PnNAC2 promotes the biosynthesis of Panax notoginseng saponins and induces early flowering.

KEY MESSAGE: PnNAC2 positively regulates saponin biosynthesis by binding the promoters of key biosynthetic genes, including PnSS, PnSE, and PnDS. PnNAC2 accelerates flowering through directly associating with the promoters of FT genes. NAC transcription factors play an important regulatory role in both terpenoid biosynthesis and flowering. Saponins with multiple pharmacological activities are recognized as the major active components of Panax notoginseng. The P. notoginseng flower is crucial for growth and used for medicinal and food purposes. However, the precise function of the P. notoginseng NAC transcription factor in the regulation of saponin biosynthesis and flowering remains largely unknown. Here, we conducted a comprehensive characterization of a specific NAC transcription factor, designated as PnNAC2, from P. notoginseng. PnNAC2 was identified as a nuclear-localized protein with transcription activator activity. The expression profile of PnNAC2 across various tissues mirrored the accumulation pattern of total saponins. Knockdown experiments of PnNAC2 in P. notoginseng calli revealed a significant reduction in saponin content and the expression level of pivotal saponin biosynthetic genes, including PnSS, PnSE, and PnDS. Subsequently, Y1H assays, dual-LUC assays, and electrophoretic mobility shift assays (EMSAs) demonstrated that PnNAC2 exhibits binding affinity to the promoters of PnSS, PnSE and PnDS, thereby activating their transcription. Additionally, an overexpression assay of PnNAC2 in Arabidopsis thaliana witnessed the acceleration of flowering and the induction of the FLOWERING LOCUS T (FT) gene expression. Furthermore, PnNAC2 demonstrated the ability to bind to the promoters of AtFT and PnFT genes, further activating their transcription. In summary, these results revealed that PnNAC2 acts as a multifunctional regulator, intricately involved in the modulation of triterpenoid saponin biosynthesis and flowering processes.

Incidence of and Risk Factors for Active Tuberculosis Disease in Individuals With Glomerular Disease: A Canadian Cohort Study.

RATIONALE & OBJECTIVE: Kidney failure is an established risk factor for active tuberculosis (TB) but the risk of TB has not been reported in specific kidney diseases. We sought to determine the incidence of and risk factors for active TB in patients with glomerular disease. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: A provincial kidney pathology registry (2000-2012) was used to identify 3,079 adult patients with IgA nephropathy, focal segmental glomerulosclerosis (FSGS), antineutrophil cytoplasmic antibody (ANCA)-related glomerulonephritis, lupus nephritis, membranous nephropathy, minimal change disease, or "other" glomerular diseases in British Columbia, Canada. EXPOSURE: Predictors included demographics, immigration status, comorbidities, immunosuppression use, estimated glomerular filtration rate (eGFR), and proteinuria. OUTCOME: A diagnosis of active TB was ascertained using administrative data linkages and defined based on (1) the dispensation of 1 or more unique combinations of medications used to treat active TB, or (2) physician or hospital visits for active TB. ANALYTICAL APPROACH: The definition of TB was validated in an external cohort linked to the Provincial TB registry at the BC Centre for Disease Control (BCCDC). Standardized incidence ratios were calculated using the age-matched general population. Risk factors for active TB were identified using Cox proportional hazards regression analysis. RESULTS: The sensitivity and specificity of the outcome definition of active TB were 87.6% and 99.5%, respectively. During a median follow-up of 6.2 years, 41 patients developed active TB with an incidence of 197 of 100,000 person-years, approximately 23 times as high as the general population and>6 times higher than the threshold of 30 per 100,000 used to define high TB incidence. A high incidence was observed in all glomerular diseases (range, 110-403 per 100,000), in both Canadian- and foreign-born patients (range, 124-424 per 100,000), and in patients exposed or not to immunosuppression (282 vs 147 per 100,000). Factors associated with higher TB risk included immigration from a high-incidence country (HR, 3.90 [95% CI, 1.75-8.68]), diminished eGFR (HR, 2.81 [95% CI, 1.18-6.69]), higher levels of proteinuria (HR, 1.15 [95% CI, 1.04-1.27]), lupus nephritis (HR, 2.79 [95% CI, 1.37-5.68]), and immunosuppression use (HR, 2.13 [95% CI, 1.13-4.03]). LIMITATIONS: A relatively low number of events contributed to uncertainty in risk estimates. CONCLUSIONS: Patients with glomerular disease have a high incidence of active TB irrespective of disease type, demographics, or use of immunosuppression. Prospective studies are needed to evaluate the utility of screening for latent TB infection in this population. PLAIN-LANGUAGE SUMMARY: Patients with kidney failure are at high risk of developing tuberculosis (TB), a major infection that can be prevented by identifying and treating patients who have had prior exposure to TB. The risk of TB in specific kidney diseases is unknown. In this Canadian study of 3,079 patients with glomerular disease, a group of autoimmune kidney conditions, the rate of TB was 23 times higher than in the general population. The rate was high irrespective of the use of immunosuppressive drugs or whether patients had immigrated to Canada from another country. These findings suggest that screening patients with glomerular disease for prior TB exposure may be beneficial; however, this needs to be evaluated in a prospective study.

De novo familial adenomatous polyposis associated thyroid cancer with a c.2929delG frameshift deletion mutation in APC: a case report and literature review.

