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The need to search for new measures describing the classification of a logistic regression model stems from the difficulty in searching for previously unknown factors that predict the occurrence of a disease. A classification quality assessment can be performed by testing the change in the area under the receiver operating characteristic curve (AUC). Another approach is to use the Net Reclassification Improvement (NRI), which is based on a comparison between the predicted risk, determined on the basis of the basic model, and the predicted risk that comes from the model enriched with an additional factor. In this paper, we draw attention to Cohen’s Kappa coefficient, which examines the actual agreement in the correction of a random agreement. We proposed to extend this coefficient so that it may be used to detect the quality of a logistic regression model reclassification. The results provided by Kappa‘s reclassification were compared with the results obtained using NRI. The random variables’ distribution attached to the model on the classification change, measured by NRI, Kappa, and AUC, was presented. A simulation study was conducted on the basis of a cohort containing 3971 Poles obtained during the implementation of a lower limb atherosclerosis prevention program.

In this study involving 2103 men with elevated PSA levels, the use of both MRI-targeted and 12-core systematic biopsies was more effective at detecting clinically significant prostate cancers than either biopsy method alone.

Abstract Background The National Kidney Foundation recently endorsed the refit Chronic Kidney Disease Collaboration (CKD-EPI) equation for estimated glomerular filtration rate (eGFR) using creatinine, age and sex [2021 eGFRCr(AS)] without a coefficient for race. We evaluated the impact of adopting the 2021 eGFRCr(AS) equation or a variation of the 2009 CKD-EPI eGFR equation without race [2009 CKD-EPI eGFRCr(ASR-NB)] compared to the original CKD-EPI eGFR [2009 eGFRCr(ASR)]. Methods The studied population included patients with a clinically ordered iothalamate clearance (n = 33 889). Bias was assessed as the difference between measured and estimated GFR, P30 was defined as the percentage of estimates within 30% of measured GFR, and concordance was determined according to relevant clinical thresholds. Results Among Black patients, the median bias for 2009 eGFRCr(ASR), 2009 eGFRCr(ASR-NB), and 2021 eGFRCr(AS) was −1.32 mL min−1 (1.73 m2)−1 (95CI −2.46 to −0.26), −8.81 mL min−1 (1.73 m2)−1 (95CI −9.93 to −7.58), and −6.08 mL min−1 (1.73 m2)−1 (95CI −7.18 to −4.92), respectively. The median bias among non-Black patients was −0.15 m min−1 (1.73 m2)−1 (95CI −0.84 to −0.08) for 2021 eGFRcr(AS) compared to −3.09 mL min−1 (1.73 m2)−1 (95CI −3.17 to −3.03) for the 2009 eGFRCr(ASR). P30 and concordance were not significantly different in either racial group. The net reclassification improvement at a measured GFR <20 mL min−1 (1.73 m2)−1 was 6.4% (95CI 0.36 to 12.4) for Black patients and −5.1% (95CI −6.0 to −4.1) for non-Black patients using the 2021 eGFRCr(AS) equation. Conclusions Overall, the change in reported eGFR was minimal. However, these changes led to significant reclassification improvements at lower eGFR, which will indirectly improve equitable access to CKD resources.

The ability to block specific cytokine pathways has revealed pathophysiological differences among autoimmune diseases (e.g., the efficacy of TNF inhibitors in arthritides and inflammatory bowel disorders and their inefficacy in giant-cell arteritis and multiple sclerosis), providing a framework for reclassification.

The East-Central European region has undergone a unique urbanisation process during socialist and postsocialist periods. These peculiarities result from social and economic development delays, which the statehas tried to remedy through massive interventions. One such intervention is urban reclassification, where the state promotes certain places it deems crucial, granting them urban status, often without actual developmentor urban characteristics. Due to its artificial character, this intervention is called formal urbanisation in our approach being a specific local feature of the urbanisation process. The visible result is the growth of the urbanpopulation, often only by administrative causes, with the reclassification of villages as towns. The emergence of numerous small towns, which we refer to as newest towns, has significantly influenced urbanisation, alteredthe concept of towns and cities3, and generated significant debates. In this paper, we compare the formal urbanisation of the socialist and post-socialist eras, trying to estimate the added value of formal urbanisation inthe latter period. We compare the administrative backgrounds of formal urbanisation in selected ECE countries for similarities and differences. Throughout the research, we analyse their formal urbanisation involvingapproximately 800 municipalities promoted since 1990 in Poland, Czechia, Hungary, and Romania, trying to identify common and unique features in the processes. Based on historical determination, modernisation, and integration into new spatial processes, considering demographic and functional changes, we developedtypes of formal urbanisation. Our research has revealed several common factors in the reclassification process, such as local initiatives, while we have also identified disparities between principles and practices and varyinglevels of control from regional and national actors. The study has also led to a deeper understanding of formal urbanisation in the context of the urbanisation process as a whole.

