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Earlier diagnosis of lung cancer is crucial for reducing mortality and morbidity in high-risk patients. Liquid biopsy is a critical technique for detecting the cancer earlier and tracking the treatment outcomes. However, noninvasive biomarkers are desperately needed due to the lack of therapeutic sensitivity and early-stage diagnosis. Therefore, we have utilized transcriptomic profiling of early-stage lung cancer patients to discover promising biomarkers and their associated metabolic functions. Initially, PCA highlights the diversity level of gene expression in three stages of lung cancer samples. We have identified two major clusters consisting of highly variant genes among the three stages. Further, a total of 7742, 6611, and 643 genes were identified as DGE for stages I-III respectively. Topological analysis of the protein–protein interaction network resulted in seven candidate biomarkers such as JUN, LYN, PTK2, UBC, HSP90AA1, TP53, and UBB cumulatively for the three stages of lung cancers. Gene enrichment and KEGG pathway analyses aid in the comprehension of pathway mechanisms and regulation of identified hub genes in lung cancer. Importantly, the medial survival rates up to ~ 70 months were identified for hub genes during the Kaplan–Meier survival analysis. Moreover, the hub genes displayed the significance of risk factors during gene expression analysis using TIMER2.0 analysis. Therefore, we have reason that these biomarkers may serve as a prospective targeting candidate with higher treatment efficacy in early-stage lung cancer patients. [ABSTRACT FROM AUTHOR]

Background and objectives: Understanding factors affecting the timing of critical clinical events in ALS progression. Methods: We captured ALS progression based on the timing of critical events (tollgates), by augmenting 6366 patients’ data from the PRO-ACT database with tollgate-passed information using classification. Time trajectories of passing ALS tollgates after the first visit were derived using Kaplan–Meier analyses. The significant prognostic factors were found using log-rank tests. Decision-tree-based classifications identified significant ALS phenotypes characterized by the list of body segments involved at the first visit. Results: Standard (e.g., gender and onset type) and tollgate-related (phenotype and initial tollgate level) prognostic factors affect the timing of ALS tollgates. For instance, by the third year after the first visit, 80–100% of bulbar-onset patients vs. 43–48% of limb-onset patients, and 65–73% of females vs. 42–49% of males lost the ability to talk and started using a feeding tube. Compared to the standard factors, tollgate-related factors had a stronger effect on ALS progression. The initial impairment level significantly impacted subsequent ALS progression in a segment while affected segment combinations further characterized progression speed. For instance, patients with normal speech (Tollgate Level 0) at the first visit had less than a 10% likelihood of losing speech within a year, while for patients with Tollgate Level 1 (affected speech), this likelihood varied between 23 and 53% based on additional segment (leg) involvement. Conclusions: Tollgate- and phenotype-related factors have a strong effect on the timing of ALS tollgates. All factors should be jointly considered to better characterize patient groups with different progression aggressiveness. [ABSTRACT FROM AUTHOR]

Cutaneous warts are caused by human papillomavirus (HPV) infection. Distinguishing plantar warts from clavus and tylosis can be difficult. A less‐invasive method of examining these lesions is necessary. Previously, we collected data on 90 patients with warts and related diseases to explore differentiation methods using HPV typing of tissue from the wart surface. In that study, 21 patients were diagnosed as cases with plantar warts, however, 10 of those 21 cases showed HPV‐negative by polymerase chain reaction analysis, causing some ambiguity, thus their outcomes should be confirmed. To assess the role of HPV typing in clinical practice, we followed up these 21 cases (11 HPV‐positive and 10 HPV‐negative) and analyzed their outcomes. The HPV‐positive group included HPV1a (one case), HPV27 (four cases), HPV57 (three cases), and HPV65 (three cases). The median age of the 21 patients was 43 years, that of the 11 HPV‐positive cases was 37 years, and that of the 10 HPV‐negative cases was 44 years. The sex ratios (male:female) of the HPV‐positive and HPV‐negative groups were 6:5 and 2:8, respectively. All 21 patients were treated with liquid nitrogen after surface keratin removal, concomitant with salicylic acid topical plaster or oral administration of Yokuinin. The longest follow‐up period was 548 days. Kaplan–Meier analysis was performed to assess the healing rate according to HPV‐positivity. The healing rate in HPV‐positive cases was significantly higher than in HPV‐negative cases (P = 0.001). Although the sample size was small, the results suggest HPV typing using non‐invasive surface materials facilitates accurate diagnosis and prevents prolonged treatment of plantar warts. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) have drawn significant attention for their regenerative potential and therapeutic applicability across a range of conditions, including cardiovascular diseases and age-related frailty. Despite extensive preclinical studies, there remain gaps in understanding the long-term safety and efficacy of MSC therapy in humans. This study aimed to assess the safety of intravenous MSC administration, evaluate the mean major adverse cardiac and cerebrovascular event (MACCE)-free period, and identify potential risk factors for MACCE development in patients receiving MSC therapy for various indications. Methods: A retrospective observational study was conducted on 2504 patients (mean age: 54.09 ± 11.65 years) who received intravenous adipose-derived MSC (AD-MSC) therapy between October 2014 and December 2023 at the Omotesando Helene Clinic, Tokyo, Japan. Patients received MSC doses ranging from 100 million to 2 billion cells, with the majority receiving 1–2 billion cells per treatment. Statistical analyses included multivariate Cox proportional hazards regression and Kaplan–Meier survival analysis to evaluate MACCE risk factors and event-free duration. Results: Over the follow-up period, the MACCE rate was exceptionally low at 0.2%. Multivariate analysis identified age as a significant risk factor for MACCE (hazard ratio: 1.127; 95% CI: 1.0418–1.219; p = 0.0029), while sex and MSC dose showed no significant association. Minor adverse events occurred in 0.8% of patients, with no severe adverse events reported. The study found MSC therapy to be safe, with a low adverse event rate and minimal risk of MACCE. Conclusions: This study demonstrates the safety of intravenous MSC therapy in a large cohort of patients, with a low incidence of MACCE and minimal adverse effects. Age was the only significant predictor of MACCE risk. Further prospective randomized studies are needed to validate these findings and explore the potential of MSC therapy in reducing MACCE risk and improving clinical outcomes across diverse indications. [ABSTRACT FROM AUTHOR]

