High Risk Of Progression Research Articles

#1986 Incidence of renal anemia among patients with atrial fibrillation and chronic kidney disease stage IIIb-V

Abstract Background and Aims According to the QICKD study, the prevalence of anemia in stage IIIb-V chronic kidney disease (CKD) is 22%. The incidence of renal anemia ranges from 8.4% in patients with stage I CKD to 83.7% in patients with stage V CKD. In patients on program hemodialysis, anemia develops in 94.5% of cases. The problem is associated with an increased risk of unfavorable outcome of CKD, therefore, the study of aspects of anemia among patients receiving anticoagulant therapy with atrial fibrillation (AF) and CKD remains the most relevant today. The purpose of the study is to study the prevalence of renal anemia among patients with AF and CKD stages IIIb-V. Method 794 patients were admitted to the cardiology department with a diagnosis of AF and late stages of CKD—IIIb (glomerular filtration rate (GFR) 45–30 ml/min/1.73 m2), IV (GFR 29–15 ml/min/1.73 m2), V (GFR <15 ml/min/1.73 m2), for the first identified sustained decrease in glomerular filtration rate (FISD in GFR) of less than 45 ml/min/1.73 m2. The classification of renal anemia was carried out according to the recommendations of the World Health Organization. Results Renal anemia was diagnosed in 505 (63%) patients with AF and GFR less than 45 ml/min/1.73 m2. In total, among patients with CKD stage IIIb, anemia was detected in 207 (59%) patients, with CKD stage IV—in 110 (89%), with CKD stage V—in 43 (97%), with FISD in GFR—in 145 (51%). A mild degree of anemia (hemoglobin (Hb) in men 110-129 g/l, in women 110-119 g/l) was diagnosed in 39% of patients, with CKD stage IIIb in 85 (24%) patients, with CKD stage IV in 28 (22%) patients, with CKD stage V in 9 (20%) patients, with FISD in GFR in 75 (26%) patients. A moderate degree of anemia (Hb 81-109 g/l) was detected in 47.3% of cases, with CKD stage IIIb in 86 (25%) patients, with CKD stage IV in 60 (48%) patients, with CKD stage V in 29 (66%) patients, with FISD in GFR in 64 (23%) patients. Severe anemia (Hb 81-109 g/l) was detected in 47.3% of patients, with CKD stage IIIb in 36 (10%) patients, with CKD stage IV in 22 (19%) patients, with CKD stage V in 5 (11%) patients, with FISD in GFR in 6 (2%) patients. Conclusion Every fourth patient in the cardiology department with AF and GFR <45 ml/min/1.73 m2 was diagnosed with renal anemia, and its prevalence increases with a decrease in GFR. The above results indicate that a more careful selection of anticoagulant therapy is recommended for this patient population due to the high risk of progression of renal anemia in this cohort of patients.

Three-dimensional telomere profiling predicts risk of progression in smoldering multiple myeloma.

Smoldering multiple myeloma (SMM) is a precursor stage that precedes multiple myeloma (MM). SMM is heterogenous with nearly 40% of patients progressing to MM in the first 5 years. The high rate of progression of SMM patients highlights the need for early intervention, which underscores the importance of identifying SMM patients with the highest risk of progression. Several risk stratification models showed utility in identifying high-risk SMM patients; however, these systems showed limited sensitivity. To date, identifying high-risk SMM patients remains an important clinical need. In this study, we present the 3-dimensional telomere profiling as a structural biomarker capable of stratifying SMM patients as a function of genomic instability. Quantifying telomere dysfunction using the TeloView technology showed utility in risk stratification of cancer patients, particularly hematological malignancies. In this study, we analyzed 168 SMM patients. We report an AUC in ROC analysis of 0.8 using a subset of the patients as a training dataset. We then conducted a blind validation on a different cohort and demonstrated a positive predictive value of 85% and negative predictive value of 73%, with sensitivity and specificity of 83% and 76%, respectively. We examined the correlation between the TeloView prediction and the 20-2-20 scoring system, and cytogenetic abnormalities. We report a correlation of 53% with the 20-2-20 scores and over 60% correlation with cytogenetic abnormalities. The result of this study presents the telomere profiling as an effective biomarker able to stratify SMM patients to their respective risk groups with high sensitivity and specificity.

Individualized Risk of CKD Progression among US Adults.

