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.

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.

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.

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.

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.

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.

Augmented reality navigation-guided intraoperative pulmonary nodule localization: a pilot study.

Background: With the increasing number of small pulmonary nodules detected, effective localization of pulmonary nodules has become an issue. The goal of this study is to determine the safety and feasibility of a newly developed augmented reality navigation technology for intraoperative localization of small pulmonary nodules. Methods: We conducted a prospective single-center feasibility study of a novel augmented reality navigation system and lung localization (LungBrella) marker on ten patients between July and October 2020. For augmented reality navigation-guided localization, a preoperative chest computed tomography scan was performed to generate 3-dimensional (3D) virtual images and individualized localization plan, which were uploaded into Hololens (a head-mounted augmented reality device). Under the guidance of established procedure plan displayed by HoloLens, localization marker was placed in operating room. Segmentectomy or wedge resection was subsequently performed. The primary endpoint was the localization procedure success rate, and the secondary endpoints were localization time, operation time, and complications. Results: Localization was successful in seven of the ten procedures. Due to different reasons, failures were noted in three cases, after which immediate adjustments were made. In the successful cases, the LungBrella marker was positioned at a median of 5.8 mm (range, 0-10 mm) from the edge of the nodule. Median localization time was 9.4 min (range, 5-19 min), and median operation time was 172.9 min (range, 105-200 min). There were no complications during the entire process. Conclusions: This exploratory study suggests that augmented reality navigation-guided pulmonary nodule localization is a safe and feasible technique (ClinicalTrials.gov identifier, NCT04211051).

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.

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.

An Inflammatory Checkpoint Generated by IL1RN Splicing Offers Therapeutic Opportunity for KRAS-Mutant Intrahepatic Cholangiocarcinoma.

KRAS mutations are causally linked to protumor inflammation and are identified as driving factors in tumorigenesis. Here, using multiomics data gathered from a large set of patients, we showed that KRAS mutation was associated with a specific landscape of alternative mRNA splicing that connected to myeloid inflammation in intrahepatic cholangiocarcinoma (iCCA). Then, we identified a negative feedback mechanism in which the upregulation of interleukin 1 receptor antagonist (IL1RN)-201/203 due to alternative splicing confers vital anti-inflammatory effects in KRAS-mutant iCCA. In KRAS-mutant iCCA mice, both IL1RN-201/203 upregulation and anakinra treatment ignited a significant antitumor immune response by altering neutrophil recruitment and phenotypes. Furthermore, anakinra treatment synergistically enhanced anti-PD-1 therapy to activate intratumoral GZMB+ CD8+ T cells in KRAS-mutant iCCA mice. Clinically, we found that high IL1RN-201/203 levels in patients with KRAS-mutant iCCA were significantly associated with superior response to anti-PD-1 immunotherapy. SIGNIFICANCE: This work describes a novel inflammatory checkpoint mediated by IL1RN alternative splicing variants that may serve as a promising basis to develop therapeutic options for KRAS-mutant iCCA and other cancers. This article is featured in Selected Articles from This Issue, p. 2109.

COVID-19 Vaccine Effectiveness Among Patients With Maintenance Dialysis; Observations From Population Level Cohort Studies in 2 Large Canadian Provinces.

