Individual Treatment Decisions Research Articles

Suhexiang pill for acute ischemic stroke in real-world practice setting (SUNRISE): protocol of a multicenter registry

BackgroundSuhexiang (SHX) pill is widely used for treating acute ischemic stroke (AIS). Experimental and randomized controlled trials suggested that SHX pill was beneficial for patients with AIS. However, the effectiveness of SHX pill in real-world practice setting remains unclear. It is of great importance to investigate the effectiveness and safety of SHX pill in patients with acute ischemic stroke in real-world clinical practice with long-term follow-up.MethodsThe Suhexiang pill for acute ischemic stroke in Real-world Practice Setting (SUNRISE) is a multicenter, prospective, product-specific, observational study designed to provide insight into the administration of SHX pill for patients with AIS in the real-world clinical practice setting, with an initial sample size of 1000. Eligible patients treated with SHX pill within seven days of AIS onset will be consecutively included in this registry. The primary outcome is the proportion of patients independent at 3 months after stroke onset defined by an mRS score of 0, 1, or 2.ConclusionThe findings of the SUNRISE registry will not only provide insights into the characteristics of patients who may benefit from SHX treatment, but also may enable the individualized treatment decision-making of SHX pill in real-world practice setting.Study registrationThis study was registered with the ClinicalTrials.gov (URL: https://clinicaltrials.gov/, Unique identifier: NCT05833932).

Predictive value of technetium-99m sodium pertechnetate thyroid scintigraphy in determining the permanence of congenital hypothyroidism

Objectives: We aim to investigate the predictive value of [99mTc] pertechnetate thyroid scintigraphy in determining the permanence of congenital hypothyroidism (CH). Material and Methods: A retrospective analysis of [99mTc] pertechnetate thyroid scans performed for evaluation of CH at the Nuclear Medicine Unit of a hospital in Hong Kong between January 1, 2008, and December 31, 2018, was conducted. Scintigraphic findings and parameters at diagnosis, including thyroid stimulating hormone (TSH), free thyroxine (fT4), gender, and gestational age, were reviewed. The need for lifelong thyroxine replacement therapy was reviewed. Results: The study included 85 subjects, with 74 (87.1%) presenting with eutopic thyroid and 11 (12.9%) showing thyroid dysgenesis. Patients with scintigraphic evidence of thyroid dysgenesis required permanent thyroid hormone replacement therapy. Among the patients with eutopic thyroid, a higher TSH level was associated with the need for lifelong thyroid hormone replacement therapy (cutoff TSH value 18.72 mIU/L, sensitivity 77.3% and specificity 53.8%). Gender, gestational age, and fT4 did not show significant differences between the transient and permanent CH groups in patients with eutopic thyroid. Conclusion: Scintigraphic findings of thyroid dysgenesis indicate a high prevalence of permanent CH. In patients with eutopic thyroid, higher TSH levels predict the requirement for lifelong thyroid hormone replacement therapy. These results provide insights into the prediction of CH and aid in individualized treatment decisions for patients with CH.

A recurrence model for non-puerperal mastitis patients based on machine learning.

Non-puerperal mastitis (NPM) is an inflammatory breast disease affecting women during non-lactation periods, and it is prone to relapse after being cured. Accurate prediction of its recurrence is crucial for personalized adjuvant therapy, and pathological examination is the primary basis for the classification, diagnosis, and confirmation of non-puerperal mastitis. Currently, there is a lack of recurrence models for non-puerperal mastitis. The aim of this research is to create and validate a recurrence model using machine learning for patients with non-puerperal mastitis. We retrospectively collected laboratory data from 120 NPM patients, dividing them into a non-recurrence group (n = 59) and a recurrence group (n = 61). Through random allocation, these individuals were split into a training cohort and a testing cohort in a 90%:10% ratio for the purpose of building the model. Additionally, data from 25 NPM patients from another center were collected to serve as an external validation cohort for the model. Univariate analysis was used to examine differential indicators, and variable selection was conducted through LASSO regression. A combination of four machine learning algorithms (XGBoost、Logistic Regression、Random Forest、AdaBoost) was employed to predict NPM recurrence, and the model with the highest Area Under the Curve (AUC) in the test set was selected as the best model. The finally selected model was interpreted and evaluated using Receiver Operating Characteristic (ROC) curves, calibration curves, Decision curve analysis (DCA), and Shapley Additive Explanations (SHAP) plots. The logistic regression model emerged as the optimal model for predicting recurrence of NPM with machine learning, primarily utilizing three variables: FIB, bacterial infection, and CD4+ T cell count. The model showed an AUC of 0.846 in the training cohort and 0.833 in the testing cohort. The calibration curve indicated excellent calibration of the model. DCA revealed that the model possessed favorable clinical utility. Furthermore, the model effectively achieved in the external validation group, with an AUC of 0.825. The machine learning model developed in this study, serving as an effective tool for predicting NPM recurrence, aids doctors in making more individualized treatment decisions, thereby enhancing therapeutic efficacy and reducing the risk of recurrence.