BACKGROUND: Germline mutations in the APC gene located on chromosome 5q 21-22 can lead to familial adenomatous polyposis (FAP) and the development of colorectal cancer (CRC) if left untreated. As a rare extracolonic manifestation, thyroid cancer is diagnosed in about 2.6% of FAP patients. The genotype-phenotype correlation in FAP patients with thyroid cancer remains unclear. CASE PRESENTATION: We present a 20-year-old female of FAP with thyroid cancer as the initial manifestation. The patient was asymptomatic and developed colon cancer liver metastases 2 years after the diagnosis of thyroid cancer. The patient underwent multiple surgical treatments in several organs, and regular colonoscopy with endoscopic polypectomy was performed. Genetic testing demonstrated the c.2929delG (p.Gly977Valfs*3) variant in exon 15 of the APC gene. This represents a previously undescribed APC mutation. This mutation causes loss of multiple structures on the APC gene including the 20-amino acid repeats, the EB1 binding domain, and the HDLG binding site, which may be pathogenic through ß-catenin accumulation, cell cycle microtubule dysregulation, and tumor suppressor inactivation. CONCLUSIONS: We report a de novo FAP case with thyroid cancer presenting atypically aggressive features harboring a novel APC mutation and review APC germline mutations in patients with FAP-associated thyroid cancer.

A Population-Based Analysis of the Risk of Glomerular Disease Relapse after COVID-19 Vaccination.

BACKGROUND: Although case reports have described relapses of glomerular disease after COVID-19 vaccination, evidence of a true association is lacking. In this population-level analysis, we sought to determine relative and absolute risks of glomerular disease relapse after COVID-19 vaccination. METHODS: In this retrospective population-level cohort study, we used a centralized clinical and pathology registry (2000-2020) to identify 1105 adult patients in British Columbia, Canada, with biopsy-proven glomerular disease that was stable on December 14, 2020 (when COVID-19 vaccines first became available). The primary outcome was disease relapse, on the basis of changes in kidney function, proteinuria, or both. Vaccination was modeled as a 30-day time-varying exposure in extended Cox regression models, stratified on disease type. RESULTS: During 281 days of follow-up, 134 (12.1%) patients experienced a relapse. Although a first vaccine dose was not associated with relapse risk (hazard ratio [HR]=0.67; 95% confidence interval [95% CI], 0.33 to 1.36), exposure to a second or third dose was associated with a two-fold risk of relapse (HR=2.23; 95% CI, 1.06 to 4.71). The pattern of relative risk was similar across glomerular diseases. The absolute increase in 30-day relapse risk associated with a second or third vaccine dose varied from 1%-2% in ANCA-related glomerulonephritis, minimal change disease, membranous nephropathy, or FSGS to 3%-5% in IgA nephropathy or lupus nephritis. Among 24 patients experiencing a vaccine-associated relapse, 4 (17%) had a change in immunosuppression, and none required a biopsy. CONCLUSIONS: In a population-level cohort of patients with glomerular disease, a second or third dose of COVID-19 vaccine was associated with higher relative risk but low absolute increased risk of relapse.

Robotic-assisted Versus Video-assisted Thoracoscopic Lobectomy: Short-term Results of a Randomized Clinical Trial (RVlob Trial).

OBJECTIVE: To determine whether RAL affects perioperative outcomes and long-term efficacy in NSCLC patients, compared with traditional VAL. SUMMARY OF BACKGROUND DATA: RAL is a promising treatment for NSCLC. However, its efficacy has not been fully evaluated. METHODS: A single-center, open-labeled prospective randomized clinical trial was launched in May 2017 to compare the efficacy of RAL and VAL. By May 2020, 320 patients were enrolled. The perioperative results of RAL and VAL were compared. RESULTS: The 320 enrolled patients were randomly assigned to the RAL group (n = 157) and the VAL group (n = 163). Perioperative outcomes were comparable between the 2 groups, including the length of hospital stay (P = 0.76) and the rate of postoperative complications (P = 0.45). No perioperative mortality occurred in either group. The total amount of chest tube drainage {830 mL [interquartile range (IQR), 550-1130 mL] vs 685 mL [IQR, 367.5-1160 mL], P = 0.007} and hospitalization costs [$12821 (IQR, $12145-$13924) vs $8009 (IQR, $7014-$9003), P < 0.001] were significantly higher in the RAL group. RAL group had a significantly higher number of LNs harvested [11 (IQR, 8-15) vs 10 (IQR, 8-13), P = 0.02], higher number of N1 LNs [6 (IQR, 4-8) vs 5 (IQR, 3-7), P = 0.005], and more LN stations examined [6 (IQR, 5-7) vs 5 (IQR, 4-6), P < 0.001]. CONCLUSIONS: Both RAL and VAL are safe and feasible for the treatment of NSCLC. RAL achieved similar perioperative outcomes, together with higher LN yield. Further follow-up investigations are required to evaluate the long-term efficacy of RAL. (ClinicalTrials.gov identifier: NCT03134534).

The Risk of Cardiovascular Events in Individuals With Primary Glomerular Diseases.