In recent years Janus kinase inhibitors (JAKi) have joined tumor necrosis factor inhibitors (TNFi) and interleukin (IL)-17 inhibitors (IL-17i) as approved disease modifying anti-rheumatic drugs (DMARD) for moderate to severe forms of axial spondyloarthritis (axSpA). Drug survival in axSpA patients has not been well studied in a real-world outpatient scenario since the approval of JAKi. We aimed to analyze the three drug classes based on modes of actions (MoA) for their persistence rates among German axSpA outpatients. A retrospective analysis of the RHADAR database for axSpA patients with a new initiation of TNFi, IL-17i, or JAKi treatment between January 2015 and October 2023 was conducted. Analyses included Kaplan-Meier curves and adjusted Cox regressions for drug discontinuation. 1222 new biological DMARD (TNFi [n = 954], IL-17i [n = 190]) or JAKi (n = 78) treatments were reported. The median drug survival was 31 months for TNFi, 25 for IL-17i, and 18 for JAKi. The corresponding 2-year drug survival rate was 79.6%, 72.6%, and 62.8% for TNFi, IL-17i, and JAKi, respectively. The probability for discontinuation for JAKi was significantly higher compared with TNFi (HR 1.91 [95% CI 1.22–2.99]) as well as for IL-17i compared with TNFi (HR 1.43 [95% CI 1.02–2.01]), possibly related to more frequent use of TNFis as first-line therapy. IL-17i and JAKi discontinuation probabilities were similar. Primary non-response was the reason for drug discontinuation in most cases across all MoA. TNFi treatment might persist longer than JAKi and IL-17i in German axSpA outpatients, possibly related to more severe or refractory disease in patients with JAKi-treated or IL-17i-treated axSpA. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to provide benchmarks for the rates of complications by type of surgery performed. Study Design. Prospective multicenter database. Background. We have previously examined overall construct survival and complication rates for ASD surgery. However, the relationship between type of surgery and construct survival warrants more detailed assessment. Materials and Methods. Eight surgical scenarios were defined based on the levels treated, previous fusion status [primary (P) vs. revision (R)], and three-column osteotomy use (3CO): short lumbar fusion, LT-pelvis with 5 to 12 levels treated (P, R, or 3CO), UT-pelvis with 13 levels treated (P, R, or 3CO), and thoracic to lumbar fusion without pelvic fixation, representing 92.4% of the case in the cohort. Complication rates for each type were calculated and Kaplan-Meier curves with multivariate Cox regression analysis was used to evaluate the effect of the case characteristics on construct survival rate, while controlling for patient profile. Results. A total of 1073 of 1494 patients eligible for 2-year follow-up (71.8%) were captured. Survival curves for major complications (with or without reoperation), while controlling for demographics differed significantly among surgical types (P < 0.001). Fusion procedures short of the pelvis had the best survival rate, while UT-pelvis with 3CO had the worst survival rate. Longer fusions and more invasive operations were associated with lower 2-year complication-free survival, however, there were no significant associations between type of surgery and renal, cardiac, infection, wound, gastrointestinal, pulmonary, implant malposition, or neurological complications (all P > 0.5). Conclusions. This study suggests that there is an inherent increased risk of complication for some types of ASD surgery independent of patient profile. The results of this paper can be used to produce a surgery-adjusted benchmark for ASD surgery with regard to complications and survival. Such a tool can have very impactful applications for surgical decision-making and more informed patient counseling. Level of Evidence. Level III. [ABSTRACT FROM AUTHOR]

(1) Background: As Kaplan–Meier (KM) analysis is limited to single unidirectional endpoints, most advanced cancer randomized clinical trials (RCTs) are powered for either progression-free survival (PFS) or overall survival (OS). This discards efficacy information carried by partial responses, complete responses, and stable disease that frequently precede progressive disease and death. Chauhan Weighted Trajectory Analysis (CWTA) is a generalization of KM that simultaneously assesses multiple rank-ordered endpoints. We hypothesized that CWTA could use this efficacy information to reduce sample size requirements and expedite efficacy signals in advanced cancer trials. (2) Methods: We performed 100-fold and 1000-fold simulations of solid tumor systemic therapy RCTs with health statuses rank-ordered from complete response (Stage 0) to death (Stage 4). At increments of the sample size and hazard ratio, we compared KM PFS and OS with CWTA for (i) sample size requirements to achieve a power of 0.8 and (ii) the time to first significant efficacy signal. (3) Results: CWTA consistently demonstrated greater power, and it reduced the sample size requirements by 18% to 35% compared to KM PFS and 14% to 20% compared to KM OS. CWTA also expedited time-to-efficacy signals by 2- to 6-fold. (4) Conclusions: CWTA, by incorporating all efficacy signals in the cancer treatment trajectory, provides a clinically relevant reduction in the required sample size and meaningfully expedites the efficacy signals of cancer treatments compared to KM PFS and KM OS. Using CWTA rather than KM as the primary trial outcome has the potential to meaningfully reduce the numbers of patients, trial duration, and costs to evaluate therapies in advanced cancer. [ABSTRACT FROM AUTHOR]

Abstract The purpose of this study was to evaluate the fatigue survival of 5Y-PSZ zirconia infiltrated with an experimental glass and bonded onto dentin analogues. Disc-shaped specimens of a 5Y-PSZ (Katana UTML Kuraray Noritake) were cemented onto dentin analogs (NEMA G10) and divided into four groups (n = 15): Zctrl Group (control, without infiltration); Zglz Group (Glaze, compression surface); Zinf-comp Group (Experimental Glass, compression surface); Zinf-tens Group (Experimental Glass, tension surface). Surface treatments were varied. Cyclic fatigue loading, oblique transillumination, stereomicroscope examination, and scanning electron microscopy were performed. Fatigue data were analyzed (failure load and number of cycles) using survival analysis (Kaplan–Meier and Log-Rank Mantel–Cox). There was no statistically significant difference in fatigue survival between the Zglz, Zctrl, and Zinf-comp groups. The Zinf-tens group presented a significantly higher failure load when compared to the other groups and exhibited a different failure mode. The experimental glass effectively infiltrated the zirconia, enhancing structural reliability, altering the failure mode, and improving load-bearing capacity over more cycles, particularly in the group where the glass was infiltrated into the tensile surface of the zirconia. Glass infiltration into 5Y-PSZ zirconia significantly enhanced structural reliability and the ability to withstand loads over an increased number of cycles. This approach has the potential to increase the durability of zirconia restorations, reducing the need for replacements and save time and resources, promoting efficiency in clinical practice.

Background: Drug-resistant tuberculosis is a burgeoning threat to public health requiring novel strategies to combat the infection. Although national tuberculosis elimination programs focus on improving health services, challenges in eradicating tuberculosis still exist. Factors attributing to unfavorable outcomes are unknown in Warangal district of Telangana state. Methods: This study included 296 patients diagnosed with multidrug-resistant pulmonary tuberculosis. The study participants followed up for a maximum of 20 months to determine treatment outcomes. Statistical applications of Kaplan-Meier curve and log-rank test used to find the survival probabilities in subgroups. Results: The survival of multidrug-resistant pulmonary tuberculosis patients was ascertained, in male and female patients, aged between 31 and 50 years. Resistance to rifampicin was prominent. The study found a survival rate of 76.68% and a mortality rate of 23.31%. The log-rank test revealed a significant difference in survival in subcategories with and without comorbidities (P =.03), non-adherence to treatment (P =.0001), treatment duration (P =.02), regimens (P =.01), and grading of radiograph (P =.0001). Conclusion: This study identified factors that influenced the survival probability of multidrug-resistant pulmonary tuberculosis patients, including comorbidities, weight band, non-adherence to treatment, treatment duration, regimens, and grading of radiograph. These findings emphasize the need for enhanced management strategies to improve treatment outcomes. [ABSTRACT FROM AUTHOR]

Telescopic crown-retained dentures (TCDs) are one of the most common types of prosthetic restorations for partially edentulous patients; however, post and core (PC) treatment shows the worst survival probability if the tooth is used as an abutment for the TCD. Due to extra axial forces, abutment tooth fracture is a common cause of failure for TCDs; thus, PC treatment is often needed to refit the existing telescopic crown (TC). However, there are no clinical survival data on whether the PC treatment was used to refit the TC after abutment tooth fracture (PC2) or the PC was already fitted at the time of TCD treatment (PC1). A total of 246 patients with 399 PC treatments were retrospectively evaluated for follow-ups up to 17.33 years. The files were analysed for PC1 and PC2. Furthermore, the influence of the jaw, type of tooth, luting material, PC material, bone attachment, therapist and cause of failure was recorded. For statistical analysis, Kaplan–Meier and Cox regression analyses were conducted. PC2 showed highly significant lower survival probabilities than PC1 (p < 0.001). Moreover, the bone attachment and the age of the patient at the time of fitting the PC crown had an influence on the survival (p < 0.001). Therefore, PC2 should be carefully discussed with the patient and PC1 should be favoured in endodontically treated abutment teeth for TCDs. [ABSTRACT FROM AUTHOR]