Local excision for T1 rectal cancer: A population-based study of practice patterns and oncological outcomes.

Local excision (LE) for T1 rectal cancer may be recommended in those with low-risk disease, while resection is typically recommended in those with a high risk of luminal recurrence or lymph node metastasis. The aim of this work was to compare survival between resection and LE. This was a population-based retrospective cohort study set in the Canadian province of Ontario. Patients were individuals with T1Nx rectal cancer between 2010 and 2014 and demographics, disease characteristics, treatments and outcomes were determined using linked administrative databases. This study does not include clinical information regarding individual patient treatment decisions. The main outcome measure was overall survival (OS). A total of 719 patients were identified, including 359 with upfront resection, 113 with LE and immediate resection (<90 days) and 247 with LE with definitive intent. The majority of LEs were performed via colonoscopy. Piecemeal excision (42% vs. 49%, p = 0.28) and positive margin (50% vs. 77%, p < 0.01) rates were high in both LE groups, with the highest rate in those with immediate resection. The prevalence of poor differentiation (<5%, p = 0.70) and lymphovascular invasion (LVI) (14%, p = 0.80) was similar across groups. In those with LE with definitive intent, 21% ultimately underwent resection (median 150 days, interquartile range 114-181 days) and 4% received radiation. There was no difference in 5-year OS between groups (resection83.2% vs. LE and immediate resection82.3% vs. definitive LE 83.3%; p = 0.33). Adjusted analyses demonstrated no association between approach and survival [definitive intent LE hazard ratio (HR) 0.97 (95% CI 0.70-1.35), LE and immediate resection HR 0.97 (95% CI 0.60-1.45), upfront resection HR 1 (Ref); p = 0.98]. Differentiation, piecemeal excisions and LVI were not associated with OS in the LE groups. There were no observed differences in survival between those who underwent resection, LE and immediate resection and definitive intent LE. Although, these are observational data, they call into question the reflexive decision to offer radical resection for those with suspected T1 rectal cancer.

Development of metastasis and survival prediction model of luminal and non-luminal breast cancer with weakly supervised learning based on pathomics.

Breast cancer stands as the most prevalent form of cancer among women globally. This heterogeneous disease exhibits varying clinical behaviors. The stratification of breast cancer patients into risk groups, determined by their metastasis and survival outcomes, is pivotal for tailoring personalized treatments and therapeutic interventions. The pathological sections of radical specimens encompass a diverse range of histological information pertinent to the metastasis and survival of patients. In this study, our objective is to develop a deep learning model utilizing pathological images to predict the metastasis and survival outcomes for breast cancer patients. This study utilized pathological sections from 204 radical mastectomy specimens obtained between January 2013 and December 2014 at the Second Affiliated Hospital of the Medical College of Zhejiang University. The 204 pathological slices were scanned and transformed into whole slide imaging (WSI), with manual labeling of all tumor areas. The WSI was then partitioned into smaller tiles measuring 512 × 512 pixels. Three networks, namely Densely Connected Convolutional Network 121 (DenseNet121), Residual Network (ResNet50), and Inception_v3, were assessed. Subsequently, we combined patch-level predictions, probability histograms, and Term Frequency-Inverse Document Frequency (TF-IDF) features to create comprehensive participants representations. These features served as the foundational input for developing a machine learning algorithm for metastasis analysis and a Cox regression model for survival analysis. Our results show that the Inception_v3 model shows a particularly robust patch recognition ability for estrogen receptor (ER) recognition. Our pathological model shows high accuracy in predicting tumor regions. The train area under the curve (AUC) of the Inception_v3 model based on supervised learning is 0.975, which is higher than the model established by weakly supervised learning. But the AUC of the metastasis prediction in training and testing sets is higher than value based on supervised learning. Furthermore, the C-index of the survival prediction model is 0.710 in the testing sets, which is also better than the value by supervised learning. Our study demonstrates the significant potential of deep learning models in predicting breast cancer metastasis and prognosis, with the pathomic model showing high accuracy in identifying tumor areas and ER status. The integration of clinical features and pathomics signature into a nomogram further provides a valuable tool for clinicians to make individualized treatment decisions.

