Therapeutic Decisions Research Articles

Retrospective study assessing the role of theandrogen receptor in clear cell renal cell cancer patients treated with VEGFR inhibitors in monotherapy.

Despite that incorporating antiangiogenic in combination with immune-checkpoint inhibitors as the standard first-line treatment for advanced clear cell renal cell cancer (ccRCC) yields promising outcomes, these regimens often lead to significant toxicity. However, a subgroup of patients has shown responsiveness to VEGFR tyrosine-kinase inhibitors (TKIs) in monotherapy, leading tothe question ofwhether employing combination therapies can significantly enhance overall survival in all patients over monotherapy. Thus, we aim to identify gene expression signatures that can predict TKI response within subpopulations that might benefit from single-agent therapies, to minimize unnecessary exposure to combination therapies and their associated toxicities, as well as to discover new potential therapeutic targets to improve ccRCC treatment. Based on prior data, the androgen receptor (AR) might meet both conditions. We evaluated the association between AR expression, assessed through NanoString® technology-derived mRNA counts, and the clinical outcomes of 98 ccRCC patients treated with first-line antiangiogenics and determined its association with other genes implicated in ccRCC tumorigenesis. Higher AR-expression correlates significantly with better prognosis and survival based on the MSKCC risk score, and longer PFS. Furthermore, we have identified a gene set signature associated with AR-overexpression and several genes involved in angiogenesis and transcriptional targets of the hypoxia-inducible factor, a cornerstone of ccRCC. AR-overexpression and its association with other genes could favor a transcriptomic signature set to aidin identifying patients suitable for TKI in monotherapy, rather than aggressive combinations, enhancing thus, precision and personalized therapeutic decisions.

An Updated Comprehensive Review on Diseases Associated with Nephrotic Syndromes.

There have been exciting advances in our knowledge of primary glomerular diseases and nephrotic syndromes in recent years. Beyond the histological pattern from renal biopsy, more precise phenotyping of the diseases and the use of modern nephrogenetics helps to improve treatment decisions and sometimes also avoid unnecessary exposure to potentially toxic immunosuppression. New biomarkers have led to easier and more accurate diagnoses and more targeted therapeutic decisions. The treatment landscape is becoming wider with a pipeline of promising new therapeutic agents with more sophisticated approaches. This review focuses on all aspects of entities that are associated with nephrotic syndromes with updated information on recent advances in each field. This includes podocytopathies (focal segmental glomerulosclerosis and minimal-change disease), membranous nephropathy, membranoproliferative glomerulonephritis, IgA nephropathy, fibrillary glomerulonephritis, amyloidosis, and monoclonal gammopathy of renal significance in the context of the nephrotic syndrome, but also renal involvement in systemic diseases, diabetic nephropathy, and drugs that are associated with nephrotic syndromes.

Noninvasive Respiratory Support for Pediatric Critical Asthma.

Pediatric asthma is a significant cause of emergency department visits and hospital admissions. While most patients respond well to standard pharmacologic treatments, those with more severe disease frequently require noninvasive respiratory support (NRS) and adjunct therapies, or admission to an intensive care unit-a condition termed critical asthma. NRS modalities include high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), and noninvasive ventilation (NIV) to deliver standard air-oxygen mixtures or helium-oxygen (heliox). Each NRS modality offers distinct physiological benefits, primarily aimed at reducing work of breathing, enhancing gas exchange, and optimizing aerosol delivery. Despite the growing use of NRS, robust evidence supporting its efficacy in pediatric critical asthma is limited, with few published clinical trials and a heavy reliance on observational studies to inform clinical practice. This narrative review explores the current evidence, physiological rationale, practical considerations, and future research directions for the use of NRS in pediatric critical asthma. The goal is to provide clinicians with a comprehensive overview of the benefits and limitations of NRS modalities to better inform therapeutic decisions and improve patient outcomes.