RATIONALE & OBJECTIVE: Little is known about the risk of cardiovascular disease (CVD) in patients with various primary glomerular diseases. In a population-level cohort of adults with primary glomerular disease, we sought to describe the risk of CVD compared with the general population and the impact of traditional and kidney-related risk factors on CVD risk. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: Adults with membranous nephropathy (n = 387), minimal change disease (n = 226), IgA nephropathy (n = 759), and focal segmental glomerulosclerosis (n = 540) from a centralized pathology registry in British Columbia, Canada (2000-2012). EXPOSURE: Traditional CVD risk factors (diabetes, age, sex, dyslipidemia, hypertension, smoking, prior CVD) and kidney-related risk factors (type of glomerular disease, estimated glomerular filtration rate [eGFR], proteinuria). OUTCOME: A composite CVD outcome of coronary artery, cerebrovascular, and peripheral vascular events, and death due to myocardial infarction or stroke. ANALYTICAL APPROACH: Subdistribution hazards models to evaluate the outcome risk with non-CVD death treated as a competing event. Standardized incidence rates (SIR) calculated based on the age- and sex-matched general population. RESULTS: During a median 6.8 years of follow-up, 212 patients (11.1%) experienced the CVD outcome (10-year risk, 14.7% [95% CI, 12.8%-16.8%]). The incidence rate was high for the overall cohort (24.7 per 1,000 person-years) and for each disease type (range, 12.2-46.1 per 1,000 person-years), and was higher than that observed in the general population both overall (SIR, 2.46 [95% CI, 2.12-2.82]) and for each disease type (SIR range, 1.38-3.98). Disease type, baseline eGFR, and proteinuria were associated with a higher risk of CVD and, when added to a model with traditional risk factors, led to improvements in model fit (R2 of 14.3% vs 12.7%), risk discrimination (C-statistic of 0.81 vs 0.78; difference, 0.02 [95% CI, 0.01-0.04]), and continuous net reclassification improvement (0.4 [95% CI, 0.2-0.6]). LIMITATIONS: Ascertainment of outcomes and comorbidities using administrative data. CONCLUSIONS: Patients with primary glomerular disease have a high absolute risk of CVD that is approximately 2.5 times that of the general population. Consideration of eGFR, proteinuria, and type of glomerular disease may improve risk stratification of CVD risk in these individuals. PLAIN-LANGUAGE SUMMARY: Patients with chronic kidney disease are known to be at high risk of cardiovascular disease. Cardiovascular risk in patients with primary glomerular diseases is poorly understood because these conditions are rare and require a kidney biopsy for diagnosis. In this study of 1,912 Canadian patients with biopsy-proven IgA nephropathy, minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy, the rate of cardiovascular events was 2.5 times higher than in the general population and was high for each disease type. Consideration of disease type, kidney function, and proteinuria improved the prediction of cardiovascular events. In summary, our population-level study showed that patients with primary glomerular diseases have a high cardiovascular risk, and that inclusion of kidney-specific risk factors may improve risk stratification.

Nutritional Status, Nutritional Phenotypes, and Oral Nutritional Supplement Prescription Patterns Among Patients With Non-Dialysis Chronic Kidney Disease in British Columbia.

OBJECTIVES: Management of protein-energy wasting and undernutrition with oral nutritional supplements (ONS) has not been systematically studied in the non-dialysis chronic kidney disease (CKD-ND) population. We aimed to describe nutritional status, identify phenotypes of patients prescribed ONS, and evaluate ONS prescription patterns among CKD-ND patients in British Columbia. DESIGN AND METHODS: This observational study assessed adult CKD-ND patients who entered multidisciplinary CKD clinics during 2013-2018 in British Columbia. Descriptive statistics were used to describe baseline nutrition and inflammation parameters among patients prescribed ONS versus patients not prescribed ONS within 1 year of clinic entry. Hierarchical clustering method with consensus clustering was applied to identify phenotypes of patients prescribed ONS. Multivariable logistic regression was used to assess the associations between ONS prescription and health region/dietitian full-time equivalents per 1,000 CKD patients. RESULTS: Of 15,859 CKD-ND patients, 9% of patients entering CKD clinics were prescribed ONS within 1 year of clinic entry, and these patients demonstrated lower baseline estimated glomerular filtration rate, body mass index (BMI), serum albumin, bicarbonate, as well as greater age, serum phosphate, and neutrophil-to-lymphocyte ratio compared with those not receiving ONS. Cluster analysis revealed 5 phenotypes of ONS users: cluster 1 had the highest mean neutrophil-to-lymphocyte ratio; cluster 2 had the lowest mean albumin; cluster 3 had the lowest mean BMI; cluster 4 had the highest mean BMI; and cluster 5 had the lowest mean bicarbonate. There was regional variability in ONS prescription, and an odds ratio for ONS prescription of 1.32 (95% confidence interval 1.16-1.50) for every 1-unit increase in dietitian full-time equivalents per 1,000 patients. Over 3 years of follow-up, overall ONS use among CKD-ND patients remained stable. CONCLUSIONS: This study demonstrates appropriate prescribing of ONS to patients with suboptimal nutritional status, although regional variation exists. Patients receiving ONS represent a heterogenous group with phenotypes reflecting several clinical and biochemical features of the protein-energy wasting syndrome. These findings will assist with updating ONS policy, planning quality improvement initiatives, and informing dietitian resource allocation.

Quantifying Duration of Proteinuria Remission and Association with Clinical Outcome in IgA Nephropathy.

BACKGROUND: On the basis of findings of observational studies and a meta-analysis, proteinuria reduction has been proposed as a surrogate outcome in IgA nephropathy. How long a reduction in proteinuria needs to be maintained to mitigate the long-term risk of disease progression is unknown. METHODS: In this retrospective multiethnic cohort of adult patients with IgA nephropathy, we defined proteinuria remission as a ≥25% reduction in proteinuria from the peak value after biopsy, and an absolute reduction in proteinuria to <1 g/d. The exposure of interest was the total duration of first remission, treated as a time-varying covariate using longitudinal proteinuria measurements. We used time-dependent Cox proportional hazards regression models to quantify the association between the duration of remission and the primary outcome (ESKD or a 50% reduction in eGFR). RESULTS: During a median follow-up of 3.9 years, 274 of 1864 patients (14.7%) experienced the primary outcome. The relationship between duration of proteinuria remission and outcome was nonlinear. Each 3 months in sustained remission up to approximately 4 years was associated with an additional 9% reduction in the risk of disease progression (hazard ratio [HR], 0.91; 95% confidence interval [95% CI], 0.89 to 0.93). Thereafter, each additional 3 months in remission was associated with a smaller, nonsignificant risk reduction (HR, 0.99; 95% CI, 0.96 to 1.03). These findings were robust to multivariable adjustment and consistent across clinical and histologic subgroups. CONCLUSIONS: Our findings support the use of proteinuria as a surrogate outcome in IgA nephropathy, but additionally demonstrate the value of quantifying the duration of proteinuria remission when estimating the risk of hard clinical endpoints.