A stratified treatment algorithm in psychiatry: a program on stratified pharmacogenomics in severe mental illness (Psych-STRATA): concept, objectives and methodologies of a multidisciplinary project funded by Horizon Europe.

Schizophrenia (SCZ), bipolar (BD) and major depression disorder (MDD) are severe psychiatric disorders that are challenging to treat, often leading to treatment resistance (TR). It is crucial to develop effective methods to identify and treat patients at risk of TR at an early stage in a personalized manner, considering their biological basis, their clinical and psychosocial characteristics. Effective translation of theoretical knowledge into clinical practice is essential for achieving this goal. The Psych-STRATA consortium addresses this research gap through a seven-step approach. First, transdiagnostic biosignatures of SCZ, BD and MDD are identified by GWAS and multi-modal omics signatures associated with treatment outcome and TR (steps 1 and 2). In a next step (step 3), a randomized controlled intervention study is conducted to test the efficacy and safety of an early intensified pharmacological treatment. Following this RCT, a combined clinical and omics-based algorithm will be developed to estimate the risk for TR. This algorithm-based tool will be designed for early detection and management of TR (step 4). This algorithm will then be implemented into a framework of shared treatment decision-making with a novel mental health board (step 5). The final focus of the project is based on patient empowerment, dissemination and education (step 6) as well as the development of a software for fast, effective and individualized treatment decisions (step 7). The project has the potential to change the current trial and error treatment approach towards an evidence-based individualized treatment setting that takes TR risk into account at an early stage.

Evaluating the Effectiveness of Shockwave Lithotripsy vs Ureteroscopic Lithotripsy for Treatment of Renal Stones: A Prospective Cohort Study.

Renal stones are a prevalent condition requiring effective treatment strategies. This study evaluates the comparative effectiveness of shockwave lithotripsy (SWL) and ureteroscopic lithotripsy (URSL) in treating renal stones in a Pakistani cohort, focusing on stone clearance, recurrence, and complications. This prospective cohort study involved 250 patients aged 18-55 diagnosed with renal stones. Participants were divided into two groups based on treatment selection (SWL or URSL) and followed for 12 months. Primary outcomes included stone clearance rates, while secondary outcomes encompassed recurrence and complications. Statistical analyses, including chi-square tests and Mann-Whitney U tests, assessed demographic and clinical characteristics, with significance set at p < 0.05. The mean age of participants was 35.05 years, with an equal distribution between SWL and URSL groups. Both treatments demonstrated similar stone clearance rates, with no significant difference in success (p > 0.05). Complications were noted in 64.4% of cases, with bleeding (34.0%) and infection (30.4%) as the most frequent issues. Recurrence rates were comparable (p = 0.800), affecting 49.2% of patients. Re-treatment was required in 51.2% of cases, equally distributed between the groups. SWL and URSL exhibit comparable effectiveness in treating renal stones, with similar success and recurrence rates. While complications were common, they were manageable. Both approaches are effective options for renal stone management, emphasizing the need for individualized treatment decisions based on patient and stone characteristics.

Risk Stratification in Pulmonary Hypertension in the UAE

Risk stratification in pulmonary arterial hypertension is critical in determining therapeutic strategies for patients. Patients are stratified into low-, intermediate-, and high-risk groups based on determinants of prognosis like clinical assessment, exercise tests, biochemical markers, echocardiography, and haemodynamic tests. The primary objective of treatment is to shift each of the component tests into a low-risk zone either by treatment escalation alone, as in the case of intermediate-risk patients, or by a combination of treatment escalation and repeat evaluation by right heart catheterisation in high-risk patients. Low-risk patients should be clinically assessed at least every 3 months, but follow-up is more frequent for intermediate- and high-risk patients. Apart from improving survival rates, health-related quality of life is also assessed at baseline and followup visits, which may predict the prognosis. Additionally, therapeutic drug monitoring is also essential during visits due to the risk of major side effects during treatment initiation or dose escalation. Initial and follow-up risk stratification can prevent delays in the intensification of therapy, but insurance denials act as a barrier to this approach. Therefore, a dedicated insurance team is required for approval of testing and therapies and a fasttrack process to communicate with the pulmonary hypertension expert centre. It can be concluded that risk stratification improves the treatment approach and helps make individualised treatment decisions. It also helps healthcare professionals better allocate treatment resources in cases of scarcity.

