Anserine bursa palpation tenderness is a risk factor for knee osteoarthritis progression and arthroplasty: data from the Osteoarthritis Initiative.

OBJECTIVE: Anserine bursa pain (ABP) is defined as the presence of palpation tenderness medially below the joint line, which is 2 cm from the tibial tuberosity. This study aimed to determine a link between ABP and three knee outcomes: frequent pain, joint space narrowing (JSN) progression, and total knee arthroplasty (TKA). METHODS: Participants from the Osteoarthritis Initiative cohort were included in this study. Frequent ABP was defined as presenting thrice at four-time points. The Chi-square test and binary logistic regression analyses examined the associations between ABP and the three knee outcomes. Furthermore, Cox Proportional Hazards Model explored the association between ABP and TKA. RESULTS: Baseline ABP was linked to a higher risk of frequent pain (odds ratio (OR): 2.28, 95% confidence interval (CI): 1.76-2.97, P < 0 .001) and TKA (OR: 1.54, 95% CI 1.01-2.36, P = 0 .044) after adjusting for gender, baseline age, body mass index (BMI), and Kellgren-Lawrence (KL) grade. In the frequent ABP group from baseline to the 4-year follow-up (≥ 3 of four-time points), frequent pain (OR: 3.14, 95% CI: 2.34-4.22, P < 0 .001) and TKA (OR: 1.79, 95% CI: 1.11-2.90, P = 0 .017) had a high association with ABP after adjusting for gender, baseline age, BMI, and KL grade. CONCLUSION: This study highlights the association between ABP and knee outcomes; therefore, clinicians should pay closer attention during the physical examination, especially in middle-aged and older female patients. Moreover, understanding ABP cause aids in better diagnosis and treatment. Key Points • This is the first study to identify an association between anserine bursa palpation tenderness and symptomatic knee osteoarthritis. • As opposed to most studies, which focus on intra-articular symptoms and signs, this study focused on extra-articular symptoms and signs. • Clinically, anserine bursa palpation tenderness can be utilized to determine patients at risk for the progression of knee osteoarthritis, thereby aiding in providing early therapeutic intervention.

Effective Skill Transfer From Fundamentals of Arthroscopic Surgery Training to Shoulder Arthroscopic Simulator in Novices.

PURPOSE: To investigate whether novices could improve performance on a shoulder arthroscopic simulator (high-fidelity) through short-term training on a Fundamentals of Arthroscopic Surgery Training (FAST) simulator (low-fidelity). METHODS: Twenty-eight novices with no experience in arthroscopy were recruited to perform a pre-test on a shoulder arthroscopic simulator. Then they were randomized into two groups: the experimental group practiced five modules on the FAST simulator three times, and the control group did nothing. The experimental group performed a post-test immediately after FAST simulator practice. Control group rested for 70 minutes after experiencing pre-test before performing post-test. All parameters were recorded by the simulator. RESULTS: The experimental group outperformed the control group in terms of total score, procedure time, camera path length, and grasper path length. However, there was no statistical difference in scratching of humerus cartilage or glenoid cartilage. Significant differences were found in the improvement of both groups in total score, procedure time, and camera path length. CONCLUSIONS: Arthroscopic skills gained after short-term training on FAST simulator could be transferred to the shoulder arthroscopic simulator. This research provides important evidence of the benefits of FAST simulator in shoulder arthroscopy training program.

Risk factors for postoperative delirium in elderly urological patients: A meta-analysis.

