Independent Predictive Factors Research Articles

Rhinoconjunctivitis severity induced by cat exposure influences early and late asthmatic responses: Evidence from an environmental exposure chamber.

The impact of allergic rhinoconjunctivitis on the early (EAR) and late asthmatic response (LAR) has yet to be assessed during optimal allergen exposure conditions. We aimed to assess predictive factors of the EAR and LAR and to evaluate the relation between rhinitis, conjunctivitis and asthma induced by cat allergen exposure in an environmental exposure chamber (EEC). Data from two cohort studies involving asthmatic patients with cat allergy who performed a cat allergen exposure challenge in ALYATEC EEC were analysed. Spirometry, visual analogue scale (VAS) for asthma, VAS for rhinitis, Total Nasal Symptoms Score, Total Ocular Symptoms Score (TOSS), Rhinoconjunctivitis Total Symptoms Score and Abelson score were used to assess asthma, rhinitis and conjunctivitis during and after exposure. An EAR occurred in 65.1% of patients, 32.1% of whom had a LAR. The diameter of the prick test to cat allergens and non-specific bronchial hypersensitivity level were independent risk factors for EAR (p < .05). No independent risk factors for LAR were identified. Rhinoconjunctivitis severity during exposure correlated with the asthma VAS during EAR and LAR (p < .05). Allergen exposure time needed to trigger an EAR correlated with the Abelson score during exposure (p < .05). The asthma VAS and TOSS during exposure correlated with faster LAR occurrence (p < .05). Prick test size and non-specific bronchial hypersensitivity level were confirmed as independent predictive factors of EAR during allergen exposure in an EEC. This study demonstrated the relation between the severity of rhinitis, conjunctivitis and asthma induced by allergen exposure for both EAR and LAR.

The Association of Heterozygous p.R4810K of RNF213 and Long-Term Unfavorable Outcomes after Encephaloduroarteriosynangiosis in Chinese Pediatric Patients with Moyamoya Disease

Background. Previous studies have established that heterozygous mutation for the p.R4810K variant can influence the severity of the clinical phenotype in patients with moyamoya disease (MMD) at disease onset. However, the relationship between the p.R4810K variant and the clinical phenotype of long-term unfavorable outcomes in Chinese pediatric patients remains unclear. Objectives. The primary aim of this study was to examine the association of heterozygous p.R4810K of RNF213 and long-term unfavorable outcomes after encephaloduroarteriosynangiosis (EDAS) in Chinese pediatric patients with MMD. Method. In this retrospective cohort study, we included 259 pediatric patients with MMD who possessed the known p.R4810K genotype. These individuals underwent EDAS along with genotyping analysis for p.R4810K via a TaqMan probe and the QuantStudio 6 Flex Real-Time PCR System. Subsequently, we evaluated their long-term outcomes. The variables we assessed were age at diagnosis, gender, p.R4810K genotypes, initial modified Rankin scale (mRS), clinical manifestations (such as hemorrhage and ischemia), posterior cerebral artery (PCA) involvement combined with angiographic stage, and their history of risk factors like hyperlipidemia and hyperhomocysteinemia. Furthermore, we scrutinized long-term unfavorable outcomes using both univariate analyses and multivariate logistic regression to identify independent predictive factors. Results. This study enrolled 259 Chinese pediatric patients with MMD, which included both newly and previously diagnosed cases, who underwent EDAS. The cohort comprised 130 male participants (50.19%) and 129 female participants (49.81%), with a median onset age of 8 years (median, IQR: 6-12 years). Among these patients, homozygous mutations were exceptionally rare, identified in only 4 individuals (1.54%), while the prevalence of heterozygous mutations was relatively higher, observed in 85 children (32.82%). The multivariate logistic regression showed that several factors were significantly associated with long-term unfavorable outcomes: older age at diagnosis (OR, 0.82 [95% CI, 0.7-0.96], P=0.014), onset with hematoma (OR, 12.76 [95% CI, 1.52-106.89], P=0.019), initial mRS (OR, 24.53 [95% CI, 6.51-92.41], P&lt;0.001), perioperative infarction (OR, 22.16 [95% CI, 1.45-337.96], P=0.026), and infarction during follow-up (OR, 14.5 [95% CI, 2.04-103.12], P=0.008). Furthermore, the cumulative incidence of initial infarction suggested that pediatric patients with homozygous or heterozygous mutations typically present at a younger age and exhibit a higher incidence of initial infarction compared to those carrying wild-type genotypes. Conclusions. The study suggests that the p.R4810K variant is associated with the onset age of MMD in Chinese pediatric patients, potentially impacting long-term outcomes. Surprisingly low recurrent stroke rates were observed across all genotypes, including homozygous individuals for the pathogenic variant, indicating that nongenetic factors may also play a role in the course and outcomes of MMD in this population.