Multidimensional phenotyping to distinguish among central (CSA), obstructive (OSA) and co-existing central and obstructive sleep apnea (CSA-OSA) phenotypes in real-world data

PurposeWhen navigating the landscape of obstructive sleep apnea (OSA), central sleep apnea (CSA) and intersection of the two diseases (co-existing CSA-OSA), there are significant knowledge gaps. Data are scarce regarding the respective prevalence and differences in clinical presentation of the three conditions. One major issue for characterization of the prevalence of the different sleep apnea entities is the scoring of central versus obstructive hypopneas which is not included in the routine practice of many sleep laboratories. MethodWe prospectively assessed multidomain symptoms and collected data on comorbidities, medications and treatment indications in a large monocentric real-life dataset (n > 2400) of patients referred for suspicion of sleep apnea. We have systematically distinguished central versus obstructive hypopneas to define OSA, CSA and co-existing CSA-OSA. ResultsWhen CSA was defined by the proportion of central apneas (and hypopneas were considered obstructive by default), the prevalence of CSA was 4.59 % (co-existing CSA-OSA: 11.03 %, and OSA: 84.37 %). When the distinction between obstructive and central hypopneas was used to classify the sleep disordered breathing, the prevalence of CSA was fourfold higher at 19.69 % (co-existing: 19.16 %, OSA: 61.16 %). The burden of cardiovascular and metabolic comorbidities was the highest in the CSA and co-existing sleep apnea subgroups. The three sleep apnea groups exhibited different constellations of symptoms but most of the patients with CSA, co-existing and OSA were symptomatic after comprehensive evaluation. The CSA group exhibited the most severe disturbances in sleep architecture on polysomnography. Therapeutic indications differed depending on the subtype of respiratory events. ConclusionOur findings imply that not differentiating between central and obstructive hypopneas will underestimate the severity of central sleep disordered breathing abnormalities that mislead therapeutic decisions and might limit improvements in quality of life and sleepiness that are expected in appropriately treated patients with CSA.

Use of ultra-low contrast dose CT aortography for the management of aortic aneurysmal disease

PurposeComputed tomography aortography (CTA) is used in the assessment of aortic pathologies and planning of surgical intervention. However, its dependence on iodinated contrast can result in development of contrast-induced acute kidney injury (CI-AKI). The potential concern of CI-AKI has spurred research into the potential of administration of low contrast volumes in CTA investigations while maintaining overall diagnostic appeal. Several studies have shown that CTA using contrast volumes as low as 30 mL (equivalent to 10.5 g of iodine) can still yield scans of diagnostic quality. We present a retrospective pilot study to evaluate the feasibility of utilising an ultra-low volume of iodinated intravenous contrast in a population of patients with severe renal insufficiency with referral from our vascular surgery unit for CTA evaluation of the thoracic and abdominal aorta.MethodsThis retrospective pilot study examined 12 CTA scans performed with 20 mLs of iodinated contrast and assessed image quality with both quantitative and qualitative markers. All scans were performed on a Siemens SOMATOM Force dual-source CT scanner. Quantitative assessment values were measured via attenuation values at eight aortoiliac locations and used to calculate a signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) at each location. Qualitative analysis of image quality and viability for surgical intervention was obtained from subjective clinical assessment by an interventional radiologist and vascular surgeon.ResultsObtained quantitative assessment values included mean attenuation 189.9 HU, mean SNR 9.6 and mean CNR 8.0. All 12 scans demonstrated individual mean SNR values above predetermined quality thresholds while only five scans produced individual mean CNR values above threshold. Eleven of 12 scans were determined to be of sufficient quality for diagnosis and planning of surgical intervention.ConclusionsOur results suggest that CTA utilising an ultra-low contrast dose of 20 mLs (6 g iodine) yields scans of diagnostic quality for therapeutic decision-making in vascular surgical intervention.

A-231 A modified Sampson LDL-C equation to improve concordance with the reference method at low levels of LDL-C