BACKGROUND: Avoiding postoperative delirium (POD) can have a significant detrimental effect on the rehabilitation and prognosis of elderly urological patients. It is necessary to explore the risk factors associated with POD in elderly urology to provide a basis for clinical recognition of delirium. METHODS: For relevant studies, we comprehensively searched Embase, MEDLINE, Ovid, PubMed, Scopus, The Cochrane Library, and Web of Science. The search deadline was September 2021. RESULTS: We identified 2046 studies, 8 of which were included in the ultimate analysis. A total of 8 articles, including 356 cases in the delirium group and 1813 cases in the non-delirium group, were included in the relevant literature. The 2 groups mentioned above differed significantly in the following factors: history of delirium (odds ratio [OR] = 6.98, 95% confidence interval [CI]: 1.63-29.86, P = .009); Preoperative use of psychotropic drugs (OR = 1.97, 95% CI: 1.11-3.52, P = .02); age (OR = 3.10, 95% CI: 2.08-4.12, P < .0001). The meta-analysis demonstrated that smoking, alcohol consumption, gender (male), mode of anesthesia (general anesthesia) and being unmarried did not have a significant effect on POD in elderly urological patients. CONCLUSION: The risk factors for POD in elderly urological patients include history of delirium, preoperative use of psychotropic drugs, and age. The present study provides guidance for taking targeted preventive measures to reduce risks.

Mechanotransduction Regulates the Interplays Between Alveolar Epithelial and Vascular Endothelial Cells in Lung.

Mechanical stress plays a critical role among development, functional maturation, and pathogenesis of pulmonary tissues, especially for the alveolar epithelial cells and vascular endothelial cells located in the microenvironment established with vascular network and bronchial-alveolar network. Alveolar epithelial cells are mainly loaded by cyclic strain and air pressure tension. While vascular endothelial cells are exposed to shear stress and cyclic strain. Currently, the emerging evidences demonstrated that non-physiological mechanical forces would lead to several pulmonary diseases, including pulmonary hypertension, fibrosis, and ventilation induced lung injury. Furthermore, a series of intracellular signaling had been identified to be involved in mechanotransduction and participated in regulating the physiological homeostasis and pathophysiological process. Besides, the communications between alveolar epithelium and vascular endothelium under non-physiological stress contribute to the remodeling of the pulmonary micro-environment in collaboration, including hypoxia induced injuries, endothelial permeability impairment, extracellular matrix stiffness elevation, metabolic alternation, and inflammation activation. In this review, we aim to summarize the current understandings of mechanotransduction on the relation between mechanical forces acting on the lung and biological response in mechanical overloading related diseases. We also would like to emphasize the interplays between alveolar epithelium and vascular endothelium, providing new insights into pulmonary diseases pathogenesis, and potential targets for therapy.

A nomogram prediction model for early death in patients with persistent pulmonary hypertension of the newborn.

Background: Persistent pulmonary hypertension of the newborn (PPHN) is a major lethal disorder in neonates that leads to an extremely high mortality rate. Thus, the early identification of adverse outcomes in PPHN is critical for clinical practice. This research attempted to develop a nomogram prediction system for assessing the mortality of newborns with PPHN. Methods: Two hundred and three newborns with PPHN diagnosed from January 2015 to March 2022 were involved in the study. The clinical features of these newborns and pregnancy details were compared between newborns in the survival and lethal groups. Univariable and multivariate analyses were established in sequence to demonstrate the essential risk factors. The nomogram prediction model was built. Results: A total of 203 newborns were included in the analysis. 136 (67.0%) newborns represented the hospital survival group. Plasma pH value (OR = 0.606, p = 0.000, 95% CI 0.45715-0.80315), septicemia (OR = 3.544, p = 0.000, 95% CI 1.85160-6.78300), and abnormal pregnancy history (OR = 3.331, p = 0.008, 95% CI 1.37550-8.06680) were identified as independent risk factors for neonatal death in newborns associated with PPHN. Finally, the nomogram predictive model was established based on multivariate analysis results, indicating the efficacies of prediction and calibration. Conclusion: This study generated an applicable risk score formula using the plasma pH value, septicemia, and abnormal pregnancy history to recognize neonatal death in newborns with PPHN, presenting a sufficient predictive value and calibration.

Association Between Traditional Herbal Diet and Nasopharyngeal Carcinoma Risk: A Prospective Cohort Study in Southern China.