Background: It was unknown if the effectiveness of COVID-19 vaccines could vary between regions. Objective: To explore key differences in COVID-19 pandemics in British Columbia (BC) and Ontario (ON) and to investigate if the vaccine effectiveness (VE) among maintenance dialysis population could vary between these 2 provinces. Study Design: Retrospective cohort. Setting and Patients: This retrospective cohort study included patients from population-level registry in BC who were on maintenance dialysis from December 14, 2020, to December 31, 2021. The COVID-19 VE among BC patients were compared to the previously published VE among similar patient population in ON. Two-sample t-test for unpaired data were used to investigate if the VE estimates from BC and ON were statistically significantly different. Exposure: Exposure to COVID-19 vaccines (BNT162b2, ChAdOx1nCoV-19, mRNA-1273) was modeled in a time-dependent fashion. Outcome: Reverse transcription polymerase chain reaction (RT-PCR) confirmed COVID-19 infection and related severe outcome defined by hospitalization or death. Analytical Approach: Time-dependent Cox regression analysis. Results: This study using BC data included 4284 patients. Median age was 70 years and 61% was male. Median follow-up time was 382 days. 164 patients developed COVID-19 infection. The ON study by Oliver et al included 13 759 patients with a mean age of 68 years. 61% of the study sample was male. Median follow-up time for patients in the ON study was 102 days. A total of 663 patients developed COVID-19 infection. During the overlapped study periods, BC had 1 pandemic wave compared to 2 in Ontario with substantially higher infection rates. Vaccination timing and roll out among the study population were substantially different. Median time between first and second dose was 77 days (interquartile range [IQR] 66-91) in BC compared to 39 days (IQR = 28-56) in Ontario. Distribution of COVID-19 variants during the study period appeared to be similar. In BC, compared to pre-vaccination person-time, risk of developing COVID-19 infection was 64% (aHR [95% CI] 0.36 [0.21, 0.63]), 80% (0.20 [0.12, 0.35]) and 87% (0.13 [0.06, 0.29]) less when exposed to 1 dose, 2 doses, and 3 doses, respectively. In contrast, risk reduction among Ontario patients was 41% (0.59 [0.46, 0.76]) and 69% (0.31 [0.22, 0.42]) for 1 dose and 2 doses, respectively (patients did not receive the third dose by study end date of June 30, 2021). VE against COVID-19 infection in BC and ON was not statistically significantly different, the P values for exposure to 1 dose and 2 doses comparisons were 0.103 and 0.163, respectively. Similarly, in BC, risk of developing COVID-19-related hospitalization or death were 54% (0.46 [0.24, 0.90]), 75% (0.25 [0.13, 0.48]) and 86% (0.14 [0.06, 0.34]) less for 1 dose, 2 doses, and 3 doses, respectively. Interestingly, exposure to second dose appeared to provide better protection against severe outcomes in Ontario versus BC, risk reduction was 83% (aHR = 0.17, 95% CI [0.10, 0.30]) and 75% (aHR = 0.25, 95% CI [0.13, 0.48]), respectively. However, the adjusted hazard ratios were not statistically significantly different between BC and ON, the P values were 0.676 and 0.369 for exposure to 1 dose and 2 doses, respectively. Limitations: Infection rate, variant distribution, and vaccination strategies were compared using publicly available data. VE estimates were compared from 2 independent cohort studies from 2 provinces without patient-level data sharing. Conclusions: Health Canada approved COVID-19 vaccines were highly effective among patients with maintenance dialysis from BC and ON. Although there appeared to be between province differences in pandemic waves and vaccination strategies, the VE against COVID-19 infection as well as related severe outcome appeared to be not statistically significantly different. A nationally representative VE could be estimated using pooled data from multiple regions.

