Therapeutic Decisions Research Articles

Dilation of the ascending aorta: diagnosis, clinical presentation, and indication for surgery. The crucial role of the cardiologist

The diagnosis of ascending aortic aneurysm, its precise assessment criteria and indications for surgery represent a chapter of great stimulus and interest for the clinical cardiologist. There are many factors influencing the classification of patients, but it is the contemporary evolution of knowledge in this field that contributes to a more global view of the aorta. The approach is increasingly multidisciplinary, both in clinical and genetic terms, and multimodal imaging is a crucial support for therapeutic decisions and monitoring. All these aspects, together with the most recent developments, will be explored and reasoned about in this review.

Clinical comparison of laparoscopic and open surgical approaches for uterus-preserving myomectomy: a retrospective analysis on patient-reported outcome, postoperative morbidity and pregnancy outcomes.

Uterine fibroids pose clinical challenges due to varied symptoms and impact on fertility. Aim of this research is to compare open and laparoscopic myomectomy, with focus on evaluating their effects on patients' quality of life and analyzing their implications for pregnancy outcomes. This retrospective study compares open and laparoscopic myomectomy outcomes in 168 patients treated October 2017 and July 2023. Preoperative characteristics and postoperative outcomes in terms of symptoms and pregnancy outcomes were examined. The patient cohort comprised patients with a high symptom burden. Only 51.2% expressing a desire for future pregnancies, highlighting diverse motivations for uterus-preservation. No significant differences were observed in preoperative symptoms. Larger and multiple myomas were associated with a higher likelihood of laparotomy. Recurrence rates were lower after laparoscopy (10.2% vs. 23.8%, p = 0.02). Cesarean section recommendations were more frequent post-laparotomy group (36.6% vs. 86.6%, p = 0.000). Morbidities and satisfaction showed no significant differences between approaches, with slightly better bleeding improvement after laparotomy. Despite similar pregnancy outcomes, a high proportion of patients did not conceive postoperatively (75.4%). Among patients who became pregnant postoperatively (n = 31), most patients conceived after one year or more, with no dependence on the surgical approach (p = 0.227). Both open and laparoscopic myomectomy surgeries showed high patient satisfaction, symptom alleviation, and comparable pregnancy results. A preference emerged for laparoscopy in terms of cesarean section recommendations and recurrence risk. Laparoscopic procedures tended to offer higher operative satisfaction and fewer complications. The study emphasized the complexity of therapeutic decision-making.

Atypical Teratoid Rhabdoid Tumor of the Brain in a Young Adult With Down Syndrome: Case Report and Literature Review.

Atypical teratoid/rhabdoid tumor (ATRT) is an aggressive, malignant embryonal tumor with dismal long-term survival despite aggressive multimodal therapy. While this tumor typically presents in infancy or early childhood, there are published case reports of adult-onset ATRT. Making prognostic conclusions or therapeutic decisions for this older patient population remains challenging due to the paucity of these reports. A 25-year-old female with Down syndrome presented with dysphagia and facial droop and was found to have an avidly enhancing, cerebellopontine angle mass. Histology demonstrated sheets of rhabdoid cells with loss of INI1 expression, pathognomonic for ATRT. Further sequencing detected a frameshift SMARCB1 mutation and methylation profiling matched with high confidence to the MYC subclass of ATRT. The patient was treated with subtotal surgical resection and focal proton beam irradiation, followed by chemotherapy on a modified regimen due to concern for heightened risk of treatment-related toxicity. On most recent follow-up 22 months from diagnosis, the patient remains without evidence of disease. This report represents the first known case of ATRT in a young adult patient with Down syndrome, offering unique mechanistic insight into the tumorigenesis of ATRT. Further studies are needed to define an appropriate risk-adapted and standardized therapeutic approach for this patient population.