Objective: Treatment options with disease-modifying antirheumatic drugs (DMARDs) for psoriatic arthritis (PsA) have evolved over recent years. In addition to Janus kinase inhibitors (JAKi), four classes of biologic DMARDs (bDMARDs; interleukin [IL]-23 inhibitors [IL-23i], IL-12/23 inhibitors [IL-12/23i], tumor necrosis factor inhibitors [TNFi], and IL-17 inhibitors [IL-17i]) are currently approved for moderate to severe PsA treatment. There is minimal evidence of the persistence of these drugs among PsA outpatients in a real-world scenario during the period following the approval of JAKi. Therefore, we aimed to analyze the drug survival rates of biologic and JAKi therapies among German PsA outpatients during routine clinical care. Methods: We retrospectively analyzed PsA patients with a new prescription for a biologic or JAKi in the RHADAR database between January 2015 and October Results: 1352 new prescriptions with bDMARDs (IL-12/23i [n=50], IL-23i [n=31], TNFi [n=774], IL-17i [n=360]) or JAKi (n=137) were identified. The 5-year drug survival rate was 67.8% for IL-17i, 62.3% for TNFi, 53.3% for JAKi, and 46.0% for IL-12/23i. Discontinuation probabilities for JAKi and IL-12/23i were significantly higher compared with TNFi (JAKi hazard ratio [HR] 1.66, [95% CI 1.23-2.24], p=0.001; IL-12/23i HR 1.54, [95% CI 1.02-2.33], p=0.042) and IL-17i (JAKi HR 1.77, [95% CI 1.27-2.47], p=0.001; IL-12/23i HR 1.64, [95% CI 1.06-2.55], p=0.027). JAKi-treated patients had more severe disease and more osteoarthritis (OA) compared to TNFi and more OA compared to IL-17i. Conclusion: German PsA outpatients might persist longer with TNFi and IL-17i compared with IL-12/23i or JAKi. For TNFi, differences in subgroup characteristics and comorbidities (OA) may have affected drug survival rates. For IL-17i, the longer drug survival might not only be related to less OA compared to JAKi and, therefore, might be affected by other factors. [ABSTRACT FROM AUTHOR]

This study builds on previous research indicating that breast cancer survival time is influenced by several underlying factors. The study covered a period of 10 years from January 2012 to December 2022, and 140 cases were considered within the study cohort. The study considered breast cancer patients from North East Nigeria. The methodologies used are Cox hazard proportional regression and Kaplan–Meier analysis. The mean patient survival time is 592.2 days, with an average age of 44.61 years, average number of children of 5, and mean weight difference of 1.95 kg while on treatment. Kaplan-Meier analysis and the log rank test were used to investigate how the various covariates affect survival time, and it was found that age and family history have significant effects on the survival time in the studied population. The p-value of 0.04 for radiotherapy indicates statistical significance, in contrast to other treatment options such as surgery (p-value 0.7), targeted therapy (p-value 0.7), and chemotherapy (p-value 0.6). Residual diagnostic analysis with a component for assessment of Variance Inflation Factors (VIF) was used to detect multicollinearity among the independent variables. A total of 60 events (deaths) occurred within the study period with a concordance value of 0.73, which indicates a moderate level of agreement. This implies that the model's predictions align reasonably well with the observed outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Paediatric patients with acute lymphoblastic leukaemia (ALL) have shown a better overall survival (OS) and event-free survival (EFS) over the recent decades. This is due to advancement of diagnostic modalities, individualized treatment and improved supportive care. This study was done to determine common clinical presentations, prognostic factors associated with disease outcome and the overall survival in patients treated with UKALL protocol. Materials and methods: This was a retrospective cohort study done in the year 2022 involving data interpretation from medical records of children diagnosed with ALL and received treatment with UKALL protocol in Hospital Universiti Sains Malaysia from 1st January 2008 until 31st December 2018. Kaplan-Meier analysis with log-rank were performed to determine the 3-year survival probability. Multivariate analysis with simple and multiple Cox regression were performed to determine the significant prognostic factors of poor disease outcome. Results: A total of 97 patients were included in the study. The commonest clinical presentations were fever (83.5%), pallor (82.5%) and lethargy (52.6%). Clinical examinations revealed most patients had hepatomegaly (92.8%), splenomegaly (83.5%) and lymphadenopathy (82.5%). The 3-year OS is 72.2%. In this study, Kaplan -Meier analysis showed that the weight percentile (p=0.002), and the presence of blast in CSF (p=0.023) were significant factors in survival analysis of leukaemia patients. Multivariate analysis showed that the weight percentile of 10th – 95th percentile, significantly predicted the poor survival outcome (p=0.002) in this study. Conclusion: Most of paediatric ALL patients usually presented with common clinical presentations of acute leukaemia. Our overall survival (OS) is comparable to other developing countries. Patient with weight percentile of 10th -95th percentile and blast in CSF significantly predicted poor survival outcomes. [ABSTRACT FROM AUTHOR]

Myoepithelial carcinoma (MECA) is a rare type of carcinoma for which the clinicopathological features and prognostic factors have not yet been fully clarified. A retrospective study of 42 patients diagnosed with salivary gland MECA was performed, focusing on the clinicopathological features and prognostic factors. Of the 42 patients, 20 died of cancer, 20 lived without tumour, one lived with distant metastasis, and one was lost to follow-up. Overall, 69.0% had tumour recurrence, 16.7% had cervical nodal metastasis, and 21.4% had distant metastasis. The 5-year overall survival rate was 70.2%. Kaplan–Meier analysis revealed that patients with pathological positive lymph nodes (pN+), multiple recurrences of tumour, and higher histological grade had worse overall survival. Multivariate Cox analysis indicated pN+ and higher histological grade to be independent predictors of decreased survival. The 5-year overall survival rate in the pN0 group was 87.5%, while that in the pN+ group was 28.6%. In conclusion, myoepithelial carcinoma can be defined as a tumour with a high incidence of recurrence and poor prognosis, especially in pN+ patients. Pathological positive lymph nodes and histological grade may serve as predictors of survival. [ABSTRACT FROM AUTHOR]

Objective To evaluate the clinical implications of ARL5B in esophageal cancer and its underlying mechanisms by using bioinformatics methods. Methods ARL5B transcriptomic expression data were obtained from The Cancer Genome Atlas (TCGA), R software was employed to detect the differential expression mRNAs, and related clinical information was collected for survival analysis. To validate the bioinformatics results, Real-time quantitative PCR (qRT-PCR) and Western blotting were carried out for clinical specimens of esophageal cancer tumor tissues and adjacent tissues. Immunohistochemistry was used to evaluate the expression of ARL5B and its associated clinicopathologic features. The underlying mechanisms of ARL5B in esophageal cancer were preliminarily explored by bioinformatics and qRT-PCR. Results Bioinformatics method showed that the expression of ARL5B in human esophageal cancer tissues was significantly higher than in adjacent tissues and correlated with poor prognosis. Clinical specimens were detected, the expressions of ARL5B mRNA and protein were the highest in metastases lymph node, followed by esophageal cancer tissues and adjacent tissues, which corresponded with bioinformatics results. The expression of ARL5B was strongly correlated with lymph node metastases and advanced clinical stage. Kaplan-Meier analysis results denoted high ARL5B level, indicating poor prognosis. Enrichment analysis showed that ARL5B was associated the biological processes such as vacuolar transport, late endosome to lysosome transport, and organelle localization. Protein-protein interaction analysis (PPI) suggested that ARL5B might interact with VPS16, KIF1A and TOM1, whose expressions were verified by qRT-PCR and positively correlated with ARL5B expression. Conclusion ARL5B was highly expressed in esophageal cancer and associated with lymph node metastases, advanced clinical stage, and poor prognosis. ARL5B may be involved in the progression of esophageal cancer with several molecular mechanisms. [ABSTRACT FROM AUTHOR]

