Therapeutic Decisions Research Articles

Exploring the Continuous Glucose Monitoring in Pediatric Diabetes: Current Practices, Innovative Metrics, and Future Implications.

Continuous glucose monitoring (CGM) systems, including real-time CGM and intermittently scanned CGM, have revolutionized diabetes management, particularly in children and adolescents with type 1 diabetes (T1D). These systems provide detailed insights into glucose variability and detect asymptomatic and nocturnal hypoglycemia, addressing limitations of traditional self-monitoring blood glucose methods. CGM devices measure interstitial glucose concentrations constantly, enabling proactive therapeutic decisions and optimization of glycemic control through stored data analysis. CGM metrics such as time in range, time below range, and coefficient of variation are crucial for managing T1D, with emerging metrics like time in tight range and glycemia risk index showing potential for enhanced glycemic assessment. Recent advancements suggest the utility of CGM systems in monitoring the early stages of T1D and individuals with obesity complicated by pre-diabetes, highlighting its therapeutic versatility. This review discusses the current CGM systems for T1D during the pediatric age, established and emerging metrics, and future applications, emphasizing the critical role of CGM devices in improving glycemic control and clinical outcomes in children and adolescents with diabetes.

The effect of prognostic nutritional index on diabetic patients with myocardial infarction

BackgroundThe prognostic nutritional index (PNI), a simple and comprehensive predictor of nutritional and immunological health, is connected to cancer and cardiovascular disease. The effects of PNI on myocardial infarction (MI) in individuals with diabetes remain unclear. Thus, we aim to investigate the correlation of PNI with predictive outcomes in this specific population group to inform therapeutic decision-making.MethodsThis prospective observational study included 417 diabetic patients with MI who underwent coronary angiography intervention at Fujian Medical University Union Hospital from May 2017 to May 2020. We collected follow-up and prognostic data from these patients at 6, 12, 18, and 24 months post-procedure via outpatient visits or phone interviews. The main focus of the study was on major adverse cardiovascular events (MACE) in the two years after surgery. Based on the median PNI, patients were categorized into two groups: high PNI (H-PNI) and low PNI (L-PNI). Data were analyzed using IBM SPSS 25.0. Kalpan-Meier survival curves and Cox proportional hazards regression analysis were utilized to examine the associations between preoperative PNI and the prognosis of diabetic patients with MI.ResultsIn the study, 417 participants were observed for two years. Of these patients, 159 (38.1%) had MACE. According to the Kaplan–Meier curves, patients in the L-PNI group had more MACE than those in the H-PNI group (log-rank p < 0.001) and had a heightened susceptibility to all categories of MACE. After adjusting for confounding variables, the corrected hazard ratio for developing unstable angina in the L-PNI group was 2.55 (95% CI 1.57–4.14, p < 0.001).ConclusionLow PNI levels are associated with MACE after coronary angiography intervention in diabetic patients with myocardial infarction. This highlights the prognostic value of PNI and broadens its potential use in larger populations.Trial registration: Not applicable.

Understanding willingness and barriers to participate in clinical trials during pregnancy and lactation: findings from a US study

BackgroundDue to the exclusion of pregnant and lactating people from most clinical trials, there is an incomplete understanding of the risks and benefits of medication use in these populations and therapeutic decision-making is often conducted without adequate evidence. To change this paradigm, it is imperative to understand the perspectives of pregnant and lactating individuals concerning their participation in clinical trials.ObjectivesTo describe attitudes, perceptions, barriers, and preferences of pregnant and postpartum people in the United States (US) regarding participation in clinical trials and to identify factors influencing participation.MethodsIn November 2022, individuals aged ≥ 18 residing in the US who self-identified as pregnant or pregnant within the last 12 months were invited to complete an online survey about their perspectives regarding clinical trial participation. The survey included questions about demographic characteristics, health history, behaviors, and willingness to participate in clinical trials while pregnant and/or lactating. Multivariable logistic regression models were fit to identify predictors of clinical trial participation.ResultsAmong the 654 respondents, 34.8% and 40.9% reported being likely or extremely likely to participate in a clinical trial for a new medication while pregnant or lactating, respectively; and 24.5% and 41.7% for a new vaccine while pregnant or lactating, respectively. Higher educational attainment (≥ Bachelor’s degree) was associated with greater likelihood of clinical trial participation in pregnancy (odds ratio (OR) = 1.50, 95% Confidence Interval (CI): 1.01, 2.25 for medications; OR = 2.00, 95% CI: 1.28, 3.12 for vaccines). Chronic medical conditions were associated with a greater likelihood of participation in clinical trials for vaccines during lactation (OR = 1.59, 95% CI: 1.07, 2.36). The most cited motivator for participation in a clinical trial while pregnant or lactating was anticipated personal medical benefit (85.8% and 75.6%, respectively), while the primary deterrent was possible risk to the fetus or baby (97.9% and 97.2%, respectively).ConclusionsWillingness of a US sample to participate in clinical trials while pregnant or lactating varied by demographics and health status, with safety to the fetus being a nearly universal concern. These findings have implications for enhancing inclusion of pregnant and lactating people in clinical research and developing effective and equitable recruitment strategies.