Do presenting symptoms predict treatment decisions and survival in glioblastoma? Real-world data from 1458 patients in the Swedish brain tumor registry

Abstract Background Glioblastoma is the most common malignant brain tumor in adults. Non-invasive clinical parameters could play a crucial role in treatment planning and serve as predictors of patient survival. Our register-based real-life study aimed to investigate the prognostic value of presenting symptoms. Methods Data on presenting symptoms and survival, as well as known prognostic factors, were retrieved for all glioblastoma patients in Sweden registered in the Swedish Brain Tumor Registry between 2018 and 2021. The prognostic impact of different presenting symptoms was calculated using the Cox proportional hazard model. Results Data from 1458 adults with pathologically verified IDH wild-type glioblastoma were analyzed. Median survival time was 345 days. The 2-year survival rate was 21.5%. Registered presenting symptoms were focal neurological deficits, cognitive dysfunction, headache, epilepsy, signs of raised intracranial pressure, and cranial nerve symptoms, with some patients having multiple symptoms. Patients with initial cognitive dysfunction had significantly shorter survival than patients without; 265 days (245–285) vs. 409 days (365–453; P &amp;lt; .001). The reduced survival remained after Cox regression adjusting for known prognostic factors. Patients presenting with seizures and patients with headaches had significantly longer overall survival compared to patients without these symptoms, but the difference was not retained in multivariate analysis. Patients with cognitive deficits were less likely to have radical surgery and to receive extensive anti-neoplastic nonsurgical treatment. Conclusions This extensive real-life study reveals that initial cognitive impairment acts as an independent negative predictive factor for treatment decisions and adversely affects survival outcomes in glioblastoma patients.

Mean computed tomography value to predict spread through air spaces in clinical N0 lung adenocarcinoma

BackgroundThe aim of this study was to assess the ability of radiologic factors such as mean computed tomography (mCT) value, consolidation/tumor ratio (C/T ratio), solid tumor size, and the maximum standardized uptake (SUVmax) value by F-18 fluorodeoxyglucose positron emission tomography to predict the presence of spread through air spaces (STAS) of lung adenocarcinoma.MethodsA retrospective study was conducted on 118 patients those diagnosed with clinically without lymph node metastasis and having a pathological diagnosis of adenocarcinoma after undergoing surgery. Receiver operating characteristics (ROC) analysis was used to assess the ability to use mCT value, C/T ratio, tumor size, and SUVmax value to predict STAS. Univariate and multiple logistic regression analyses were performed to determine the independent variables for the prediction of STAS.ResultsForty-one lesions (34.7%) were positive for STAS and 77 lesions were negative for STAS. The STAS positive group was strongly associated with a high mCT value, high C/T ratio, large solid tumor size, large tumor size and high SUVmax value. The mCT values were − 324.9 ± 19.3 HU for STAS negative group and − 173.0 ± 26.3 HU for STAS positive group (p < 0.0001). The ROC area under the curve of the mCT value was the highest (0.738), followed by SUVmax value (0.720), C/T ratio (0.665), solid tumor size (0.649). Multiple logistic regression analyses using the preoperatively determined variables revealed that mCT value (p = 0.015) was independent predictive factors of predicting STAS. The maximum sensitivity and specificity were obtained at a cutoff value of − 251.8 HU.ConclusionsThe evaluation of mCT value has a possibility to predict STAS and may potentially contribute to the selection of suitable treatment strategies.

Concordance of HER2 status between core needle biopsy and surgical resection specimens of breast cancer: an analysis focusing on the HER2-low status

BackgroundHuman epidermal growth factor receptor 2 (HER2)-low status has recently gained attention because of the potential therapeutic benefits of antibody–drug conjugates (ADCs) in breast cancer patients. We aimed to investigate the concordance of HER2 status between core needle biopsy (CNB) and subsequent surgical resection specimens focusing on the HER2-low status.MethodsThis retrospective study was conducted in 1,387 patients with invasive breast cancer whose HER2 status was evaluated in both CNB and surgical resection specimens. The discordance rates between CNB and surgical resection specimens and the clinicopathological features associated with HER2 status discordance were analyzed.ResultsThe overall concordance rates of HER2 status between CNB and surgical resection specimens were 99.0% (κ = 0.925) for two-group classification (negative vs. positive) and 78.5% (κ = 0.587) for three-group classification (zero vs. low vs. positive). The largest discordance occurred in CNB-HER2-zero cases with 42.8% of them reclassified as HER2-low in surgical resection. HER2 discordance was associated with lower histologic grade, tumor multiplicity, and luminal A subtype. In multivariate analysis, tumor multiplicity and estrogen receptor (ER) positivity were independent predictive factors for HER2-zero to low conversion.ConclusionsIncorporation of HER2-low category in HER2 status interpretation reduces the concordance rate between CNB and surgical resection specimens. Tumor multiplicity and ER positivity are predictive factors for conversion from HER2-zero to HER2-low status. Therefore, HER2 status should be re-evaluated in resection specimens when considering ADCs in tumors exhibiting multiplicity and ER positivity.