Contexte: On ignore si l'efficacité des vaccins contre la COVID-19 varie d'une région à l'autre. Objectif: Examiner les principales différences entre les infections à la COVID-19 en Colombie-Britannique (C.-B.) et en Ontario et déterminer si l'efficacité des vaccins (EV) varie entre ces deux provinces dans la population des personnes sous dialyze d'entretien. Type d'étude: Étude de cohorte rétrospective. Sujets et cadre de l'étude: Cette étude de cohorte rétrospective porte sur des patients issus du registre de la population de Britanno-Colombiens sous dialyze d'entretien entre le 14 décembre 2020 et le 31 décembre 2021. L'EV contre la COVID-19 chez les patients de la C.-B. a été comparée à l'EV précédemment publiée pour une population de patients similaires en Ontario. Un test t à deux échantillons de données non appariées a été utilisé pour déterminer si les estimations de l'EV en C.-B. et en Ontario étaient statistiquement différentes. Exposition: L'exposition aux vaccins contre la COVID-19 (BNT162b2, ChAdOx1nCoV-19, mRNA-1273) a été modélisée en fonction du temps. Résultats: La RT-PCR a confirmé l'infection à la COVID-19 et les résultats graves liés à la maladie ont été définis par une hospitalization ou le décès. Approche analytique: Analyze par régression Cox dépendante du temps. Résultats: L'étude en cours utilisant les données de la C.-B. incluait 4 284 patients. L'âge médian était de 70 ans et 61 % étaient des hommes. Le temps médian de suivi était de 382 jours. De ces patients, 164 avaient contracté la COVID-19. L'étude de l'Ontario (Oliver et coll.) porte sur 13 759 patients (61 % d'hommes) dont la moyenne d'âge était de 68 ans. Le temps médian de suivi pour les patients de l'étude ontarienne était de 102 jours. Un total de 663 patients avait contracté la COVID-19. Au cours des périodes d'étude qui se sont chevauchées, la Colombie-Britannique a connu une vague pandémique, contre deux en Ontario, avec des taux d'infection beaucoup plus élevés. Le calendrier et le déploiement de la vaccination parmi la population étudiée étaient sensiblement différents. Le temps médian entre la première et la deuxième dose de vaccin était de 77 jours en C.-B. (ÉIQ: 66-91) et de 39 jours en Ontario (ÉIQ: 28-56). La répartition des différents variants du virus de la COVID-19 au cours de la période d'étude semble similaire. En C.-B., comparativement au temps-personne avant la vaccination, le risque de contracter la COVID-19 était réduit de 64 % (risque relatif corrigé [IC 95 %]: 0,36 [0,21-0,63]) après une dose, de 80 % (RRc: 0,20 (0,12-0,35)) après deux doses et de 87 % (RRc: 0,13 (0,06-0,29)) après 3 doses. En Ontario, la réduction de ce même risque était de 41 % (RRc: 0,59 (0,46-0,76)) après une dose et de 69 % (RRc: 0,31 (0,22-0,42)) après deux doses (les patients n'avaient pas reçu de troisième dose le 30 juin 2021, la date de fin de l'étude). L'EV contre une infection à la COVID-19 n'était pas statistiquement différente entre les deux provinces, avec des valeurs p pour les comparaisons d'exposition respectivement de 0,103 et de 0,163 pour la 1re et 2e dose. De même, en Colombie-Britannique, le risque d'être hospitalisé ou de décéder en raison d'une infection à la COVID-19 était réduit de 54 % (RRc: 0,46 (0,24-0,90)) après une dose, de 75 % (RRc: 0,25 (0,13-0,48)) après deux doses et de 86 % (RRc: 0,14 [0,06-0,34] après trois doses. Il est intéressant de noter que la deuxième dose semblait offrir une meilleure protection contre les complications graves aux patients de l'Ontario par rapport à ceux de la C.-B., avec une réduction du risque de 83 % [RRc: 0,17 (0,10-0,30)] et de 75 % [RRc: 0,25 (0,13-0,48)], respectivement. Les valeurs du risque relatif corrigé n'étaient cependant pas statistiquement différentes, leurs valeurs p s'établissant à 0,676 après la 1re dose et à 0,369 après la 2e. Limites: Le taux d'infection, la distribution des variants et les stratégies de vaccination ont été comparés à partir des données disponibles au public. Les estimations de l'EV ont été comparées à partir de deux études de cohortes indépendantes dans deux provinces, sans partage de données au niveau des patients. Conclusion: Les vaccins contre la COVID-19 approuvés par Santé Canada ont été très efficaces chez les patients sous dialyze d'entretien en Colombie-Britannique et en Ontario. Bien qu'il y ait des différences entre les provinces en ce qui concerne les vagues de pandémie et les stratégies de vaccination, l'efficacité des vaccins contre une infection à la COVID-19 et ses complications graves ne semble pas significativement différente. Une estimation représentative à l'échelle nationale de l'efficacité des vaccins pourrait être calculée à partir de données regroupées provenant de plusieurs régions.

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.

Health-Related Quality of Life Following Robotic-Assisted or Video-Assisted Lobectomy in Patients With Non-Small Cell Lung Cancer: Results From the RVlob Randomized Clinical Trial.