Machine learning-driven mast cell gene signatures for prognostic and therapeutic prediction in prostate cancer

BackgroundThe role of Mast cells has not been thoroughly explored in the context of prostate cancer's (PCA) unpredictable prognosis and mixed immunotherapy outcomes. Our research aims to employs a comprehensive computational methodology to evaluate Mast cell marker gene signatures (MCMGS) derived from a global cohort of 1091 PCA patients. This approach is designed to identify a robust biomarker to assist in prognosis and predicting responses to immunotherapy. MethodsThis study initially identified mast cell-associated biomarkers from prostate adenocarcinoma (PRAD) patients across six international cohorts. We employed a variety of machine learning techniques, including Random Forest, Support Vector Machine (SVM), Lasso regression, and the Cox Proportional Hazards Model, to develop an effective MCMGS from candidate genes. Subsequently, an immunological assessment of MCMGS was conducted to provide new insights into the evaluation of immunotherapy responses and prognostic assessments. Additionally, we utilized Gene Set Enrichment Analysis (GSEA) and pathway analysis to explore the biological pathways and mechanisms associated with MCMGS. ResultsMCMGS incorporated 13 marker genes and was successful in segregating patients into distinct high- and low-risk categories. Prognostic efficacy was confirmed by survival analysis incorporating MCMGS scores, alongside clinical parameters such as age, T stage, and Gleason scores. High MCMGS scores were correlated with upregulated pathways in fatty acid metabolism and β-alanine metabolism, while low scores correlated with DNA repair mechanisms, homologous recombination, and cell cycle progression. Patients classified as low-risk displayed increased sensitivity to drugs, indicating the utility of MCMGS in forecasting responses to immune checkpoint inhibitors. ConclusionThe combination of MCMGS with a robust machine learning methodology demonstrates considerable promise in guiding personalized risk stratification and informing therapeutic decisions for patients with PCA.

Risk of new-onset diabetes and efficacy of pharmacological weight loss therapy.

To develop a clinical risk model to identify individuals at higher risk of developing new-onset diabetes and who might benefit more from weight loss pharmacotherapy. A total of 21 143 patients without type 2 diabetes at baseline from two TIMI clinical trials of stable cardiovascular patients were divided into a derivation (~2/3) and validation (~1/3) cohort. The primary outcome was new-onset diabetes. Twenty-seven candidate risk variables were considered, and variable selection was performed using multivariable Cox regression. The final model was evaluated for discrimination and calibration, and for its ability to identify patients who experienced a larger benefit from the weight loss medication lorcaserin in terms of risk of new-onset diabetes. During a median (interquartile range) follow-up of 2.3 (1.8-2.7) years, new-onset diabetes occurred in 1013 patients (7.7%). The final model included five independent predictors (glycated haemoglobin, fasting glucose, age, body mass index, and triglycerides/high-density lipoprotein). The clinical risk model showed good discrimination (Harrell's C-indices 0.802, 95% confidence interval [CI] 0.788-0.817 and 0.807, 95% CI 0.788-0.826) in the derivation and validation cohorts. The calibration plot demonstrated adequate calibration (2.5-year area under the curve was 81.2 [79.1-83.5]). While hazard ratios for new-onset diabetes with a weight-loss therapy were comparable across risk groups (annual risks of <1%, 1%-5%, and >5%), there was a sixfold gradient in absolute risk reduction from lowest to highest risk group (p = 0.027). The developed clinical risk model effectively predicts new-onset diabetes, with potential implications for personalized patient care and therapeutic decision making.

Targeted Quantitative Plasma Metabolomics Identifies Metabolite Signatures that Distinguish Heart Failure with Reduced and Preserved Ejection Fraction.