Followers' unclear demands during the COVID-19 pandemic can undermine leaders' well-being: A moderated mediation model from an entrapment perspective.

Although effective leaders are important for reducing employee stress during the COVID-19, limited studies have examined how follower behaviors can influence leader stress and well-being during the COVID-19. This study draws on defeat-entrapment theory to examine how followers' unclear demands during the COVID-19 consequently impact leaders' psychological states and well-being. We conducted a three-wave time-lagged investigation with a sample of 281 leaders in the United Kingdom and found that followers' unclear demands could generate feelings of entrapment in leaders, leading to decreased levels of well-being outcomes in leaders. Importantly, we found that leaders who have higher levels of leadership responsibility during the COVID-19 are likely to feel trapped by followers' unclear demands. They are also likely to face higher levels of feelings of entrapment and impaired well-being compared with leaders who have lower levels of leadership responsibility. We discuss the implications for theories and practices, as well as directions for future research.

Design, synthesis, and biological activity of phenyl-pyrazole derivatives as BCR-ABL kinase inhibitors.

4-(Pyridin-3-yl)-1H-pyrazol-1-yl-phenyl-3-benzamide derivatives have been proposed as new BCR-ABL tyrosine kinase inhibitors by using combinational strategies of scaffold hopping and conformational constraint. In the present study, a series of 4-(pyridin-3-yl)-1H-pyrazol-1-yl-phenyl-3-benzamide derivatives were synthesized and their activities against BCR-ABL1 kinase in vitro were evaluated by using Kinase-Glo assay. All new compounds showed from moderate to potent activities against wild-type (wt) BCR-ABL1 kinase with an IC50 range from 14.2 to 326.0nM. Among them, seven compounds exhibited BCR-ABL1 kinase inhibitory activities with IC50 values less than 50nM. Compound 7a displayed the most potent inhibitory activity to BCR-ABL kinase (IC50: 14.2nM). Docking simulation was performed for compounds 7a and 7i into the BCR-ABL kinase structure active site to determine the probable binding model. The preliminary structure-activity relationship was discussed. The interesting activities of these compounds may make them promising candidates as therapeutic agents for chronic myelogenous leukemia.

[Detection of Adulteration in Milk Powder with Starch Near Infrared].

Three China trademarks of milk powder called Mengniu, Yili, Wandashan were taken as testing samples. Each of them mixed varied amount of starch in different gradient, which were consisted of 32 adulterated milk powder samples mixed with starch, was taken as standard samples for constructing predicted model. To those 32 samples, the reflecting spectrum characteristics in middle wave of near infrared spectrum with Near Infrared Spectrum Analyzer (Micro NIR 1700) produced by JDSU Ltd. USA were collected for five repeats in five different days. The time span was nearly two months. Firstly, we build the model used the reflecting spectrum characteristics of those samples with biomimetic pattern recognition (BPR) arithmetic to do the qualitative analysis. The analysis included the reliability of testing result and stability of the model. When we took ninety percent as the evaluation threshold of testing result of CAR (Correct Acceptance Rate) and CRR (Correct Rejection Rate), the lowest starch content of adulterate milk powder in all tested samples which the tested result were bigger than that abovementioned threshold was designated CAR threshold (CAR-T) and CRR threshold (CRR-T). CAR means the correct rate of accepting a sample which is belong to itself, CRR means correct rate of refusing to accept a sample which is not belong to itself. The results were shown that, when we constructed a model based on the near infrared spectrum data from each of three China trademark milk powders, respectively, if we constructed a model with infrared spectrum data tested in a same day, both the CAR-T and CRR-T of adulterate starch content of a sample can reach 0.1% in predicting the remainder infrared spectrum data tested within a same day. The three China trademarks of milk powder had the same result. In addition, when we ignored the trademarks, put the spectrum data of adulterate milk powder samples mixed with the same content of starch of three China trademarks milk powder together to construct a model, the CAR-T of mixed starch content of a sample may reach 0.1%, the CRR-T can reach 1%, if the model construction and predicting were performed with near infrared spectrum data tested in a same day. However, the CAR-T can just stably reach up to 5% and the CRR-T have the same result, if the model construction and predicting were crossly performed with mixed near infrared spectrum data tested in different days. Furthermore, the correct recognizing threshold mixed starch of a sample can stably reach up to 1% and the CAR-T can reach 5%, if the model construction was based on near infrared spectrum data combined the previous four days to predict the output of the another day. On the other hand, we also engaged quantitative analysis to the starch content in milk power with two kinds of arithmetic (PLSR, LS-SVR). In contrast with the testing outputs, the reliability of both the CAR-T and CRR-T in qualitative analysis was further validated.

[Carbonic anhydrase III and mRNA expression levels in quadriceps femoris muscle of chronic obstructive pulmonary disease patients].

OBJECTIVE: To explore the expression status of carbonic anhydrase III (CAIII) from quadriceps femoris muscle in two kinds of muscle clinical phenotype (skeletal muscle atrophy group and skeletal muscles non-atrophy group) of chronic obstructive pulmonary disease (COPD). METHODS: Totally 37 inpatients from our hospital, were divided into 11 patients without COPD and 26 patients with COPD, in addition, according to body mass index, fat free mass index and quadriceps cross-section diameter, patients with COPD were divided into 14 skeletal muscles non-atrophy patients (SMNA) and 12 skeletal muscle atrophy patients (SMA). CAIII concentration of femoris quadriceps specimens was quantitatively determined using Western blot methods, CAIIImRNA expression levels of femoris quadriceps specimens were also quantitatively measured using RT-PCR, then compared among the 3 groups. RESULTS: There was significant difference in CAIII quantitative concentration and CAIIImRNA expression level in each group (P < 0.05) , further more, CAIII concentration expression level was significantly higher (P < 0.01) in SMA group (1.260 ± 0.068) than in SMNA group (1.110 ± 0.014) , the latter was significantly higher (P < 0.01) than in the control group (1.000 ± 0.062) . CAIIImRNA expression level was significantly higher (P < 0.01) in SMNA group (2.170 ± 0.412) than in the control group (1.000 ± 0.115) , and was significantly lower than in SMA group (3.770 ± 0.788; P < 0.01). CAIII concentration and CAIIImRNA expression level increased at equal pace in SMNA group and SMA group, however, CAIII quantitative concentration and CAIIImRNA expression level were inconsistent in the two groups. CONCLUSION: The expression status of CAIII in quadriceps femoris muscle was different in two kinds of muscle clinical phenotype of COPD.

