and 70 men, with a mean age of 60.90 years. SNPs of BMP-4, BRINP3, CD14, FGF-3, FGF-10, GBP-1, IL-1α, IL-1β, IL-10, LTF, OPG and RANKL proteins were selected. We performed a univariate and bivariate analysis using IBM SPSS® v.28 statistical software.ResultsPresence of SNPs GBP1 rs7911 (p = 0.041) and BRINP3 rs1935881 (p = 0.012) was significantly more common in patients with PI. Patients with PI who smoked (> 10 cig/day) showed a higher presence of OPG rs2073617 SNP (p = 0.034). Also, BMP-4 rs17563 (p = 0.018) and FGF-3 rs1893047 (p = 0.014) SNPs were more frequent in patients with PI and Type II diabetes mellitus.ConclusionsOur findings suggest that PI could be favoured by an alteration in the osseointegration of dental implants, based on an abnormal immunological response to peri-implant infection in patients from the Basque Country (Spain).