Chronic kidney disease (CKD) is currently defined using glomerular filtration rate (GFR) or albuminuria. This is based on the relative risk of mortality and kidney outcomes compared to a healthy population and does not consider an individual's absolute risk of CKD progression. Using National Health and Nutrition Examination Survey data from 1999-2020, we characterized the individual-level absolute 3-year risk of ≥40% decline in estimated GFR (eGFR, mL/min/1.73 m2) or kidney failure (3-year risk) among US adults. We categorized the 3-year risk and considered ≥5% high risk. Among 199.81 million US adults, 8.42 million (4%) had a 3-year risk ≥5%, including 1.04 million adults without CKD (eGFR ≥60 and albuminuria <30 mg/g). These high-risk adults without CKD as currently defined had risk factors including hypertension (98%), heart failure (72%), and diabetes (44%). 15.51 million adults had CKD with preserved eGFR (eGFR ≥60 and albuminuria ≥30 mg/g)-3.73 million had a 3-year risk ≥5%, 41% of whom did not have diabetes and thus would not be screened for albuminuria using current screening recommendations. The 3-year risk of CKD progression was low (risk <5%) in 94% of the 5.66 million US adults with CKD stage G3a-A1 (eGFR 45 to <60 and albuminuria <30 mg/g). Assessment of the individual's absolute risk of CKD progression allows further risk stratification of patients with CKD and identifies individuals without CKD, as currently defined, that are at high risk of CKD progression.

Active Rheumatoid Arthritis and Scoliosis: A Mid-Term Cohort Study.

Retrospective cohort study. To elucidate the factors related to progression of scoliosis in patients with rheumatoid arthritis (RA) using longitudinal cohort data. Thirty percent of patients with RA have lumbar scoliosis. However, the effectiveness of current treatment methods in preventing the progression of scoliosis is not well-understood due to a lack of longitudinal studies. We enrolled 180 patients with RA who were followed up for over two years, all of whom underwent standing spinal X-rays. These patients were categorized based on their disease activity score-28 with erythrocyte sedimentation rate (DAS28-ESR) into two groups: those in remission (n=76) and those in non-remission (n=104). We evaluated various radiographic measures, including C7 center sacral vertical line (C7-CSVL), pelvic obliquity, major Cobb angle, and curve location. Fifty-three (29.4%) patients presented progression of scoliosis during a mean follow-up period of 4.8 years. Patients in the non-remission showed larger Cobb angle at baseline and final follow-up, compared to those in remission. The annual progression rate of the curve was also greater in the non-remission group (1.04 degree /year), than in the remission group (0.59 degree /year, P=0.001). There was no difference in the incidence of new vertebral fractures. The presence of a baseline cobb angle of 10 degree or more (OR: 3.14; 95% CI: 1.38-7.13; P=0.006), glucocorticoid use (OR: 2.88; 95% CI: 1.18-7.06; P=0.021), and non-remission at baseline (OR: 2.83; 95% CI: 1.25-6.41; P=0.012) were significant risk factors for progression of scoliosis. RA disease activity is linked to progression of scoliosis in patients with RA. Patients with RA who present with an initial scoliosis of 10 degrees or greater, require glucocorticoids for treatment and are in non-remission at baseline may be at high risk for scoliosis progression.

Deep Learning for Predicting Progression of Patellofemoral Osteoarthritis Based on Lateral Knee Radiographs, Demographic Data, and Symptomatic Assessments.

