Clinical Management Of Patients Research Articles

Chondroitin sulfate proteoglycan 4 (CSPG4) increases invasion of recessive dystrophic epidermolysis bullosa-associated cutaneous squamous cell carcinoma by modifying TGFβ signaling.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic skin-blistering disorder often progressing to metastatic cutaneous squamous cell carcinoma (cSCC) at chronic wound sites. Chondroitin sulfate proteoglycan 4 (CSPG4) is a cell-surface proteoglycan that is an oncoantigen in multiple malignancies, where it modulates oncogenic signaling, drives epithelial-to-mesenchymal transition (EMT), and enables cell motility. To evaluate CSPG4 expression and function in RDEB-cSCC. RDEB-cSCC cell lines were used to assess CSPG4-dependent changes in invasive potential, TGFβ1-stimulated signal activation, and clinically relevant cytopathology metrics in an in vitro full-thickness tumor model. CSPG4 expression in RDEB-cSCC and non-RDEB cSCC tumors was analyzed via immunohistochemistry and single-cell RNA sequencing (scRNA-seq), respectively. Inhibiting CSPG4 expression reduced invasive potential in multiple RDEB-cSCC cell lines and altered membrane-proximal TGFβ signal activation through changes in SMAD3 phosphorylation. CSPG4 expression was uniformly localized to basal-layer keratinocytes in fibrotic RDEB skin and tumor cells at the tumor/stroma interface at the invasive front in RDEB-cSCC tumors in vivo. Analysis of published scRNA-seq data revealed that CSPG4 expression was correlated with an enhanced EMT transcriptomic signature in cells at the tumor/stroma interface of non-RDEB cSCC tumors. Cytopathological metrics, like nucleus:cell area ratio, were influenced by CSPG4 expression in in vitro tumor models. We determined that CSPG4 expression in RDEB-cSCC cell lines enhanced invasive potential. Mechanistically, CSPG4 was found to enhance membrane-proximal TGFβ-stimulated signaling through SMAD3, which is a key mediator of EMT in RDEB-cSCC. The implication of these studies is that CSPG4 may represent a therapeutic target that can be leveraged for clinical management in patients with RDEB-cSCC.

Consumer wearable devices for evaluation of heart rate control using digoxin versus beta-blockers: the RATE-AF randomized trial.

Consumer-grade wearable technology has the potential to support clinical research and patient management. Here, we report results from the RATE-AF trial wearables study, which was designed to compare heart rate in older, multimorbid patients with permanent atrial fibrillation and heart failure who were randomized to treatment with either digoxin or beta-blockers. Heart rate (n = 143,379,796) and physical activity (n = 23,704,307) intervals were obtained from 53 participants (mean age 75.6 years (s.d. 8.4), 40% women) using a wrist-worn wearable linked to a smartphone for 20 weeks. Heart rates in participants treated with digoxin versus beta-blockers were not significantly different (regression coefficient 1.22 (95% confidence interval (CI) -2.82 to 5.27; P = 0.55); adjusted 0.66 (95% CI -3.45 to 4.77; P = 0.75)). No difference in heart rate was observed between the two groups of patients after accounting for physical activity (P = 0.74) or patients with high activity levels (≥30,000 steps per week; P = 0.97). Using a convolutional neural network designed to account for missing data, we found that wearable device data could predict New York Heart Association functional class 5 months after baseline assessment similarly to standard clinical measures of electrocardiographic heart rate and 6-minute walk test (F1 score 0.56 (95% CI 0.41 to 0.70) versus 0.55 (95% CI 0.41 to 0.68); P = 0.88 for comparison). The results of this study indicate that digoxin and beta-blockers have equivalent effects on heart rate in atrial fibrillation at rest and on exertion, and suggest that dynamic monitoring of individuals with arrhythmia using wearable technology could be an alternative to in-person assessment. ClinicalTrials.gov identifier: NCT02391337 .

Genito Urinary Infection and Urinary Tract Infection in Patients with Type 2 Diabetes Mellitus Receiving SGLT2 Inhibitors: Evidence from a Systematic Literature Review of Landmark Randomized Clinical Trial.