Two general phenotypes of heart failure (HF) are recognized: HF with reduced ejection fraction (HFrEF) and with preserved EF (HFpEF). To develop HF disease phenotype-specific approaches to define and guide treatment, distinguishing biomarkers are needed. The goal of this study was to utilize quantitative metabolomics on a large, diverse population to replicate and extend existing knowledge of the plasma metabolic signatures in human HF. Quantitative, targeted LC/MS plasma metabolomics was conducted on 787 samples collected by the Penn Medicine BioBank from subjects with HFrEF (n=219), HFpEF (n=357), and matched non-failing Controls (n=211). A total of 90 metabolites were analyzed, comprising 28 amino acids, 8 organic acids, and 54 acylcarnitines. 733 of these samples were also processed via an OLINK protein panel for proteomic profiling. Consistent with previous studies, unsaturated forms of medium/long chain acylcarnitines were elevated in the HFrEF group to a greater extent than the HFpEF group compared to Controls. A number of amino acid derivatives, including 1- and 3-methylhistidine, homocitrulline, and symmetric (SDMA) and asymmetric (ADMA) dimethylarginine were elevated in HF, with ADMA elevated uniquely in HFpEF. Plasma branched-chain amino acids (BCAA) were not different across the groups; however, short-chain acylcarnitine species indicative of BCAA catabolism were significantly elevated in both HF groups. The ketone body 3-hydroxybutyrate (3-HBA) and its metabolite C4-OH carnitine were uniquely elevated in the HFrEF group. Linear regression models demonstrated a significant correlation between plasma 3-HBA and NT-proBNP in both forms of HF, stronger in HFrEF. These results identify plasma signatures that are shared as well as potentially distinguish between HFrEF and HFpEF. Metabolite markers for ketogenic metabolic reprogramming in extra-cardiac tissues were identified as unique signatures in the HFrEF group, possibly related to the lipolytic action of increased levels of BNP. Future studies will be necessary to further validate these metabolites as HF biosignatures that may guide phenotype-specific therapeutics and provide insight into the systemic metabolic responses to HFpEF and HFrEF.

Determination of endometrial cancer molecular subtypes using a whole exome-sequencing based single-method approach

AimEndometrial cancer (EC) is heterogeneous with respect to epidemiology, clinical course, histopathology and tumor biology. Recently, The Cancer Genome Atlas (TCGA) network has identified four molecular subtypes with distinct clinical courses by an integrated multi-omics approach. These subtypes are of critical importance in the clinical management of EC. However, determination of TCGA molecular subtypes requires a complex methodological approach that is resource intensive and difficult to implement in diagnostic routine procedures. In this context, Talhouk et al. reported the precise determination of modified subtypes based on molecular surrogates obtained by a two-method approach comprising immunohistochemistry and DNA-sequence analysis (Proactive Molecular Risk Classifier for Endometrial Cancer; ProMisE). In this study, we aimed to identify EC molecular subtypes in analogy to TCGA and ProMisE applying an innovative whole exome-sequencing (WES) based single-method approach.MethodsWES was performed in a cohort comprising N = 114 EC patients. WES data were analyzed using the oncology treatment decision support software MH Guide (Molecular Health, Heidelberg, Germany) and EC molecular subtypes in analogy to TCGA and ProMisE were determined. Results from both classifications were compared regarding their prognostic values using overall survival and progression-free survival analyses.ResultsApplying a single-method WES-approach, EC molecular subtypes analogue to TCGA and ProMisE were identified in the study cohort. The surrogate marker-analogue classification precisely identified high-risk and low-risk EC, whereas the TCGA-analogue classification failed to obtain significant prognostic values in this regard.ConclusionOur data demonstrate that determination of EC molecular subtypes analogue to TCGA and ProMisE is feasible by using a single-method WES approach. Within our EC cohort, prognostic implications were only reliably provided by applying the surrogate marker-analogue approach. Designation of molecular subtypes in EC will be increasingly important in routine clinical practice. Thus, the single-method WES approach provides an important simple tool to tailor therapeutic decisions in EC.

Immunohistochemistry Markers in Ovarian and Fallopian Tube Neoplasms: a Comprehensive Review.