BACKGROUND: Robot-assisted lobectomy (RAL) is increasingly used as an alternative to video-assisted lobectomy (VAL) for resectable non-small cell lung cancer (NSCLC). However, there is little evidence of any difference in postoperative health-related quality of life (HRQoL) between these two approaches. RESEARCH QUESTION: Is RAL superior to VAL in improving quality of life in patients with resectable NSCLC? STUDY DESIGN AND METHODS: We performed a single-center, open-label randomized clinical trial from May 2017 to May 2020 with 320 enrolled patients undergoing RAL or VAL for resectable NSCLC (RVlob trial; NCT03134534). Postoperative pain was evaluated by visual analog score or numeric rating score on postoperative day 1 and at weeks 4, 24, and 48. The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30), EORTC Quality of Life Questionnaire in Lung Cancer (QLQ-LC13), and the European Quality of Life 5 Dimensions (EQ-5D) questionnaire were also administered at weeks 4, 24, and 48 after surgery. RESULTS: One hundred and fifty-seven patients underwent RAL and 163 underwent VAL. The mean pain score of patients after RAL was significantly lower at week 4 (2.097 ± 0.111 vs 2.431 ± 0.108; P = .032). QLQ-C30 and QLQ-LC13 summary scores (P > .05) were similar for both RAL and VAL during the first 48 weeks of follow-up. HRQoL scores assessed with the EQ-5D questionnaire were also comparable between the two groups (P > .05) during the whole study period. INTERPRETATION: Both RAL and VAL showed satisfactory and comparable HRQoL and postoperative pain up to 48 weeks after surgery, despite some minor statistical differences at week 4. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03134534; URL: www. CLINICALTRIALS: gov.

Measurement of buccolingual inclination of posterior teeth and the curve of Wilson in patients with different sagittal skeletal patterns using cone-beam computed tomography / 口腔疾病防治

Objective@# To study the buccolingual inclination of posterior premolars and molars and the curve of Wilson in patients with different sagittal skeletal patterns, to explore the compensation mechanism of horizontal inclination of posterior teeth in patients with different sagittal skeletal patterns and to provide a reference for the control of posterior tooth inclination in the treatment of bone malocclusion.@*Methods@#This study was reviewed and approved by the Ethics Committee, and informed consent was obtained from the patients. Ninety CBCT scans of adults and ninety scans of adolescents before orthodontic treatment were evaluated in this cross-sectional study. There were 30 skeletal Class I, Class Ⅱ, and Class Ⅲ patients in the adult group and adolescent group. The inclination angles of posterior teeth and the curve of Wilson of first and second molars were measured, and data were analyzed between adolescents and adults with different sagittal skeletal patterns.@*Results @#Compared with skeletal Class Ⅰ adult patients, the upper posterior molar inclination of skeletal Class Ⅱ patients was significantly lower, and the lower posterior molar inclination was significantly higher. Compared with skeletal ClassⅠ adult patients, the upper posterior molar inclination of skeletal Class Ⅲ adult patients was higher, and the lower posterior molar inclination was significantly lower. The Wilson curve of the second molar in skeletal Class Ⅱ adult patients was significantly higher than that in the other groups. Compared with skeletal ClassⅠ adolescent patients, skeletal Class Ⅲ adolescent patients had a significantly higher upper posterior molar inclination; however, no difference was found between the inclination of the posterior teeth between skeletal Class Ⅰ, Class Ⅱ and Class Ⅲ adolescent patients. Comparing adolescent and adult samples, in skeletal Class Ⅱ patients, adults showed more lingual inclination than adolescents in the upper posterior teeth and less lingual inclination in the lower posterior teeth except for the mandibular first molar. Comparing adolescent and adult samples, in skeletal Class Ⅲ patients, adults showed more lingual inclination than adolescents in the lower posterior teeth except for the mandibular second molars and showed no difference in the upper posterior teeth.@*Conclusions@#The inclination of the posterior teeth and the curve of Wilson show significant differences between the three sagittal skeletal patterns. Compared with those of skeletal Class Ⅰ patients, the posterior teeth of skeletal Class Ⅱ patients show more lingual inclination in the upper arch and less lingual inclination in the lower arch. Meanwhile, posterior teeth of skeletal Class Ⅲ patients show more lingual inclination in the lower arch and maintain the inclination in the upper arch.