Background. surgery is the main method of treatment of colon cancer (cc). Radical surgery performed in non-specialized hospitals can lead to the adverse outcomes.The aim of this study was to assess CC survival after radical surgery performed in state hospitals of the arkhangelsk region (North-West Russia) in 2010–21.Material and Methods. data on all the 2142 cases of radical surgery of CC were obtained from the arkhangelsk regional cancer registry (ARCR). One- and five-year cancer-specific survival rates were estimated by the survival tables; cumulative survival function was calculated by the Kaplan–meier method. Univariate and multiple cox regression analysis was carried out to identify independent predictors associated with CC death risk after radical surgery in state hospitals (incl. sex, age at the time of diagnosis, topography, morphology and stage of CC).Results. less than half (42.8 %) of patients underwent surgery at the arkhangelsk clinical cancer center (accc), a single specialized hospital. one- and five-year survival rates of all patients were 86.5 % (95 % CI: 84.9–87.9 %) and 65.1 % (95 % ci: 62.7–67.4 %), respectively. The 5-year survival rate of patients who underwent surgery in the accc was significantly higher than that in patients who underwent surgery in other state non-specialized hospitals (76.0 % (95 % ci: 72.5–79.0 % versus 49.3–73.8 %, p

Abstract Background Early evaluation of severe mycoplasma pneumoniae pneumonia (SMPP) and the prompt utilization of fiberoptic bronchoscopic manipulation can effectively alleviate complications and restrict the progression of sequelae. This study aim to establish a nomogram forecasting model for SMPP in children and explore an optimal early therapeutic bronchoalveolar lavage (TBAL) treatment strategy. Methods This retrospective study included children with mycoplasma pneumoniae pneumonia (MPP) from January 2019 to December 2021. Multivariate logistic regression analysis was used to screen independent risk factors for SMPP and establish a nomogram model. The bootstrap method was employed and a receiver operator characteristic (ROC) curve was drawn to evaluate the accuracy and robustness of the model. Kaplan–Meier analysis was used to assess the effect of lavage and hospitalization times. Results A total of 244 cases were enrolled in the study, among whom 68 with SMPP and 176 with non-SMPP (NSMPP). A prediction model with five independent risk factors: left upper lobe computed tomography (CT) score, sequential organ failure assessment (SOFA) score, acute physiology and chronic health assessment (APACHE) II score, bronchitis score (BS), and c-reactive protein (CRP) was established based on the multivariate logistic regression analysis. The ROC curve of the prediction model showed the area under ROC curve (AUC) was 0.985 (95% confidence interval (CI) 0.972–0.997). The Hosmer–Lemeshow goodness-of-fit test results showed that the nomogram model predicted the risk of SMPP well (χ2 = 2.127, P = 0.977). The log-rank result suggested that an early BAL treatment could shorten MPP hospitalization time (P = 0.0057). Conclusion This nomogram model, based on the left upper lobe CT score, SOFA score, APACHE II score, BS, and CRP level, represents a valuable tool to predict the risk of SMPP in children and optimize the timing of TBAL.

Amyloid-β (Aβ) and tau are important biomarkers to predict the progression of cognitively unimpaired (CU) to dementia due to Alzheimer's disease (AD), according to the diagnosis framework from the US National Institute on Aging and the Alzheimer's Association (NIA-AA). However, it is clinically difficult to predict those subjects who were already with Aβ positive (A +) or tau positive (T +). As a typical characteristic of neurodegeneration in the diagnosis framework, the hypometabolism of the posterior cingulate cortex (PCC) has significant clinical value in the early prediction and prevention of AD. In this paper, we proposed the glucose metabolism in the PCC as a biomarker supplement to Aβ and tau biomarkers. First, we calculated the standard uptake value ratio (SUVR) of PCC based on fluorodeoxyglucose positron emission computed tomography (FDG PET) imaging. Secondly, we performed Kaplan–Meier (KM) survival analyses to explore the predictive performance of PCC SUVR, and the hazard ratio (HR) was calculated. Finally, we performed Pearson correlation analyses to explore the physiological significance of PCC SUVR. As a result, the PCC SUVR showed a consistent downward trend along the AD continuum. KM analyses showed better predictive performance when we combined PCC SUVR with cerebro-spinal fluid (CSF) Aβ42 (from HR = 2.56 to 3.00 within 5 years; from HR = 2.76 to 4.20 within 10 years) and ptau-181 (from 2.83 to 3.91 within 5 years; from HR = 2.32 to 4.17 within 10 years). There was a slight correlation between Aβ42/Aβ40 and PCC SUVR (r = 0.14, p = 0.02). In addition, several cognition scales were also correlated to PCC SUVR (from r = –0.407 to 0.383, p < 0.05). Our results showed that glucose metabolism in PCC may be a potential biomarker supplement to the Aβ and tau biomarkers to predict the progression of CU to AD. [ABSTRACT FROM AUTHOR]

Telescopic crown-retained dentures (TCDs) are one of the most common types of prosthetic restorations for partially edentulous patients; however, post and core (PC) treatment shows the worst survival probability if the tooth is used as an abutment for the TCD. Due to extra axial forces, abutment tooth fracture is a common cause of failure for TCDs; thus, PC treatment is often needed to refit the existing telescopic crown (TC). However, there are no clinical survival data on whether the PC treatment was used to refit the TC after abutment tooth fracture (PC2) or the PC was already fitted at the time of TCD treatment (PC1). A total of 246 patients with 399 PC treatments were retrospectively evaluated for follow-ups up to 17.33 years. The files were analysed for PC1 and PC2. Furthermore, the influence of the jaw, type of tooth, luting material, PC material, bone attachment, therapist and cause of failure was recorded. For statistical analysis, Kaplan–Meier and Cox regression analyses were conducted. PC2 showed highly significant lower survival probabilities than PC1 (p < 0.001). Moreover, the bone attachment and the age of the patient at the time of fitting the PC crown had an influence on the survival (p < 0.001). Therefore, PC2 should be carefully discussed with the patient and PC1 should be favoured in endodontically treated abutment teeth for TCDs.

Background: Early evaluation of severe mycoplasma pneumoniae pneumonia (SMPP) and the prompt utilization of fiberoptic bronchoscopic manipulation can effectively alleviate complications and restrict the progression of sequelae. This study aim to establish a nomogram forecasting model for SMPP in children and explore an optimal early therapeutic bronchoalveolar lavage (TBAL) treatment strategy. Methods: This retrospective study included children with mycoplasma pneumoniae pneumonia (MPP) from January 2019 to December 2021. Multivariate logistic regression analysis was used to screen independent risk factors for SMPP and establish a nomogram model. The bootstrap method was employed and a receiver operator characteristic (ROC) curve was drawn to evaluate the accuracy and robustness of the model. Kaplan–Meier analysis was used to assess the effect of lavage and hospitalization times. Results: A total of 244 cases were enrolled in the study, among whom 68 with SMPP and 176 with non-SMPP (NSMPP). A prediction model with five independent risk factors: left upper lobe computed tomography (CT) score, sequential organ failure assessment (SOFA) score, acute physiology and chronic health assessment (APACHE) II score, bronchitis score (BS), and c-reactive protein (CRP) was established based on the multivariate logistic regression analysis. The ROC curve of the prediction model showed the area under ROC curve (AUC) was 0.985 (95% confidence interval (CI) 0.972–0.997). The Hosmer–Lemeshow goodness-of-fit test results showed that the nomogram model predicted the risk of SMPP well (χ2 = 2.127, P = 0.977). The log-rank result suggested that an early BAL treatment could shorten MPP hospitalization time (P = 0.0057). Conclusion: This nomogram model, based on the left upper lobe CT score, SOFA score, APACHE II score, BS, and CRP level, represents a valuable tool to predict the risk of SMPP in children and optimize the timing of TBAL. [ABSTRACT FROM AUTHOR]