INTRODUCTION: Prospective evidence for herbal diet and nasopharyngeal carcinoma (NPC) development is absent. We therefore evaluated the associations of herbal soup and herbal tea with NPC in a prospective cohort study in southern China. METHODS: Based on an NPC screening cohort established in 2008-2015, information on herbal diet consumption, potential confounding factors, and Epstein-Barr virus (EBV) antibody levels were collected from 10,179 individuals aged 30-69 years in Sihui city, southern China. Cox regression models were performed to examine herbal diet with NPC risk, and logistic regression models were used to examine herbal diet with EBV reactivation. RESULTS: During a median of 7.54 years of follow-up, 69 participants developed NPC. Herbal soup consumption was associated with decreased NPC risk, with HRs of 0.31 (95% confidence interval (CI): 0.15-0.62) for the highest intake frequency and 0.29 (95% CI: 0.16-0.51) for a longer duration. However, herbal tea was not significantly associated. Moreover, we identified herbal soup was inversely associated with EBV seropositivity among all the participants at baseline, with the adjusted ORs being 0.78 (95% CI: 0.65-0.93) for immunoglobulin A antibodies against EBV capsid antigens (VCA-IgA) and 0.76 (95% CI: 0.64-0.91) for nuclear antigen 1 (EBNA1-IgA) in those with the highest frequency and 0.70 (95% CI: 0.59-0.84) for VCA-IgA and 0.64 (95% CI: 0.54-0.77) for EBNA1-IgA in those with the longer duration. Inverse associations were also observed in non-NPC individuals. CONCLUSIONS: With inhibition of EBV reactivation by plants, herbal soup could significantly decrease the risk of NPC in endemic areas.

College of American Pathologists Tumor Regression Grading System for Long-Term Outcome in Patients with Locally Advanced Rectal Cancer.

BACKGROUND: The National Comprehensive Cancer Network's Rectal Cancer Guideline Panel recommends American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) system to evaluate pathologic response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC). Yet, the clinical significance of the AJCC/CAP TRG system has not been fully defined. MATERIALS AND METHODS: This was a multicenter, retrospectively recruited, and prospectively maintained cohort study. Patients with LARC from one institution formed the discovery set, and cases from external independent institutions formed a validation set to verify the findings from discovery set. Overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were assessed by Kaplan-Meier analysis, log-rank test, and Cox regression model. RESULTS: The discovery set (940 cases) found, and the validation set (2,156 cases) further confirmed, that inferior AJCC/CAP TRG categories were closely /ccorrelated with unfavorable survival (OS, DFS, LRFS, and DMFS) and higher risk of disease progression (death, accumulative relapse, local recurrence, and distant metastasis) (all p < .05). Significantly, pairwise comparison revealed that any two of four TRG categories had the distinguished survival and risk of disease progression. After propensity score matching, AJCC/CAP TRG0 category (pathological complete response) patients treated with or without adjuvant chemotherapy displayed similar survival of OS, DFS, LRFS, and DMFS (all p > .05). For AJCC/CAP TRG1-3 cases, adjuvant chemotherapy treatment significantly improved 3-year OS (90.2% vs. 84.6%, p < .001). Multivariate analysis demonstrated the AJCC/CAP TRG system was an independent prognostic surrogate. CONCLUSION: AJCC/CAP TRG system, an accurate prognostic surrogate, appears ideal for further strategizing adjuvant chemotherapy for LARC. IMPLICATIONS FOR PRACTICE: The National Comprehensive Cancer Network recommends the American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) four-category system to evaluate the pathologic response to neoadjuvant treatment for patients with locally advanced rectal cancer; however, the clinical significance of the AJCC/CAP TRG system has not yet been clearly addressed. This study found, for the first time, that any two of four AJCC/CAP TRG categories had the distinguished long-term survival outcome. Importantly, adjuvant chemotherapy may improve the 3-year overall survival for AJCC/CAP TRG1-3 category patients but not for AJCC/CAP TRG0 category patients. Thus, AJCC/CAP TRG system, an accurate surrogate of long-term survival outcome, is useful in guiding adjuvant chemotherapy management for rectal cancer.

Prospective assessment of a nasopharyngeal carcinoma risk score in a population undergoing screening.