Prediction of mucinous adenocarcinoma in colorectal cancer with mucinous components detected in preoperative biopsy diagnosis.

Endoscopic biopsy diagnosis for the preoperative assessment of mucinous components in patients with colorectal cancer is limited. This study investigated a radiomics model and established an explainable prediction model by using machine learning to differentiate between adenocarcinoma with mucinous components and mucinous adenocarcinoma. The derivation cohort included 312 patients with colorectal cancer with mucinous components detected during preoperative endoscopic biopsy diagnosis. These patients were randomly divided into training and validation sets in a 7:3 ratio. Radiomics features were extracted, followed by feature engineering, to create a radiomic score (radscore). Subsequently, 24 features, including the radscore, clinical data, and serological characteristics, were used to develop machine learning models by using nine different machine learning algorithms. The SHapley Additive exPlanation (SHAP) method was employed to elucidate the workings of the machine learning models and visualize individual variable predictions. The radiomics model achieved an area under the curve (AUC) of 0.810. The random forest model outperformed the other models and had the highest AUC of 0.832; thus, this model was defined as the hybrid model. The clinical model, which was built using clinical data and serological characteristics, had an AUC of 0.732, whereas the radiomics model achieved an AUC of 0.810. SHAP model interpretation revealed that among the 14 features with non-zero SHAP values, the radscore and clinical T stage had notably higher values. This interpretable predictive model effectively differentiates between adenocarcinoma with mucinous components and mucinous adenocarcinoma in patients with colorectal cancer, thereby facilitating informed treatment decisions for individuals in whom mucinous components are identified during preoperative biopsy diagnosis.

Implementation of an Oncogeriatric Unit for Frail Older Patients with Breast Cancer: Preliminary Results.

(1) Background: Breast cancer (BC) has a high incidence in Europe, particularly in older adults. Traditionally under-represented in clinical trials, this age group is often undertreated due to ageism. This study aims to characterize frail older adults (≥70 years) with BC based on a comprehensive geriatric assessment, to guide individualized treatment decision-making. (2) Methods: A descriptive analysis of older adults with BC treated from January 2021 to December 2022 was performed. Data were analyzed based on anonymized electronic medical records. (3) Results: Of 123 patients (mean age 84.0 ± 5.6 years), 122 (99.2%) were women. The mean G8 screening score was 12.1 ± 2.5. Most had functional dependence (69.9% Barthel Index, 81.3% Lawton/Brody Scale) and a moderate-to-high risk of falling (76.4% Tinetti index). Cognitive impairment and malnutrition risk were present in 15.4% and 30.1%, respectively. Prehabilitation inclusive strategies led to adapted treatment in 55.3% of cases. Endocrine therapy, surgery, radiotherapy, and chemotherapy was used in 99.2%, 56.1%, 35.0%, and 8.9% of patients, respectively. (4) Conclusions: Our comprehensive oncogeriatric strategy promotes personalized oncologic treatment, improves outcomes by addressing frailty, and enhances treatment tolerability in older patients with BC, validating the expansion of this combined team approach to other cancer types and institutions.

In Vivo Cardiovascular Molecular Imaging: Contributions to Precision Medicine and Drug Development.

Conventional forms of noninvasive cardiovascular imaging that evaluate morphology, function, flow, and metabolism play a vital role in individual treatment decisions, often based on guidelines. Innovations in molecular imaging have enhanced our ability to spatially quantify the expression of a wider array of disease-related proteins, genes, or cell types, or the activity of specific pathogenic pathways. These techniques, which usually rely on design of targeted imaging probes, have already been used extensively in cancer medicine and have now become part of cardiovascular care in conditions such as amyloidosis and sarcoidosis. The recognition that common cardiovascular conditions are caused by a substantial diversity of pathobiologic pathways and the diversity of therapies available for use have rekindled interest in expanding the role of molecular imaging of tissue phenotype to improve precision in diagnosis and therapeutic decision-making. The intent of this article is to raise awareness and understanding of approaches to molecular or cellular imaging of phenotype with targeted probes, and their potential to promote the principles of precision medicine. Also addressed are the diverse roles of molecular imaging to improve precision and efficiency of new drug development at the stages of candidate identification, preclinical testing, and clinical trials.