Shuo Li,&ast; Yiding Xiao,&ast; Yang Wang, Ming Bai, Fengzhou Du, Hailin Zhang Department of Plastic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hailin Zhang, Email hailin_pumc@126.comPurpose: Madelung’s disease (MD) is a rare condition of massive deposits of fat accumulations between superficial and deep fascia at typical locations. There is an absence of systematic studies related to MD in the Chinese cohort. Thus, the objective of the study was to investigate the clinical features of the MD cases in our institution and to explore the clinical variables associated with postoperative recurrence.Materials and Methods: We retrospectively analyzed the clinical information of 21 individuals with MD from 2013 to 2021 enrolled in our institution. The paired t-test and χ2 test were, respectively, used to determine the difference between continuous and classified variables. The univariate Kaplan–Meier analysis by log-rank and multivariate stepwise Cox regression analysis were used to explore variables possibly associated with postoperative recurrence in MD individuals.Results: In the current study, 90.48% of the studied patients were male with a mean age of 48.76 years old. About 61.90% exhibited type I MD. MD patients who experienced postoperative recurrence had a higher age, BMI, incidence of chronic complications, and prevalence of alcoholism than the other MD patients without recurrence (P < 0.05). The univariate Kaplan–Meier analysis by log-rank identified that age, BMI, alcoholism, and comorbidities were influencing factors related with postoperative recurrence (P < 0.05).Conclusion: Demographic characteristics of the 21 studied Chinese cases with MD were generally in accordance with previously published data of other foreign populations. The factors possibly influencing the postoperative recurrence for patients with MD were age, BMI, alcoholism, and a combination of comorbidities. This is the first time that a summarization of clinical characteristics and postoperative recurrence variables of Chinese patients with MD has been reported.Keywords: Madelung’s disease, MD, clinicopathological characteristics, recurrence influencing factors, Kaplan–Meier analysis, Cox proportional hazards regression

Our study aimed to analyse delaying factors amongst patients with a length of stay (LOS) > 15 days during the COVID-19 pandemic using time-to-event analysis. A total of 390 patients were admitted between March 2020–February 2021 to the subacute complex discharge unit in St James's Hospital: 326 (83.6%) were >65 years of age and 233 (59.7%) were female. The median (IQR) age was 79 (70–86) years with a median (IQR) of 19.4 (10–41) days. A total of 237 (60.7%) events were uncensored, with LOS > 15 days, of which 138 (58.2%) were female and 124 (52.32%) had >4 comorbidities; 153 (39.2%) were censored into LOS ≤ 15 days, and death occurred in 19 (4.8%). Kaplan–Meier's plot compared factors causing a delay in discharge to the single factors: age, gender, and multimorbidity. A multivariate Cox regression analysis adjusted to age, gender, and multimorbidity predicted factors affecting LOS. Further research is required to explore multimorbidity as a risk factor for mortality in patients with prolonged LOS within a complex discharge unit and target gender-specific frailty measures to achieve high-quality patient management. [ABSTRACT FROM AUTHOR]

(1) Background: Oxidative stress is crucial in carcinogenesis and the response of tumors to treatment. Antioxidant genes are important determinants of resistance to chemotherapy and radiotherapy. We hypothesized that genes involved in the oxidative stress response may be valuable as prognostic biomarkers for the survival of cancer patients and as druggable targets. (2) Methods: We mined the KM Plotter and TCGA Timer2.0 Cistrome databases and investigated 205 antioxidant genes in 21 different tumor types within the context of this investigation. (3) Results: Of 4347 calculations with Kaplan–Meier statistics, 84 revealed statistically significant correlations between high gene expression and worse overall survival (p < 0.05; false discovery rate ≤ 5%). The tumor types for which antioxidant gene expression was most frequently correlated with worse overall survival were renal clear cell carcinoma, renal papillary cell carcinoma, and hepatocellular carcinoma. Seventeen genes were clearly overexpressed in tumors compared to their corresponding normal tissues (p < 0.001), possibly qualifying them as druggable targets (i.e., ALOX5, ALOX5AP, EPHX4, G6PD, GLRX3, GSS, PDIA4, PDIA6, PRDX1, SELENOH, SELENON, STIP1, TXNDC9, TXNDC12, TXNL1, TXNL4A, and TXNRD1). (4) Conclusions: We concluded that a sub-set of antioxidant genes might serve as prognostic biomarkers for overall survival and as druggable targets. Renal and liver tumors may be the most suitable entities for this approach. [ABSTRACT FROM AUTHOR]

In this study, it was reported that basement membrane-associated long non-coding ribonucleic acid predicts prognosis and effectively enhances the individualized treatment of breast cancer by effectively identifying hot and cold tumors. Breast cancer transcriptional sequencing data were downloaded from The Cancer Genome Atlas and searched for prognostic long non-coding ribonucleic acids associated with basement membrane by univariate Cox regression and co-expression analysis. The least absolute shrinkage and selection operator analysis was employed to investigate the long non-coding ribonucleic acid prognostic model that is related to the basement membrane. Then, the following analyses were used to validate and evaluate the model, including univariate Cox regression, Kaplan-Meier analysis, multivariate Cox regression, receiver operating characteristic curve, calibration curves and nomogram. Immunoassay, principal component analysis, immunocytometric analysis and half-maximal inhibitory concentration analysis were conducted on the risk groups. To distinguish cold and hot tumors in terms of drug immunotherapy sensitivity, all inflammation-related long non-coding ribonucleic acids were divided into two groups. A model containing 4 basement membrane-related long non-coding ribonucleic acids was developed in this study. The area under the receiver operating characteristic curve was 0.742, 0.759 and 0.840 for 1, 2 and 3 y, respectively. High-risk patients were associated with tumor invasion and immunity and had a high immune infiltration status. Immune cells and checkpoints were infiltrated and activated in the high-risk group. Hot and cold tumors could be effectively distinguished by tumor clusters. Among the two clusters, cluster 2 was identified as hot tumors, which indicated that they were more sensitive to immunotherapeutic agents. This study provides evidence to support the hypothesis that basement membrane-related long non-coding ribonucleic acids can accurately predict patient prognosis and differentiate between hot and cold tumors. As a result, individualized immunotherapy for breast cancer patients will be improved and patients will have access to new treatment options. [ABSTRACT FROM AUTHOR]

Abstract The transcription factor cyclic-AMP response element-binding protein 1 (CREB1) responds to cAMP level and controls the expression of target genes, which regulates nutrition partitioning. The promoters of CREB1-targeted genes responsive to cAMP have been extensively investigated and characterized with the presence of both cAMP response element and TATA box. Compelling evidence demonstrates that CREB1 also plays an essential role in promoting tumor development. However, only very few genes required for cell survival, proliferation and migration are known to be constitutively regulated by CREB1 in tumors. Their promoters mostly do not harbor any cAMP response element. Thus, it is very likely that CREB1 regulates the expressions of distinct sets of target genes in normal tissues and tumors. The whole gene network constitutively regulated by CREB1 in tumors has remained unrevealed. Here, we employ a systematical and integrative approach to decipher this gene network in the context of both tissue cultured cancer cells and patient samples. We combine transcriptomic, Rank-Rank Hypergeometric Overlap, and Chipseq analysis, to define and characterize CREB1-regulated genes in a multidimensional fashion. A strong cancer relevance of those top-ranked targets, which meet the most stringent criteria, is eventually verified by overall survival analysis of cancer patients. These findings strongly suggest the importance of genes constitutively regulated by CREB1 for their implicative involvement in promoting tumorigenesis.