Immunohistochemistry (IHC) has emerged as a crucial tool in diagnosing and managing ovarian cancer, offering invaluable insights into tumor biology and guiding therapeutic decisions. The intricate histopathological landscape of ovarian cancer presents challenges in accurate diagnosis and classification. IHC offers a complementary approach, aiding in the characterization of tumor subtypes, prognostication, and prediction of treatment response. By targeting specific biomarkers, IHC enables the identification of diverse histological features and molecular alterations associated with ovarian malignancies. The integration of IHC into routine diagnostic workflows enhances diagnostic accuracy, aids in the subclassification of ovarian tumors, and facilitates personalized treatment strategies. Emphasis is placed on the judicious selection of antibody panels tailored to specific clinical scenarios, ensuring optimal utilization of resources and minimizing diagnostic pitfalls. Overall, this review underscores the pivotal role of IHC in refining the diagnosis, prognostication, and management of ovarian cancer, highlighting its significance in the era of precision medicine. By leveraging the molecular insights provided by IHC, clinicians and pathologists can optimize patient care and improve outcomes in ovarian cancer management.

Different efficacy of tyrosine kinase inhibitors by KIT and PGFRA mutations identified in circulating tumor DNA for the treatment of refractory gastrointestinal stromal tumors

BackgroundWhile advanced gastrointestinal stromal tumors (GISTs) are primarily treated with tyrosine kinase inhibitors (TKIs), acquired resistance from specific mutations in KIT or PDGFRA frequently occurs. We aimed to assess the utility of circulating tumor DNA (ctDNA) as a modality of therapeutic decision-making in advanced GIST.MethodsWe conducted a pooled analysis of SCRUM-Japan studies for advanced GIST patients. We compared patient characteristics analyzed with tissue and blood samples, assessed gene alteration profiles, and evaluated prognostic implications from ctDNA status.ResultsIn 133 patients, tissue and blood samples were analyzed for 89 and 44 patients, respectively. ctDNA was detected in 72.7% of cases; no prior treatment or progressive disease was significantly associated with ctDNA-positivity. ctDNA-positive patients had significantly shorter progression-free survival compared with ctDNA-negative patients (hazard ratio = 3.92; P = 0.007). ctDNA genotyping revealed a complex landscape of gene alterations, characterized by multi-exonic mutations in KIT, compared with tissue-based analysis. Patients who received TKIs matched to the identified KIT mutation in ctDNA demonstrated significantly longer PFS than those with unmatched treatment (median, 8.23 vs. 2.43 months; P < 0.001).ConclusionsctDNA-based analysis facilitates assessment of disease status and genomic profiles, thus potentially assisting in identifying optimal therapeutic strategies for advanced GIST patients.

Clinical Management of Postoperative Growth Hormone Deficiency in Hypothalamic-Pituitary Tumors.

The present review focuses on growth hormone (GH) deficiency in pediatric and adult patients following surgery for hypothalamic-pituitary tumors, with a special emphasis on hormone replacement therapy with recombinant human growth hormone (rhGH). The symptoms and metabolic changes associated with GH deficiency are reviewed, and the potential risks and therapeutic outcomes of rhGH treatment in these patients are discussed. This review emphasizes the importance of rhGH in the normalization of growth in children and the improvement of quality of life (QoL) and metabolic health in adults. Aspects related to efficacy, safety, dosage, duration of treatment, and QoL in this population are analyzed. The need for regular follow-up and dose adjustment to maintain the optimal IGF-I levels in these patients is emphasized, as is the importance of individualized assessment and collaboration with a specialized multidisciplinary medical team to make the appropriate therapeutic decisions. Furthermore, continuous follow-up are necessary to optimize the clinical outcomes in this patient population.

EPOS-OHCA: Early Predictors of Outcome and Survival after non-traumatic Out-of-Hospital Cardiac Arrest