The clinical significance of sarcopenia in patients with hepatocellular carcinoma treated with lenvatinib and PD-1 inhibitors.

Sarcopenia has gained considerable attention in the context of hepatocellular carcinoma, as it has been correlated with a poorer prognosis among patients undergoing sorafenib or lenvatinib treatment for hepatocellular carcinoma (HCC). The clinical significance of sarcopenia in first-line advanced HCC patients treated with lenvatinib and programmed death-1 (PD-1) inhibitors needs to be clarified. Sarcopenia was diagnosed using CT (Computed tomography) or MRI (Magnetic Resonance Imaging), with the psoas muscle index (PMI) as the surrogate marker. Patients were grouped based on sarcopenia presences, and a comparative analysis examined characteristics, adverse events, and prognosis. The Cox regression analysis was applied to identify independent prognostic factors for survival, while nomograms were constructed to predict 1-year survival. Among 180 patients, 46 had sarcopenia. Patients with baseline sarcopenia demonstrated significantly inferior median progression-free survival (mPFS) (3.0 vs. 8.3 months) and median overall survival (mOS) (7.3 vs. 21.6 months). The same results for mPFS (3.3 vs. 9.2 months) and mOS (9.4 vs. 24.2 months) were observed in patients who developed sarcopenia after treatment. Furthermore, significantly higher grade 3 or higher adverse events (AEs) (73.91% vs 41.79%, p<0.001) were recorded in the sarcopenia group compared to the non-sarcopenia group. In the multivariate analysis, distant metastasis, elevated PLR and CRP levels, and low PMI remained independent predictive factors for poor OS. Additionally, skeletal muscle loss remained a significant independent risk factor for PFS. We developed a nomogram incorporating these four indicators, which predicted 12-month survival with a C-index of 0.853 (95% CI, 0.791 - 0.915), aligning well with actual observations. The prognosis of patients with HCC and sarcopenia is significantly worse when treated with lenvatinib and PD-1 inhibitors. The combination regimen of lenvatinib plus PD-1 inhibitors should be cautiously recommended due to the inferior prognosis and higher AEs.

Clinical feasibility of the preoperative C-reactive protein–albumin–lymphocyte index to predict short- and long-term outcomes of patients with gastric cancer

BackgroundGastric cancer (GC) is a major leading cause of cancer-related death worldwide. Systemic inflammation and the nutrition-based score are feasible prognostic markers for malignancies. Emerging evidence has also revealed the C-reactive protein–albumin–lymphocyte (CALLY) index to be a prognostic marker for several cancer types. However, its clinical significance to predict surgical and oncologic outcomes of patients with GC remains unclear. MethodsWe assessed the preoperative CALLY index in 426 patients with GC who received gastrectomy. ResultsA low preoperative CALLY index was significantly correlated to all well-established clinicopathologic factors for disease development, including an advanced T stage, the presence of venous invasion, lymphatic vessel invasion, lymph node metastasis, distant metastasis, and an advanced TNM stage. A low preoperative CALLY index was also an independent prognostic factor for overall survival (hazard ratio [HR], 2.64; 95 % CI, 1.66–4.2; P < .0001) and disease-free survival (HR, 1.76; 95 % CI, 1.01–3.05; P = .045). In addition, a low preoperative CALLY index was an independent predictive factor for postoperative surgical site infection (odds ratio, 2.64; 95 % CI, 1.42–4.89; P = .002). ConclusionThe preoperative CALLY index is valuable for perioperative and oncologic management of patients with GC.