Identification of a Prognostic Pyroptostic-Related Model for Head and Neck Squamous Cell Carcinoma Based on LASSO-Cox Regression Analysis.

Pyroptosis is associated with the biological behavior of the tumor and with tumor immunity. We investigated the effect of pyroptosis on the tumor microenvironment and tumor immunity in head and neck squamous cell carcinoma (HNSCC). RNA sequencing data and clinical information of HNSCC were downloaded from TCGA. Differentially expressed pyroptosis-related genes in HNSCC were identified between HNSCC and normal tissue. Pyroptosis-related classification of HNSCC was conducted based on consensus clustering analysis. LASSO-Cox regression analysis was used to construct a prognostic risk model-based pyroptosis-related gene. Evaluation of the immune microenvironment was conducted in prognostic risk signature based on pyroptosis-related genes. Total 22 differentially expressed pyroptosis-related genes were identified in HNSCC. Six prognostic-related genes were included to construct a LASSO regression model with a prognostic risk score = (0.133 ∗ GSDME (DFNA5) + 0.084 ∗ NOD1 + 0.039 ∗ IL6 + 0.003 ∗ IL1B + 0.084 ∗ CASP3 + 0.028 ∗ NLRP2). Higher fraction of resting memory CD4+ T cells and macrophages M1 was infiltrated in the high-risk group compared with the low-risk group in HNSCC. Furthermore, the PI3K-Akt signaling pathway and the IL-17 signaling pathways were identified to be involved in the development of high-risk HNSCC. Our study constructed a prognostic risk signature based on pyroptosis-related genes, which emphasizes the critical importance of pyroptosis in HNSCC and provided a novel perspective of HNSCC therapy.

Findings of Sodium-Glucose Cotransporter-2 Inhibitor Kidney Outcome Trials Applied to a Canadian Chronic Kidney Disease Population: A Retrospective Cohort Study.

Background: The canagliflozin and renal endpoints in diabetes with established nephropathy clinical evaluation (CREDENCE) and dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trials have demonstrated significant kidney benefits with sodium-glucose cotransporter-2 (SGLT2) inhibitors. SGLT2 inhibitors are now standard of care for patients with diabetic kidney disease and have also been shown to be effective in those with albuminuric CKD with or without diabetes. Objective: We sought to determine how many patients in nephrology care in British Columbia, Canada, would have been eligible for those trials, to compare rates of outcomes, and to estimate cost avoidance arising from widespread use of SGLT2 inhibitors in this cohort. Study design: Retrospective cohort study. Setting: British Columbia, Canada. Participants: CKD patients followed in the Kidney Care Clinics in British Columbia. Measurements: We compared the outcomes of kidney failure, sustained estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2, dialysis, transplant, death from any cause, and doubling of serum creatinine. We also compared the composite outcome of kidney failure and doubling of serum creatinine. Methods: The cohort was derived using a provincial database by combining the inclusion criteria of CREDENCE and DAPA-CKD trials. We included adult patients aged ≥18 years, urine albumin to creatinine ratio (UACR) ≥20 mg/mmol, and eGFR between 25 and 90 mL/min/1.73 m2, between April 1, 2014 and March 31, 2017. The primary outcome was compared with the outcomes experienced in the placebo arms of CREDENCE and DAPA-CKD. The composite outcome stratified by eGFR categories were compared in the British Columbia cohort and the CREDENCE trial. Cost avoidance was estimated based on the number needed to treat to prevent one instance of kidney failure. Results: A total of 17.5% (3138/17 963) of patients were eligible, resulting in a cohort with a mean age of 69.7 years and 38% women. The eGFR slope of the British Columbia cohort was -4.21 ± 0.47 mL/min. The mean eGFR was 37.0 mL/min/1.73 m2, median UACR was 55.3 mg/mmol, and use of renin-angiotensin-aldosterone system inhibitors was 56.6%. The British Columbia cohort experienced nearly double the outcomes of kidney failure, death from any cause, and doubling of serum creatinine than the placebo arms of CREDENCE and DAPA-CKD. When stratified by eGFR, the British Columbia cohort and the CREDENCE placebo arm had similar event rates for those with an eGFR <45 mL/min but there were still higher rates of outcome in the greater than 45 mL/min eGFR groups in the British Columbia cohort. Treating the British Columbia cohort with canagliflozin could lead to net cost avoidance of $2.31 million over 2.6 years. Limitations: The database only captures those referred to the Kidney Care Clinics by nephrologists, which may lead to selection bias of higher risk patients in the British Columbia cohort. The cost avoidance analysis was a limited high-level analysis. Conclusions: The British Columbia cohort represents a high-risk group in whom implementation of the use of SGLT2 inhibitors may well improve outcomes and reduce health care system costs.