Despite evidence suggesting the utility of Epstein-Barr virus (EBV) markers to stratify individuals with respect to nasopharyngeal carcinoma (NPC) risk in NPC high-risk regions, no validated NPC risk prediction model exists. We aimed to validate an EBV-based NPC risk score in an endemic population undergoing screening for NPC. This prospective study was embedded within an ongoing NPC screening trial in southern China initiated in 2008, with 51 235 adult participants. We assessed the score's discriminatory ability (area under the receiver-operator-characteristics curve, AUC). A new model incorporating the EBV score, sex and family history was developed using logistic regression and internally validated using cross-validation. AUCs were compared. We also calculated absolute NPC risk combining the risk score with population incidence and competing mortality data. A total of 151 NPC cases were detected in 2008 to 2016. The EBV-based score was highly discriminating, with AUC = 0.95 (95% CI = 0.93-0.97). For 90% specificity, the score had 87.4% sensitivity (95% CI = 81.0-92.3%). As specificity increased from 90% to 99%, the positive predictive value increased from 2.4% (95% CI = 1.9-3.0%) to 12.5% (9.9-15.5%). Correspondingly, the number of positive tests per detected NPC case decreased from 272 (95% CI = 255-290) to 50 (41-59). Combining the score with other risk factors (sex, first-degree family history of NPC) did not improve AUC. Men aged 55 to 59 years with the highest risk profile had the highest 5-year absolute NPC risk of 6.5%. We externally validated the discriminatory accuracy of a previously developed EBV score in a high-risk population. Adding nonviral risk factors did not improve NPC prediction.

Dynamic Changes in the Neutrophil-to-Lymphocyte Ratio Predict the Prognosis of Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

PURPOSE: To examine the effect of dynamic changes in neutrophil-to-lymphocyte ratio (NLR) on tumor response and overall survival (OS) in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). PATIENTS AND METHODS: Data from 181 patients with HCC were retrospectively collected. White blood cell, neutrophil and lymphocyte counts, and the NLR were obtained 1-3 days before as well as 3-6 weeks and 3 months after TACE. Patients were divided into two groups at each time point according to the mean value of NLR, and also divided into continuous decrease, fluctuating increase-decrease (I-D), fluctuating decrease-increase (D-I), and continuous increase groups according to the dynamic changes in the NLR. The dynamic changes in blood counts and NLR were analyzed using repeated-measures ANOVA. The odds ratios (ORs) for tumor response in different NLR groups were examined using a multivariate logistic regression model. Finally, the prognostic value of the dynamic changes in the NLR was examined using Cox regression models. RESULTS: Continuous decline of white blood cell counts, neutrophil counts and lymphocyte counts were observed at 3-6 weeks and 3 months after TACE treatment. The NLR increased slightly and then decreased substantially in responders, while it increased slightly and then significantly in non-responders, with a significant interaction effect of Time × Tumor response (P = 0.005). NLR grouping before TACE, 3-6 weeks and 3 months after TACE was not associated with tumor response, and only 3 months after TACE did, it shows a significant difference in univariate survival analyses (NLR > 2.5 vs NLR ≤ 2.5, hazard ratio [HR] = 2.442, 95% confidence interval (CI): 1.545, 3.860). The changes in the NLR were significantly correlated with tumor response and OS. Non-responders for TACE were more common in the continuous NLR increase group (OR = 6.230, 95% CI: 1.848-21.001) and in the fluctuating D-I group (OR = 5.702, 95% CI: 1.480-21.957). Multivariate analyses revealed that these two patient groups also showed poorer OS (HR = 2.351, 95% CI: 1.120-4.605 and HR = 2.320, 95% CI: 1.187-4.533, respectively). CONCLUSION: Dynamic changes in the NLR may be better predictors of tumor response and OS than static NLR values, but more data are needed.

Chinese nonmedicinal herbal diet and risk of nasopharyngeal carcinoma: A population-based case-control study.