Abstract Background Patients at high risk for Atherosclerotic Cardiovascular Disease (ASCVD), who do not achieve adequate lowering of LDL-cholesterol (LDL-C) with maximally tolerated statins or who are statin-intolerant, are often treated with proprotein convertase subtilisin/kexin (type 9) serine protease inhibitor (PCSK9-inh) therapy. The LDL-C reference method, Beta-Quantitation (BQ), is not routinely performed in these patients. Because low values are measured less accurately with current methods, a variety of equations have been developed to calculate LDL-C from the standard lipid panel test results (total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C)). We further modified the Sampson LDL-C (S-LDL-C) equation by a novel approach by combining logistic regression (LR) and linear regression to minimize errors when compared to BQ for low LDL-C. Methods A dataset of BQ results from Mayo Medical Labs was divided randomly into a training set (TG ≤ 1500 mg/dL, TC ≤ 1050 mg/dL, n=19,639) and a validation set (TG ≤ 800 mg/dL, BQ-LDL-C ≤ 130 mg/dL, n=12,910). The training dataset was analyzed by LR, using BQ-LDL-C to classify patients as being above or below the 70 mg/dL cut-point. Dependent variables in the LR model were the S-LDL-C, HDL-C, TC, TG and an interaction term (TG x NonHDL-C). The sum of the exponential terms in the trained LR equation for the dependent variables were then fitted by least squares linear regression to match BQ-LDL-C to develop the modified S-LDL-C equation (mS-LDL-C). We used the validation dataset to compare Friedewald (F-LDL-C), extended Martin (eM-LDL-C), Sampson (S-LDL-C) and modified Sampson (mS-LDL-C) equations by Cohen’s kappa coefficient for agreement with BQ-LDL-C and normalized Matthew’s correlation coefficient (MCC), which considers any imbalances in the number of false high versus false low results. Results The mS-LDL-C equation (mS-LDL-C = (TC/0.9423 - HDL-C/0.9582 - TG/9.397 - ((TGxNonHDL-C)/1305) + TG2/8569) - 5.688), primarily differs from the S-LDL-C equation in the value of the coefficients that include TG as a variable. For S-LDL-C ≤100 mg/dL, mS-LDL-C had the best concordance with BQ-LDL-C in terms of the total percent of patients misclassified as either high or low (mS-LDL-C: 21.4%, S-LDL-C: 24.4%, eM-LDL-C: 25.4% F-LDL-C: 30.8%). mS-LDL-C also had the best kappa score when compared to BQ (mS-LDL-C: 0.833, S-LDL-C: 0.810, eM-LDL-C: 0.789, F-LDL-C: 0.743). MCC was also the highest for mS-LDL-C (mS-LDL-C: 0.916, S-LDL-C: 0.906, eM-LDL-C: 0.894, F-LDL-C: 0.879). Finally, mS-LDL-C also showed the best concordance with BQ-LDL-C when an alternative lower LDL-C therapeutic decision cut-point of 55 mg/dL is used (kappa of 0.766 versus 0.724) but showed an increasingly poorer performance than S-LDL-C for higher LDL-C whenever it exceeded 150 mg/dL. Conclusions A strategy to maximize the overall accuracy of estimated LDL-C could provide an automatic reflex in a laboratory information system to the mS-LDL-C equation whenever S-LDL-C is <100 mg/dL. By doing so, the use of the more accurate mS-LDL-C equation for low LDL-C should improve PCSK9-inh therapeutic decision making over the other LDL-C equations.

Improving the Prognostic and Predictive Value of Circulating Tumor Cell Enumeration: Is Longitudinal Monitoring the Answer?

Circulating tumor cell (CTC) numbers in the blood of cancer patients can indicate the progression and invasiveness of tumors, and their prognostic and predictive value has been repeatedly demonstrated. However, the standard baseline CTC count at the beginning of treatment, while informative, is not completely reliable and may not adequately reflect the state of the disease. A growing number of studies indicate that the long-term monitoring of CTC numbers in the same patient provides more comprehensive prognostic data and should be incorporated into clinical practice, as a factor that contributes to therapeutic decisions. This review describes the current status of CTC enumeration as a prognostic and predictive factor, highlights the shortcomings of current solutions, and advocates for longitudinal CTC analysis as a more effective method of the evaluation of developing disease, treatment efficacy, and the long term-monitoring of the minimal residual disease. As evidenced by the described reports, the longitudinal monitoring of CTCs should provide a better and more sensitive prediction of the course of the disease, and its incorporation in clinical practice should be beneficial.