The Genitourinary Pathology Society (GUPS) reviewed recent advances in renal neoplasia, particularly post-2016 World Health Organization (WHO) classification, to provide an update on existing entities, including diagnostic criteria, molecular correlates, and updated nomenclature. Key prognostic features for clear cell renal cell carcinoma (RCC) remain WHO/ISUP grade, AJCC/pTNM stage, coagulative necrosis, and rhabdoid and sarcomatoid differentiation. Accrual of subclonal genetic alterations in clear cell RCC including SETD2, PBRM1, BAP1, loss of chromosome 14q and 9p are associated with variable prognosis, patterns of metastasis, and vulnerability to therapies. Recent National Comprehensive Cancer Network (NCCN) guidelines increasingly adopt immunotherapeutic agents in advanced RCC, including RCC with rhabdoid and sarcomatoid changes. Papillary RCC subtyping is no longer recommended, as WHO/ISUP grade and tumor architecture better predict outcome. New papillary RCC variants/patterns include biphasic, solid, Warthin-like, and papillary renal neoplasm with reverse polarity. For tumors with ‘borderline’ features between oncocytoma and chromophobe RCC, a term “oncocytic renal neoplasm of low malignant potential, not further classified” is proposed. Clear cell papillary RCC may warrant reclassification as a tumor of low malignant potential. Tubulocystic RCC should only be diagnosed when morphologically pure. MiTF family translocation RCCs exhibit varied morphologic patterns and fusion partners. TFEB-amplified RCC occurs in older patients and is associated with more aggressive behavior. Acquired cystic disease (ACD) RCC-like cysts are likely precursors of ACD-RCC. The diagnosis of renal medullary carcinoma requires a negative SMARCB1 (INI-1) expression and sickle cell trait/disease. Mucinous tubular and spindle cell carcinoma (MTSCC) can be distinguished from papillary RCC with overlapping morphology by losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22. MTSCC with adverse histologic features shows frequent CDKN2A/2B (9p) deletions. BRAF mutations unify the metanephric family of tumors. The term “fumarate hydratase deficient RCC” (“FH-deficient RCC”) is preferred over “hereditary leiomyomatosis and RCC syndrome-associated RCC”. A low threshold for FH, 2SC, and SDHB immunohistochemistry is recommended in difficult to classify RCCs, particularly those with eosinophilic morphology, occurring in younger patients. Current evidence does not support existence of a unique tumor subtype occurring after chemotherapy/radiation in early childhood.

The current classification of diabetes, based on hyperglycaemia, islet-directed antibodies and some insufficiently defined clinical features, does not reflect differences in aetiological mechanisms and in the clinical course of people with diabetes. This review discusses evidence from recent studies addressing the complexity of diabetes by proposing novel subgroups (subtypes) of diabetes. The most widely replicated and validated approach identified, in addition to severe autoimmune diabetes, four subgroups designated severe insulin-deficient diabetes, severe insulin-resistant diabetes, mild obesity-related diabetes and mild age-related diabetes subgroups. These subgroups display distinct patterns of clinical features, disease progression and onset of comorbidities and complications, with severe insulin-resistant diabetes showing the highest risk for cardiovascular, kidney and fatty liver diseases. While it has been suggested that people in these subgroups would benefit from stratified treatments, RCTs are required to assess the clinical utility of any reclassification effort. Several methodological and practical issues also need further study: the statistical approach used to define subgroups and derive recommendations for diabetes care; the stability of subgroups over time; the optimal dataset (e.g. phenotypic vs genotypic) for reclassification; the transethnic generalisability of findings; and the applicability in clinical routine care. Despite these open questions, the concept of a new classification of diabetes has already allowed researchers to gain more insight into the colourful picture of diabetes and has stimulated progress in this field so that precision diabetology may become reality in the future.