Clinical guideline for non-invasive imaging techniques in diagnosing adult cardiomyopathies (2024 edition)

Cardiomyopathies encompass a spectrum of disorders characterized by alterations in cardiac structure, function, histology, and the conduction system due to myocardial cell injury, with significant variability in clinical presentation and prognosis. Despite overlapping morphological features among different types of cardiomyopathies, phenotypic similarities limit the precision of diagnosis and consequently affect the development of therapeutic strategies and prognosis assessment. Diagnosis begins with the screening of myocardial morphology and function abnormalities, primarily relying on multimodal non-invasive imaging techniques such as echocardiography, CT scans, and cardiac magnetic resonance imaging. These techniques comprehensively summarize the structural, functional, and tissue characteristics of various cardiomyopathies, highlighting differences among them. In view of the unique needs and current situation in this field in China, an expert group has jointly developed the"Clinical guideline for non-invasive imaging techniques in diagnosing adult cardiomyopathies (2024 edition)."These guidelines integrate the latest evidence, and systematically introduce the diagnosis and monitoring of cardiomyopathy, the application of non-invasive imaging techniques, and the analysis of features of cardiomyopathies, thereby to enhance the precise diagnosis of cardiomyopathy and aid in offering information for therapeutic decision-making, aiming to provide reasonable recommendations for clinicians in China.

The role of the SOX2 gene in cervical cancer: focus on ferroptosis and construction of a predictive model

BackgroundThe intricate interplay between stemness markers and cell death pathways significantly influences the pathophysiology of cervical cancer. SOX2, a pivotal regulator of stem cell pluripotency, has recently been implicated in the modulation of ferroptosis, a specialized form of iron-dependent cell death, in cancer dynamics. This study delineates the role of SOX2 in the ferroptotic landscape of cervical carcinoma.ObjectiveTo delineate the association between SOX2 expression and ferroptosis in cervical cancer and develop a robust, SOX2-centric model for predicting prognosis and enhancing personalized treatment.MethodsA multidimensional approach integrating advanced bioinformatics, comprehensive molecular profiling, and state-of-the-art machine learning algorithms was employed to assess SOX2 expression patterns and their correlation with ferroptosis marker expression patterns in cervical cancer tissues. A prognostic model incorporating the expression levels of SOX2 and ferroptosis indicators was meticulously constructed.ResultsThis investigation revealed a profound and intricate correlation between SOX2 expression and ferroptotic processes in cervical cancer, substantiated by robust molecular evidence. The developed predictive model based on SOX2 expression exhibited superior prognostic accuracy and may guide therapeutic decision-making.ConclusionThis study underscores the critical role of SOX2 in orchestrating the ferroptosis pathway in cervical cancer and presents a novel prognostic framework. The SOX2-centric predictive model represents a significant advancement in prognosis evaluation, offering a gateway to personalized treatment for gynaecologic cancers.

Whole lung and sequential bronchoscopic lavage for pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is a diffuse lung disease that results from the accumulation of lipoproteinaceous material in the alveoli due to abnormal surfactant homeostasis. Since its introduction in the 1960s, whole lung lavage (WLL) has been the primary treatment for PAP. This review focuses on WLL, including its technique modifications, and sequential bronchoscopic lavage. Autoimmune PAP, which accounts for the majority of cases, occurs when antigranulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies lead to the deficiency of bioavailable GM-CSF. At present, there are no international guidelines or consensus statements for PAP treatment. Traditionally, therapeutic decisions are made based on the severity and type of PAP. Despite emerging data on GM-CSF-based therapies, WLL remains a central component in the therapeutic strategy for PAP. Although the technique of WLL has evolved over time, there is still no universally adopted, standardized protocol. However, key periprocedural aspects - such as preprocedural planning, patient evaluation, anesthetic technique, lavage protocol, and postprocedural care - remain essential to ensuring the safety and success of WLL.

Development of a metabolome-based respiratory infection prognostic during COVID-19 arrival.