SGLT2 inhibitors are class of drugs that are used in adults with type 2 diabetes through a novel mechanism of action by reducing renal tubular glucose reabsorption, leading to a reduction in blood glucose without stimulating insulin release. In this systematic review, we report the effects of treatment with SGLT2 inhibitors on urinary tract infection (UTI) and genitourinary infection (GUI). The study integrated data from landmark trials of SGLT2 inhibitors (CANVAS, CREDENCE, DECLARE-TIMI 58, and EMPA-REG) to interpret the association of SGLT2 inhibitors with genital infection (GI) and UTI. We reported the review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome was a composite of participants reporting UTI and GUI prescribed on SGLT2 inhibitors. The analysis of four studies involving 38,723 participants revealed incidences of both UTIs and GUI. In the SGLT2 inhibitor group, comprising 21,266 participants, 222 (1.04%) experienced UTIs, and 477 (2.24%) reported GUI. In contrast, among the placebo group consisting of 17,457 participants, 201 (1.15%) reported UTIs, and 70 (0.40%) reported genital infections. These findings underscore the elevated risk associated with SGLT2 inhibitor use, particularly regarding GUI, necessitating careful consideration in clinical practice and patient management strategies. The incidence of UTIs and particularly more pronounced GUI associated with SGLT2 inhibitors highlights the importance of careful risk assessment and monitoring in clinical decision-making, underscoring the need for patient management strategies.

PET imaging of gliomas: Status quo and quo vadis?

PET imaging, particularly using amino acid tracers, has become a valuable adjunct to anatomical MRI in the clinical management of patients with glioma. Collaborative international efforts have led to the development of clinical and technical guidelines for PET imaging in gliomas. The increasing readiness of statutory health insurance agencies, especially in European countries, to reimburse amino acid PET underscores its growing importance in clinical practice. Integrating artificial intelligence and radiomics in PET imaging of patients with glioma may significantly improve tumor detection, segmentation, and response assessment. Efforts are ongoing to facilitate the clinical translation of these techniques. Considerable progress in computer technology developments (eg quantum computers) may be helpful to accelerate these efforts. Next-generation PET scanners, such as long-axial field-of-view PET/CT scanners, have improved image quality and body coverage and therefore expanded the spectrum of indications for PET imaging in Neuro-Oncology (eg PET imaging of the whole spine). Encouraging results of clinical trials in patients with glioma have prompted the development of PET tracers directing therapeutically relevant targets (eg the mutant isocitrate dehydrogenase) for novel anticancer agents in gliomas to improve response assessment. In addition, the success of theranostics for the treatment of extracranial neoplasms such as neuroendocrine tumors and prostate cancer has currently prompted efforts to translate this approach to patients with glioma. These advancements highlight the evolving role of PET imaging in Neuro-Oncology, offering insights into tumor biology and treatment response, thereby informing personalized patient care. Nevertheless, these innovations warrant further validation in the near future.

Drug survival for biologics in psoriasis patients: real world evidence for Greece during the period 2016-2020.

Drug persistence is a crucial aspect of treatment success in psoriasis. The scope of this manuscript is to record real-world evidence concerning drug survival of biologic agents used for psoriasis treatment and to detect associated modifying factors in Greece. This was a retrospective cohort study based on data extracted from the nationwide Greek prescription system. Psoriatic patients, with or without concomitant psoriatic arthritis (PsA), that had initiated biologics between January 1st 2016 and December 31st 2020 were included. We included 8,819 patients who received 13,359 treatment lines. Among them, 76.8% were biologic naïve patients and 16.5% were diagnosed with concomitant PsA. The overall median drug survival was 34.3 (95% CI: 32.6-36.5) months. Drug persistence at 12, 24, 36 and 48 months of follow-up was 71.9%, 57.7%, 49.0% and 43.7%, respectively. Patients receiving brodalumab had the highest drug survival rate in the first two years, while secukinumab had the highest rates beyond this period. Overall, drug survival rates were higher in the 1st [median, 51.1 (95% CI: 47.1, not reached (NR) months] compared to the 2nd treatment line and onwards [median, 21.7 (95% CI: 20.0, 23.5) months]. Treatment line, PsA status, age and sex were found to significantly affect drug survival rates. Our findings confirm previous reports regarding the importance of efficient 1st line biologics and the vulnerability of patients to co-existent PsA. The utilitzation of antibodies against interleukins confer to high drug survival rates. These results will assist clinical management of psoriasis patients in Greece.