Contexte: Les essais cliniques CREDENCE et DAPA-CKD ont démontré que les inhibiteurs du cotransporteur sodium-glucose-2 (SGLT2) présentent des avantages significatifs pour les reins. Les inhibiteurs du SGLT2 sont désormais la norme en matière de soins pour les patients atteints de néphropathie diabétique et se sont également avérés efficaces chez les patients atteints d'une insuffisance rénale chronique (IRC) albuminurique avec ou sans diabète. Objectifs: Déterminer le nombre de patients suivis en néphrologie en Colombie-Britannique (Canada) qui auraient été admissibles à ces essais, afin de comparer les résultats et estimer les coûts pouvant être évités par une utilisation généralisée des inhibiteurs du SGLT2 dans cette cohorte. Type d'étude: Étude de cohorte rétrospective. Cadre: Colombie-Britannique (Canada). Sujets: Les patients atteints d'IRC suivis dans les cliniques de prévention rénale (Kidney Care Clinics) en Colombie-Britannique. Mesures: Nous avons comparé les résultats de l'insuffisance rénale terminale (baisse soutenue du taux de filtration glomérulaire estimé [DFGe] à moins de 15 ml/min/1,73 m2, dialyse, transplantation), les décès de toutes causes confondues et le doublement de la concentration de créatinine sérique. Nous avons également comparé le critère composite de l'insuffisance rénale terminale et du doublement de la concentration de créatinine sérique. Méthodologie: La cohorte a été dérivée d'une base de données provinciale en combinant les critères d'inclusion des essais CREDENCE et DAPA-CKD. Ont été inclus les patients adultes répertoriés entre le 1er avril 2014 et le 31 mars 2017 avec un rapport albumine/créatinine urinaire (RACu) ≥ 20 mg/mmol et un DFGe entre 25 et 90 ml/min/1,73 m2. Le critère de jugement principal a été comparé aux résultats observés dans les groupes placebos des essais CREDENCE et DAPA-CKD. Le critère composite, stratifié selon les catégories de DFGe, a été comparé dans la cohorte de la Colombie-Britannique et l'essai CREDENCE. Les coûts évités ont été estimés en fonction du nombre de traitements nécessaires pour prévenir un cas d'insuffisance rénale terminale. Résultats: Des 17 963 patients répertoriés, 3 138 (17,5 %) auraient été admissibles (38 % de femmes; âge moyen: 69,7 ans). La pente du DFGe pour la cohorte de la Colombie-Britannique était de −4,21 ± 0,47 ml/min. Dans cette même cohorte, le DFGe moyen s'établissait à 37,0 ml/min/1,73 m2, le RACu moyen à 55,3 mg/mmol et le taux d'utilisation des inhibiteurs du système rénine-angiotensine-aldostérone à 56,6 %. La cohorte de la Colombie-Britannique a connu près de deux fois plus d'événements liés à l'insuffisance rénale terminale, de décès de toutes causes confondues et de doublement de la concentration de créatinine sérique que les groupes placebos des essais CREDENCE et DAPA-CKD. Après la stratification selon le DFGe, la cohorte de la Colombie-Britannique et le groupe placebo de l'essai CREDENCE ont montré des taux d'événements similaires pour les patients présentant un DFGe < 45 ml/min, mais la cohorte de la Colombie-Britannique a montré des taux plus élevés d'événements dans les groupes avec un DFGe supérieur à 45 ml/min. Le traitement de la cohorte de la Colombie-Britannique par la canagliflozine pourrait permettre d'éviter un coût net de 2,31 M$ canadiens sur 2,6 ans. Limites: La base de données ne contient que les patients orientés par des néphrologues vers les cliniques de prévention rénale (Kidney Care Clinics), ce qui peut entraîner un biais favorisant la sélection des patients à risque élevé dans la cohorte de la Colombie-Britannique. L'analyse des coûts évités était une analyse de haut niveau limitée. Conclusion: La cohorte de la Colombie-Britannique représente un groupe de patients à haut risque chez qui l'utilisation des inhibiteurs du SGLT2 pourrait améliorer les résultats en matière d'insuffisance rénale et permettre de réduire les coûts pour le système de santé.