FAP Serves as a Prognostic Biomarker in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) poses significant challenges with poor survival rates and limited therapeutic strategies. Our study, using The Cancer Genome Atlas (TCGA) data, assesses cancer-associated fibroblast (CAF) gene signatures' clinical relevance. In our analysis across TCGA tumor types, differential gene expression analysis revealed that fibroblast activation protein (FAP) is upregulated in tumor tissues and associated with poorer survival rates in HNSCC. Furthermore, mechanistic studies employing gene-silencing techniques substantiated that FAP knockout led to a significant decrease in cellular proliferation, invasion, and migration in HNSCC cell lines. Through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, we established that high FAP expression correlates with vital biological processes such as extracellular matrix organization, angiogenesis, and cellular motility. Importantly, FAP was found to regulate these processes by promoting the expression of key proteins involved in epithelial-mesenchymal transition-related pathways. Additionally, our analysis revealed a significant correlation between FAP expression and the expression profiles of immune checkpoint molecules, underscoring its potential role in immune modulation. Collectively, our findings illuminate FAP's pivotal role in HNSCC pathogenesis and its potential as a prognostic biomarker and therapeutic target. This research lays the groundwork for understanding the multifaceted roles and regulatory mechanisms of CAFs in HNSCC, thereby offering valuable perspectives for the development of targeted therapeutic strategies aimed at improving patient outcomes.

Margin quality analysis for wedge resection of lung cancer and construction of a predictive model.

Background: Insufficient pulmonary wedge resection margin is associated with malignant positive margins and high local recurrence risk for lung cancer. This study aimed to identify the risk factors of insufficient or guideline discordant resection margin distance and establish a predictive model to preoperatively estimate the risk of discordant margin for individual patient. Methods: Guideline discordant resection margin was defined as ratio of resection margin distance to tumor size less than one. Patients who had pulmonary malignancies and underwent wedge resection between April 2014 and February 2023 were enrolled and stratified by quality of resection margin. Multivariable logistic regression analysis was employed to identify risk factors of guideline discordant margin and a predictive model was developed. Data from March 2023 to January 2024 were collected for internal validation. Results: A total of 530 patients were included. The incidence of guideline discordant wedge resection margin was 37.2%. Longer tumor's max distance to pleura and larger tumor size were variables associated with increased risk and included in the final model. Preoperative localization and right-side surgery were protective variables in the predictive model. A nomogram was built based on the predictive model. The model showed satisfying predictive performance with a concordance index of 0.720 for the predictive model, and 0.761 for internal validation. The goodness-if-fit tests were non-significant for both model development and internal validation data set. Conclusions: The preoperative predictive model and nomogram show good predictive performance to estimate the risk of guideline discordant wedge resection margin. Individualized surgical plans or preoperative nodule localization can be made for high-risk patients.

Assessing Discharge Communication and Follow-up of Acute Kidney Injury in British Columbia: A Retrospective Chart Review.

Background and objective: Acute kidney injury (AKI) affects up to 20% of hospitalizations and is associated with chronic kidney disease, cardiovascular disease, increased mortality, and increased health care costs. Proper documentation of AKI in discharge summaries is critical for optimal monitoring and treatment of these patients once discharged. Currently, there is limited literature evaluating the quality of discharge communication after AKI. This study aimed to evaluate the accuracy and quality of documentation of episodes of AKI at a tertiary care center in British Columbia, Canada. Methods design setting patients and measurements: This was a retrospective chart review study of adult patients who experienced AKI during hospital admission between January 1, 2018, and December 31, 2018. Laboratory data were used to identify all admissions to the cardiac and general medicine ward complicated by AKI defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. A random sample of 300 AKI admissions stratified by AKI severity (eg, stages 1, 2, and 3) were identified for chart review. Patients were excluded if they required ongoing renal replacement therapy after admission, had a history of kidney transplant, died during their admission, or did not have a discharge summary available. Discharge summaries were reviewed for documentation of the following: presence of AKI, severity of AKI, AKI status at discharge, practitioner and laboratory follow-up plans, and medication changes. Results: A total of 1076 patients with 1237 AKI admissions were identified. Of the 300 patients selected for discharge summary review, 38 met exclusion criteria. In addition, AKI was documented in 140 (53%) discharge summaries and was more likely to be documented in more severe AKI: stage 1, 38%; stage 2, 51%; and stage 3, 75%. Of those with their AKI documented, 94 (67%) documented AKI severity, and 116 (83%) mentioned the AKI status or trajectory at the time of discharge. A total of 239 (91%) of discharge summaries mentioned a follow-up plan with a practitioner, but only 23 (10%) had documented follow-up with nephrology. Patients with their AKI documented were more likely to have nephrology follow-up than those without AKI documented (17% vs 1%). Regarding laboratory investigations, 92 (35%) of the summaries had documented recommendations. In summaries that included medications typically held during AKI, only about half made specific reference to those medications being held, adjusted, or documented a post-discharge plan for that medication. For those with nonsteroidal anti-inflammatory drugs (NSAIDs) listing, 64% of discharge summaries mentioned holding, and 9% mentioned a discharge plan. For those with angiotensin converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARB) listing, 38% mentioned holding these medications, and 46% mentioned a discharge plan. In summaries with diuretics listed, 35% mentioned holding, and 51% included a discharge plan. Conclusions and limitations: We found suboptimal quality and completeness of discharge reporting in patients hospitalized with AKI. This may contribute to inadequate follow-up and post-hospitalization care for this patient population. Strategies are required for increasing the presence and quality of AKI reporting in discharge summaries. Limitations include our definition of AKI based on lab criteria, which may have missed some of the injuries that met the criteria based on urine output. Another limitation is that our definition of AKI based on the highest and lowest creatinine during admission may have led to some overclassification. In addition, without outpatient laboratories, it is possible that we have not captured the true baseline creatinine in some patients.