Coronary artery inflammation inhibits adipogenesis in adjacent perivascular fat. A novel imaging biomarker—the perivascular fat attenuation index (FAI)—captures coronary inflammation by mapping spatial changes of perivascular fat attenuation on coronary computed tomography angiography (CTA). However, the ability of the perivascular FAI to predict clinical outcomes is unknown. In the Cardiovascular RISk Prediction using Computed Tomography (CRISP-CT) study, we did a post-hoc analysis of outcome data gathered prospectively from two independent cohorts of consecutive patients undergoing coronary CTA in Erlangen, Germany (derivation cohort) and Cleveland, OH, USA (validation cohort). Perivascular fat attenuation mapping was done around the three major coronary arteries—the proximal right coronary artery, the left anterior descending artery, and the left circumflex artery. We assessed the prognostic value of perivascular fat attenuation mapping for all-cause and cardiac mortality in Cox regression models, adjusted for age, sex, cardiovascular risk factors, tube voltage, modified Duke coronary artery disease index, and number of coronary CTA-derived high-risk plaque features. Between 2005 and 2009, 1872 participants in the derivation cohort underwent coronary CTA (median age 62 years [range 17–89]). Between 2008 and 2016, 2040 patients in the validation cohort had coronary CTA (median age 53 years [range 19–87]). Median follow-up was 72 months (range 51–109) in the derivation cohort and 54 months (range 4–105) in the validation cohort. In both cohorts, high perivascular FAI values around the proximal right coronary artery and left anterior descending artery (but not around the left circumflex artery) were predictive of all-cause and cardiac mortality and correlated strongly with each other. Therefore, the perivascular FAI measured around the right coronary artery was used as a representative biomarker of global coronary inflammation (for prediction of cardiac mortality, hazard ratio [HR] 2·15, 95% CI 1·33–3·48; p=0·0017 in the derivation cohort, and 2·06, 1·50–2·83; p<0·0001 in the validation cohort). The optimum cutoff for the perivascular FAI, above which there is a steep increase in cardiac mortality, was ascertained as −70·1 Hounsfield units (HU) or higher in the derivation cohort (HR 9·04, 95% CI 3·35–24·40; p<0·0001 for cardiac mortality; 2·55, 1·65–3·92; p<0·0001 for all-cause mortality). This cutoff was confirmed in the validation cohort (HR 5·62, 95% CI 2·90–10·88; p<0·0001 for cardiac mortality; 3·69, 2·26–6·02; p<0·0001 for all-cause mortality). Perivascular FAI improved risk discrimination in both cohorts, leading to significant reclassification for all-cause and cardiac mortality. The perivascular FAI enhances cardiac risk prediction and restratification over and above current state-of-the-art assessment in coronary CTA by providing a quantitative measure of coronary inflammation. High perivascular FAI values (cutoff ≥–70·1 HU) are an indicator of increased cardiac mortality and, therefore, could guide early targeted primary prevention and intensive secondary prevention in patients. British Heart Foundation, and the National Institute of Health Research Oxford Biomedical Research Centre.

Identification of individuals at highest risk of coronary artery disease (CAD)—ideally before onset—remains an important public health need. Prior studies have developed genome-wide polygenic scores to enable risk stratification, reflecting the substantial inherited component to CAD risk. Here we develop a new and significantly improved polygenic score for CAD, termed GPS Mult , that incorporates genome-wide association data across five ancestries for CAD (>269,000 cases and >1,178,000 controls) and ten CAD risk factors. GPS Mult strongly associated with prevalent CAD (odds ratio per standard deviation 2.14, 95% confidence interval 2.10–2.19, P  < 0.001) in UK Biobank participants of European ancestry, identifying 20.0% of the population with 3-fold increased risk and conversely 13.9% with 3-fold decreased risk as compared with those in the middle quintile. GPS Mult was also associated with incident CAD events (hazard ratio per standard deviation 1.73, 95% confidence interval 1.70–1.76, P  < 0.001), identifying 3% of healthy individuals with risk of future CAD events equivalent to those with existing disease and significantly improving risk discrimination and reclassification. Across multiethnic, external validation datasets inclusive of 33,096, 124,467, 16,433 and 16,874 participants of African, European, Hispanic and South Asian ancestry, respectively, GPS Mult demonstrated increased strength of associations across all ancestries and outperformed all available previously published CAD polygenic scores. These data contribute a new GPS Mult for CAD to the field and provide a generalizable framework for how large-scale integration of genetic association data for CAD and related traits from diverse populations can meaningfully improve polygenic risk prediction. A polygenic risk score for coronary artery disease developed using data from individuals of five different ancestries has increased accuracy across diverse populations.

Type I interferons have been suspected for decades to have a crucial role in the pathogenesis of systemic lupus erythematosus (SLE). Evidence has now overturned several long-held assumptions about how type I interferons are regulated and cause pathological conditions, providing a new view of SLE pathogenesis that resolves longstanding clinical dilemmas. This evidence includes data on interferons in relation to genetic predisposition and epigenetic regulation. Importantly, data are now available on the role of interferons in the early phases of the disease and the importance of non-haematopoietic cellular sources of type I interferons, such as keratinocytes, renal tubular cells, glial cells and synovial stromal cells, as well as local responses to type I interferons within these tissues. These local effects are found not only in inflamed target organs in established SLE, but also in histologically normal skin during asymptomatic preclinical phases, suggesting a role in disease initiation. In terms of clinical application, evidence relating to biomarkers to characterize the type I interferon system is complex, and, notably, interferon-blocking therapies are now licensed for the treatment of SLE. Collectively, the available data enable us to propose a model of disease pathogenesis that invokes the unique value of interferon-targeted therapies. Accordingly, future approaches in SLE involving disease reclassification and preventative strategies in preclinical phases should be investigated.In this Review, Psarras, Wittmann and Vital discuss evidence of the production of type I interferons by cells and tissues other than haematopoietic cells. These interferons can have local effects, and their roles in the pathogenesis of systemic lupus erythematosus suggest the value of interferon-blocking therapies for treatment of this condition.