BACKGROUND: An association between a nonmedicinal herbal diet and nasopharyngeal carcinoma (NPC) has often been hypothesized but never thoroughly investigated. METHODS: This study enrolled a total of 2469 patients with incident NPC and 2559 population controls from parts of Guangdong and Guangxi Provinces in southern China between 2010 and 2014. Questionnaire information was collected on the intake of traditional herbal tea and herbal soup as well as the specific herbal plants used in soups and other potentially confounding lifestyle factors. Multivariate logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the NPC risk in association with herbal tea and soup intake. RESULTS: Ever consumption of herbal tea was not associated with NPC risk (OR, 1.03; 95% CI, 0.91-1.17). An inverse association was observed for NPC among ever drinkers of herbal soup (OR, 0.78; 95% CI, 0.67-0.90) but without any monotonic trend with an increasing frequency or duration of herbal soup consumption. Inverse associations with NPC risk were detected with 9 herbal plants used in herbal soup, including Ziziphus jujuba, Fructus lycii, Codonopsis pilosula, Astragalus membranaceus, Semen coicis, Smilax glabra, Phaseolus calcaratus, Morinda officinalis, and Atractylodes macrocephala (OR range, 0.31-0.79). CONCLUSIONS: Consuming herbal soups including specific plants, but not herbal tea, was inversely associated with NPC. If replicated, these results might provide potential for NPC prevention in endemic areas.

Smoking can increase nasopharyngeal carcinoma risk by repeatedly reactivating Epstein-Barr Virus: An analysis of a prospective study in southern China.

BACKGROUND: The association between smoking and nasopharyngeal carcinoma (NPC) is still uncertain. The aim of this study was to validate smoking effect on NPC and explore if smoking can induce NPC by persistently reactivating EBV in long-term based on a prospective cohort design. METHODS: A NPC screening cohort with 10 181 eligible residents in Sihui city, southern China was conducted from 2008 to 2015. The smoking habit was investigated through the trained interviewers and EBV antibodies (VCA-IgA, EBNA1-IgA) as screening markers were tested periodically. New NPC cases were identified through local cancer registry. Cox's regression model was used to estimate the adjusted hazard ratios (aHRs) of smoking on NPC incidence. In the non-NPC participants, the associations between smoking and EBV seropositivity in different periods were assessed by logistic regression and generalized estimating equations (GEE). RESULTS: With a median of 7.54 years, 71 NPCs were diagnosed ≥1 year after recruitment. Compared with never smokers, the aHRs of developing NPC among ever smokers were 3.00 (95%CI: 1.46-6.16). Stratified by sex, the HRs of ever smoking were 2.59 (95%CI: 1.07-6.23) for male and 3.75 (95%CI: 1.25-11.20) for female, respectively. Among the non-NPC individuals, ever smoking was not only associated with EBV seropositivity at baseline, but also in the 3-5 years of follow up, with adjusted odds ratios (aORs) of 1.68 (95%CI: 1.29-2.18) for VCA-IgA and 1.92 (95%CI: 1.42-2.59) for EBNA1-IgA. Among the smokers who were tested EBV antibodies at least twice, the similar results were obtained using GEE. CONCLUSION: Smoking could significantly increase the long-term risk of NPC in southern China, partly by persistently reactivating EBV.

Decreased macrophage inflammatory protein (MIP)-1α and MIP-1ß increase the risk of developing nasopharyngeal carcinoma.