Thymic Squamous Cell Carcinoma and Brain Metastases: Case Report and Literature Review

Thymic squamous cell carcinoma (TSCC) is a rare cancer that is typically characterized by low rates of brain metastases. However, when it does occur, brain metastases of TSCC can have significant clinical implications due to its rarity and lack of established management guidelines. In this literature review and case report, we explore the clinical presentation, management, and outcomes of patients with brain metastases of TSCC.Our literature review found that brain metastases of TSCC are relatively rare, with an estimated incidence of 5-10 % among patients with advanced-stage disease. Management of brain metastases of TSCC often involves a combination of surgical resection, radiation therapy, and chemotherapy. However, due to the rarity of this condition, there is currently limited evidence to guide optimal treatment strategies.We also present a case report of a patient with TSCC who was presented with a brain metastasis. This case highlights the importance of early diagnosis and prompt management of brain metastasis of TSCC to improve patient outcomes. Our review and case report underscore the need for further research to improve our understanding of the clinical characteristics, optimal management, and prognosis of patients with brain metastasis of TSCC.

Exploring Fibrosis Pathophysiology in Lean and Obese Metabolic-Associated Fatty Liver Disease: An In-Depth Comparison.

While obesity-related nonalcoholic fatty liver disease (NAFLD) is linked with metabolic dysfunctions such as insulin resistance and adipose tissue inflammation, lean NAFLD more often progresses to liver fibrosis even in the absence of metabolic syndrome. This review aims to summarize the current knowledge regarding the mechanisms of liver fibrosis in lean NAFLD. The most commonly used lean NAFLD models include a methionine/choline-deficient (MCD) diet, a high-fat diet with carbon tetrachloride (CCl4), and a high-fructose and high-cholesterol diet. The major pro-fibrogenic mechanisms in lean NAFLD models include increased activation of the extracellular signal-regulated kinase (ERK) pathway, elevated expression of α-smooth muscle actin (α-SMA), collagen type I, and TGF-β, and modulation of fibrogenic markers such as tenascin-X and metalloproteinase inhibitors. Additionally, activation of macrophage signaling pathways promoting hepatic stellate cell (HSC) activation further contributes to fibrosis development. Animal models cannot cover all clinical features that are evident in patients with lean or obese NAFLD, implicating the need for novel models, as well as for deeper comparisons of clinical and experimental studies. Having in mind the prevalence of fibrosis in lean NAFLD patients, by addressing specific pathways, clinical studies can reveal new targeted therapies along with novel biomarkers for early detection and enhancement of clinical management for lean NAFLD patients.

Development and validation of a nomogram to predict overall survival in patients with glioma: a population-based study.

The objective is to investigate the prognostic factors associated with gliomas and to develop and assess a predictive nomogram model connected to survival that may serve as an additional resource for the clinical management of glioma patients. From 2010 to 2015, participants included in the study were chosen from the Surveillance Epidemiology and End Results (SEER) database. Gliomas were definitively diagnosed in each of them. They were divided into the training group and the validation cohort at random (7/3 ratio) using a random number table. To identify the independent predictive markers for overall survival (OS), Cox regression analysis was utilized. Subsequently, the training cohort's survival-related nomogram predictive model for OS was created by incorporating the fundamental patient attributes. Following that, the training cohort's model underwent internal validation. The nomogram model's authenticity and reliability were assessed through the computation of receiver operating characteristic (ROC) curves and concordance index (C-index). To evaluate the degree of agreement between the observed and predicted values in the training and validation cohorts, calibration plots were created. Age, primary site, histological type, surgery, chemotherapy, marital status, and grade were the independent predictive factors for OS in the training cohort, according to Cox regression analysis. Moreover, the nomogram model for predicting 1-year, 3-year, and 5-year OS was built using these variables. The C-indexes of OS for glioma patients in the training cohort and internal validation cohort were found to be 0.779 (95% CI=0.769-0.789) and 0.776 (95% CI=0.760-0.792), respectively, according to the results. The ROC curves also demonstrated good discrimination. Additionally, calibration plots demonstrated a fair amount of agreement. In summary, the nomogram prediction model of OS demonstrated a moderate level of reliability in its predictive performance, offering valuable reference data to enable doctors to quickly and easily determine the survival likelihood of patients with gliomas.