Impact of attaining aggressive vs. conservative PK/PD target on the clinical efficacy of beta-lactams for the treatment of Gram-negative infections in the critically ill patients: a systematic review and meta-analysis

BackgroundTo perform a systematic review with meta-analysis with the dual intent of assessing the impact of attaining aggressive vs. conservative beta-lactams PK/PD target on the clinical efficacy for treating Gram-negative infections in critical patients, and of identifying predictive factors of failure in attaining aggressive PK/PD targets.MethodsTwo authors independently searched PubMed-MEDLINE and Scopus database from inception to 23rd December 2023, to retrieve studies comparing the impact of attaining aggressive vs. conservative PK/PD targets on clinical efficacy of beta-lactams. Independent predictive factors of failure in attaining aggressive PK/PD targets were also assessed. Aggressive PK/PD target was considered a100%fT>4xMIC, and clinical cure rate was selected as primary outcome. Meta-analysis was performed by pooling odds ratios (ORs) extrapolated from studies providing adjustment for confounders using a random-effects model with inverse variance method.ResultsA total of 20,364 articles were screened, and 21 observational studies were included in the meta-analysis (N = 4833; 2193 aggressive vs. 2640 conservative PK/PD target). Attaining aggressive PK/PD target was significantly associated with higher clinical cure rate (OR 1.69; 95% CI 1.15–2.49) and lower risk of beta-lactam resistance development (OR 0.06; 95% CI 0.01–0.29). Male gender, body mass index > 30 kg/m2, augmented renal clearance and MIC above the clinical breakpoint emerged as significant independent predictors of failure in attaining aggressive PK/PD targets, whereas prolonged/continuous infusion administration of beta-lactams resulted as protective factor. The risk of bias was moderate in 19 studies and severe in the other 2.ConclusionsAttaining aggressive beta-lactams PK/PD targets provided significant clinical benefits in critical patients. Our analysis could be useful to stratify patients at high-risk of failure in attaining aggressive PK/PD targets.

Pre-operative enhanced magnetic resonance imaging combined with clinical features predict early recurrence of hepatocellular carcinoma after radical resection.

Indentifying predictive factors for postoperative recurrence of hepatocellular carcinoma (HCC) has great significance for patient prognosis. To explore the value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) combined with clinical features in predicting early recurrence of HCC after resection. A total of 161 patients with pathologically confirmed HCC were enrolled. The patients were divided into early recurrence and non-early recurrence group based on the follow-up results. The clinical, laboratory, pathological results and Gd-EOB-DTPA enhanced MRI imaging features were analyzed. Of 161 patients, 73 had early recurrence and 88 were had non-early recurrence. Univariate analysis showed that patient age, gender, serum alpha-fetoprotein level, the Barcelona Clinic Liver Cancer stage, China liver cancer (CNLC) stage, microvascular invasion (MVI), pathological satellite focus, tumor size, tumor number, tumor boundary, tumor capsule, intratumoral necrosis, portal vein tumor thrombus, large vessel invasion, nonperipheral washout, peritumoral enhancement, hepatobiliary phase (HBP)/tumor signal intensity (SI)/peritumoral SI, HBP peritumoral low signal and peritumoral delay enhancement were significantly associated with early recurrence of HCC after operation. Multivariate logistic regression analysis showed that patient age, MVI, CNLC stage, tumor boundary and large vessel invasion were independent predictive factors. External data validation indicated that the area under the curve of the combined predictors was 0.861, suggesting that multivariate logistic regression was a reasonable predictive model for early recurrence of HCC. Gd-EOB-DTPA enhanced MRI combined with clinical features would help predicting the early recurrence of HCC after operation.

Predictive value of the systemic immune-inflammation index on one-year mortality in geriatric hip fractures.

Geriatric hip fractures are associated with a high incidence of mortality. This study examines the predictive value of the systemic immune-inflammation index (SII) on one-year mortality in elderly hip fracture patients. A single-center retrospective study was conducted between February 2017 and October 2020. Three hundred and eleven surgically treated consecutive hip fracture patients were included in the study. Admission, postoperative first day, and postoperative fifth-day SII values were calculated. The receiver operating characteristic (ROC) curve was used to calculate the cut-off values, and patients were divided into high and low groups according to these cut-off values. After univariate Cox regression analysis, significant factors were included in the multivariate Cox proportional hazards model to adjust the effect of covariates and explore independent predictive factors associated with mortality. Further subgroup analysis was performed to evaluate the accuracy of the results for different clinical and biological characteristics. The mean age was 80.7 ± 8.0 years, and women made up the majority (67.8%) of the patients. The one-year mortality rate was 28.0%. After univariate and multivariate analyses, high postoperative fifth-day SII remained an independent predictor of one-year mortality (adjusted HR 2.16, 95% CI 1.38-3.38, p = 0.001). Older age, male gender, Charlson comorbidity index (CCI) ≥ 2, and hypoalbuminemia were found to be other independent predictors. The optimal cut-off value of the postoperative fifth-day SII was calculated at 1751.9 units (p < 0.001). The postoperative fifth-day SII is a simple and useful inflammatory biomarker for predicting one-year mortality in patients with hip fracture.

Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable hepatocellular carcinoma.

The efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib plus programmed cell death protein-1 (PD-1) for unresectable hepatocellular carcinoma (HCC) have rarely been evaluated and it is unknown which factors are related to efficacy. To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC. This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022. Overall survival (OS) and progression-free survival (PFS) were determined. The objective response rate (ORR) and disease control rate (DCR) were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors. Additionally, the prognostic factors affecting the clinical outcome were assessed. One hundred and two patients were enrolled with a median follow-up duration of 12.63 months. The median OS was 26.43 months (95%CI: 17.00-35.87), and the median PFS was 10.07 months (95%CI: 8.50-11.65). The ORR and DCR were 61.76% and 81.37%, respectively. The patients with Barcelona Clinic Liver Cancer Classification (BCLC) B stage, early neutrophil-to-lymphocyte ratio (NLR) response (decrease), or early alpha-fetoprotein (AFP) response (decrease > 20%) had superior OS and PFS than their counterparts. This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC. The patients with BCLC B-stage disease with early NLR response (decrease) and early AFP response (decrease > 20%) may achieve better clinical outcomes with this triple therapy.

Could Pan-Immune-Inflammation Value be a Marker for the Diagnosis of Coronary Slow Flow Phenomenon?

Inflammation plays a key role in the pathogenesis of the coronary slow flow phenomenon (CSFP). The newly developed inflammatory marker, pan-immune-inflammation value (PIV), is associated with adverse cardiovascular events. This study investigated the predictive value of PIV for diagnosing CSFP in comparison to other inflammation-based markers. A total of 214 patients, 109 in the CSFP group and 105 in the normal coronary flow (NCF) group, were retrospectively included in the study. Coronary flow was calculated using the Thrombolysis in Myocardial Infarction frame count method. In addition to PIV, other inflammatory markers such as neutrophil-lymphocyte ratio, platelet-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were calculated for the patients. The average age of patients was 50.3 ± 8.4, with a male ratio of 55.1%. Compared to the NCF group, patients in the CSFP group had higher levels of hyperlipidemia, glucose, triglyceride, NLR, PLR, SII, and PIV, while their high-density lipoprotein cholesterol (HDL-C), was lower (p < 0.05). Logistic regression analysis demonstrated that HDL-C, glucose, triglyceride, and PIV were independent predictor factors for CSFP (p < 0.05). PIV is a strong and independent predictor factor for CSFP and superior in predicting CSFP compared to other inflammatory markers.

Preoperative predictive factors for positive peritoneal cytology results in patients with pancreatic ductal adenocarcinomas: a retrospective study.

The clinical importance of positive peritoneal cytology results in patients with pancreatic ductal adenocarcinomas remains controversial. We evaluated the prognosis of these patients and the predictive preoperative risk factors for positive peritoneal cytology results. We retrospectively reviewed patients who underwent curative-intent surgery at our institution between May 2010 and June 2020. Preoperative risk factors for positive peritoneal cytology results were identified using logistic regression analysis. A scoring model was constructed using the total number of significant independent predictors for positive peritoneal cytology results. Of 233 patients, 18 (7.7%) had positive peritoneal cytology results. The recurrence-free survival and cancer-specific survival were markedly worse in patients with positive peritoneal cytology results than in those with negative peritoneal cytology results (recurrence-free survival: 6.0months vs. 16.6months, p = 0.050; cancer-specific survival: 19.4months vs. 47.5months, p = 0.034). Tumor location (odds ratio: 3.760, 95% confidence interval: 1.099-11.818, p = 0.023), tumor size > 25mm (odds ratio: 3.410, 95% confidence interval: 1.031-11.277, p = 0.046), preoperative serosal invasion (odds ratio: 5.193, 95% confidence interval: 1.099-24.531, p = 0.038), and preoperative carcinoembryonic antigen level > 5.6ng/mL (odds ratio: 3.816, 95% confidence interval: 1.248-10.667, p = 0.019) were identified as significant independent predictive factors. Our predictive model's optimal cutoff and positive predictive values for positive peritoneal cytology results were 3 and 27.9%, respectively. The indications for curative-intent surgery should be considered carefully in patients with high-risk factors for positive peritoneal cytology results.

Integrative analysis of the bladder cancer from a cell cycle NCAM1 perspective at both single cell and bulk resolution.