In a new respiratory virus pandemic, optimizing allocation of scarce medical resources becomes an urgent challenge. Infection prognosis takes on particular importance when allocating scarce antiviral antibodies and drugs, which are most effective when administered before the onset of severe disease. During arrival of the COVID-19 pandemic to the United States in 2020, we conducted a prognostic biomarker discovery and validation effort based upon metabolomic profiling with a liquid-chromatography-mass spectrometer (LC-MS) type used clinically for rapid toxicology. We obtained urine specimens from 163 patients presenting for evaluation. We obtained LC-MS profiles in the initial cohort and used machine learning methods to define a simplified urine metabolomic signature associated with respiratory failure or death by 90 days. This signature was composed of three metabotypes linked to intestinal microbiome metabolism and anticonvulsant use, with a receiver-operator characteristic area under the curve (ROC AUC) of 89.4%. Blinded application of this signature to the subsequent validation cohort yielded a ROC AUC of 81.2%. A model trained on the two baseline metabotypes present before intubation exhibited similar performance in the validation cohort. This study demonstrates the plausibility and promise of rapid metabolome-based prognostic discovery and validation in the opening wave of a pandemic. The approach used here could be used to inform therapeutic and resource allocation decisions early in a future epidemic.IMPORTANCEIn a new respiratory virus pandemic, the ability to identify patients at greatest risk for severe disease is essential to direct scarce medical resources to those most likely to benefit from them. Tools to predict disease severity are best developed early in a pandemic, but laboratory-based resources to develop these may be limited by available technology and by infection precautions. Here, we show that an accessible metabolic profiling approach could identify a prognostic signature of severe disease in the initial wave of COVID-19, when patients presenting for care often exceeded the available doses of convalescent plasma and remdesivir. In a future pandemic, this approach, alongside efforts to identify clinical disease severity predictors, could improve patient outcomes and facilitate therapeutic trials by identifying individuals at high risk for severe disease.

Using Deep Learning to Suggest Treatment for Proximal Humerus Fractures.

Proximal humeral fractures are among the most common fractures seen in emergency departments. Accurately diagnosing and selecting the most appropriate treatment for these fractures can be challenging, and consultation with a senior orthopedic surgeon can be time-consuming for both the patient and the emergency unit. We developed a machine learning model for predicting the type of treatment based on injury radiographic images. The model distinguishes between nonoperative and operative treatment options, achieving an accuracy of 86% and an interobserver reliability (kappa) of 0.722 for test-dataset, which is more than the interobserver agreement between shoulder surgeons. This model has the potential to serve as a therapeutic decision support system for the practitioners in the emergency departments to expedite treatment decisions and to reduce patients' waiting time.

Dynamics of measurable residual disease for risk stratification and guiding allogeneic transplant in acute myeloid leukaemia patients with myelodysplasia-related mutations in first remission.

Accurate classification and risk prediction are critical for therapeutic decision-making in patients with acute myeloid leukaemia (AML). Myelodysplasia-related (MR) gene mutations are classified as adverse genetic factors by the European LeukaemiaNet-2022 guidelines. However, their prognostic value in de novo AML remains controversial. This study retrospectively analysed 188 patients with de novo AML-MR, stratifying them into four subgroups based on dynamic measurable residual disease (MRD) after induction, one or two courses of consolidation chemotherapy. The median follow-up was 36.8 months (4.6-73.7). Patients with persistent or recurrent MRD positivity after the second consolidation had the poorest 3-year relapse-free survival (RFS), overall survival (OS) and cumulative incidence of relapse compared to the other groups (p < 0.001). Multivariable analysis identified this high-risk group as an independent risk factor for both RFS and OS. We observed significant heterogeneity of OS benefit from allogeneic stem cell transplantation (allo-SCT) by MRD-risk groups, with substantial OS advantage for patients in subgroup D (3-year OS: allo-SCT 70.0% vs. 18.2% without, p < 0.001) but no benefit for others (p = 0.047 for interaction). This study underscores the importance of dynamic MRD in refining risk stratification and identifying de novo AML patients with MR mutations who would benefit from allo-SCT during the first complete remission.