Contexte et objectif: L'insuffisance rénale aiguë (IRA) complique jusqu'à 20 % des hospitalisations; elle est associée à l'insuffisance rénale chronique, aux maladies cardiovasculaires, à une mortalité accrue et à une augmentation des coûts de santé. La documentation appropriée de l'IRA dans les résumés de départ est essentielle pour optimiser la surveillance et le traitement des patients après leur sortie de l'hôpital. Il existe peu de littérature évaluant la qualité de la documentation de l'IRA dans les résumés de départ. Cette étude visait à évaluer l'exactitude et la qualité de la documentation des épisodes d'IRA dans un center de soins tertiaires de la Colombie-Britannique (Canada). Méthodologie conception et cadre de l'étude sujets et mesures: Il s'agit d'une étude rétrospective des dossiers de patients adultes ayant présenté une IRA au cours de leur admission à l'hôpital entre le 1er janvier 2018 et le 31 décembre 2018. Les données de laboratoire ont été utilisées pour répertorier toutes les admissions compliquées par une IRA (définie par les critères KDIGO) dans les services de cardiologie et de médecine générale. Un échantillon aléatoire de 300 admissions avec IRA stratifiée selon sa gravité (p. ex., stade, 1, 2 et 3) a été constitué pour l'examen des dossiers. Ont été exclus les patients qui avaient eu besoin d'une thérapie de suppléance rénale continue après leur admission, ceux qui avaient des antécédents de transplantation rénale, ceux qui étaient décédés pendant leur admission et ceux pour qui aucun résumé de départ n'était disponible. Les résumés de départ ont été examinés à la recherche d'une mention des éléments suivants : présence d'une IRA, gravité de l'IRA, statut de l'IRA à la sortie, plans de suivi pour les tests de laboratoire et suivi avec un praticien, changements dans la médication. Résultats: En tout, 1 076 patients avec un total de 1 237 admissions avec IRA ont été identifiés. Parmi les 300 patients sélectionnés pour l'examen du résumé de départ, 38 répondaient aux critères d'exclusion. L'IRA avait été documentée dans 140 (53 %) des cas et plus elle était grave, plus elle était susceptible d'être documentée (stade 1 = 38 %; stade 2 = 51 %; stade 3 = 75 %). Parmi ceux où l'IRA était documentée, 94 (67 %) mentionnaient sa gravité et 116 (83 %) mentionnaient son statut ou sa trajectoire à la sortie du patient. Un plan de suivi avec le praticien était mentionné dans 239 (91 %) des résumés de départ, mais seuls 23 (10 %) mentionnaient un suivi en néphrologie. Les patients dont l'IRA était documentée étaient plus susceptibles de faire l'objet d'un suivi en néphrologie que ceux sans mention de l'IRA (17 % contre 1 %). En ce qui concerne les plans de suivi de laboratoire, 92 (35 %) des résumés contenaient des recommandations. Dans les résumés qui mentionnaient des médicaments normalement maintenus pendant un épisode d'IRA, seule la moitié environ faisait spécifiquement référence à ces médicaments comme ayant été cessés, ajustés ou documentés dans un plan post-sortie. Dans les résumés de départ qui listaient des AINS, 64 % mentionnaient qu'ils avaient été cessés temporairement et 9 % comprenaient un plan au congé de l'hôpital. Dans les résumés de départ qui listaient des IECA/ARA, 38 % mentionnaient que ces médicaments avaient été cessés temporairement et 46 % comprenaient un plan au congé de l'hôpital. Dans les résumés qui listaient des diurétiques, 35 % mentionnaient qu'ils avaient été cessés temporairement et 51 % comprenaient un plan au congé de l'hôpital. Limites et conclusion: Nous avons constaté que la qualité et l'exhaustivité des résumés de départ étaient sous-optimales chez les patients hospitalisés ayant vécu un épisode d'IRA. Cette situation peut contribuer à l'inadéquation du suivi et des soins post-hospitalization pour cette population de patients. Des stratégies sont nécessaires pour accroître la documentation d'un épisode d'IRA dans les résumés de départ et augmenter la qualité de sa communication. Les résultats de cette étude sont notamment limités par notre définition de l'IRA fondée sur des critères de laboratoire qui pourraient avoir manqué des patients répondant aux critères fondés sur la production d'urine. Notre définition de l'IRA fondée sur le taux de créatinine le plus élevée et le plus faible pendant l'admission pourrait également avoir conduit à un surdiagnostic. En outre, sans les résultats de laboratoires externes, il est possible que nous n'ayons pas saisi la mesure initiale réelle de la créatinine chez certains patients.

Oral Nutritional Supplement Prescription and Patient-Reported Symptom Burden Among Patients With Late-Stage Non-Dialysis Chronic Kidney Disease.