BACKGROUND: The association of circulating inflammation markers with nasopharyngeal carcinoma (NPC) is still largely unclear. This study aimed to comprehensively explore the relationship between circulating cytokine levels and the subsequent risk of NPC with a two-stage epidemiologic study in southern China. METHODS: The serum levels of 33 inflammatory cytokines were first measured in a hospital-based case-control study (150 NPC patients and 150 controls) using multiplex assay platforms. Marker levels were categorized into two or more groups based on the proportion of sample measurements that was above the lower limit of detection. Odds ratios (ORs) and 95% confidence intervals (CIs) relating the serum marker concentration to the risk of NPC were computed by multivariable logistic regression models. The associations were validated in 60 patients with NPC and 120 controls in a subsequent nested case-control study within a NPC screening trial. Potential interactions between serum cytokines and Epstein-Barr virus (EBV) relating to the risk of NPC were assessed using a likelihood ratio test. RESULTS: The levels of serum macrophage inflammatory protein (MIP)-1α and MIP-1ß in the highest categories were associated with a decreased risk of NPC in both the case-control study (MIP-1α: OR = 0.49, 95% CI = 0.26-0.95; MIP-1ß: OR = 0.47, 95% CI = 0.22-1.00) and the nested case-control study (MIP-1α: OR = 0.13, 95% CI = 0.03-0.62; MIP-1ß: OR = 0.20, 95% CI = 0.04-0.94), compared with those in the lowest categories. Furthermore, individuals with lower levels of these two cytokine markers who were EBV seropositive presented with a largely higher risk of NPC compared with patients with higher levels who were EBV seronegative in both the case-control study (MIP-1α: OR = 16.28, 95% CI = 7.11-37.23; MIP-1ß: OR = 12.86, 95% CI = 5.9-28.05) and the nested case-control study (MIP-1α: OR = 86.12, 95% CI = 10.58-701.03; MIP-1ß: OR = 115.44, 95% CI = 13.92-957.73). CONCLUSIONS: Decreased preclinical MIP-1α and MIP-1ß levels might be associated with a subsequently increased risk of NPC. More mechanistic studies are required to fully understand this finding.

Evaluation of seven recombinant VCA-IgA ELISA kits for the diagnosis of nasopharyngeal carcinoma in China: a case-control trial.

OBJECTIVE: Seven recombinant viral capsid antigen-IgA (VCA-IgA) ELISA kits are widely used in China, but their diagnostic effects have not been evaluated. In this study, we evaluated whether the diagnostic effects of these kits are similar to those of the standard kit (EUROIMMUN, Lübeck, Germany). METHODS: A diagnostic case-control trial was conducted with 200 cases of nasopharyngeal carcinoma (NPC) and 200 controls from NPC-endemic areas in southern China. The areas under the curve (AUCs), the sensitivities and the specificities of testing kits were compared with those of the standard kit. The test-retest reliability of each kit was determined by intraclass correlation coefficient (ICC). Their diagnostic accuracy in combination with Epstein-Barr virus nuclear antigen 1-IgA (EBNA1-IgA) was also evaluated in logistic models. RESULTS: Three testing kits-BB, HA and KSB-showed diagnostic accuracy equal to that of the standard kit, with good performance in the AUCs (0.926-0.945), and no significant differences in sensitivity were found between early-stage and advanced-stage NPCs. ICCs exceeded 0.8. Three logistic regression models were built, and the AUCs of these models (0.961-0.977) were better than those of the individual VCA-IgA kits. All new models had diagnostic accuracy equal to that of the standard kit. New cut-off values of these three kits and their corresponding combinations for researchers to replicate and use in NPC early detection and screening in the future were provided. CONCLUSIONS: Three recombinant VCA-IgA kits-BB,HA and KSB-had diagnostic effects equal to those of the standard kit, and, in combination with EBNA1-IgA in logistic regression models, can be used in future screening for NPC.

Precision-engineering the Pseudomonas aeruginosa genome with two-step allelic exchange.

Allelic exchange is an efficient method of bacterial genome engineering. This protocol describes the use of this technique to make gene knockouts and knock-ins, as well as single-nucleotide insertions, deletions and substitutions, in Pseudomonas aeruginosa. Unlike other approaches to allelic exchange, this protocol does not require heterologous recombinases to insert or excise selective markers from the target chromosome. Rather, positive and negative selections are enabled solely by suicide vector-encoded functions and host cell proteins. Here, mutant alleles, which are flanked by regions of homology to the recipient chromosome, are synthesized in vitro and then cloned into allelic exchange vectors using standard procedures. These suicide vectors are then introduced into recipient cells by conjugation. Homologous recombination then results in antibiotic-resistant single-crossover mutants in which the plasmid has integrated site-specifically into the chromosome. Subsequently, unmarked double-crossover mutants are isolated directly using sucrose-mediated counter-selection. This two-step process yields seamless mutations that are precise to a single base pair of DNA. The entire procedure requires ∼2 weeks.