The impact of chronic kidney disease on prognosis in acute stroke: unraveling the pathophysiology and clinical complexity for optimal management.

Chronic kidney disease (CKD) significantly increases stroke risk and severity, posing challenges in both acute management and long-term outcomes. CKD contributes to cerebrovascular pathology through systemic inflammation, oxidative stress, endothelial dysfunction, vascular calcification, impaired cerebral autoregulation, and a prothrombotic state, all of which exacerbate stroke risk and outcomes. This review synthesizes evidence from peer-reviewed literature to elucidate the pathophysiological mechanisms linking CKD and stroke. It evaluates the efficacy and safety of acute reperfusion therapies-intravenous thrombolysis and endovascular thrombectomy-in CKD patients with acute ischemic stroke. Considerations, such as renal function, drug dosage adjustments, and the risk of contrast-induced nephropathy, are critically analyzed. Evidence-based recommendations and research priorities are drawn from an analysis of current practices and existing knowledge gaps. CKD influences stroke outcomes through systemic and local pathophysiological changes, necessitating tailored therapeutic approaches. Reperfusion therapies are effective in CKD patients but require careful monitoring of renal function to mitigate risks, such as contrast-induced nephropathy and thrombolytic complications. The bidirectional relationship between stroke and CKD highlights the need for integrated management strategies to address both conditions. Early detection and optimized management of CKD significantly reduce stroke-related morbidity and mortality. Optimizing stroke care in CKD patients requires a comprehensive understanding of their pathophysiology and clinical management challenges. This article provides evidence-based recommendations, emphasizing individualized treatment decisions and coordinated care. It underscores the importance of integrating renal considerations into stroke treatment protocols and highlights the need for future research to refine therapeutic strategies, address knowledge gaps, and consider tailored interventions to improve outcomes and quality of life for this high-risk population.

Prognostic Value of PD-L1, BAP-1 and ILK in Pleural Mesothelioma.

Background: Pleural mesothelioma (PM) is a rare type of cancer with poor prognosis. Prognostic and predictive biomarkers could improve treatment strategies in these patients. Programmed death ligand 1 (PD-L1), integrin-linked kinase (ILK) and breast cancer gene 1-associated protein (BAP-1) have been proposed to predict outcomes in PM, but existing data are limited and controversial. Design and Methods: This single-center, retrospective study analyzed data on expression patterns and the prognostic role of PD-L1, ILK and BAP-1 in consecutive patients diagnosed with PM. Results: Of all patients (n = 52) included, more than half showed a positive PD-L1 expression (52% TPS ≥ 1%, 65% CPS ≥ 1), 69% showed a BAP-1 loss and 80% an ILK ≥ 50%. Positive PD-L1 expression was more frequent in the non-epithelioid subtype (p = 0.045). ILK intensity (p = 0.032) and positive PD-L1 (p = 0.034) were associated with more advanced tumor stages. The median overall survival (OS) was 16.9 (95% CI 13.1-25.2) months. Multimodality therapy (MMT) including surgery and early stage were independent prognostic factors for longer OS (MMT: HR 0.347, 95% CI 0.13-0.90, p = 0.029; advanced stage: HR 4.989; 95% CI 1.64-15.13, p = 0.005). Patients with an expression of PD-L1 TPS ≥ 1% or BAP-1 positivity showed numerically worse survival with a median OS of 15.3 (11.5; 24.4) vs. 20.0 (11.2; 34.9) and 11.3 (5.6; 31.0) vs. 20.0 (15.2; 28.1) months, respectively. Furthermore, PD-L1 was associated with worse survival in patients receiving MMT (PD-L1 TPS ≥ 1%: 15.8 (12.1-25.4) vs. 31.3 (17.4-95.4) p = 0.053). ILK expression ≥50% did not influence survival. The combinations of CPS ≥ 1% with BAP-1 positivity or ILK expression ≥50% were associated with worse survival (p = 0.045, p = 0.019). Conclusions: In this real-world analysis, expressions of PD-L1 and BAP-1 were associated with worse survival in patients with PM. ILK showed no prognostic value. Further studies with larger cohorts are needed to identify prognostic and predictive biomarkers facilitating optimized individual treatment decision in this rare type of cancer.