In this study, we propose a novel framework that utilizes deep learning and attention mechanisms to predict the radiographic progression of patellofemoral osteoarthritis (PFOA) over a period of 7 years. This study included subjects (1,832 subjects, 3,276 knees) from the baseline of the Multicenter Osteoarthritis Study (MOST). Patellofemoral joint regions of interest were identified using an automated landmark detection tool (BoneFinder) on lateral knee X-rays. An end-to-end deep learning method was developed for predicting PFOA progression based on imaging data in a five-fold cross-validation setting. To evaluate the performance of the models, a set of baselines based on known risk factors were developed and analyzed using gradient boosting machine (GBM). Risk factors included age, sex, body mass index, and Western Ontario and McMaster Universities Arthritis Index score, and the radiographic osteoarthritis stage of the tibiofemoral joint (Kellgren and Lawrence [KL] score). Finally, to increase predictive power, we trained an ensemble model using both imaging and clinical data. Among the individual models, the performance of our deep convolutional neural network attention model achieved the best performance with an area under the receiver operating characteristic curve (AUC) of 0.856 and average precision (AP) of 0.431, slightly outperforming the deep learning approach without attention (AUC = 0.832, AP = 0.4) and the best performing reference GBM model (AUC = 0.767, AP = 0.334). The inclusion of imaging data and clinical variables in an ensemble model allowed statistically more powerful prediction of PFOA progression (AUC = 0.865, AP = 0.447), although the clinical significance of this minor performance gain remains unknown. The spatial attention module improved the predictive performance of the backbone model, and the visual interpretation of attention maps focused on the joint space and the regions where osteophytes typically occur. This study demonstrated the potential of machine learning models to predict the progression of PFOA using imaging and clinical variables. These models could be used to identify patients who are at high risk of progression and prioritize them for new treatments. However, even though the accuracy of the models were excellent in this study using the MOST dataset, they should be still validated using external patient cohorts in the future.

Molnupiravir Use Among Patients with COVID-19 in Real-World Settings: A Systematic Literature Review.

Molnupiravir (MOV) is an oral antiviral for the treatment of individuals with mild-to-moderate COVID-19 and at high risk of progression to severe disease. Our objective was to conduct a systematic literature review (SLR) of evidence on the effectiveness of MOV in reducing the risk of severe COVID-19 outcomes in real-world outpatient settings. The SLR was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and using pre-determined population, intervention, comparison, outcome, time, and study design inclusion criteria. Eligible studies were published between January 1, 2021, and March 10, 2023, and evaluated the real-world effectiveness of MOV compared to no treatment in reducing the risk of severe COVID-19 outcomes among outpatients ≥ 18years of age with a laboratory-confirmed diagnosis of SARS-CoV-2 infection. Nine studies from five countries were included in the review. The size of the MOV-treated group ranged from 359 to 7818 individuals. Omicron variants of SARS-CoV-2 were dominant in all study periods. Most studies noted differences in the baseline characteristics of the MOV-treated and untreated control groups, with the treated groups generally being older and with more comorbidities. Eight studies reported that treatment with MOV was associated with a significantly reduced risk of at least one severe COVID-19 outcome in at least one age group, with greater benefits consistently observed among older age groups. In this SLR study, treatment with MOV was effective in reducing the risk of severe outcomes from COVID-19 caused by Omicron variants, especially for older individuals. Differences in the ages and baseline comorbidities of the MOV-treated and control groups may have led to underestimation of the effectiveness of MOV in many observational studies. Real-world studies published to date thus provide additional evidence supporting the continued benefits of MOV in non-hospitalized adults with COVID-19.

Comparative analysis of morphological changes in the mucosa of the small and large bronchi in non-small cell lung cancer

Background. Despite advances in surgical and therapy techniques, non-small cell lung cancer (NSCLC) is one of the most common cancers and the leading cause of cancer-related death. Therefore, it is increasingly important to search for markers that predict the risk of tumor progression. The study of the morphology of the epithelium of the bronchi of different calibers has great potential for solving this problem. The aim of the study was to comparatively evaluate the characteristics and frequency of occurrence of various combinations of morphological changes in the epithelium of the bronchi of large and small calibers in patients with lung squamous cell carcinoma and lung adenocarcinoma. Material and methods. lung samples were collected from 151 NSCLC patients (stage T1–4N0–3M0), who underwent surgery at the cancer Research institute, TNRMC. Various morphological changes in the bronchial epithelium were analyzed. Results. The study of the frequency of occurrence of various morphological changes in small-caliber bronchi showed that basal cell hyperplasia occurred in 90.8 % of cases. Diffuse isolated basal cell hyperplasia was observed in 33.8 % of cases. Focal basal cell hyperplasia was diagnosed in 38.4 % of cases. A combination of basal cell hyperplasia with squamous metaplasia was observed in 18.5 % of cases. The study of the frequency of occurrence in large-caliber bronchi demonstrated that basal cell hyperplasia was the most common morphological variant (93.4 %, including diffuse isolated basal cell hyperplasia in 33.8 % and focal basal cell hyperplasia in 38.4 %). The combination of basal cell hyperplasia and squamous metaplasia was found in 19.8 %. The combination of basal cell hyperplasia with squamous metaplasia and dysplasia was found in 1.3 % compared to the epithelium of small-caliber bronchi. Conclusion. The obtained results on the frequency of occurrence of morphological changes in large-caliber bronchi are of theoretical interest for further research to identify groups at high risk of progression of non-small cell lung cancer.