Bladder cancer (BLCA) is a prevalent and deadly form of urinary cancer, and there is a need for effective therapies, particularly for muscle-invasive bladder cancer (MIBC). Cell cycle inhibitors show promise in restoring control of the cell cycle in BLCA cells, but their clinical prognosis evaluation is limited. Transcriptome and scRNA-seq data were collected from the Cancer Genome Atlas Program (TCGA)-BLCA and GSE190888 cohort, respectively. R software and the Seurat package were used for data analysis, including cell quality control, dimensionality reduction, and identification of differentially expressed genes. Genes related to the cell cycle were obtained from the genecards website, and a protein-protein interaction network analysis was performed using cytoscape software. Functional enrichment analysis, immune infiltration analysis, drug sensitivity analysis, and molecular docking were conducted using various tools and packages. BLCA cell lines were cultured and transfected for in vitro experimental assays, including RT-qPCR analysis, and CCK-8 cell viability assays. We identified 32 genes as independent risk or protective factors for BLCA prediction. Functional enrichment analysis revealed their involvement in cell cycle regulation, apoptosis, and various signaling pathways. Using these genes, we developed a nomogram for predicting BLCA survival, which displayed high prognosis stratification efficacy in BLCA patients. Four cell cycle associated key genes identified, including NCAM1, HBB, CKD6, and CTLA4. We also identified the main cell types in BLCA patients and investigated the functional differences between epithelial cells based on their expression levels of key genes. Furthermore, we observed a high positive correlative relationship between the infiltration of cancer-associated fibroblasts and the risk score value. Finally, we conducted in vitro experiments to demonstrate the suppressive role of NCAM1 in BLCA cell proliferation. These findings suggest that cell cycle associated genes could serve as potential biomarkers for predicting BLCA prognosis and may represent therapeutic targets for the development of more effective therapies. Hopefully, these findings provide valuable insights into the molecular mechanisms and potential therapeutic targets in BLCA from the perspective of cell cycle. Moreover, NCAM1 was a novel cell proliferation suppressor in the BLCA carcinogenesis.

Neoadjuvant pertuzumab plus trastuzumab in combination with chemotherapy for human epidermal growth factor receptor 2 positive breast cancer: a real-world retrospective single-institutional study in China

IntroductionReal-world studies on neoadjuvant dual anti-HER2 therapy combined with chemotherapy for breast cancer (BC) are scarce in China. This study aimed to evaluate the efficacy and safety of neoadjuvant dual anti-HER2 therapy combined with chemotherapy in a real-world setting. Moreover, differences in estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and proliferation cell nuclear antigen (Ki-67) expression pre- and post-neoadjuvant therapy were analyzed.MethodsClinical and pathological data of patients with HER2-positive BC who received neoadjuvant dual anti-HER2 therapy combined with chemotherapy at Liaoning Cancer Hospital & Institute, China, between September 2021 and September 2023, were retrospectively reviewed.ResultsAmong 179 included patients, a pathologic complete response (pCR) was achieved in 109 patients (60.9%). The univariate analysis results indicated that the hormone receptor (HR) status (P = 0.013), HER2 status (P = 0.003), and cycles of targeted treatment (P = 0.035) were significantly correlated with pCR. Subsequent multivariable analysis showed that HR negative and HER2 status 3 + were independent predictive factors of pCR. Anemia was the most common adverse event (62.0%), and the most common grade 3–4 adverse event was neutropenia (6.1%). The differences in HER2 (34.5%) and Ki-67 (92.7%) expression between core needle biopsy and the residual tumor after neoadjuvant therapy were statistically significant, whereas the differences were insignificant in terms of ER or PR status.ConclusionsThe combination of neoadjuvant trastuzumab and pertuzumab with chemotherapy showed good efficiency, and the toxic side effects were tolerable in patients with BC. In cases where pCR was not achieved after neoadjuvant therapy, downregulation of HER2 and Ki-67 expressions was observed.