Development and integration of a clinical dashboard within a dental school setting.

To describe the development and integration of an electronic health record-driven, student dashboard that displays real-time data relative to the students' patient management and clinic experiences at the University of Illinois Chicago, College of Dentistry. Following development and implementation of the student dashboard, various objective metrics were evaluated to identify any improvements in the clinical patient management. A cross-sectional retrospective chart review was completed of the electronic health record (axiUm, Exan, Coquitlam, BC, Canada) from January 2019 to April 2022 evaluating four performance metrics: student lockouts, note/code violations, overdue active patients, and overdue recall patients. Descriptive statistics were analyzed. The Kolmogorov-Smirnov test was applied to assess the normal distribution of data. Data were analyzed by the Kruskal-Wallis tests for potential differences between pre-dashboard and post-dashboard implementation years with the mean overdue active/recall patient to student ratio variables. Mann-Whitney U-tests for between-groups comparisons with Bonferroni correction for multiple comparisons were performed (α=0.05). Descriptive statistics were performed to analyze the student utilization frequency of the dashboard. Post-implementation analysis indicated a slight decrease in the number of lockouts and note/code violation; and a statistically significant decrease in overdue active patients post-dashboard (P<0.001). On average, students accessed their dashboards 3.3 times a week. Implementation of a student dashboard through the electronic health record platform within an academic dental practice has the potential to assist students with patient management and is utilized regularly by the students.

Clinical implications of the 2022 WHO classification on the multidisciplinary management of PitNETS patients.

The review explores the 2022 update to the World Health Organization (WHO) classification of pituitary adenomas, now referred to as pituitary neuroendocrine tumors (PitNETs), and his possible impact on the clinical management of PitNET patients. The review highlights the differences and the evolution from the 2017 to 2022 version, with the current classification considering the lineage of the tumor cells, cell type, hormones produced, and other auxiliary characteristics for a comprehensive histological classification. The revision in terminology reflects a broader perspective on neuroendocrine neoplasia. The new approach based on transcription factors, hormone expression and other biomarkers has allowed a major revision of the nomenclature and a more accurate classification of pituitary adenomas. Furthermore, in some cases this approach is also assuming a prognostic value, useful in clinical practice. However, despite this elaborate classification and stratification, the review points out the lack of a robust grading or staging system and suggests the need for further research and validation of diagnostic methods. Despite these limitations, the revised classification presents a significant step towards understanding and managing PitNETs patients.

PET/CT-Based Absorbed Dose Maps in 90Y Selective Internal Radiation Therapy Correlate with Spatial Changes in Liver Function Derived from Dynamic MRI.

Functional liver parenchyma can be damaged from treatment of liver malignancies with 90Y selective internal radiation therapy (SIRT). Evaluating functional parenchymal changes and developing an absorbed dose (AD)-toxicity model can assist the clinical management of patients receiving SIRT. We aimed to determine whether there is a correlation between 90Y PET AD voxel maps and spatial changes in the nontumoral liver (NTL) function derived from dynamic gadoxetic acid-enhanced MRI before and after SIRT. Methods: Dynamic gadoxetic acid-enhanced MRI scans were acquired before and after treatment for 11 patients undergoing 90Y SIRT. Gadoxetic acid uptake rate (k1) maps that directly quantify spatial liver parenchymal function were generated from MRI data. Voxel-based AD maps, derived from the 90Y PET/CT scans, were binned according to AD. Pre- and post-SIRT k1 maps were coregistered to the AD map. Absolute and percentage k1 loss in each bin was calculated as a measure of loss of liver function, and Spearman correlation coefficients between k1 loss and AD were evaluated for each patient. Average k1 loss over the patients was fit to a 3-parameter logistic function based on AD. Patients were further stratified into subgroups based on lesion type, baseline albumin-bilirubin scores and alanine transaminase levels, dose-volume effect, and number of SIRT treatments. Results: Significant positive correlations (ρ = 0.53-0.99, P < 0.001) between both absolute and percentage k1 loss and AD were observed in most patients (8/11). The average k1 loss over 9 patients also exhibited a significant strong correlation with AD (ρ ≥ 0.92, P < 0.001). The average percentage k1 loss of patients across AD bins was 28%, with a logistic function model demonstrating about a 25% k1 loss at about 100 Gy. Analysis between patient subgroups demonstrated that k1 loss was greater among patients with hepatocellular carcinoma, higher alanine transaminase levels, larger fractional volumes of NTL receiving an AD of 70 Gy or more, and sequential SIRT treatments. Conclusion: Novel application of multimodality imaging demonstrated a correlation between 90Y SIRT AD and spatial functional liver parenchymal degradation, indicating that a higher AD is associated with a larger loss of local hepatocyte function. With the developed response models, PET-derived AD maps can potentially be used prospectively to identify localized damage in liver and to enhance treatment strategies.