High Expression of MRPL23 Is Associated with Poor Survival in Clear-Cell Renal Cell Carcinoma

Background: This study aimed to investigate the expression and prognostic significance of the MRPL23 protein and mRNA in clear-cell renal cell carcinoma (ccRCC) and adjacent non-tumorous tissues. The goal was to assess the impact of MRPL23 expression on tumor behavior, progression, and patient outcomes. Methods: Using immunohistochemistry (IHC), MRPL23 protein expression was analyzed in 99 cases of ccRCC and 30 adjacent non-tumorous tissues. mRNA levels were assessed using data from The Cancer Genome Atlas (TCGA). Correlations between MRPL23 expression and clinicopathological features were examined, and survival outcomes were evaluated using Kaplan–Meier survival curves and Cox regression analyses. Results: MRPL23 protein expression was significantly lower in ccRCC tissues compared to normal tissues. In contrast, mRNA levels of MRPL23 were significantly elevated in ccRCC tissues. Expression levels were correlated with clinicopathological features, including gender, tumor grade, pT status, and disease stage, underlining their impact on tumor progression. Elevated MRPL23 protein expression was associated with poorer overall survival (OS) in ccRCC patients and remained an independent prognostic marker for adverse outcomes after adjustment for confounding variables. While high MRPL23 mRNA expression was also linked to worse OS, it did not retain its status as an independent prognostic factor after adjustments. Conclusion: MRPL23 protein expression is a potential independent prognostic biomarker in ccRCC, emphasizing its utility in predicting patient outcomes and potentially guiding therapeutic decisions. These findings highlight the importance of further research into the role of MRPL23 in ccRCC pathogenesis and its potential as a therapeutic target.

Cardiac autonomic neuropathy: impact on severe hypoglycemic unawareness and orthostatic hypotension in diabetic dysautonomia, a case series and review.

Diabetic autonomic neuropathy (DAN) and its associated cardiovascular autonomic neuropathy (CAN) can lead to potentially fatal complications. We analyzed two distinct cases of DAN/CAN based on comprehensive cardiovascular autonomic reflex tests (CARTs). Case 1 involves a 27-year-old patient with T1DM suffering from recurrent severe hypoglycemic unawareness due to DAN. After implementing an automated insulin delivery system, the glucose management improved significantly. Case 2 describes a 60-year-old patient with type 2 diabetes experiencing debilitating orthostatic hypotension. The initiation of Midodrine and Fludrocortisone markedly improved symptoms and capacity of daily activities. This observational study highlights the critical yet frequently overlooked severe manifestations of DAN/CAN, specifically hypoglycemic unawareness and orthostatic hypotension. CARTs play a pivotal role in confirming the diagnosis and guiding therapeutic decisions. Tailored interventions, including advanced technologies like automated insulin delivery systems for T1DM and pharmacotherapy targeting neurogenic orthostasis, can significantly improve patient outcomes and quality of life.

Pre- and Postoperative Ultrasound Assessment of Biceps Brachial Tendon Tears.

Rupture of the distal biceps brachii tendon is a rare but debilitating injury, resulting in significant loss of strength. Diagnosis of complete rupture is based on clinical history and physical tests, with surgical repair often recommended due to functional discomfort. Ultrasound (US) is a powerful tool for diagnosing and classifying ruptures, particularly partial ruptures, which is crucial for therapeutic decisions. A good understanding of the tendon's anatomical arrangement in two twisted bundles enables optimal analysis. If several surgical techniques are available, the minimally invasive approach to reinsert the tendon on the radial tuberosity is often preferred. Postoperative assessment includes radiographs, US, and sometimes magnetic resonance imaging, revealing postoperative changes with constant thickening of the repaired tendon. With accurate diagnosis and appropriate surgical technique, surgical repair has a low complication rate. Single-incision repairs show higher rates of re-tears and nerve injuries, and double-incision repairs are prone to heterotopic ossification.