Prescription Pattern of Cation Exchange Resins and Their Efficacy in Treating Chronic Hyperkalemia Among Patients With Chronic Kidney Diseases: Findings From a Population-Based Analysis in British Columbia, Canada.

Background: Little was known about how chronic hyperkalemia (cHK) in patients with chronic kidney disease (CKD) is managed in British Columbia, Canada. Objective: To investigate the trend in sodium polystyrene sulfonate (SPS) and calcium polystyrene sulfonate (CPS) utilization and their efficacy in treating cHK in CKD patients from British Columbia, Canada. Study Design: Retrospective cohort. Setting & Patients: CKD patients aged ≥18 years, followed in Kidney Care Clinic (KCC), who had at least 2 potassium values ≥5.0 mmol/L separated by no more than 91 days during the period of June 1, 2015, to July 31, 2021, were included. Index date was the first date of the 2 potassium values ≥5.0 mmol/L. Patients who received SPS or CPS within 90 days before index date were excluded. Patients who were on dialysis or received kidney transplantation on or before index date were also excluded. Exposure: Continuous exposure to SPS and CPS. Outcome: SPS/CPS prescription utilization trend was described by the proportion of patients ever treated with SPS/CPS, median time in days between cHK diagnosis and initiating treatment with SPS/CPS, total and median number of SPS/CPS prescriptions dispensed. Change in mean serum potassium concentration before and after a 90-day continuous treatment with SPS/CPS was estimated. Analytical Approach: Descriptive. Results: This study included 10 495 patients with cHK (median age 74 years, 60% were male). Median follow-up time was 625 days. Only 2864 (27%) patients were dispensed at least 1 prescription of either SPS or CPS. A total 7300 prescriptions were dispensed; median prescriptions dispensed per patients were 2 (interquartile range [IQR]: 1-3). Median time from index date to the first prescription dispensing date was 154 days (IQR: 36-455). Continuous 90-day treatment with SPS/CPS decreased the mean serum potassium concentration by 0.60 mmol/L, from 5.58 to 4.98 mmol/L. Limitations: Descriptive observational study without control group. Conclusions: In British Columbia, only 1 in 4 CKD patients with cHK were dispensed with SPS/CPS, mostly with higher degrees of hyperkalemia. These medications appeared to be moderately effective in reducing the serum potassium concentration. Future research is necessary to evaluate the comparative effectiveness of newer generation medications.