Is young adult idiopathic scoliosis a distinct clinical entity from adolescent idiopathic scoliosis? a Systematic Review and Meta-analysis comparing pre-operative characteristics and operative outcomes.

This study aims to conduct a systematic review of the literature comparing pre-operative, intraoperative, and post-operative characteristics between adolescent idiopathic scoliosis (AIS) and young adult idiopathic scoliosis (YAdIS) patients. Following PRISMA guidelines, we conducted a search of the PubMed/Medline, EMBASE, and Cochrane Central databases to identify full-text articles in the English-language literature. Our inclusion criteria were studies that compared preoperative, intraoperative, and postoperative characteristics between AIS and YAdIS patients. We performed a meta-analysis reporting mean difference (MD) for continuous variables and Odds ratios (ORs) to assess differences in postoperative complications. Seven studies consisting of 1562 patients were included in the meta-analysis. The AIS group exhibited less intraoperative bleeding and shorter surgical procedures, with a mean difference between groups of 122.3ml (95% CI 46.2-198.4, p = 0.002) and 28.7min (95% CI 6.5-50.8, p = 0.01), respectively. Although the preoperative Cobb angle did not differ between groups (p = 0.65), patients with AIS achieved superior postoperative deformity correction, with a mean difference of 7.3% between groups, MD -7.3 (95% CI -9.7, -4.8, p < 0.00001), and lower postoperative Cobb angles of the major curve, MD 4.2 (95% CI 3.1, 5.3, p < 0.00001). YAdIS patients were fused, on average, 0.2 more vertebral levels than AIS patients, MD 0.2 (95% CI 0.01, 0.5, p = 0.04). AIS patients experienced a significantly shorter length of stay after the surgical procedure, with an MD of 0.8days (95% CI 0.1, 1.6, p = 0.02). No significant difference was found between groups in terms of complications (p = 0.19). YAdIS should be regarded as a distinct surgical entity, characterized by increased bleeding, longer surgical duration, greater deformity correction challenges, and the need for fusion of additional vertebral levels compared to AIS. Surgeons should be mindful of these differences and discuss them with patients and their families, especially in cases where the correction of the AIS deformity is delayed and there is a high risk of progression after skeletal maturity. Further research is needed to explore alternative surgical techniques and enhance outcomes for YAdIS patients.

Predicting Alzheimer’s progression in MCI: a DTI-based white matter network model

ObjectiveThis study aimed to identify features of white matter network attributes based on diffusion tensor imaging (DTI) that might lead to progression from mild cognitive impairment (MCI) and construct a comprehensive model based on these features for predicting the population at high risk of progression to Alzheimer’s disease (AD) in MCI patients.MethodsThis study enrolled 121 MCI patients from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Among them, 36 progressed to AD after four years of follow-up. A brain network was constructed for each patient based on white matter fiber tracts, and network attribute features were extracted. White matter network features were downscaled, and white matter markers were constructed using an integrated downscaling approach, followed by forming an integrated model with clinical features and performance evaluation.ResultsAPOE4 and ADAS scores were used as independent predictors and combined with white matter network markers to construct a comprehensive model. The diagnostic efficacy of the comprehensive model was 0.924 and 0.919, sensitivity was 0.864 and 0.900, and specificity was 0.871 and 0.815 in the training and test groups, respectively. The Delong test showed significant differences (P < 0.05) in the diagnostic efficacy of the combined model and APOE4 and ADAS scores, while there was no significant difference (P > 0.05) between the combined model and white matter network biomarkers.ConclusionsA comprehensive model constructed based on white matter network markers can identify MCI patients at high risk of progression to AD and provide an adjunct biomarker helpful in early AD detection.

Predicting amyloid-PET and clinical conversion in apolipoprotein E ε3/ε3 non-demented individuals with multidimensional factors.