BackgroundPost-cardiac arrest syndrome (PCAS) after out-of-hospital cardiac arrest (OHCA) poses significant challenges due to its complex pathomechanisms involving inflammation, ischemia, and reperfusion injury. The identification of early available prognostic indicators is essential for optimizing therapeutic decisions and improving patient outcomes. MethodsIn this retrospective single-center study, we analyzed real-world data from 463 OHCA patients with either prehospital or in-hospital return of spontaneous circulation (ROSC), treated at the Cardiac Arrest Center of the University Hospital of Marburg (MCAC) from January 2018 to December 2022. We evaluated demographic, prehospital, and clinical variables, including initial rhythms, resuscitation details, and early laboratory results. Statistical analyses included logistic regression to identify predictors of survival and neurological outcomes. ResultsOverall, 46.9% (n = 217) of patients survived to discharge, with 70.1% (n = 152) achieving favorable neurological status (CPC 1 or 2). Age, initial shockable rhythm, resuscitation time to return of spontaneous circulation (ROSC), and early laboratory parameters like lactate, C-reactive protein, and glomerular filtration rate were identified as independent and combined Early Predictors of Outcome and Survival (EPOS), with high significant predictive value for survival (AUC 0.86 [95% CI 0.82–0.89]) and favorable neurological outcome (AUC 0.84 [95% CI 0.80–0.88]). ConclusionIntegration of EPOS into clinical procedures may significantly improve clinical decision making and thus patient prognosis in the early time-crucial period after OHCA. However, further validation in other patient cohorts is needed.

T1ρ relaxation mapping in osteochondral lesions of the talus: a non-invasive biomarker for altered biomechanical properties of hyaline cartilage?

BackgroundTo evaluate T1ρ relaxation mapping in patients with symptomatic talar osteochondral lesions (OLT) and healthy controls (HC) at rest, with axial loading and traction.MethodsParticipants underwent 3-T ankle magnetic resonance imaging at rest and with 500 N loading and 120 N traction, without axial traction for a subcohort of 17/29 HC. We used a fast low-angle shot sequence with variable spin-lock intervals for monoexponential T1ρ fitting. Cartilage was manually segmented to extract T1ρ values.ResultsWe studied 29 OLT patients (age 31.7 ± 7.5 years, 15 females, body mass index [BMI] 25.0 ± 3.4 kg/m2) and 29 HC (age 25.2 ± 4.3 years, 17 females, BMI 22.5 ± 2.3 kg/m2. T1ρ values of OLT (50.4 ± 3.4 ms) were higher than those of intact cartilage regions of OLT patients (47.2 ± 3.4 ms; p = 0.003) and matched HC cartilage (48.1 ± 3.3 ms; p = 0.030). Axial loading and traction induced significant T1ρ changes in the intact cartilage regions of patients (loading, mean difference -1.1 ms; traction, mean difference 1.4 ms; p = 0.030 for both) and matched HC cartilage (-2.2 ms, p = 0.003; 2.3 ms, p = 0.030; respectively), but not in the OLT itself (-1.3 ms; p = 0.150; +1.9 ms; p = 0.150; respectively).ConclusionIncreased T1ρ values may serve as a biomarker of cartilage degeneration in OLT. The absence of load- and traction-induced T1ρ changes in OLT compared to intact cartilage suggests that T1ρ may reflect altered biomechanical properties of hyaline cartilage.Trial registrationDRKS, DRKS00024010. Registered 11 January 2021, https://drks.de/search/de/trial/DRKS00024010.Relevance statementT1ρ mapping has the potential to evaluate compositional and biomechanical properties of the talar cartilage and may improve therapeutic decision-making in patients with osteochondral lesions.Key PointsT1ρ values in osteochondral lesions increased compared to intact cartilage.Significant load- and traction-induced T1ρ changes were observed in visually intact regions and in healthy controls but not in osteochondral lesions.T1ρ may serve as an imaging biomarker for biomechanical properties of cartilage.Graphical

Systematic Improvement of a Bolus Calculator That Is on the Market: A User-Centric Approach.

State-of-the-art diabetes self-management includes the usage of (software) tools, such as Bolus Calculators, to support patients with their therapeutic decisions. The development of such medical devices comes with strict obligations to ensure the safety and performance for the user; however, it is also necessary to continue to evaluate such aspects after the products are introduced into the market. In addition, such aspects cannot always be sufficiently validated by clinical trials; they need real-world evaluation to systematically improve such tools while they are on the market. The approach described here uses innovative ways of generating user-centric evidence to improve the bolus calculator, including (1) human factor engineering, (2) analysis of glycemic real-world data, (3) patient-reported outcomes, and (4) machine-generated behavioral measurements. The combination of the diverse techniques to optimize the bolus calculator triggered changes in the user experience: a significant reduction in hypoglycemic events, -0.52% (±0.05), P < .01, n=3480, an increased diabetes treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire [DTSQ] +9.90, P < .01, n=217), as well as an increased acceptance rate of bolus calculations, +15.73 (±0.89), P < .01, n=3436, were observed. Altogether, human factor engineering and different forms of real-world data support fast and direct adaptations and improvements in products used for diabetes therapy.