Contexte: On savait peu de choses sur la façon dont l'hyperkaliémie chronique (HKc) est prise en charge chez les patients atteints d'insuffisance rénale chronique (IRC) de la Colombie-Britannique (C.-B.), au Canada. Objectif: Étudier les tendances d'utilisation du sulfonate de polystyrène sodique (SPS) et du sulfonate de polystyrène calcique (SPC), ainsi que l'efficacité de ces agents dans le traitement de l'HKc chez les patients britanno-colombiens atteints d'IRC. Type d'étude: étude de cohorte rétrospective. Sujets et cadre de l'étude: Ont été inclus des adultes atteints d'IRC suivis en clinique de soins rénaux qui avaient au moins 2 valeurs de potassium ≥ 5,0 mmol/L mesurées à moins de 91 jours d'intervalle entre le 1er juin 2015 et le 31 juillet 2021. La date de la première des deux valeurs de potassium ≥ 5,0 mmol/L constitue la date indice. Les patients qui avaient reçu du SPS ou du SPC dans les 90 jours précédant la date indice ont été exclus. Les patients sous dialyse ou ayant reçu une greffe rénale avant ou à la date indice ont également été exclus. Exposition: Exposition continue au SPS et au SPC. Résultats: La tendance d'utilisation de SPS/SPC a été décrite par la proportion de patients ayant déjà été traités par SPS/SPC, par le temps médian en jours entre le diagnostic d'hyperkaliémie chronique et le début du traitement par SPS/SPC, et par le nombre total et médian de prescriptions de SPS/SPC délivrées. La variation de la concentration moyenne de potassium sérique avant et après un traitement continu de 90 jours avec SPS/SPC a été estimée. Approche analytique: Descriptive. Résultats: L'étude porte sur 10 495 patients atteints d'hyperkaliémie chronique (60 % d'hommes; âge médian: 74 ans). Le temps médian de suivi était de 625 jours. Seulement 2 864 (27 %) patients avaient reçu au moins une prescription de SPS ou de SPC. Au total, 7 300 ordonnances ont été délivrées; la moyenne d'ordonnances délivrées par patient était de 2 (IIQ: 1, 3). Le délai médian entre la date indice et la date de la première ordonnance était de 154 jours (IIQ: 36, 455). Un traitement continu de 90 jours avec SPS/SPC a abaissé la concentration moyenne de potassium sérique de 0,60 mmol/L, la faisant passer de 5,58 à 4,98 mmol/L. Limites: Étude observationnelle descriptive sans groupe témoin. Conclusion: En C.-B., seul un patient sur quatre atteint d'IRC avec HKc avait reçu une prescription de SPS/SPC, la plupart présentaient des degrés plus élevés d'hyperkaliémie. Ces médicaments se sont avérés modérément efficaces pour réduire la concentration sérique en potassium. Des recherches supplémentaires sont nécessaires pour évaluer l'efficacité comparative des médicaments de nouvelle génération.

YTHDC1 Promotes Stemness Maintenance and Malignant Progression in Head and Neck Squamous Cell Carcinoma.

Background: YTH domain containing 1 (YTHDC1), an N6-methyladenosine (m6A) modification reading protein, plays a key role in regulating RNA translation and degradation. However, the role of YTHDC1 in head and neck squamous cell carcinoma (HNSCC) cancer stem cells remains largely unknown. This study is aimed at investigating the role of YTHDC1 in HNSCC and exploring its role in regulating cancer stem cells. Methods: RNA sequencing was used to detect differentially expressed genes (DEGs) between SCC9 spheres and SCC9 cells and to uncover molecular pathways and target molecules associated with CSCs. We detected YTHDC1 expression in The Cancer Genome Atlas (TCGA) database data and clinical samples. Subsequently, YTHDC1 gene suppression assays were performed in HNSCC cell lines to investigate the effect of YTHDC1 on tumor cell stemness maintenance, proliferation, and migration capacity. To further confirm the role of YTHDC1 in regulating cancer stem cells in HNSCC, we analyzed online HNSCC single-cell transcriptomic data to investigate YTHDC1 expression patterns at the single-cell level and the correlation of these levels with the expression of stem cell markers. Results: YTHDC1 expression levels were significantly upregulated in SCC9 spheres, and YTHDC1 was aberrantly expressed in HNSCC tumor tissues. The increased YTHDC1 expression was closely correlated with the clinical characteristics of HNSCC patients. YTHDC1 regulates the malignant phenotype of HNSCC in both in vivo and in vitro studies. Further single-cell transcriptomic data analysis revealed that YTHDC1 positively correlated with malignant epithelial cell stemness capacity at the single-cell level, and that YTHDC1 was involved in regulating stemness maintenance in HNSCC. Conclusions: These findings suggest that YTHDC1 may serve as a biomarker for stem maintenance and malignant progression in HNSCC, providing new insights into the treatment of 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.