The apolipoprotein E (APOE) ε4 is a well-established risk factor of amyloid-β (Aβ) in Alzheimer's disease (AD). However, because of the high prevalence of APOE ε3, there may be a large number of people with APOE ε3/ε3 who are non-demented and have Aβ pathology. There are limited studies on assessing Aβ status and clinical conversion in the APOE ε3/ε3 non-demented population. Two hundred and ninety-three non-demented individuals with APOE ε3/ε3 from ADNI database were divided into Aβ-positron emission tomography (Aβ-PET) positivity (+) and Aβ-PET negativity (-) groups using cut-off value of >1.11. Stepwise regression searched for a single or multidimensional clinical variables for predicting Aβ-PET (+), and the receiver operating characteristic curve (ROC) assessed the accuracy of the predictive models. The Cox regression model explored the risk factors associated with clinical conversion to mild cognitive impairment (MCI) or AD. The results showed that the combination of sex, education, ventricle and white matter hyperintensity (WMH) volume can accurately predict Aβ-PET status in cognitively normal (CN), and the combination of everyday cognition study partner total (EcogSPTotal) score, age, plasma p-tau 181 and WMH can accurately predict Aβ-PET status in MCI individuals. EcogSPTotal score were independent predictors of clinical conversion to MCI or AD. The findings may provide a non-invasive and effective tool to improve the efficiency of screening Aβ-PET (+), accelerate and reduce costs of AD trial recruitment in future secondary prevention trials or help to select patients at high risk of disease progression in clinical trials.

Association Between Residual Urine Volume and Recurrence Among Patients at High Risk of Non-Muscle-Invasive Bladder Carcinoma With Versus Without Bacillus Calmette-Guérin Treatment.

Non-muscle-invasive bladder carcinoma often occurs in older adults, who often also have urinary dysfunction. The residual urine volume is an important indicator of urinary dysfunction. However, the impact of the residual urine volume on intravesical recurrence remains unclear. In the present study, we analyzed the data of 372 patients at high or very high risk of cancer progression according to the Japanese Urological Association classification who had undergone transurethral resection of a bladder tumor. In univariate analysis, postoperative absence of intravesical Bacillus Calmette-Guérin (BCG) induction was an independent risk factor for intravesical recurrence (hazard ratio 1.94, absence versus presence, p = 0.0019). The incidence of intravesical recurrence did not significantly differ between the mild, intermediate, and severe residual urine groups in the total cohort. Among the BCG-treated cohort, the three groups showed similar trends. Among the non-BCG-treated cohort, although the patients with more than 100 ml of residual urine tended to have more intravesical recurrence than patients with a smaller residual urine volume, this difference did not reach statistical significance. BCG treatment is recommended for patients at high risk of bladder carcinoma. Patients with a large residual urine volume without BCG treatment may be at high risk of intravesical recurrence.

Effectiveness of Nirmatrelvir-Ritonavir for the Prevention of COVID-19-Related Hospitalization and Mortality: A Systematic Literature Review.

Nirmatrelvir/ritonavir (NMV/r) is an oral antiviral drug used to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in patients aged 12 years or older at high risk of progression to severe disease (eg, hospitalization and death). Despite being the preferred option for outpatient treatment in the majority of countries worldwide, NMV/r is currently underutilized in real-world clinical practice. As numerous real-world studies have described patient outcomes following treatment with NMV/r, this systematic literature review provides a comprehensive summary of evidence on NMV/r effectiveness against hospitalization and mortality further organized by clinically meaningful categories, such as acute versus longer-term follow-up, age, underlying health conditions, and vaccination status, to help inform health care decision making. We searched Embase and PubMed (December 22, 2021-March 31, 2023) and congress abstracts (December 1, 2021-December 31, 2022) for reports describing NMV/r effectiveness. In total, 18 real-world studies met final selection criteria. The evidence showed that NMV/r significantly reduced postinfection risk of all-cause and COVID-19-related hospitalization and mortality in both acute (≤30 days) (21%-92%) and longer-term (>30 days) (1%-61%) follow-up. The reduction in postinfection risk was higher when treatment was received within 5 days of symptom onset. Real-world effectiveness of NMV/r treatment was observed regardless of age, underlying high-risk conditions, and vaccination status. The systematic literature review findings demonstrated the effectiveness of NMV/r against hospitalization and mortality during the Omicron period among individuals at high risk of progression to severe COVID-19 disease.