Identification of immune-associated biomarker for predicting lung adenocarcinoma: bioinformatics analysis and experiment verification of PTK6

BackgroundAbnormal expression of protein tyrosine kinase 6 (PTK6) has been proven to be involved in the development of gynecological tumors. However, its immune-related carcinogenic mechanism in other tumors remains unclear.ObjectiveThe aim of this study was to identify PTK6 as a novel prognostic biomarker in pan-cancer, especially in lung adenocarcinoma (LUAD), which is correlated with immune infiltration, and to clarify its clinicopathological and prognostic significance.MethodsThe prognostic value and immune relevance of PTK6 were investigated by using bio-informatics in this study. PTK6 expression was validated in vitro experiments (lung cancer cell lines PC9, NCI-H1975, and HCC827; human normal lung epithelial cells BEAS-2B). Western blot (WB) revealed the PTK6 protein expression in lung cancer cell lines. PTK6 expression was inhibited by Tilfrinib. Colony formation and the Cell Counting Kit-8 (CCK-8) assay were used to detect cell proliferation. The wound healing and trans-well were performed to analyze the cell migration capacity. Then flow cytometry was conducted to evaluate the cell apoptosis. Eventually, the relationship between PTK6 and immune checkpoints was examined. WB was used to estimate the PD-L1 expression at different Tilfrinib doses.ResultsPTK6 was an independent predictive factor for LUAD and was substantially expressed in LUAD. Pathological stage was significantly correlated with increased PTK6 expression. In accordance with survival analysis, poor survival rate in LUAD was associated with a high expression level of PTK6. Functional enrichment of the cell cycle and TGF-β signaling pathway was demonstrated by KEGG and GSEA analysis. Moreover, PTK6 expression considerably associated with immune infiltration in LUAD, as determined by immune analysis. Thus, the result of vitro experiments indicated that cell proliferation and migration were inhibited by the elimination of PTK6. Additionally, PTK6 suppression induced cell apoptosis. Obviously, PD-L1 protein expression level up-regulated while PTK6 was suppressed.ConclusionPTK6 has predictive value for LUAD prognosis, and could up regulated PD-L1.

Duration of detrusor overactivity as an independent predictive factor of upper urinary tract deterioration in patients with traumatic spinal cord injury: results of a retrospective cohort study.

To determine whether duration of detrusor overactivity (DO) during a cystometric study is an independent predictive factor of upper urinary tract deterioration (UUTD) in patients with traumatic spinal cord injury (TSCI). Retrospective cohort study. A rehabilitation facility in Chiang Mai, Thailand. Data were obtained from medical records of patients who underwent cystometric evaluation at 6-12 months after TSCI. The independent predictor of interest is the duration of DO, which was evaluated by the DO/cystometry ratio (DOratio). Other conventional urodynamic parameters (maximum detrusor pressure, cystometric capacity, bladder compliance, and detrusor-sphincter dyssynergia) and clinical parameters (age, sex, level and severity of injury, comorbidities, bladder emptying method, and history of urinary tract infection) were determined. The outcome was UUTD, which is indicated by chronic kidney disease (GFR < 60 ml/min/1.73 m2), hydronephrosis, and/or vesicoureteral reflux. Multivariable Cox regression analysis was used to determine the independent associations between DOratio and UUTD by adjusting with all other parameters. Medical records of 194 patients with TSCI were included in the study. During a combined total of 1260 follow-up years of those patients, 34 UUTD events were identified, indicating an incidence rate of 27.0 cases per 1000 person-years. After adjusting for all other parameters, a high DOratio (≥0.33) was significantly associated with UUTD (hazard ratio = 3.00 [95% CI: 1.12-7.99], p = 0.025). DOratio may be an independent cystometric predictor of UUTD in patients with TSCI. However, further prospective study is needed prior to applying DOratio as a predictor of UUTD in clinical settings. There was no clinical trial registration since this study is not a clinical trial.

A novel nomogram for the prediction of subsyndromal delirium in patients in intensive care units: A prospective, nested case-controlled study

BackgroundSubsyndromal delirium is a dynamic, recognizable condition commonly observed in intensive care unit (ICU) patients that can lead to poor patient prognosis, and its prompt recognition and management can prevent disease progression. However, no evidence-based predictive tool has been developed specifically to assess the occurrence of subsyndromal delirium in the ICU. ObjectiveTo develop and validate a novel, simple and effective tool for estimating the risk of subsyndromal delirium among ICU patients. DesignA prospective, nested case-controlled study. Data sourcesA total of 731 patients were recruited from the central ICU of a tertiary hospital in southwestern China from August 2021 to November 2022. MethodsThe least absolute shrinkage and selection operator was applied to screen potential features for univariate and multivariate logistic regression. A nomogram was constructed using the selected variables. The performance of the nomogram was evaluated by combining the area under the receiver operating characteristic curve (AUC), calibration curves and decision curve analysis (DCA). ResultsThe prevalence of subsyndromal delirium among ICU patients was 23.06 %. Multiple logistic regression analysis revealed that the independent predictive factors for subsyndromal delirium among ICU patients were vision impairment, a history of falls, the use of restraint, blood transfusion, the use of antibiotics, surgery, the Caprini score, and the Braden score, all of which were used to construct the nomogram. The AUCs for the model were 0.710 (95 % CI, 0.654–0.766, P < 0.001) and 0.825 (95 % CI, 0.732–0.917, P < 0.001) in the training and validation cohorts, respectively, indicating that the model had high accuracy in distinguishing patients with and without subsyndromal delirium. The calibration curve of the nomogram showed good consistency between the predicted and actual probabilities. The DCA indicated that the nomogram has clinical application for patients in the ICU. ConclusionsWe developed an easy-to-use nomogram for identifying subsyndromal delirium in ICU patients with satisfactory predictive ability based on simple and easily accessible clinical features. The nomogram can identify ICU patients at high-risk for subsyndromal delirium and may be a useful subsyndromal delirium tool for current ICU physicians.