Validation of Artificial Intelligence in the Classification of Adolescent Idiopathic Scoliosis and the Compairment to Clinical Manual Handling.

The accurate measurement of Cobb angles is crucial for the effective clinical management of patients with adolescent idiopathic scoliosis (AIS). The Lenke classification system plays a pivotal role in determining the appropriate fusion levels for treatment planning. However, the presence of interobserver variability and time-intensive procedures presents challenges for clinicians. The purpose of this study is to compare the measurement accuracy of our developed artificial intelligence measurement system for Cobb angles and Lenke classification in AIS patients with manual measurements to validate its feasibility. An artificial intelligence (AI) system measured the Cobb angle of AIS patients using convolutional neural networks, which identified the vertebral boundaries and sequences, recognized the upper and lower end vertebras, and estimated the Cobb angles of the proximal thoracic, main thoracic, and thoracolumbar/lumbar curves sequentially. Accordingly, the Lenke classifications of scoliosis were divided by oscillogram and defined by the AI system. Furthermore, a man-machine comparison (n = 300) was conducted for senior spine surgeons (n = 2), junior spine surgeons (n = 2), and the AI system for the image measurements of proximal thoracic (PT), main thoracic (MT), thoracolumbar/lumbar (TL/L), thoracic sagittal profile T5-T12, bending views PT, bending views MT, bending views TL/L, the Lenke classification system, the lumbar modifier, and sagittal thoracic alignment. In the AI system, the calculation time for each patient's data was 0.2 s, while the measurement time for each surgeon was 23.6 min. The AI system showed high accuracy in the recognition of the Lenke classification and had high reliability compared to senior doctors(ICC 0.962). The AI system has high reliability for the Lenke classification and is a potential auxiliary tool for spinal surgeons.

Construction of a novel prognostic scoring model for HBV-ACLF liver failure based on dynamic data

Early prognostic assessment of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is important for guiding clinical management and reducing mortality. The aim of this study was to dynamically monitor the clinical characteristics of HBV-ACLF patients, thereby allowing the construction of a novel prognostic scoring model to predict the outcome of HBV-ACLF patients. Clinical data was prospectively collected for 518 patients with HBV-ACLF and randomly divided into training and validation sets. We constructed day-1, day-2, and day-(1 + 3) prognostic score models based on dynamic time points. The prognostic risk score constructed for day-3 was found to have the best predictive ability. The factors included in this scoring system, referred to as DSM-ACLF-D3, were age, hepatic encephalopathy, alkaline phosphatase, total bilirubin, triglycerides, very low-density lipoprotein, blood glucose, neutrophil count, fibrin, and INR. ROC analysis revealed the area under the curve predicted by DSM-ACLF-D3 for 28-day and 90-day mortality (0.901 and 0.889, respectively) was significantly better than those of five other scoring systems: COSSH-ACLF IIs (0.882 and 0.836), COSSH-ACLFs (0.863 and 0.832), CLIF-C ACLF (0.838 and 0.766), MELD (0.782 and 0.762) and MELD-Na (0.756 and 0.731). Dynamic monitoring of the changes in clinical factors can therefore significantly improve the accuracy of scoring models. Evaluation of the probability density function and risk stratification by DSM-ACLF-D3 also resulted in the best predictive values for mortality. The novel DSM-ACLF-D3 prognostic scoring model based on dynamic data can improve early warning, prediction and clinical management of HBV-ACLF patients.

Combining telemedicine and in-person visits to deliver care to patients with severe chronic kidney disease (CKD): Lessons learned from COVID-19.