Multi-parametric MRI: can we assess renal function differently?

Abstract We are lacking tools to evaluate renal performance. In this review, we presented the current knowledge and potential future applications in nephrology of new magnetic resonance imaging (MRI) techniques, focusing on Diffusion-weighted (DWI) MRI, Blood oxygen Level Dependent (BOLD) MRI, and magnetic resonance relaxometry (T1 and T2 mapping). These sequences are sensitive to early changes in biological processes such as perfusion, oxygenation, oedema or fibrosis without requiring contrast medium injection and avoids irradiation and nephrotoxicity. Combining these different sequences into the so-called ‘multiparametric MRI’ enables non-invasive, repeated exploration of renal performance on each kidney separately. DWI MRI, which evaluates the movement of water molecules, is a promising tool for non-invasive assessment of interstitial fibrosis and the cortical restricted diffusion has a prognostic value for the deterioration of renal function in diabetic nephropathy. BOLD MRI is sensitive to changes in renal tissue oxygenation based on the paramagnetic properties of deoxyhemoglobin and is of particular interest in the setting of renal artery stenosis to assess tissue oxygenation in the post-stenotic kidney. This sequence can be used for predicting degradation of renal function in CKD and might be useful in preclinical studies to assess nephroprotective and nephrotoxic effects of drugs in development. T1 and T2 relaxation times change with tissue water content and might help assessing renal fibrosis. A corticomedullary dedifferentiation in T1 has been observed in CKD and negatively correlates with glomerular filtration rate. Data on the significance of T2 values in renal imaging is more limited. Multiparametric MRI has the potential to provide a better understanding of renal physiology and pathophysiology, a better characterization of renal lesions, an earlier and more sensitive detection of renal disease, and an aid to personalized patient-centered therapeutic decision-making. Further data and clinical trials are needed to allow its routine application in clinical practice.

Review Article: Green Management of IBD—New Paradigms for an Eco‐Friendly Approach

ABSTRACTBackgroundThe worldwide prevalence of inflammatory bowel disease (IBD) is increasing, with its potential evolution as a global disease and a consequent increase in its burden on healthcare systems. These estimates do not factor in the ‘real’ price of IBD, which, beyond curbing career aspirations, instilling social stigma, and impairing the quality of life in patients, could also significantly affect the environment.AimTo highlight potential areas for intervention and develop management strategies aimed at minimising environmental impacts in the field of IBD over time.MethodsVarious aspects of IBD care (organisation of IBD centres, diagnostics and therapeutics) are examined from an environmental sustainability perspective.ResultsEach stage, from the patient's means of transport to the hospital to the physician's diagnostic and therapeutic decisions, contribute to CO2 and waste production. Strategies to contain the environmental impact are feasible. Some are easy to implement, such as ensuring the appropriateness of the diagnostic and therapeutic pathway for patients; others need to be implemented in synergy with healthcare providers' policies and pharmaceutical companies.ConclusionsWith an inevitable increase in the number of patient visits, endoscopies, laboratory testing, and long‐term therapeutic strategies for IBD, the clinical community should be aware of environmental concerns and investigate possible strategies to reduce the environmental impact of IBD care.

What is proven in the treatment of lipid disorders?

Cardiovascular diseases are still the leading global cause of mortality. Modifiable cardiovascular risk factors have been well-defined for many years and are amenable to multimodal treatment. The scope of pharmaceutical interventions targeting atherogenic lipoproteins in general and low-density lipoprotein (LDL)-cholesterol concentrations in particular, has significantly broadened over the last years, leading to an intensification of appropriate treatment targets, which are not sufficiently achieved in the clinical routine. Current prevention guidelines issued by the European Society for Cardiology (ESC) define patient cohorts according to their individual cardiovascular risk, which results in arisk-adapted lipid-lowering treatment. The aim is to avoid overtreatment of patients with a low or moderate risk and undertreatment of patients with a high or very high risk. In addition to secondary prevention in patients with an already established cardiovascular disease, primary prevention uses age-adapted risk stratification algorithms to assess the 10-year risk, e.g., systematic coronary risk evaluation 2 (SCORE2), SCORE2-older persons (SCORE2-OP) and the lifetime risk, e.g., lifetime-perspective cardiovascular disease model (LIFE-CVD) as the foundation for therapeutic decision making. Special patient groups with known elevated cardiovascular risk (familial hypercholesterolemia, diabetes mellitus, chronic kidney disease) are stratified by incorporating disease-specific parameters and are treated according to defined lipid-lowering targets.