B-227 Customized molecular tests for minimal residual disease: a tool for therapeutic decisions in follicular lymphoma patients

Abstract Background Monitoring of minimal residual disease (MRD) is based on accurate laboratory tests which can recognize a small fraction of malignant cells that survived the course of treatment. Several studies of the B-non-Hodgkin lymphoma group have been presented that MRD positivity at the end of treatment is a negative prognostic index. Follicular lymphoma (FL) is a chronic indolent malignancy, which response highly to immuno-chemotherapy followed by prolonged remissions but with inevitable relapse in most patients. The GALLIUM study showed that immuno-chemotherapy combinations, 6 cycles of bendamustine-obinutuzumab (BO), is the most efficacious treatment, but with severe side effects .In addition, 90% of patients achieved negative MRD from peripheral blood (PB) or bone marrow (BM) after only 3 BO cycles. These findings raise the possibility for MRD based treatment approach, where the duration of chemotherapy could be decided according to MRD status at mid-induction (MI). Identification of a marker in the PB and/or BM of each FL patient which will be use to the design of a sensitive RQ-PCR test for MRD detection for follow-up. Methods Qualitative PCR for translocation 14:18 and for the VDJ rearrangement sequence of the immunoglobulin heavy chain was used for marker identification. MRD monitoring was done by RQ-PCR. MRD monitoring for VDJ was designed specifically to each patients based on his VDJ sequence. MRD was assessed on PB and BM at MI. Results Marker for monitoring was identified at 11/21 patients in this study. After 3 combined therapy cycles, 7 patients were found to have MRD negativity by RQ-PCR therefore continue with immuno-therapy only. MRD positivity was assessed in BM of 3 patients (0.11%, 0.022%, and 0.133%). These 3 patients continued with the combined therapy. RQ-PCR sensitivity was 10-4-10-5. Conclusions This study will reveal the ability to use sensitive and specific MRD that has to be designed for each patient according to his marker and enable the establishment of a treatment with a high safety profile for FL patients. Correlation between MRD status and clinical and safety parameters will be assessed at the end of the study, 30 months after the first treatment, taking into account MRD status from different time point of the follow-up period.

Comparison of DNA methylation based classification models for precision diagnostics of central nervous system tumors

As part of the advancement in therapeutic decision-making for brain tumor patients at St. Jude Children’s Research Hospital (SJCRH), we developed three robust classifiers, a deep learning neural network (NN), k-nearest neighbor (kNN), and random forest (RF), trained on a reference series DNA-methylation profiles to classify central nervous system (CNS) tumor types. The models’ performance was rigorously validated against 2054 samples from two independent cohorts. In addition to classic metrics of model performance, we compared the robustness of the three models to reduced tumor purity, a critical consideration in the clinical utility of such classifiers. Our findings revealed that the NN model exhibited the highest accuracy and maintained a balance between precision and recall. The NN model was the most resistant to drops in performance associated with a reduction in tumor purity, showing good performance until the purity fell below 50%. Through rigorous validation, our study emphasizes the potential of DNA-methylation-based deep learning methods to improve precision medicine for brain tumor classification in the clinical setting.

The Use of Midazolam as an Antiseizure Medication in Neonatal Seizures: Single Center Experience and Literature Review.

Existing therapeutic alternatives for neonatal crises have expanded in recent decades, but no consensus has been reached on protocols based on neonatal seizures. In particular, little is known about the use of midazolam in newborns. The aim of our study is to evaluate the response to midazolam, the appearance of side effects, and their impact on therapeutic decisions. This is a STROBE-conformed retrospective observational study of 10 patients with neonatal seizures unresponsive to common antiseizure drugs, admitted to San Marco University Hospital's neonatal intensive care (Catania, Italy) from September 2015 to October 2022. In our database search, 36 newborns were treated with midazolam, but only ten children met the selection criteria for this study. Response was assessed both clinically and electrographic. Only 4 patients at the end of the treatment showed a complete electroclinical response; they were full-term infants with a postnatal age greater than 7 days. Non-responders and partial responders are all premature (4/10) or full-term neonates who started therapy in the first days of life (< 7th day) (2/10). Neonatal seizures in preterm show a lower response rate to midazolam than seizures in full-term infants, with poorer prognosis. Liver and renal function and central nervous system development are incomplete in premature infants and the first days of life. In this study, we show that midazolam, a short-acting benzodiazepine, appears to be most effective in full-term infants and after 7 days of life.