Telemedicine has been widely used to deliver healthcare to outpatients during the COVID-19 pandemic. The effectiveness of this modality is unclear in patients with a pre-dialysis stage of chronic kidney disease (CKD). This study aims to describe the clinical characteristics and management of CKD patients receiving telemedicine care during the COVID-19 pandemic. A retrospective single-center cohort study enrolled outpatients with pre-dialytic stage of CKD from March 9 to June 21, 2020. Telemedicine was proposed for all patients with a stable CKD to reduce the risk of in-hospital transmission whereas in-person visit was performed for patients requiring urgent evaluation. In a 15-week period, 97 patients received 116 nephrological visits. According to the modality of healthcare delivery, the patients were subdivided into telemedicine (66%) and in-person visit (34%) groups. Mean age of all CKD patients was 72.8 ± 12.5 years and males were 50.5% of the population. The average estimated glomerular filtration rate (eGFR) was 14.6±6 mL/min. Patients evaluated by telemedicine had better kidney function (GFR, 16.2±6.4 vs. 13.6±5.9 mL/min/1.73m2; p=0.037), a lower body mass index (BMI) (24.1 ± 1.7 vs. 30.6 ± 5.7; p=0.019), and a lower risk of CKD progression (51.1 vs. 25.4%, p=0.017) than patients requiring in-person visit. Telemedicine-visit patients experienced a significantly lower number of pharmacological changes than patients managed in the ambulatory setting. Telemedicine was also used to conduct 20% of educational meetings on the choice of dialysis modality and 18.9% of pre-eligibility visits for kidney transplantation. Telemedicine made it possible to provide care to and maintain close monitoring of 2/3 of patients with pre-dialytic stage of CKD during the COVID-19 pandemic.

Cardiac implantable electronic devices: An update.

Cardiac implantable electronic devices (CIEDs) are a core component in the management of heart rhythm disorders. The complexity of devices, the information gathered and therapy delivered by CIEDs continues to advance at pace. The aim of this paper is to provide an update on advances in CIED technology and how this applies to managing patients with CIEDs in general practice. In recent years, there have been notable advances in CIED technology. These include widespread magnetic resonance imaging compatibility and automated algorithms to assist in the clinical management of patients. There is the ability for clinicians and pacemaker clinics to monitor devices remotely, avoiding in-clinic visits. Options are now available for leadless pacemakers and subcutaneous defibrillators as an alternative to indwelling leads and associated infection and vascular issues. Techniques have been developed to allow leads to capture the native conduction system, providing physiological cardiac activation (conduction system pacing) for treatment and prevention of heart failure.

Intraplaque neovascularization combined with plaque elasticity for predicting ipsilateral stroke in patients with asymptomatic mild carotid stenosis.

Intraplaque neovascularization (IPN) is a biomarker for vulnerable atherosclerotic plaques and can be effectively visualized via contrast-enhanced ultrasound (CEUS). Plaque elasticity is influenced by elements such as lipid core and fibrosis and can be quantitatively assessed on shear wave elastography (SWE). Studies combining the use of CEUS and SWE for the assessment of stroke risk are currently lacking. Our study thus aimed to determine the predictive value of IPN combined with plaque elasticity among patients with asymptomatic carotid plaque. Consecutive patients with mild carotid stenosis who underwent CEUS and SWE were retrospectively analyzed. IPN was graded according to the presence and location of microbubbles within the plaque, while plaque elasticity was measured in terms of mean shear wave velocity (SWV). All patients were followed up for 6 months to monitor the development of ischemic stroke. The predictive values of IPN and SWV, individually and in combination, were assessed. A total of 121 patients were included, of whom 95 (78.5%) were male. The mean age was 63.1±10.7 years. Both grade 2 IPN [hazard ratio (HR) =2.37, 95% confidence interval (CI): 1.58-9.65; P=0.039] and SWV (HR =0.43, 95% CI: 0.20-0.95; P=0.038) were independently associated with future ischemic stroke events. The combined model demonstrated a significantly better predictive performance (HR =3.243, 95% CI: 1.87-6.17; P=0.027). The combination of IPN and SWV demonstrated significantly better predictive value for the risk of stroke. Our combined model thereby has the potential to guide the clinical stratification and management of patients with asymptomatic mild carotid stenosis.