Association of diabetes mellitus with long-term prognosis after ablation therapy for patients with hepatocellular carcinoma: A single-center cohort study.

This study investigated the clinical efficacy and prognostic factors of ablative treatment in hepatocellular carcinoma (HCC) patients with and without diabetes mellitus (DM). Retrospective data were collected from HCC patients who underwent ablation between January 2016 and December 2019. The baseline clinicopathological characteristics and long-term outcomes, such as overall survival (OS) and recurrence-free survival (RFS), were compared between those with and without DM. Predictive factors associated with survival and recurrence were identified through univariable and multivariable Cox regression analyses. Of the 3528 patients enrolled in the study, 588 (16.7%) had concurrent DM. The 1-, 3-, and 5-year RFS rates in patients with DM (73.8%, 33.7%, and 5.8%, respectively) were significantly (P < 0.001) lower than those in the non-DM patients (70.4%, 37.6%, and 18.6%, respectively). Likewise, significant differences (P < 0.001) in the 1-, 3-, and 5-year OS rates were observed between the DM (99.9%, 78.1%, and 29.1%, respectively) and non-DM (99.9%, 85.9%, and 54.3%, respectively) patients. Multivariable Cox regression analysis identified DM as an independent risk factor for OS [hazard ratio (HR), 1.982; P < 0.001] and RFS (HR, 1.175; P = 0.002). Patients with DM exhibited a poorer oncological prognosis than those without DM following ablation for HCC. DM was identified as an independent factor influencing the prognosis of HCC patients after curative ablation. Thus, active therapies targeting DM might enhance oncological outcomes and facilitate individualized treatment decisions.

Errorless and errorful learning in people with aphasia across novel-object pairing and word retrieval tasks

ABSTRACT Background While linguistic deficits are key to diagnosing and treating aphasia, there is growing interest in the cognitive processes important for rehabilitation outcomes, particularly the role of learning. Of relevance to the current study, research has manipulated instructional methods (errorless vs. errorful) to assess their effects on outcomes. However, it is still unclear whether individualized profiles of errorless and errorful learning exist in aphasia and whether they might be meaningful for clinical practice. Aims The current study aimed to examine learning in people with aphasia, manipulating instruction method (errorless, errorful) and linguistic demands of learning. Methods & procedures Nine people with stroke-induced aphasia participated in this preliminary study. Participants engaged in errorless and errorful novel object pairing and word retrieval tasks. Learning outcomes were assessed on the same day, next day, and after one week. Participants also completed cognitive-linguistic assessments to investigate the contribution of memory, language, and executive functioning abilities on learning outcomes. Outcomes & results At the group level, participants performed significantly better following errorful training for novel object pairing (p = 0.001) relative to errorless training. An errorful advantage was observed at the individual level in 7 participants during same day testing, with the highest overall performers on the task showing the most persistent errorful learning benefits. In the word retrieval practice task, group and individual-level differences in scores following errorless and errorful practice were minimal. Scores in errorful novel object pair learning correlated with verbal short-term memory and nonverbal long-term memory assessments, while no other correlations were found between learning scores and cognitive-linguistic variables. Conclusions Findings are consistent with prior research that suggests that successful effortful retrieval may pose an advantage over errorless learning when acquiring novel information and the potential contributions of verbal short-term memory and nonverbal long term memory on learning. Results from the word retrieval practice task draw attention to differences between practicing lexical access and novel learning. The lack of an errorful advantage in word retrieval may alternatively be due to task design and merits further research. Results support the hypothesis that people with aphasia display variable learning profiles that may stem from differences in underlying cognitive-linguistic abilities. Continuing research is needed to characterize learning in aphasia to consider its potential influence on rehabilitation outcomes and support speech-language pathologists in considering and accounting for different learning and cognitive-linguistic abilities when individualizing treatment decisions.