The EMMY longitudinal, cohort study: real-world data to describe multiple myeloma management and outcomes as more therapeutic options emerge

The therapeutic management of patients with multiple myeloma (MM) is complex. Despite substantial advances, MM remains incurable, and management involves cycles of treatment response, disease relapse, and further therapy. Currently, evidence to support the therapeutic decision is limited. Thus, the EMMY longitudinal, real-world study was designed to annually assess therapeutic management of MM in France to provide evidence to support physicians. During an annual prespecified 3-month recruitment period, eligible patients will be identified from their medical records. Adults aged ≥18 years diagnosed with symptomatic MM and requiring systemic treatment will be eligible. The primary objective, the evolution of MM therapeutic management, will be described, as well as the impact on the following outcomes: time-to-next treatment (TTNT), progression-free survival (PFS), and overall survival (OS). The study plans to recruit 5000 patients over 6 years: 700 to 900 patients annually. EMMY is a unique opportunity to collect real-world data to describe the evolving MM therapeutic landscape and record outcomes in France. These data will provide annual snapshots of various aspects of MM management. This knowledge will provide physicians with real-life, evidence-based data for therapeutic decision-making and ultimately improve treatment for MM patients.

A case of AZOOR under immunomodulatory treatment.

To describe the clinical course and treatment response of a case of Acute Zonal Occult Outer Retinopathy (AZOOR). This is an observational case report. The examinations included ophthalmic examination, longitudinal multimodal imaging, visual field testing, electrophysiological recordings, serologic analyses and whole genome sequencing. In this report, the authors present the case of an otherwise healthy 33-year-old female with bilateral AZOOR manifestation. Other possible causes of the observed retinal lesions were ruled out by extensive diagnostic work-up. Treatment with oral prednisolone therapy led to temporal disease control but progression was observed after prednisolone discontinuation. A tapered oral prednisolone therapy in combination with adalimumab initiation prevented further progression for at least 21 months. Diagnosis of AZOOR is frequently complicated by the unspecific symptoms of the disease and significant number of differential diagnoses. Complete diagnostic work-up is important to rule out other etiologies. Due to the lack of randomized controlled trials, therapeutic decisions obligatorily rely on empiric treatment decisions in combination with frequent follow-up examinations.

Dermatology in non-human primates: a comprehensive review

There have been limited studies conducted on the anatomy, physiology, and histology of the skin of non-human primates (NHPs). The majority of this research was done by William Montagna and his colleagues in the 1960s and 1970s. Understanding the skin characteristics of NHPs is important for comprehending their biology and behavior, as well as for conducting complementary dermatological examinations and various experiments. This knowledge is particularly important in the diagnosis of specific zoonoses. However, veterinary dermatology for NHPs faces a challenge in obtaining information from both human and veterinary dermatology disciplines, which can lead to diagnostic and therapeutic decisions based on two distinct bodies of literature. Therefore, an integrated approach to dermatology in NHPs is critical, without assuming that the pathology in NHPs is identical to that in humans. This review article aims to highlight the key scientific studies related to the skin of NHPs, with the goal of expanding knowledge about their dermatological characteristics. It also seeks to provide valuable insights for researchers in the field, contributing to a better understanding of dermatology in non-human primates.

Guidelines of the Brazilian Society of Surgical Oncology for anatomopathological, immunohistochemical, and molecular testing in female tumors.

Precision medicine has revolutionized oncology, providing more personalized diagnosis, treatment, and monitoring for patients with cancer. In the context of female-specific tumors, such as breast, ovarian, endometrial, and cervical cancer, proper tissue collection and handling are essential for obtaining tissue, immunohistochemical (IHC), and molecular data to guide therapeutic decisions. To establish guidelines for the collection and handling of tumor tissue, to enhance the quality of samples for histopathological, IHC, genomic, and molecular analyses. These guidelines are fundamental in informing therapeutic decisions in cancer treatment. The guidelines were developed by a multidisciplinary panel of renowned specialists between June 12, 2013 and February 12, 2024. Initially, the panel deliberated on critical and controversial topics related to conducting precision medicine studies focusing on female tumors. Subsequently, 22 pivotal topics were identified within the framework and assigned to groups. These groups reviewed relevant literature and drafted preliminary recommendations. Following this, the recommendations were reviewed by the coordinators and received unanimous approval. Finally, the groups made the final adjustments, classified the level of evidence, and ranked the recommendations. The collection of surgical samples requires minimum quality standards to enable histopathological, IHC, genomic, and molecular analyses. These analyses provide crucial data for informing therapeutic decisions, significantly impacting potential survival gains for patients with female tumors.