Breast Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Breast cancer is treated with a multidisciplinary approach involving surgical oncology, radiation oncology, and medical oncology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget's disease, Phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of systemic therapy (preoperative and adjuvant) options for nonmetastatic breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org.

Bioengineer mesenchymal stem cell for treatment of glioma by IL‐12 mediated microenvironment reprogramming and nCD47‐SLAMF7 mediated phagocytosis regulation of macrophages

AbstractHigh expression of cellular self‐activated immunosuppressive molecules and extensive infiltration of suppressive immune cells in the tumor microenvironment are the main factors contributing to glioma's resistance to immunotherapy. Nonetheless, technology to modify the expression of glioma cellular self‐molecules through gene editing requires further development. This project advances cell therapy strategies to reverse the immunosuppressive microenvironment of glioma (TIME). Bone marrow‐derived mesenchymal stem cells (MSCs) are engineered to express bioactive proteins and demonstrate tumor‐homing characteristics upon activation by TGF‐β. These MSCs are designed to secrete the anti‐tumor immune cytokine IL‐12 and the nCD47‐SLAMF7 fusion protein, which regulates T‐cell activity and macrophage phagocytosis. The engineered MSCs are then injected in situ into the glioma site, circumventing the blood‐brain barrier to deliver high local concentrations of bioactive proteins. This approach aims to enhance the M1 polarization of infiltrating macrophages, stimulate macrophage‐mediated tumor cell phagocytosis, activate antigen‐presenting cells, and promote effector CD8+ T cell infiltration, effectively controlling glioma. Additionally, the engineered MSCs may serve as a universal treatment for other tumors that express TGF‐β at high levels. This study proposes a novel treatment strategy for the clinical management of glioma patients.

Advancing cancer drug development with mechanistic mathematical modeling: bridging the gap between theory and practice.

Quantitative predictive modeling of cancer growth, progression, and individual response to therapy is a rapidly growing field. Researchers from mathematical modeling, systems biology, pharmaceutical industry, and regulatory bodies, are collaboratively working on predictive models that could be applied for drug development and, ultimately, the clinical management of cancer patients. A plethora of modeling paradigms and approaches have emerged, making it challenging to compile a comprehensive review across all subdisciplines. It is therefore critical to gauge fundamental design aspects against requirements, and weigh opportunities and limitations of the different model types. In this review,we discuss three fundamental types of cancer models: space-structured models, ecological models, and immune system focused models. For each type, it is our goal to illustrate which mechanisms contribute to variability and heterogeneity in cancer growth and response, so that the appropriate architecture and complexity of a new model becomes clearer. We present the main features addressed by each of the three exemplary modeling types through a subjective collection of literature and illustrative exercises to facilitate inspiration and exchange, with a focus on providing a didactic rather than exhaustive overview. We close by imagining a future multi-scale model design to impact critical decisions in oncology drug development.

Disease burden, clinical management and unmet treatment need of patients with moderate to severe atopic dermatitis; consensus statements, insights and practices from CERTADE (Central/Eastern EU, Russia, Turkiye AD Experts) Delphi panel.

There is limited insight into the current disease burden and everyday clinical management of moderate-to- severe AD in Poland, Czechia, Russia, and Turkiye. Therefore, this study aimed to get information-driven insights regarding the current disease burden and clinical management of patients with moderate-to-severe AD with common and differentiating aspects of the patient journey and establish a consensus. In this modified 2-round Delphi panel, 133 questions were asked in total to 27 dermatologists. A consensus was achieved when 70% of the panel members strongly agreed or agreed (or strongly disagreed or disagreed) with an item. Statements with <40% agreement dropped from the Delphi rounds and were not repeated. The results state that AD has a significant impact on the quality of life for both patients and their families with social and economic consequences in these countries. While there were significant dissimilarities regarding the current treatment approach by preference order and treatment duration among participants, there was also a high percentage of consensus on literature and guideline-based statements. Current topical therapies and the immune response modifiers were not found to be sufficient by panelists to cover the therapeutic needs of patients with moderate-to-severe AD. Moreover, panelists highlighted the significant burden of adverse events with the off-label use of currently available immunosuppressants. These results underlined that there is a significant disease burden with an unmet treatment need for patients with moderate-to-severe AD in Poland, Czechia, Russia, and Turkiye.