Background: Malnutrition and protein-energy wasting (PEW) are nutritional complications of advanced chronic kidney disease (CKD) that contribute to morbidity, mortality, and decreased quality of life. No previous studies have assessed the effect of oral nutritional supplements (ONSs) on patient-reported symptom burden among patients with non-dialysis CKD (CKD-ND) who have or are at risk of malnutrition/PEW. Objective: The objective of this study was (1) to quantify the associations between baseline nutritional parameters and patient-reported symptom scores for wellbeing, tiredness, nausea, and appetite and (2) to compare the change in symptom scores among patients prescribed ONS with patients who did not receive ONS in a propensity-score-matched analysis. Design: This study conducted observational cohort analysis using provincial registry data. Setting: This study was done in multidisciplinary CKD clinics in British Columbia. Patients: Adult patients >18 years of age with CKD-ND entering multidisciplinary CKD clinics between January 1, 2010-July 31, 2019 who had at least 2 Edmonton Symptom Assessment System Revised: Renal (ESASr:Renal) assessments. Measurements: The measurements include nutrition-related parameters such as body mass index (BMI), serum albumin, serum phosphate, serum bicarbonate, neutrophil-to-lymphocyte ratio (NLR), and ESASr:Renal scores (overall and subscores for wellbeing, tiredness, nausea, and appetite). Methods: Multivariable linear regression was applied to assess associations between nutritional parameters and ESASr:Renal scores. Propensity-score matching using the greedy method was used to match patients prescribed ONS with those not prescribed ONS using multiple demographic, comorbidity, health care utilization, and temporal factors. Linear regression was used to assess the association between first ONS prescription and change in ESASr:Renal overall score and subscores for wellbeing, tiredness, nausea, and appetite. Results: Of total, 2076 patients were included. Higher baseline serum albumin was associated with lower overall ESASr:Renal score (-0.20, 95% confidence interval [CI] = -0.40 to -0.01 per 1 g/L increase in albumin), lower subscores for tiredness (-0.04, 95% CI = -0.07 to -0.01), nausea (-0.03, 95% CI = -0.04 to -0.01), and appetite (-0.03, 95% CI = -0.06 to -0.01). Higher BMI was associated with higher overall ESASr:Renal score (0.32, 95% CI = 0.16 to 0.48 per 1 kg/m2 increase in BMI), higher symptom subscores for wellbeing (0.02, 95% CI = 0.00 to 0.04) and tiredness (0.05, 95% CI = 0.02 to 0.07). Higher baseline NLR was associated with higher overall score (0.21, 95% CI = 0.03 to 0.39 per 1 unit increase in NLR), higher symptom subscores for wellbeing (0.03, 95% CI = 0.01 to 0.05) and nausea (0.03, 95% CI = 0.02 to 0.05). In the propensity-score-matched analysis, there were no statistically significant associations between ONS prescription and change in overall ESASr:Renal (beta coefficient for change in ESASr:Renal = 0.17, 95% CI = -2.64 to 2.99) or for subscores for appetite, tiredness, nausea, and wellbeing. Limitations: Possible residual confounding. The ESASr:Renal assessments were obtained routinely only in patients with G5 CKD-ND and/or experiencing significant CKD-related symptoms. Conclusions: This exploratory observational analysis of patients with advanced non-dialysis CKD demonstrated BMI, serum albumin, and NLR were modestly associated with patient-reported symptoms, but we did not observe an association between ONS use and change in ESASr:Renal scores.

Contexte: La malnutrition et la dénutrition protéino-énergétique (DPÉ) sont des complications nutritionnelles de l'insuffisance rénale chronique (IRC) de stade avancé qui contribuent à la morbidité, à la mortalité et à la diminution de la qualité de vie associées à la maladie. Aucune étude n'a évalué l'effet des suppléments nutritionnels administrés par voie orale (SNO) sur le fardeau des symptômes autodéclarés par les patients non dialysés atteints d'IRC (IRC-ND) et souffrant de malnutrition/DPÉ ou risquant d'en souffrir. Objectifs: (1) Quantifier les associations entre les paramètres nutritionnels initiaux et les scores des symptômes autodéclarés en lien avec le bien-être, la fatigue, les nausées et l'appétit. (2) Comparer, dans une analyse des scores de propension appariés, la variation des scores associés aux symptômes des patients ayant reçu une ordonnance de SNO par rapport aux patients n'en ayant pas reçu. Conception: Analyse de cohorte observationnelle à partir des données du registre provincial. Cadre: Cliniques multidisciplinaires d'IRC en Colombie-Britannique. Sujets: Des patients adultes atteints d'IRC-ND admis entre le 1er janvier 2010 et le 31 juillet 2019 dans des cliniques multidisciplinaires d'IRC avec au moins deux évaluations selon l'Échelle d'évaluation Edmonton pour l'insuffisance rénale (ESASr:renal­Edmonton Symptom Assessment System Revised: Renal). Mesures: Les paramètres liés à la nutrition: indice de masse corporelle (IMC), albumine sérique, phosphate sérique, bicarbonate sérique, rapport neutrophiles/lymphocytes (RNL), ainsi que les scores ESASr:renal (scores globaux et scores secondaires pour le bien-être, la fatigue, les nausées et l'appétit). Méthodologie: La régression linéaire multivariable a servi à évaluer les associations entre les paramètres nutritionnels et les scores ESASr:renal. Une correspondance des scores de propension par la méthode Greedy a été utilisée pour apparier des patients ayant reçu ordonnance de SNO avec des patients n'en ayant pas reçu selon plusieurs facteurs démographiques, les comorbidités, l'utilisation des soins de santé et des facteurs temporels. La régression linéaire a servi à évaluer l'association entre la première ordonnance de SNO et la variation des scores globaux et des scores secondaires de l'ESASr:renal pour le bien-être, la fatigue, les nausées et l'appétit. Résultats: Au total, 2 076 patients ont été inclus à l'étude. Un taux d'albumine sérique plus élevé à l'inclusion était associé à un score ESASr:rénal global plus faible (-0,20 [IC 95 %: -0,40 à -0,01 pour 1 g/L d'augmentation de l'albumine]) et à des scores secondaires plus faibles pour la fatigue (-0,04 [IC 95 %: -0,07 à -0,01]), les nausées (-0,03 [IC 95 %: -0,04 à 0,01]) et l'appétit (0,03 [IC 95 %: -0,06 à -0,01]). Un IMC plus élevé était associé à un score ESASr:renal global plus élevé (0,32 [IC 95 %: 0,16 à 0,48 par augmentation de 1 kg/m2 de l'IMC]), des scores secondaires de symptômes plus élevés pour le bien-être (0,02 [IC 95 %: 0,00 à 0,04]) et la fatigue (0,05 [IC 95 %: 0,02 à 0,07]). Un RNL initial plus élevé était associé à un score ESASr:renal global plus élevé (0,21 [IC 95 %: 0,03 à 0,39 par unité d'augmentation du RNL]), des scores secondaires de symptômes plus élevés pour le bien-être (0,03 [IC 95 %: 0,01 à 0,05]) et les nausées (0,03 [IC 95 %: 0,02 à 0,05]). Dans l'analyse des scores de propension appariés, aucune association statistiquement significative n'a été observée entre une ordonnance de SNO et une variation significative dans les scores globaux de l'ESASr:renal (coefficient bêta de variation de l'ESASr:rénal: 0,17 [IC 95 %: -2,64 ­ à 2,99]) ou les scores secondaires pour l'appétit, la fatigue, les nausées et le bien-être. Limites: Possibilité de facteurs de confusion résiduels. Les évaluations ESASr:renal ont été effectuées de routine uniquement pour les patients atteints d'IRC-ND G5 et/ou présentant des symptômes importants liés à l'IRC. Conclusion: Cette analyse observationnelle exploratoire portant sur des patients atteints d'IRC avancée non dialysés a démontré que l'IMC, l'albumine sérique et le RNL étaient associés de façon modeste aux symptômes autodéclarés. Toutefois, aucune association n'a été observée entre une ordonnance de SNO et une variation des scores ESASr:renal.