Objective: To investigate the differential expression of genes and microRNAs (miRNAs) in patients with lung adenocarcinoma and the relationship between such changes and patient prognosis. Methods: We analyzed the expression levels of genes and miRNAs in lung adenocarcinoma tissues and adjacent normal tissues using The Cancer Genome Atlas database (TCGA). We analyzed the function of the differentially expressed genes and miRNAs in a co-expression network. Finally, we performed survival analysis of differential genes and miRNAs in the co-expression network using clinical data from the TCGA database. Results: We successfully identified 6064 differentially expressed genes: 5324 upregulated genes and 740 downregulated genes. And we identified 161 differentially expressed miRNAs: 126 upregulated miRNAs and 35 downregulated miRNAs. We identified several genes that were related to each other in the co-expression network. Further analysis revealed that the high expression levels of G6PC, APOB, F2, PAQR9, and PAQR9-AS1 genes were associated with poor prognosis. However, there was no significant correlation between the expression of hsa-mir-122 with regards to patient prognosis. Conclusions: Our data showed that hsa-mir-122 and a number of related genes may affect the prognosis of patients with lung adenocarcinoma by regulating the cytoskeleton, thus promoting tumor angiogenesis and the metastasis of tumor cells. The high expression levels of some differentially expressed genes was associated with the low survival rate in patients with lung adenocarcinoma. However, the levels of hsa-mir-122 were not correlated with patient prognosis. [ABSTRACT FROM AUTHOR]

Background Despite the recent development of molecular‐targeted treatment and immunotherapy, survival of patients with esophageal adenocarcinoma (EAC) with poor prognosis is still poor due to lack of an effective biomarker. In this study, we aimed to explore the ceRNA and construct a multivariate gene expression predictor model using data from The Cancer Genome Atlas (TCGA) to predict the prognosis of EAC patients. Methods We conducted differential expression analysis using mRNA, miRNA and lncRNA transciptome data from EAC and normal patients as well as corresponding clinical information from TCGA database, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of those unique differentially expressed mRNAs using the Integrate Discovery Database (DAVID) database. We then constructed the lncRNA‐miRNA‐mRNA competing endogenous RNA (ceRNA) network of EAC and used Cox proportional hazard analysis to generate a multivariate gene expression predictor model. We finally performed survival analysis to determine the effect of differentially expressed mRNA on patients' overall survival and discover the hub gene. Results We identified a total of 488 lncRNAs, 33 miRNAs, and 1207 mRNAs with differentially expressed profiles. Cox proportional hazard analysis and survival analysis using the ceRNA network revealed four genes (IL‐11, PDGFD, NPTX1, ITPR1) as potential biomarkers of EAC prognosis in our predictor model, and IL‐11 was identified as an independent prognostic factor. Conclusions In conclusion, we identified differences in the ceRNA regulatory networks and constructed a four–gene expression‐based survival predictor model, which could be referential for future clinical research.

Objectives: Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is characterized by abnormal and potentially violent behaviors during REM sleep, typically observed in older adult subjects. Previous reports have described a high risk for neurodegeneration in patients with iRBD; however, to date, no published study has analyzed an adequate number of Japanese patients. We retrospectively analyzed the incidence of neurodegenerative disorders among patients diagnosed with iRBD in our department. Methods: The data were retrospectively collected from patients’ medical records. The patients included in the study were diagnosed with iRBD using polysomnography in our department, from May 1, 2005 to November 30, 2018, with a follow-up of ≥6 months. Using the Kaplan–Meier (KM) method, we estimated the incidence of later diagnoses of neurodegenerative disorders among this cohort of patients with iRBD. Results: Among 57 consecutive patients diagnosed with iRBD, 14 (24.6%) were later diagnosed with neurodegenerative disorders. Using the KM method, we estimated that the incidence was as high as 18.5% and 68.1% at 5 and 10 years, respectively. Of the 14 patients who developed neurodegenerative disorders, 12 (85.7%) had α-synucleinopathies (Parkinson’s disease in eight patients, Lewy body dementia in three, Alzheimer’s-type dementia in two, and multiple system atrophy in one). Conclusions: The results of this study suggest the high likelihood that iRBD may subsequently progress to neurodegenerative disorders in Japanese patients, a finding similar to those previously reported by studies performed overseas. Further studies using standardized prospective evaluation methods must be performed in Japan.

OBJECTIVE: To investigate the differential expression of genes and microRNAs (miRNAs) in patients with lung adenocarcinoma and the relationship between such changes and patient prognosis. METHODS: We analyzed the expression levels of genes and miRNAs in lung adenocarcinoma tissues and adjacent normal tissues using The Cancer Genome Atlas database (TCGA). We analyzed the function of the differentially expressed genes and miRNAs in a co-expression network. Finally, we performed survival analysis of differential genes and miRNAs in the co-expression network using clinical data from the TCGA database. RESULTS: We successfully identified 6064 differentially expressed genes: 5324 upregulated genes and 740 downregulated genes. And we identified 161 differentially expressed miRNAs: 126 upregulated miRNAs and 35 downregulated miRNAs. We identified several genes that were related to each other in the co-expression network. Further analysis revealed that the high expression levels of G6PC, APOB, F2, PAQR9, and PAQR9-AS1 genes were associated with poor prognosis. However, there was no significant correlation between the expression of hsa-mir-122 with regards to patient prognosis. CONCLUSION: Our data showed that hsa-mir-122 and a number of related genes may affect the prognosis of patients with lung adenocarcinoma by regulating the cytoskeleton, thus promoting tumor angiogenesis and the metastasis of tumor cells. The high expression levels of some differentially expressed genes was associated with the low survival rate in patients with lung adenocarcinoma. However, the levels of hsa-mir-122 were not correlated with patient prognosis. [ABSTRACT FROM AUTHOR]

The transcription factor cyclic-AMP response element-binding protein 1 (CREB1) responds to cAMP level and controls the expression of target genes, which regulates nutrition partitioning. The promoters of CREB1-targeted genes responsive to cAMP have been extensively investigated and characterized with the presence of both cAMP response element and TATA box. Compelling evidence demonstrates that CREB1 also plays an essential role in promoting tumor development. However, only very few genes required for cell survival, proliferation and migration are known to be constitutively regulated by CREB1 in tumors. Their promoters mostly do not harbor any cAMP response element. Thus, it is very likely that CREB1 regulates the expressions of distinct sets of target genes in normal tissues and tumors. The whole gene network constitutively regulated by CREB1 in tumors has remained unrevealed. Here, we employ a systematical and integrative approach to decipher this gene network in the context of both tissue cultured cancer cells and patient samples. We combine transcriptomic, Rank-Rank Hypergeometric Overlap, and Chipseq analysis, to define and characterize CREB1-regulated genes in a multidimensional fashion. A strong cancer relevance of those top-ranked targets, which meet the most stringent criteria, is eventually verified by overall survival analysis of cancer patients. These findings strongly suggest the importance of genes constitutively regulated by CREB1 for their implicative involvement in promoting tumorigenesis. [ABSTRACT FROM AUTHOR]

The information on the clinical course of coronavirus disease 2019 (COVID-19) and its correlates which are essential to assess the hospital care needs of the population are currently limited. We investigated the factors associated with hospital stay and death for COVID-19 patients for the entire state of Karnataka, India. A retrospective-cohort analysis was conducted on 445 COVID-19 patients that were reported in the publicly available media-bulletin from March 9, 2020, to April 23, 2020, for the Karnataka state. This fixed cohort was followed till 14 days (May 8, 2020) for definitive outcomes (death/discharge). The median length of hospital stay was 17 days (interquartile range: 15–20) for COVID-19 patients. Having severe disease at the time of admission (adjusted-hazard-ratio: 9.3 (3.2–27.3);P < 0.001) and being aged ≥ 60 years (adjusted-hazard-ratio: 11.9 (3.5–40.6);P < 0.001) were the significant predictors of COVID-19 mortality. By moving beyond descriptive (which provide only crude information) to survival analyses, information on the local hospital-related characteristics will be crucial to model bed-occupancy demands for contingency planning during COVID-19 pandemic.