Genomic profiling and expanded use of targeted anticancer drugs in solid cancers with exhausted evidence-based treatment options (PRECODE): study protocol of a prospective, non-randomized, cohort study

BackgroundGenomic profiling of advanced solid cancer in patients with no further evidence based standard treatment options is a novel approach to identify potential experimental treatment options based on specific genomic alterations. Due to the expected short survival of these patients timely assessment of potential druggable targets is critical to minimize the risk of deterioration during the analysis.The primary objective of this prospective study is to evaluate the turnaround time for genomic profiling and the clinical investigational procedures. The secondary objectives are to investigate how often genomic alterations in tumor tissue gives rise to a matched treatment offer and evaluate the clinical outcome.MethodsThe PRECODE study is a prospective, non-randomized, single-center cohort study conducted at Departments of Oncology and Pathology, Odense University Hospital, Denmark. Enrollment between March 1, 2019 and December 31, 2024. Eligibility criteria are age ≥ 18 years, written informed consent, advanced solid tumors, exhausted treatment options, ECOG performance status 0–2, adequate organ function and life expectancy ≥ 3 months. A core needle biopsy is analyzed by next generation sequencing using a pan-cancer comprehensive panel. Results are discussed weekly at institutional/local and national multidisciplinary tumor boards.DiscussionStrategies and methods for genomic profiling of advanced solid cancers differ. Rapid analysis and interpretation of sequencing data are key to avoiding delays in initiation potential experimental treatments, as these late-stage patients may quickly deteriorate.Although a highly optimized setup with fast-track clinical evaluation and genomic profiling has been established a subset will not be offered a targeted treatment due to deterioration. Local and national multidisciplinary teams have been established to optimize individualized treatment decisions. After genomic profiling a subset of patients will take part in clinical trials, which will constrain the reporting of overall survival or progression free survival.Trial registrationDanish Ethics Committee, Projekt-ID: S-2018014, date of approval: 27- FEB- 2019) Danish Data Protection Agency (Journal no: 18/58329, date of approval: 23-NOV-2018).ClinicalTrials.gov Identifier: NCT05385081 (retrospectively registered).

EUROVISCO Consensus Guidelines for the Use of Hyaluronic Acid Viscosupplementation in Knee Osteoarthritis Based on Patient Characteristics.

Viscosupplementation with hyaluronic acid (HA) is a commonly used intra-articular treatment for osteoarthritis (OA). We performed a Delphi consensus process to formulate guidelines for the use of intra-articular hyaluronic acid (IAHA) knee injection according to the patient's characteristics. The EUROVISCO group consists of 12 members who had expertise in clinical and/or research in the field of OA and IAHA treatment. This group drafted issues through an iterative process and subsequently voted according to a Delphi process on their level of agreement (LoA) on these recommendations. The scores were pooled to generate a median agreement score for each recommendation. The strength of the recommendation (SOR) was classified as strong if the median agreement score was ≥8. The level of consensus (LOC) was also obtained. The level of evidence was given for each recommendation. A total of 34 statements were evaluated by the expert group. A unanimous or high LoA was obtained in 16. IAHA can be considered irrespective of the age in patients with symptomatic knee OA. It can be used in patients with diabetes and/or moderate to severe obesity. It can also be used in knee OA patients with a history of gout, meniscocalcinosis and with mild-to-moderate varus/valgus malalignment. The group recommended against the use of VS in pregnant women and in OA flare. In summary, the working group provided strong recommendations for the use of IAHA injection that will facilitate individualized treatment decision algorithms in the management of knee OA.

Anterior Glenohumeral Instability

➢ Anterior glenohumeral instability is a complex orthopaedic problem that requires a detailed history, a thorough physical examination, and a meticulous review of advanced imaging in order to make individualized treatment decisions and optimize patient outcomes.➢ Nonoperative management of primary instability events can be considered in low-demand patients, including elderly individuals or younger, recreational athletes not participating in high-risk activities, and select in-season athletes. Recurrence can result in increased severity of soft-tissue and osseous damage, further increasing the complexity of subsequent surgical management.➢ Surgical stabilization following primary anterior instability is recommended in young athletes who have additional risk factors for failure, including participation in high-risk sports, hyperlaxity, and presence of bipolar bone loss, defined as the presence of both glenoid (anteroinferior glenoid) and humeral head (Hill-Sachs deformity) bone loss.➢ Several surgical treatment options exist, including arthroscopic Bankart repair with or without additional procedures such as remplissage, open Bankart repair, and osseous restoration procedures, including the Latarjet procedure.➢ Favorable results can be expected following arthroscopic Bankart repair with minimal (&lt;13.5%) bone loss and on-track Hill-Sachs lesions following a primary instability event. However, adjunct procedures such as remplissage should be performed for off-track lesions and should be considered in the setting of subcritical glenoid bone loss, select high-risk patients, and near-track lesions.➢ Bone-grafting of anterior glenoid defects, including autograft and allograft options, should be considered in cases with &gt;20% glenoid bone loss.