The reality of epilepsy in primary care in Rio de Janeiro: the importance of educational projects for better patient care.

The Basic Health Unit (Unidade Básica de Saúde - UBS, in Portuguese) is the first point of contact in the public healthcare system for people with epilepsy. Primary care professionals need to appropriately diagnose, treat, and refer, if necessary, to tertiary services. To evaluate the knowledge of UBS professionals on the management of patients with epilepsy in Rio de Janeiro. Online questionnaires were performed on the topic of epilepsy before and after exposure to classes taught by epileptologists. A total of 66 doctors participated, 54.5% of whom were residents or trained in family medicine. The majority had from 1 to 3 years of practice. Insecurity prevailed in the management of pregnant women and the elderly. Around 59.1% of the participants referred patients with seizures without examinations. A total of 78% of the participants did not correctly classify seizure types, and 2/3 did not define drug-resistant epilepsy. Induction and broad-spectrum drugs were common. The therapeutic decision depended on availability in the basic health unit (UBS) (81.8%), dosage (60.6%), side effects (34.8%), and age (36.4%). Comorbidities and sex influenced 1/4 of the sample. For 23% of the participants, the type of crisis did not affect the choice. Regarding typical non-pharmacological options, 75% of the participants were aware of cannabidiol, 40.9% of surgery, 22.7% of ketogenic diet, and 22.8% of deep brain stimulation/vagus nerve stimulation (DBS/VNS). A total of 90.2% indicated the need for training. There are deficits in the knowledge of UBS professionals in the management of epilepsy. Specialized training is imperative to optimize the care offered within SUS.

T1 colorectal cancer patients' perspective on information provision and therapeutic decision-making after local resection.

Decision-making after local resection of T1 colorectal cancer (T1CRC) is often complex and calls for optimal information provision as well as active patient involvement. The aim was to evaluate the perceptions of patients with T1CRC on information provision and therapeutic decision-making. This multicenter cross-sectional study included patients who underwent endoscopic or local surgical resection as initial treatment. Information provision was assessed using the EORTC QLQ-INFO25 questionnaire. In patients with high-risk T1CRC, we evaluated decisional involvement and satisfaction regarding the choice as to whether to undergo additional treatment after local resection, and the level of decisional conflict using the Decisional Conflict Scale. Ninety-eight patients with T1CRC were included (72% response rate; 79/98 endoscopic and 19/98 local surgical resection; 45/98 high-risk T1CRC). Median time since local resection was 28months (IQR 18); none had developed recurrence. Unmet information needs were reported by 29 patients (30%; 18 low-risk, 11 high-risk), mostly on post-treatment related topics (follow-up visits, recovery time, recurrence prevention). After local resection, 24 of the 45 high-risk patients (53%) underwent additional treatment, while others were subjected to surveillance. Higher-educated patients were more often actively involved in decision-making (93% vs. 43%, p=0.002) and more frequently underwent additional treatment (79% vs. 40%, p=0.02). Decisional conflict (p=0.19) and satisfaction (p=0.78) were comparable between higher- and lower-educated high-risk patients. Greater attention should be given to the post-treatment course during consultations following local T1CRC resection. The differences in decisional involvement and selected management strategies between higher- and lower-educated high-risk patients warrant further investigation.

First-line PARP inhibitor maintenance treatment in ovarian carcinoma for older adult women: a review of the current literature.

Ovarian cancer (OC) is the leading cause of death in women with gynecological cancers. Its diagnosis is more likely in advanced ages, with the older population being the most seen in consultations. Poly(ADP-ribose) inhibitors (PARPi) have changed OC clinical practice and evolution, showing great benefit. However, there is a lack of evidence of PARPi in elderly population that can impact the therapeutic decision and the safety/efficacy. It is necessary to avoid age as limiting factor in PARPis prescription. We conducted a review of the most relevant randomized phase III trials of maintenance PARPi after first-line treatment of advanced OC. We observed the lack of a single criterion for considering older patients, varying among trials. There is a benefit of PARPis in different populations. However, PARPi effect on quality of life is not reported, something of great relevance considering their vulnerability. Measures are needed to benefit older patients to better adapt PARPi treatment.