In our study we conducted survival analysis of 204 patients visited Scientific-Research Institute of Heart Surgery and Organs transplantation and who underwent renal transplantation in Kyrgyzstan and other Eurasian countries between 2005 and 2016 years (age range: 9-71 years, mean: 38.21 (12.74) years, median: 34.0 (0.89) years; gender: 142 male (69.6%)). During follow-up period, mortality event was observed in 16 (7.84%) patients. Survival function probabilities of patients and rational risk factors of survival functions were evaluated by Kaplan-Meier and Cox regression analyses, respectively. According to Kaplan-Meier results survival probabilities calculated for 1st year: 0.96 (0.014), for 3rd year: 0.94 (0.018), for 5th year: 0.86 (0.04), for 7th year: 0.75 (0.10). Among age groups 28-39 age ranges prevailed by 11 patients. Nevertheless, that difference did not show statistical significance: p˃0.322. The intensity of transplantation also analyzed according to years, which revealed increasing in numbers of operations by time. For instance, when in 2006 only two cases were registered in our center, but numbers of transplanted patients reached up to 48 in 2015. The association of mortality states and years of transplantation found significantly by Kaplan-Meier test (Breslow p˂0.001). The survival analysis was compared according to countries and revealed significant results (Breslow p˂0.05). From other factors influencing mortality, sex did not show strong impact on survival by Kaplan-Meier analysis, but significant association was found by Cox regression analysis.

Convalescent plasma has been used worldwide to treat patients hospitalized with coronavirus disease 2019 (COVID-19) and prevent disease progression. Despite global usage, uncertainty remains regarding plasma efficacy, as randomized controlled trials (RCTs) have provided divergent evidence regarding the survival benefit of convalescent plasma. Here, we argue that during a global health emergency, the mosaic of evidence originating from multiple levels of the epistemic hierarchy should inform contemporary policy and healthcare decisions. Indeed, worldwide matched-control studies have generally found convalescent plasma to improve COVID-19 patient survival, and RCTs have demonstrated a survival benefit when transfused early in the disease course but limited or no benefit later in the disease course when patients required greater supportive therapies. RCTs have also revealed that convalescent plasma transfusion contributes to improved symptomatology and viral clearance. To further investigate the effect of convalescent plasma on patient mortality, we performed a meta-analytical approach to pool daily survival data from all controlled studies that reported Kaplan–Meier survival plots. Qualitative inspection of all available Kaplan–Meier survival data and an aggregate Kaplan–Meier survival plot revealed a directionally consistent pattern among studies arising from multiple levels of the epistemic hierarchy, whereby convalescent plasma transfusion was generally associated with greater patient survival. Given that convalescent plasma has a similar safety profile as standard plasma, convalescent plasma should be implemented within weeks of the onset of future infectious disease outbreaks.

In this study, we aimed to screen out genes associated with a high risk of postoperative recurrence of lung adenocarcinoma and investigate the possible mechanisms of the involvement of these genes in the recurrence of lung adenocarcinoma. We identify Hub genes and verify the expression levels and prognostic roles of these genes. Datasets of GSE40791, GSE31210, and GSE30219 were obtained from the Gene Expression Omnibus database. Enrichment analysis of gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for the screened candidate genes using the DAVID database. Then, we performed protein–protein interaction (PPI) network analysis through the database STRING. Hub genes were screened out using Cytoscape software, and their expression levels were determined by the GEPIA database. Finally, we assessed the relationships of Hub genes expression levels and the time of survival. Forty-five candidate genes related to a high-risk of lung adenocarcinoma recurrence were screened out. Gene ontology analysis showed that these genes were enriched in the mitotic spindle assembly checkpoint, mitotic sister chromosome segregation, G2/M-phase transition of the mitotic cell cycle, and ATP binding, etc. KEGG analysis showed that these genes were involved predominantly in the cell cycle, p53 signaling pathway, and oocyte meiosis. We screened out the top ten Hub genes related to high expression of lung adenocarcinoma from the PPI network. The high expression levels of eight genes (TOP2A, HMMR, MELK, MAD2L1, BUB1B, BUB1, RRM2, and CCNA2) were related to short recurrence-free survival and they can be used as biomarkers for high risk of lung adenocarcinoma recurrence. This study screened out eight genes associated with a high risk of lung adenocarcinoma recurrence, which might provide novel insights into researching the recurrence mechanisms of lung adenocarcinoma as well as into the selection of targets in the treatment of the disease. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this retrospective study was to evaluate the long-term outcomes of long-span fixed dental prostheses (LSFDPs) not meeting Ante’s law. Method and Materials: This study is based on the data of 36 patients who received 41 LSFDPs. The mean survival time of the LSFDPs was calculated using the Kaplan-Meier technique. The influence of the factors (gender, localization, number of abutments, Kennedy Class, dentition of the opposing jaw) were analyzed (log-rank test and Cox regression; P < .05). Results: During the observation period, 22.0% (n = 9) of the LSFDPs ceased to function. The calculated outcome probability after 3 years was 88.3%, and 57.4% after 5 years. The only significant difference in the mean survival time could be found in LSFDPs with two abutment teeth in comparison with LSFDPs with three and more abutment teeth. Although all of the patients were invited to an oral health and maintenance program regularly, only 13.8% attended. Conclusion: The results, taken together with data from the literature, indicate that the patient’s compliance is a crucial factor in the successful implementation of a LSFDP, whereas other factors are of minor importance. [ABSTRACT FROM AUTHOR]

Abstract INTRODUCTION: Understanding the mortality-associated risk factors of coronavirus disease 2019 will impact clinical decisions. METHODS: This retrospective longitudinal study included patients hospitalized for coronavirus disease in Rio de Janeiro, Brazil. The Kaplan-Meier method and multivariate Cox regression analysis were used. RESULTS: Sequential Organ Failure Assessment score of ≥2 (hazard ratio 4.614; 95% confidence interval =2.210-9.634; p5 (hazard ratio=2.616; 95% confidence interval=1.303-5.252; p=0.007) were independently associated with mortality. CONCLUSIONS: Sequential Organ Failure Assessment score and neutrophil/lymphocyte ratio on admission can identify coronavirus disease patients at increased risk of death and guide subsequent clinical decisions.

Background: Biochemical response to treatment in patients with primary biliary cholangitis (PBC) reflects prognosis. However, the best predictive criteria to detect biochemical response remain undetermined. In addition, because these criteria need > 6 months until definition, parameters that can estimate its results before initiating treatment are needed. Methods: We conducted a single-center retrospective study on 196 patients with PBC, followed up for at least 12 months after initiating treatment. Results: Kaplan–Meier analysis showed that Paris II (p = 0.002) and Rotterdam criteria (p = 0.001) could estimate the overall survival of PBC patients, whereas Paris II (p = 0.001), Rotterdam (p = 0.001), and Rochester criteria (p= 0.025) could estimate liver-related deaths. Cox hazard analysis revealed Paris II and Rotterdam criteria as significantly independent predictors of overall survival (hazard ratio (HR) 3.948, 95% CI 1.293–12.054, p = 0.016 and HR 6.040, 95% CI 1.969–18.527, p = 0.002, respectively) and liver-related deaths (HR 10.461, 95% CI 1.231–88.936, p = 0.032 and HR 10.824, 95% CI 1.252–93.572, p = 0.032, respectively). The results of Paris II criteria could be estimated by serum prothrombin time (Odds ratio (OR) 1.052, 95% CI 1.008–1.098, p = 0.021) and alanine transaminase level (OR 0.954, 95% CI 0.919–0.991, p = 0.014) whereas, those of Rotterdam criteria could be estimated by serum albumin level (OR 3.649, 95% CI 1.098–12.128, p = 0.035) at the time of diagnosis. Conclusions: This study highlights the best prediction criteria and pre-treatment parameters that facilitate the prognosis of PBC patients. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the expression of progestin and adipoQ receptor family member VI (PAQR6, mPRδ) in prostate cancer and to explore its role in prostate cancer progression.