Descripción de un caso: ¿es factible realizar una biopsia selectiva de ganglio centinela en tumores de mama originados en el tejido ectópico axilar?

Breast cancer on axillary ectopic breast tissue is very rare, representing 0.3-0.6% of malignant breast cancers. Therefore, its early diagnosis is a real challenge. In this case, we describe a breast cancer on left axillary ectopic tissue in a 36-year-old female patient, who underwent local surgery with excision of the tissue. When approaching the nodal study of this patient, the possibility of selective study of the sentinel lymph node was considered. The absence of validated clinical guidelines in these cases and the exhaustive review of the literature led the multidisciplinary tumour committee of our hospital, the Hospital Clínico de Santiago de Compostela, to adopt the decision to attempt to perform this technique, adapting it, however, to this particular case. A double tracer was used, injecting technetium-99m in the periareolar area of the left breast and patent blue in the intratumoral area of the axillary ectopic tissue to determine whether both the breast and the tumour had the same lymphatic drainage pathways.Finally, 7 sentinel nodes and 1 palpable non-sentinel node were detected, of which the first was marked with both technetium-99m and patent blue, 4 with the radioisotope only, and 2 stained with patent blue. Two macrometastases were detected intraoperatively in the sentinel nodes, stained only with patent blue, while the rest were negative. The tumour committee took the decision to treat the axilla with radiotherapy. It is therefore concluded that in these cases the periareolar lymphatic drainage and that of the tumour itself may be different, so it would be advisable to use the double tracer injected in different areas to correctly identify the sentinel lymph node. The literature available for this type of situation is scanty and there are no approved clinical guidelines to support our therapeutic decisions, so it would be essential to study breast cancer in infrequent locations, in depth, in order to achieve protocols standardised by international societies that would serve as a benchmark for the management of these cases.

Performance and Clinical Implications of VI-RADS in detecting muscle invasion in bladder tumors: A prospective observational study.

Bladder cancer staging is pivotal for guiding therapeutic decisions. In this study, the primary objective was to assess the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI), The study aimed to classify bladder tumors as either nonmuscle-invasive bladder cancers or muscle-invasive bladder cancers (MIBC) using the Vesical Imaging Reporting and Data System (VI-RADS) scoring. A secondary objective of the study focused on the accuracy of biparametric magnetic resonance imaging (bpMRI) in comparison to mpMRI. Thirty-three patients with bladder tumors were enrolled and underwent both mpMRI and bpMRI scoring assessments. VI-RADS scores were assigned and subsequently compared with histopathological findings posttransurethral resection of bladder tumor., Statistical measures included sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for VI-RADS scores at cutoff thresholds of ≥4 and 5. MpMRI at a VI-RADS cutoff of ≥4 yielded an 83.33% sensitivity and 100% specificity, with a diagnostic accuracy of 90.91%. At a cutoff of 5, sensitivity was 100%, specificity was 77.27%, and diagnostic accuracy was 84.85%. bpMRI at a cutoff of ≥4 showed an 80% sensitivity and 100% specificity, with diagnostic accuracy matching mpMRI at 90.91%. This prospective analysis demonstrates that VI-RADS scoring with mpMRI provides reliable diagnostic accuracy for bladder cancer staging. mpMRI exhibits high sensitivity and specificity at a cutoff of ≥ 4, making it a robust tool for MIBC detection. bpMRI is an effective alternative in select patients. The study validates the use of VI-RADS scoring in clinical practice for effective treatment planning.

Clinical utility of upfront liquid biopsy in non-small cell lung cancer in the community setting.