Effect of Secukinumab Versus Adalimumab Biosimilar on Radiographic Progression in Patients With Radiographic Axial Spondyloarthritis: Results From a Head-to-Head Randomized Phase IIIb Study.

Spinal radiographic progression is an important outcome in radiographic axial spondyloarthritis (SpA). The objective of the phase IIIb SURPASS study was tocompare spinal radiographic progression in patients with radiographic axial SpA treated with secukinumab (interleukin-17A inhibitor) versus adalimumab biosimilar (Sandoz adalimumab [SDZ-ADL]; tumor necrosis factor inhibitor). Biologic-naive patients with active radiographic axial SpA, at high risk of radiographic progression (high-sensitivity C-reactive protein [hsCRP] ≥5 mg/L and/or ≥1 syndesmophyte[s] on spinal radiographs), were randomized (1:1:1) to secukinumab (150/300 mg) or SDZ-ADL (40 mg). The proportion of patients with no radiographic progression (change from baseline [CFB] in modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS] ≤0.5) on secukinumab versus SDZ-ADL at week 104 (primary endpoint), mean CFB-mSASSS, proportion of patients with ≥1 syndesmophyte(s) at baseline with no new syndesmophyte(s), and safety were evaluated. Overall, 859 patients (78.5% male, mSASSS 16.6, Bath Ankylosing Spondylitis Disease Activity Index 7.1, hsCRP 20.4 mg/L, and 73.0% with ≥1 syndesmophyte[s]) received secukinumab 150 mg (n = 287), secukinumab 300 mg (n = 286), or SDZ-ADL (n = 286). At week 104, the proportion of patients with no radiographic progression was 66.1%, 66.9%, and 65.6% (P = not significant, both secukinumab doses) and mean CFB-mSASSS was 0.54, 0.55, and 0.72 in secukinumab 150 mg, secukinumab 300 mg, and SDZ-ADL arms, respectively. Overall, 56.9%, 53.8%, and 53.3% of patients on secukinumab 150 mg, secukinumab 300 mg, and SDZ-ADL, respectively, with ≥1 syndesmophyte(s) at baseline did not develop new syndesmophyte(s) by week 104. There were no unexpected safety findings. Spinal radiographic progression over two years was low with no significant difference between secukinumab and SDZ-ADL arms. The safety of both treatments was consistent with previous reports.

Nirmatrelvir-Ritonavir (Paxlovid)

CADTH recommends that Paxlovid be reimbursed by public drug plans for the treatment of mild to moderate COVID-19 in adults with positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing and who are at high risk for progression to severe COVID-19, including hospitalization or death, if certain conditions are met. Paxlovid should only be covered to treat patients who have severe or moderate immunosuppression as described in Table 1. Treatment should be initiated as soon as possible within 5 days of symptom onset. Paxlovid should only be reimbursed if the cost is reduced.

Is It Possible to Predict Tumor Progression Through Genomic Characterization of Monoclonal Gammopathy and Smoldering Multiple Myeloma?

The study of monoclonal serum proteins has led to the generation of two major theories: one proposing that individuals who had monoclonal proteins without any symptoms or evidence of end-organ damage have a benign condition, the other one suggesting that some individuals with asymptomatic monoclonal proteins may progress to multiple myeloma and thus are affected by a monoclonal gammopathy of undetermined significance (MGUS). Longitudinal studies of subjects with MGUS have supported the second theory. Subsequent studies have characterized and defined the existence of another precursor of multiple myeloma, smoldering multiple myeloma (SMM), intermediate between MGUS and multiple myeloma. Primary molecular events, chromosome translocations, and chromosome number alterations resulting in hyperploidy, required for multiple myeloma development, are already observed in myeloma precursors. MGUS and SMM are heterogeneous conditions with the presence of tumors with distinct pathogenic phenotypes and clinical outcomes. The identification of MGUS and SMM patients with a molecularly defined high risk of progression to MM offers the unique opportunity of early intervention with a therapeutic approach on a low tumor burden.

The Role of Thrombocyte/Lymphocyte Ratio and Aspartate Transaminase/Alanine Transaminase (De Ritis) Ratio in Prediction of Recurrence and Progression in Non-muscle Invasive Bladder Cancer.