Abstract Background Identification of biomarkers associated with the prognosis of different cancer subtypes is critical to achieve better therapeutic assistance. In colorectal cancer (CRC) the discovery of stable and consistent survival markers remains a challenge due to the high heterogeneity of this class of tumors. In this work, we identified a new set of gene markers for CRC associated to prognosis and risk using a large unified cohort of patients with transcriptomic profiles and survival information. Results We built an integrated dataset with 1273 human colorectal samples, which provides a homogeneous robust framework to analyse genome-wide expression and survival data. Using this dataset we identified two sets of genes that are candidate prognostic markers for CRC in stages III and IV, showing either up-regulation correlated with poor prognosis or up-regulation correlated with good prognosis. The top 10 up-regulated genes found as survival markers of poor prognosis (i.e. low survival) were: DCBLD2, PTPN14, LAMP5, TM4SF1, NPR3, LEMD1, LCA5, CSGALNACT2, SLC2A3 and GADD45B. The stability and robustness of the gene survival markers was assessed by cross-validation, and the best-ranked genes were also validated with two external independent cohorts: one of microarrays with 482 samples; another of RNA-seq with 269 samples. Up-regulation of the top genes was also proved in a comparison with normal colorectal tissue samples. Finally, the set of top 100 genes that showed overexpression correlated with low survival was used to build a CRC risk predictor applying a multivariate Cox proportional hazards regression analysis. This risk predictor yielded an optimal separation of the individual patients of the cohort according to their survival, with a p-value of 8.25e-14 and Hazard Ratio 2.14 (95% CI: 1.75–2.61). Conclusions The results presented in this work provide a solid rationale for the prognostic utility of a new set of genes in CRC, demonstrating their potential to predict colorectal tumor progression and evolution towards poor survival stages. Our study does not provide a fixed gene signature for prognosis and risk prediction, but instead proposes a robust set of genes ranked according to their predictive power that can be selected for additional tests with other CRC clinical cohorts.

Recurrence rates of keloids have generally been reported at one time point. However, the longer the duration after treatment, the greater the likelihood that such lesions will recur. In this study, we analysed the time to recurrence during long-term follow-up. We retrospectively reviewed recurrence-free interval in 52 patients with keloid (age 8–79 years) who had been treated between June 2006 and January 2011 using a standardised protocol developed by our group. Mean duration of follow-up was 37.5 (range, 7–120) months in patients with keloid. Kaplan-Meier survival curves revealed a statistically significant difference in recurrence-free interval between ear keloids and keloids excluding ear keloids. Recurrence rate for keloids was high in the first 2 years after treatment. Kaplan-Meier analysis was useful for understanding the tendency of recurrence of keloids after treatment using a standardised protocol. • The Kaplan-Meier curve analysis is useful for evaluating the time to recurrence of keloids. • 2 years after treatment is a critical time point when considering the risk of keloids' recurrence. • Recurrence-free interval for ear keloids is significantly longer than that for other keloids. [ABSTRACT FROM AUTHOR]

The current prostate special antigen (PSA) test causes the overtreatment of indolent prostate cancer (PCa). It also increases the risk of delayed treatment of aggressive PCa. DNA methylation aberrations are important events for gene expression dysregulation during tumorigenesis and have been suggested as novel candidate biomarkers for PCa. This may improve the diagnosis and prognosis of PCa. This study assessed the differential methylation and messenger RNA (mRNA) expression between normal and PCa samples. Correlation between promoter methylation and mRNA expression was estimated using Pearson's correlation coefficients. Moreover, the diagnostic potential of candidate methylation markers was estimated by the receiver operating characteristic (ROC) curve using continuous beta values. Survival and Cox analysis was performed to evaluate the prognostic potential of the candidate methylation markers. A total of 359 hypermethylated sites 3435 hypomethylation sites, 483 upregulated genes, and 1341 downregulated genes were identified from The Cancer Genome Atlas database. Furthermore, 17 hypermethylated sites (covering 13 genes), including known genes associated with hypermethylation in PCa (e.g., AOX1 and C1orf114), showed high discrimination between adjacent normal tissues and PCa samples with the area under the ROC curve from 0.88 to 0.94. Notably, ANXA2, FGFR2, HAAO, and KCNE3 were identified as valuable prognostic markers of PCa through the Kaplan–Meier analysis. Using gene methylation as a continuous variable, four promoter hypermethylation was significantly associated with disease‐free survival in univariate Cox regression and multivariate Cox regression. This study identified four novel diagnostic and prognostic markers for PCa. The markers provide important strategies for improving the timely diagnosis and prognosis of PCa. [ABSTRACT FROM AUTHOR]

• This prospective observational study included patients with acute carbon monoxide poisoning. • Of 203 patients, 38 patients (18.8 %) developed delayed neuropsychiatric sequelae (DNS). • Low Glasgow Coma Scale score and high serum creatine kinase level are significant predictors for the development of DNS. A major challenge for physicians is to identify patients with acute carbon monoxide (CO) poisoning who are likely to develop delayed neuropsychiatric sequelae (DNS). DNS is defined as neuropsychological sequelae that develops after 2–40 days of lucid interval after CO intoxication. Currently, there is no consensus on factors that predict the prognosis of CO poisoning. Thus, the purpose of this study was to identify factors predicting the development of DNS using a Cox regression model. This prospective observational study included 310 CO-poisoned patients admitted to an emergency department in South Korea from July 2017 to February 2020. Demographic, clinical, and laboratory data were analyzed. Kaplan–Meier curves were constructed to estimate the cumulative incidence of DNS. A multivariate Cox regression model was used to identify the main predictors of the development of DNS. The incidence of DNS was 18.8 %, and the median onset time was 23.7 days (interquartile range, 14–30 days). The Kaplan–Meier survival curve showed that a serum creatine kinase (CK) level > 175.5 U/L and initial Glasgow Coma Scale (GCS) score ≤ 9 were associated with a higher cumulative incidence of DNS (log-rank test; p < 0.01 and p = 0.02, respectively). Cox regression analysis showed that a serum CK level > 175.5 U/L (hazard ratio [HR]: 2.862, 95 % confidence interval [CI]: 1.491–5.496; p < 0.01) and an initial GCS ≤ 9 (HR: 2.081, 95 % CI: 1.048–4.131; p = 0.04) were significant prognostic factors. In acute CO poisoning, an initial GCS score ≤ 9 and serum CK level > 175.5 U/L are significant predictors of DNS development. [ABSTRACT FROM AUTHOR]

Background: Despite the recent development of molecular‐targeted treatment and immunotherapy, survival of patients with esophageal adenocarcinoma (EAC) with poor prognosis is still poor due to lack of an effective biomarker. In this study, we aimed to explore the ceRNA and construct a multivariate gene expression predictor model using data from The Cancer Genome Atlas (TCGA) to predict the prognosis of EAC patients. Methods: We conducted differential expression analysis using mRNA, miRNA and lncRNA transciptome data from EAC and normal patients as well as corresponding clinical information from TCGA database, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of those unique differentially expressed mRNAs using the Integrate Discovery Database (DAVID) database. We then constructed the lncRNA‐miRNA‐mRNA competing endogenous RNA (ceRNA) network of EAC and used Cox proportional hazard analysis to generate a multivariate gene expression predictor model. We finally performed survival analysis to determine the effect of differentially expressed mRNA on patients' overall survival and discover the hub gene. Results: We identified a total of 488 lncRNAs, 33 miRNAs, and 1207 mRNAs with differentially expressed profiles. Cox proportional hazard analysis and survival analysis using the ceRNA network revealed four genes (IL‐11, PDGFD, NPTX1, ITPR1) as potential biomarkers of EAC prognosis in our predictor model, and IL‐11 was identified as an independent prognostic factor. Conclusions: In conclusion, we identified differences in the ceRNA regulatory networks and constructed a four–gene expression‐based survival predictor model, which could be referential for future clinical research. [ABSTRACT FROM AUTHOR]