316 Background: Molecular diagnosis of advanced non-small cell lung cancer (NSCLC) is critical to guide therapeutic decisions. Blood next generation sequencing (NGS) allows for non-invasive screening for targetable genetic abnormalities. Many studies have validated using the liquid biopsies to screen for resistant mutations at the emergence of treatment failure. However, the clinical utility of liquid biopsy for newly diagnosed NSCLC, as part of a comprehensive molecular profiling, is an area of active research. Methods: Retrospective analysis of the molecular landscape and clinical outcomes in NSCLC patients who had liquid biopsy done between December of 2017 to February of 2022. Patients had EGFR, ALK, ROS-1, and BRAF tested in the tissue, and underwent liquid biopsy for broad molecular profiling. The plasma genotyping was conducted using a 73-gene panel by Guardant 360 test. Actionable mutations were stratified accordingly to the OncoKB database based on the level of preclinical and clinical evidence of drug targetability. Survival analysis was conducted by August of 2023. Results: We enrolled 122 NSCLC patients who 84% were treatment-naïve and 78% had the liquid biopsy performed at the initial diagnosis. We found that 86 patients had oncogenic mutations and 43 (35%) had actionable mutations, with 37 (29%) falling under level 1 of evidence mutations. EGFR and KRAS G12C mutations were the two most common level 1 genetic abnormalities (23% and 11% of all actionable mutations, respectively). We identified two germline BRCA carriers who were referred for genetic counselling. 25 patients (20%) received treatment based on the liquid biopsy results, with 15 (12%) achieving partial response. Six patients had liquid biopsy done at progression of EGFR or MET therapies, which identified a resistance mechanism in three of them. Conclusions: Upfront liquid biopsy identified a significant proportion of patients with targetable mutations. Here, we reported actionable mutations in 35% of our patients who 84% had no prior systemic treatment. Our results complement prior literature and shows that blood next generation sequencing can be a useful tool to guide upfront therapeutical options at the community healthcare setting.

Prostate volume on computed tomography correlates well with magnetic resonance imaging measurements and is reproducible across rater training levels.

Data are lacking for the accuracy of computed tomography (CT) in measuring prostate size, which can streamline care and prevent invasive procedures. We evaluate agreement and intra/inter-observer variability in prostate sizing between CT and magnetic resonance imaging (MRI) planimetry for a wide range of gland sizes. We retrospectively reviewed 700 patients who underwent MRI fusion biopsy at a single institution and identified 89 patients that had a CT within 2years of the MRI. Six reviewers from different training levels were categorized as student, resident, or attending and each measured prostate size on CT by the prolate ellipse method. Bland-Altman analysis determined the degree of agreement between CT and MRI. Inter- and intra-observer reliability was calculated for CT. Mean CT volume was higher than MRI volume in the < 60g group (51.5g vs. 44.5g, p = 0.004), but not in the ≥ 60g group (101g vs. 100g, p = 0.458). The bias for overestimation of prostate volume by CT was 4.1g across prostate volumes, but the proportional agreement between modalities improved with size. The Pearson correlation coefficient between CT/MRI and inter/intra-rater reliability for CT increased in the ≥ 60g vs. the < 60g group for all training levels. Our data show that there is greater clinical utility for prostate size estimation by CT than previously established, particularly for larger glands where accurate size estimation may influence therapeutic decisions. In larger glands, prostate size estimation by CT is also reproducible across various training levels.

Role of Susceptibility Weighted Imaging (SWI) in Comparison to Magnetic Resonance Angiography in Assessment of the Intra-Arterial Thrombus in Patients with Acute Ischemic Stroke

Abstract Background Stroke occurs when the blood supply to the brain is cut off, usually due to a blood vessel burst or being blocked by a clot. This reduces the supply of oxygen and nutrients, causing brain tissue damage. The effects of a stroke depend on which part of the brain is injured. For this purpose, thrombus assessment in patients with acute stroke is of major clinical relevance since the location of the thrombus may determine the therapeutic decision. Aim of the Work Aim of study is to assess the role of susceptibility weighted imaging in assessment of intra-arterial thrombus in correlation with MRA and basic stroke protocol in patients with acute ischemic stroke. Patients and Methods This study is a cross-sectional study was conducted at Ain Shams University Hospitals at Radiology department. Our study included thirty patients with acute stroke symptoms in less than 24 hours of symptoms onset. The main source of data for this study was the prospectively conducted scans and clinical history of the patients referred to the MRI section of the department of Radiology, Ain Shams University Hospitals for doing MRI stroke protocol with addition of SWI sequence from November 2022 to June 2023. Results Thirty patients complaining of acute stroke symptoms in less than 24 hours of symptoms onset. Every single one of them went through MRI stroke protocol assessment and SWI sequence was added. So, SVS and TOF MRA were able to detect intra-arterial thrombus in acute stroke patients by 90 % and 95 %, respectively. There was no statistically significant difference in the rates of detection of intra-arterial thrombosis by SWI and MRA in patients with acute ischemic stroke (P = 0.57). The sensitivity of SWI for detection the intra-arterial thrombus in relation to MRA in MCA is 90%, in ACA and PCA is 100%, ICA is 66.7%. While specificity of SWI in relation to MRA in MCA is 80%, in PCA, ACA and ICA are 100%. The accuracy of SWI in assessment of intra-arterial thrombus in comparison to MRA in MCA is 94%, PCA 100%, ICA 95% and ACA 100%. The length of thrombus in SWI (lengthof SVS) could be measured ranging between 0.5-3.5 cm. Conclusion The SWI sequence needs to be incorporated into SWI stroke protocol for evaluating patients who have recently suffered an acute stroke as MRA and SWI techniques complement each other for visual detection of the occluded vessel. SWI has reasonable sensitivity, specificity and accuracy in the assessment of intra-arterial thrombosis in relation to MRA in patient of acute ischemic stroke. The „susceptibility sign' has a high sensitivity for diagnosing acute intracranial vascular blockage location and its extent in all major intracranial arteries. Also, it can be used in measuring the length of the intra-arterial thrombus over TOF MRA which cannot entirely demarcate thrombus length.