Prophylactic hyperthermic intraperitoneal chemotherapy in T4 colorectal cancer: Can it improve the oncologic prognosis? - A propensity score matching study.

BACKGROUND: Some studies show that cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) may improve overall survival and is a possible curative treatment for selected colorectal cancer (CRC) patients with restricted peritoneal metastasis (PM). The value of HIPEC in preventing PM of CRC is still controversial. MATERIALS AND METHODS: In this retrospective propensity score matching (PSM) cohort study, all patients with cT4N0-2M0 undergoing treatment at a single institution in China (2014-2018) were reviewed. The 3-year disease-free survival (DFS) was set as the primary outcome, and the 3-year PM rate was also analyzed. RESULTS: 220 patients were included in this study for analysis. After 1:3 PSM: HIPEC (n = 45) and No HIPEC (n = 135). Through analysis, it was found that prophylactic HIPEC correlated to better DFS [hazard ratio (HR) 0.43, 95 % confidence interval (CI) 0.19-0.95; p = 0.037], and N2 stage correlated to worse DFS [HR 1.97, 95 % CI 1.09-3.56; p = 0.025]. For laparoscopic surgery subgroup analyses, 3-year PM rate of patients with laparoscopic surgery was 13.8 % in No HIPEC group, and 2.6 % in HIPEC group (p = 0.070). Besides, no post-operative death occurred, the anastomotic leakage rate was 2.2 % in HIPEC group and 0.7 % in the control group (p = 0.439). CONCLUSIONS: Prophylactic HIPEC may improve the prognosis in patients with cT4N0-1M0 CRC, but not in cT4N2M0 CRC, and it does not significantly increase surgery-related complications. Laparoscopic surgery followed by HIPEC for T4 stage CRC may not increase risk of PM.

Abnormal Decrease of Macrophage ALKBH5 Expression Causes Abnormal Polarization and Inhibits Osteoblast Differentiation.

Peri-implant tissue inflammation is an inflammatory injury that occurs in the soft and hard tissues surrounding the implant and is the main cause of short- or long-term failure of implant prosthetic restorations, which is compounded by bone loss and bone destruction in the alveolar bone of diabetes patients with peri-implantitis. However, the mechanisms underlying the persistence of diabetic peri-implantitis, as well as the essential connections and key molecules that regulate its start and progression, remain unknown. In this study, we discovered that M1 macrophage polarization was abnormally enhanced in diabetic peri-implantitis and influenced the osteogenic differentiation of mesenchymal stem cells. RNA sequencing revealed that ALKBH5 expression was abnormally reduced in diabetic peri-implantitis. Further mechanism study showed that ALKBH5 and its mediated m6A can influence osteogenic differentiation, which in turn influences the persistence of diabetic peri-implantitis. Our findings present a new mechanism for the suppression of osteoblast development in diabetic peri-implantitis and a new treatment strategy to promote anabolism by inhibiting ALKBH5.

Minimum chi-square method for estimating population size in capture-recapture experiments.

Closed population capture-recapture estimation of population size is difficult under heterogeneous capture probabilities. We introduce the minimum chi-square method which can handle multi-occasion capture-recapture data. It complements likelihood methods with elements that can lead to confidence intervals and assessment of goodness-of-fit. We conduct a comprehensive study on the minimum chi-square method for estimating the size of a closed population using multiple-occasion capture-recapture data under heterogeneous capture probability. We also develop two different bootstrap techniques that can be combined with any underlying estimator, be it the minimum chi-square estimator or a likelihood estimator, to perform useful inference for estimating population size. We present a simulation study on the minimum chi-square method and apply it to analyze white stork multiple capture-recapture data. Under certain conditions, the chi-square method outperforms the likelihood based methods.