The purpose of the study was to determine the predictive value of platelet-to-lymphocyte ratio (PLR) and Aspartate transaminase (AST)/alanine transaminase (ALT) ratio (De Ritis ratio) for recurrence and progression in non-muscle-invasive bladder cancer (NMIBC). A total of 231 patients who underwent transurethral tumor resection between 2016 and 2022 were retrospectively analyzed. Preoperative test results, including AST, ALT, platelet, and lymphocyte counts, were used to calculate the PLR and De Ritis ratio. Univariate and multivariate analyses were performed to identify the predictive factors associated with recurrence and progression. Based on the ROC curve, 1.19 and 1.21 were identified as the optimal cut-off values of the De Ritis ratio for recurrence and progression, respectively. Furthermore, PLR cut-off values for recurrence and progression were 114 and 118, respectively. There is a significant difference in recurrence-free survival (RFS) and progression-free survival (PFS) between the groups of patients with high and low De Ritis ratios (p = 0.028 and p = 0.021, respectively).In multivariate analysis, De Ritis ratio ≥ 1.19 and European Organization for Research and Treatment of Cancer (EORTC) high recurrence risk were determined to be significant predictors of tumor recurrence. Multivariate analysis also determined that T1 pathological stage, high tumor grade, European Organization for Research and Treatment of Cancer (EORTC) high progression risk, and De Ritis ratio ≥ 1.21 were risk factors for tumor progression. In our study, the preoperative De Ritis ratio represented an independent predictive factor for recurrence and progression in non-muscle invasive bladder cancer. The use of this biomarker in combination with other diagnostic/predictive tools might help urologists improve the clinical decision-making process in the future.

Spatial Distribution of Macrophage and Lymphocyte Subtypes within Tumor Microenvironment to Predict Recurrence of Non-Muscle-Invasive Papillary Urothelial Carcinoma after BCG Immunotherapy.

Non-muscle-invasive papillary urothelial carcinoma (NMIPUC) of the urinary bladder is the most common type of bladder cancer. Intravesical Bacille Calmette-Guerin (BCG) immunotherapy is applied in patients with a high risk of recurrence and progression of NMIPUC to muscle-invasive disease. However, the tumor relapses in about 30% of patients despite the treatment, raising the need for better risk stratification. We explored the potential of spatial distributions of immune cell subtypes (CD20, CD11c, CD163, ICOS, and CD8) within the tumor microenvironment to predict NMIPUC recurrence following BCG immunotherapy. Based on analyses of digital whole-slide images, we assessed the densities of the immune cells in the epithelial-stromal interface zone compartments and their distribution, represented by an epithelial-stromal interface density ratio (IDR). While the densities of any cell type did not predict recurrence, a higher IDR of CD11c (HR: 0.0012, p-value = 0.0002), CD8 (HR: 0.0379, p-value = 0.005), and ICOS (HR: 0.0768, p-value = 0.0388) was associated with longer recurrence-free survival (RFS) based on the univariate Cox regression. The history of positive repeated TUR (re-TUR) (HR: 4.93, p-value = 0.0001) and T1 tumor stage (HR: 2.04, p-value = 0.0159) were associated with shorter RFS, while G3 tumor grade according to the 1973 WHO classification showed borderline significance (HR: 1.83, p-value = 0.0522). In a multivariate analysis, the two models with a concordance index exceeding 0.7 included the CD11c IDR in combination with either a history of positive re-TUR or tumor stage. We conclude that the CD11c IDR is the most informative predictor of NMIPUC recurrence after BCG immunotherapy. Our findings highlight the importance of assessment of the spatial distribution of immune cells in the tumor microenvironment.

Molnupiravir Real-World Utilization in COVID-19 Patients in the Czech Republic.

Background/Objectives: Molnupiravir (MOV), an oral antiviral COVID-19 treatment, was introduced in the Czech Republic in December 2021 for COVID-19 patients at a high risk of progression to severe disease requiring hospitalization. In this observational, retrospective study, we aimed to describe the characteristics and healthcare resource utilization in non-hospitalized, adult COVID-19 patients prescribed MOV in the Czech Republic between 1 January and 30 April 2022. Methods: A total of 621 patients were included and followed up with for 28 days. Results: The median age was 68.0 (20-99) years, 77.8% were overweight or obese, 14.1% smoked, and 85.7% were vaccinated. The overall cumulative incidence (95% CI) of all-cause hospitalization was 0.71 (0.37; 1.24) per 1000 person years or 1.9%, with similar rates across sexes, age groups, BMI category, multimorbidity category, polypharmacy category, and COVID-19 vaccination status. Among patients reported hospitalized, oxygen-based resources were not observed, and no deaths occurred. Conclusions: These data describe the characteristics and healthcare resource utilization in Czech MOV-treated patients whose clinical characteristics may put them at increased risk of severe disease.