Real-world data on direct oral anticoagulants in BCR::ABL1-negative myeloproliferative neoplasms (MPNs): a multicenter retrospective study on behalf of scientific subcommittee on MPNs for Turkish society of hematology.

BCR::ABL1-negative myeloproliferative neoplasms (MPNs) pose a substantial risk of thrombosis, leading to significant morbidity and mortality. Anticoagulant therapy, historically based on vitamin K antagonists (VKAs), has limitations in preventing recurrent thrombotic events and managing bleeding complications. Direct oral anticoagulants (DOACs) offer a potential alternative with improved pharmacokinetics and compliance. However, evidence on DOAC efficacy and safety in MPNs remains limited, necessitating further investigation. In this multicenter retrospective study in Türkiye, we assessed real-world usage patterns and outcomes of DOACs in MPN patients. Data from 220 patients with PV, ET, or PMF receiving DOACs or VKAs for thrombosis or nonvalvular atrial fibrillation (NVAF) were collected from medical records. Thrombotic events and bleeding episodes were documented based on ISTH criteria. DOACs were used in 126 patients as first-line anticoagulant therapy or following VKAs. Ninety-four patients were on VKAs, of which 83 as a first-line treatment. There were eight thromboses (6.3%) seen in 126 DOAC patients, and similarly, seven episodes (9.4%) of thrombosis were observed in 94 patients using VKA. Major bleeding occurred in seven patients (5.6%) on DOAC and 3 (3.2%) in VKA. Thrombotic and bleeding risks were comparable between DOACs and VKAs (p = 0.708 and p = 0.158, respectively). The incidence rate of thrombosis in the VKA group is 1.1% and in the DOAC group is 1.9%. The incidence of major bleeding in the VKA group is 0.6% and 1.6% in the DOAC group. To the best of our knowledge, our study included the largest number of MPN patients to date, comparing DOACs with VKA in terms of both efficacy and safety, which suggests DOACs as promising alternatives to VKAs for managing thrombotic risk in MPNs with manageable toxicity. Despite the limitations of retrospective studies, DOACs' benefits in terms of efficacy and compliance warrant further investigation through prospective trials. Individualized treatment decisions should consider patient-specific factors, emphasizing collaborative efforts between specialists to optimize DOAC therapy in patients with MPNs. Comparable efficacy and safety between DOACs and VKAs were observed in MPN patients.

NCOG-18. META-ANALYSIS OF DIRECT ENDOVASCULAR THROMBECTOMY VS BRIDGING THERAPY IN THE MANAGEMENT OF ACUTE ISCHEMIC STROKE WITH LARGE VESSEL OCCLUSION

Abstract Debates persist when using intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) for acute ischemic stroke (AIS) due to large-vessel occlusion (LVO). This systematic review and meta-analysis synthesized evidence on outcomes in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO), comparing bridging therapy (BT) with MT alone. METHOD We conducted searches of PubMed, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials from inception to July 2023 to identify pertinent clinical trials and observational studies. RESULT 76 studies, involving 37,658 patients, revealed no significant difference in 90-day functional independence between DEVT and BT. However, a trend favoring BT for achieving functional independence with a modified Rankin Scale (mRS) of 0–1 was observed, having Odds ratio (OR) of 0.75 (95% CI 0.66–0.86; p &amp;lt; 0.001). DEVT was associated with higher postprocedural mortality (OR 1.44;95% CI 1.25–1.65; p &amp;lt; 0.001), but a lower risk of symptomatic intracranial hemorrhage compared to BT (OR 0.855; 95% CI 0.621–1.177; p = 0.327). Successful recanalization rates favored BT, emphasizing the importance of individualized treatment decisions (OR 0.759; 95% CI 0.594–0.969; p = 0.027). Sensitivity analyses were conducted to identify key contributors to heterogeneity. CONCLUSION Our meta-analysis underscores the intricate equilibrium between functional efficacy and safety in the evaluation of DEVT and BT for ACS-LVO. Fundamentally, while BT appears more efficacious, concerns about safety arise due to the superior safety profile demonstrated by DEVT. Individualized treatment decisions are imperative, and further trials are warranted to enhance precision in clinical guidance.