Is the Bulbar Urethral Stricture a Single and Uniform Disease?

Objectives: Proximal and distal bulbar urethral strictures (BUS) have different disease characteristics and require different treatment strategies despite being regarded as a single condition. To clarify the differences, we analyzed our database by distinguishing the two types of BUS. Methods: We retrospectively reviewed the data of 196 patients with BUS who underwent urethroplasty at the National Defense Medical College (Japan) between August 2004 and March 2022. We divided patients into proximal (group 1) or distal (group 2) groups based on the stricture segment and compared patient background and surgical techniques for each group. We assessed whether the stricture segment was an independent predictive factor for substitution urethroplasty selection using multivariate logistic regression analysis. The recurrence rates were calculated and compared using the Kaplan–Meier method and log-rank test, respectively. Results: Patients in group 1 had a less frequent non-obliterated lumen (73% vs. 94%, p = 0.020) and significantly shorter strictures (10 mm vs. 23 mm, p &lt; 0.001) more frequently caused by external traumas (47% vs. 26%, p = 0.010) than those in group 2. Logistic regression analysis revealed that the stricture segment (distal) (p &lt; 0.001), stricture length (≥20 mm) (p &lt; 0.001), ≥2 prior transurethral procedures (p = 0.030), and a non-obliterated lumen (p = 0.020) were independent predictive factors for substitution urethroplasty. However, the recurrence rate (p = 0.18) did not significantly differ between the two groups. Conclusions: Proximal and distal BUS have substantially different anatomical characteristics and etiologies and require different reconstructive techniques.

Efficacy of programmed cell death 1 inhibitor maintenance after chimeric antigen receptor T cells in patients with relapsed/refractory B-cell non-Hodgkin-lymphoma.

Chimeric antigen receptor (CAR)-T cells obtained long-term durability in about 30% to 40% of relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL). Maintenance therapy after CAR-T is necessary, and PD1 inhibitor is one of the important maintenance therapy options. A total of 173 r/r B-NHL patients treated with PD1 inhibitor maintenance following CD19/22 CAR-T therapy alone or combined with autologous hematopoietic stem cell transplantation (ASCT) from March 2019 to July 2022 were assessed for eligibility for two trials. There were 81 patients on PD1 inhibitor maintenance therapy. In the CD19/22 CAR-T therapy trial, the PD1 inhibitor maintenance group indicated superior objective response rate (ORR) (82.9% vs 60%; P = 0.04) and 2-year progression-free survival (PFS) (59.8% vs 21.3%; P = 0.001) than the non-maintenance group. The estimated 2-year overall survival (OS) was comparable in the two groups (60.1% vs 45.1%; P = 0.112). No difference was observed in the peak expansion levels of CD19 CAR-T and CD22 CAR-T between the two groups. The persistence time of CD19 and CD22 CAR-T in the PD1 inhibitor maintenance group was longer than that in the non-maintenance group. In the CD19/22 CAR-T therapy combined with ASCT trial, no significant differences in ORR (81.4% vs 84.8%; P = 0.67), 2-year PFS (72.3% vs 74.9%; P = 0.73), and 2-year OS (84.1% vs 80.7%; P = 0.79) were observed between non-maintenance and PD1 inhibitor maintenance therapy groups. The peak expansion levels and duration of CD19 and CD22 CAR-T were not statistically different between the two groups. During maintenance treatment with PD1 inhibitor, all adverse events were manageable. In the multivariable analyses, type and R3m were independent predictive factors influencing the OS of r/r B-NHL with PD1 inhibitor maintenance after CAR-T therapy. PD1 inhibitor maintenance following CD19/22 CAR-T therapy obtained superior response and survival in r/r B-NHL, but not in the trial of CD19/22 CAR-T cell therapy combined with ASCT.