Population-based study of disease trajectory after radical treatment for high-risk prostate cancer.

To investigate long-term disease trajectories among men with high-risk localized or locally advanced prostate cancer (HRLPC) treated with radical radiotherapy (RT) or radical prostatectomy (RP). Men diagnosed with HRLPC in 2006-2020, who received primary RT or RP, were identified from the Prostate Cancer data Base Sweden (PCBaSe) 5.0. Follow-up ended on 30 June 2021. Treatment trajectories and risk of death from prostate cancer (PCa) or other causes were assessed by competing risk analyses using cumulative incidence for each event. In total, 8317 men received RT and 4923 men underwent RP. The median (interquartile range) follow-up was 6.2 (3.6-9.5) years. After RT, the 10-year risk of PCa-related death was 0.13 (95% confidence interval [CI] 0.12-0.14) and the risk of death from all causes was 0.32 (95% CI 0.31-0.34). After RP, the 10-year risk of PCa-related death was 0.09 (95% CI 0.08-0.10) and the risk of death from all causes was 0.19 (95% CI 0.18-0.21). The 10-year risks of androgen deprivation therapy (ADT) as secondary treatment were 0.42 (95% CI 0.41-0.44) and 0.21 (95% CI 0.20-0.23) after RT and RP, respectively. Among men who received ADT as secondary treatment, the risk of PCa-related death at 10 years after initiation of ADT was 0.33 (95% CI 030-0.36) after RT and 0.27 (95% CI 0.24-0.30) after RP. Approximately one in 10 men with HRLPC who received primary RT or RP had died from PCa 10 years after diagnosis. Approximately one in three men who received secondary ADT, an indication of PCa progression, died from PCa 10 years after the start of ADT. Early identification and aggressive treatment of men with high risk of progression after radical treatment are warranted.

Electronic Health Record Population Health Management for Chronic Kidney Disease Care

Large gaps in clinical care in patients with chronic kidney disease (CKD) lead to poor outcomes. To compare the effectiveness of an electronic health record-based population health management intervention vs usual care for reducing CKD progression and improving evidence-based care in high-risk CKD. The Kidney Coordinated Health Management Partnership (Kidney CHAMP) was a pragmatic cluster randomized clinical trial conducted between May 2019 and July 2022 in 101 primary care practices in Western Pennsylvania. It included patients aged 18 to 85 years with an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m2 with high risk of CKD progression and no outpatient nephrology encounter within the previous 12 months. Multifaceted intervention for CKD comanagement with primary care clinicians included a nephrology electronic consultation, pharmacist-led medication management, and CKD education for patients. The usual care group received CKD care from primary care clinicians as usual. The primary outcome was time to 40% or greater reduction in eGFR or end-stage kidney disease. Among 1596 patients (754 intervention [47.2%]; 842 control [52.8%]) with a mean (SD) age of 74 (9) years, 928 (58%) were female, 127 (8%) were Black, 9 (0.6%) were Hispanic, and the mean (SD) estimated glomerular filtration rate was 36.8 (7.9) mL/min/1.73m2. Over a median follow-up of 17.0 months, there was no significant difference in rate of primary outcome between the 2 arms (adjusted hazard ratio, 0.96; 95% CI, 0.67-1.38; P = .82). Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker exposure was more frequent in intervention arm compared with the control group (rate ratio, 1.21; 95% CI, 1.02-1.43). There was no difference in the secondary outcomes of hypertension control and exposure to unsafe medications or adverse events between the arms. Several COVID-19-related issues contributed to null findings in the study. In this study, among patients with moderate-risk to high-risk CKD, a multifaceted electronic health record-based population health management intervention resulted in more exposure days to angiotensin-converting enzyme inhibitors/angiotensin receptor blockers but did not reduce risk of CKD progression or hypertension control vs usual care. ClinicalTrials.gov Identifier: NCT03832595.