When You Get to the Fork in the Road, Take It: The Challenges in Managing Patients With Advanced Prostate Cancer.

As is the case with most solid tumors, the heterogeneity of the disease biology of prostate cancer presents clinicians managing this disease with daily challenges. However, in contrast to other common cancers such as breast, lung, and colorectal cancers, there are unique challenges in prostate cancer management, including the variety of clinicians who manage aspects of the disease (urologists, medical oncologist, radiation oncologists) and the striking absence of prospective comparative data to inform the optimal sequence of systemic therapy in patients with metastatic castration-resistant disease. The purpose of this review is to attempt to assist practicing oncologists with sorting through the myriad of prostate cancer disease subsets and the challenges in making therapeutic decisions in multiple data-free zones given the absence of level 1 comparative clinical trials in the metastatic hormone-sensitive and castration-resistant states.

Molecular subtypes and prognostic models for predicting prognosis of lung adenocarcinoma based on miRNA-related genes.

MicroRNAs (miRNAs) are crucial in cancer development and progression, and therapies targeting miRNAs demonstrate great therapeutic promise. We sought to predict the prognosis and therapeutic response of lung adenocarcinoma (LUAD) by classifying molecular subtypes and constructing a prognostic model based on miRNA-related genes. This study was based on miRNA-mRNA action pairs and ceRNA networks in the Cancer Genome Atlas (TCGA) database. Three molecular subtypes were determined based on 64 miRNA-associated target genes identified in the ceRNA network. The S3 subtype had the best prognosis, and the S2 subtype had the worst prognosis. The S2 subtype had a higher tumor mutational load (TMB) and a lower immune score. The S2 subtype was more suitable for immunotherapy and sensitive to chemotherapy. The least absolute shrinkage and selection operator (LASSO) algorithm was performed to determine eight miRNA-associated target genes for the construction of prognostic models. High-risk patients had a poorer prognosis, lower immune score, and lower response to immunotherapy. Robustness was confirmed in the Gene-Expression Omnibus (GEO) database cohort (GSE31210, GSE50081, and GSE37745 datasets). Overall, our study deepened the understanding of the mechanism of miRNA-related target genes in LUAD and provided new ideas for classification. Such miRNA-associated target gene characterization could be useful for prognostic prediction and contribute to therapeutic decision-making in LUAD.

Development and validation of a machine-learning model for preoperative risk of gastric gastrointestinal stromal tumors

BackgroundGastrointestinal stromal tumors (GISTs) have malignant potential, and treatment varies according to risk. However, no specific protocols exist for preoperative assessment of the malignant potential of gastric GISTs (gGISTs). This study aimed to use machine learning (ML) to develop and validate clinically relevant preoperative models to predict the malignant potential of gGISTs. MethodsThis study screened patients diagnosed with gGISTs at the Affiliated Hospital of North Sichuan Medical College. Moreover, this study employed the Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression to identify risk factors. Subsequently, an ensemble of ML models was used to determine the optimal classifier. In addition, this study used SHapley Additive exPlanations (SHAP) for tailored risk profiling. ResultsThis study included 318 patients with gGISTs. Using LASSO regression and multifactorial logistic regression, this study analyzed the training dataset, revealing that the presence of endoscopic ultrasound (EUS) high-risk features, tumor border clarity, tumor diameter, and monocyte-to-lymphocyte ratio (MLR) were significant predictors of high malignancy risk in gGIST. As determined by our ML approach, the logistic classification model demonstrated optimal performance, with area under the receiver operating characteristic curves of 0.919 for the training set and 0.925 for the test set. Furthermore, decision curve analysis confirmed the clinical relevance of the model. ConclusionHigh-risk EUS features, ill-defined tumor margins, larger tumor diameters, and elevated MLR independently predicted increased malignant potential in gGIST. This study developed logistic regression models based on these factors, which were further interpreted using the SHAP methodology. This analytical approach facilitated personalized therapeutic decision-making among diverse patient populations.

Secondary mitral regurgitation surgical management: a narrative review.

The most common valvular heart disease in the US is moderate to severe mitral regurgitation (MR). Function MR or secondary MR comprises many of these cases. Moderate and severe secondary MR are independently associated with increased all-cause mortality and rehospitalization for heart failure. Both ischemic and nonischemic cardiomyopathy can cause secondary MR via similar pathophysiology that leads to inadequate valve leaflets coaptation. The management of secondary MR is complex. The optimal treatment strategy for secondary MR remains controversial, reflected in the vast array of treatment options and the complexity of therapeutic decision-making. Several surgical mitral valve repair techniques have been described in the literature. Many of these aims to facilitate adequate valve leaflet coaptation. In this review, the pathophysiology of MR is described with a focus on evaluating and managing secondary MR. A literature review was performed using PubMed and Google Scholar. Clinical trials, meta-analyses, randomized controlled trials, reviews, and systematic reviews were considered from January 1, 1995 through December 31, 2022. Articles published in languages other than English with limited text availability were excluded. Optimal therapeutic approach in severe secondary MR is complex and several patient factor should be considered. We provide a framework for the surgical management of secondary MR based on echocardiographic parameters, the presence of ischemia, and myocardial viability. Further study is needed to guide the selection of patients most likely to benefit from mitral valve repair or replacement in the setting of secondary MR.

Patent Foramen Ovale and Other Cardiopathies as Causes of Embolic Stroke With Unknown Source.

In patients with stroke caused by cardiac embolism, the responsible heart diseases include atrial fibrillation, acute myocardial infarction, sick sinus syndrome, valvular disease, and significant heart failure. When there is no clear source of the embolism, the condition is referred to as "embolic stroke with unknown source (ESUS)." Recent studies have shown that the most common cause of ESUS is a right-to-left cardiac shunt through a patent foramen ovale (PFO). However, considering that PFOs are found in up to 25% of the general population, their presence does not necessarily indicate causality. In patients with ESUS associated with a PFO, either anticoagulants or antiplatelets are used for the prevention of future strokes or transient ischemic attacks. However, it currently remains unclear which treatment is superior. Nevertheless, recent randomized clinical trials have shown that percutaneous closure of the PFO more effectively reduces the incidence of recurrent strokes compared to medical therapy alone in patients with PFO-related strokes. This benefit is especially significant when the PFO carries high-risk features, such as a large shunt or the presence of an atrial septal aneurysm. Furthermore, the effectiveness of PFO closure has been well documented in young patients (<60 years) with a high-risk PFO development. In other cases, the therapeutic decision should be made through discussion among neurologists, cardiologists, and patients. Notably, in ESUS patients without a PFO, the underlying heart condition itself may be the source of embolism, with left atrial enlargement being the most important factor. Theoretically, anticoagulants such as non-vitamin K antagonist oral anticoagulants (NOACs) would be an effective therapy in these cases. However, recent trials have failed to show that NOACs are superior to antiplatelets in preventing further strokes in these patients. This may be due to the still uncertain definition of emboligenic cardiopathy and the presence of other potential embolic sources, such as mild but emboligenic arterial diseases. Overall, further research is needed to elucidate the source of embolism and to determine an effective management strategy for patients with ESUS.