Evaluation of anti-Mullerian hormone as parameter of ovarian function in patients with systemic lupus erythematosus: A systematic review and meta-analysis

HIGHLIGHTS Systemic Lupus Erythematosus (SLE) patients show a strong correlation between Anti-Mullerian Hormone (AMH) levels and ovarian function. Lower AMH levels indicate higher risk of impaired ovarian function and diminished reserve, as revealed by this meta-analysis. The comprehensive synthesis of available data in this study has important clinical implications for the management and counseling of Systemic Lupus Erythematosus (SLE) patients. ABSTRACT Objective: The assessment of ovarian function in patients with systemic lupus erythematosus (SLE) holds paramount importance for both clinicians and patients. This systematic review and meta-analysis delves into the role of anti-Mullerian hormone (AMH) as a key marker in evaluating ovarian function among SLE patients. Our study aims to provide valuable insights for clinicians managing ovarian function assessments and to offer practical recommendations for differences in therapy for patient care. Materials and Methods: Studies comparing serum AMH levels between patients with systemic lupus erythematosus and healthy controls, as well as serum AMH levels between SLE patients, are necessary. PRISMA guidelines were used for this systematic review. Databases like PubMed, SCOPUS, EuropePMC, ProQuest, and Cochrane Central were searched using specific terms ("Anti-Mullerian Hormone" or "Ovarian Function" and "Systemic Lupus Erythematosus") for publications between 2000 and 2023. After removing duplicates, authors screened remaining articles based on abstracts, then reviewed selected abstracts in full-text. Studies meeting criteria were included based on unanimous agreement among investigators, with any disagreements resolved through author consensus. Results: Data There were 12 eligible studies. In this research, we identified a link between SLE and diminished levels of AMH. Furthermore, it was observed that SLE patients undergoing cyclophosphamide (CYC) treatment also exhibited lowered AMH levels Conclusion: The systematic review underscores the heightened risk of reduced ovarian reserve in SLE patients. Importantly, CYC treatment emerged as a factor contributing to compromised ovarian reserve. For individuals with systemic lupus erythematosus, particularly women in their reproductive years, assessing serum AMH levels can serve as a pivotal tool to inform therapeutic decisions and preserve ovarian health. Our study contributes to enhanced clinical understanding and patient care within the realm of SLE and reproductive health.

Acute Myeloid Leukemia: Diagnosis and Evaluation by Flow Cytometry.

With recent technological advances and significant progress in understanding the pathogenesis of acute myeloid leukemia (AML), the updated fifth edition WHO Classification (WHO-HAEM5) and the newly introduced International Consensus Classification (ICC), as well as the European LeukemiaNet (ELN) recommendations in 2022, require the integration of immunophenotypic, cytogenetic, and molecular data, alongside clinical and morphologic findings, for accurate diagnosis, prognostication, and guiding therapeutic strategies in AML. Flow cytometry offers rapid and sensitive immunophenotyping through a multiparametric approach and is a pivotal laboratory tool for the classification of AML, identification of therapeutic targets, and monitoring of measurable residual disease (MRD) post therapy. The association of immunophenotypic features and recurrent genetic abnormalities has been recognized and applied in informing further diagnostic evaluation and immediate therapeutic decision-making. Recently, the evolving role of machine learning models in assisting flow cytometric data analysis for the automated diagnosis and prediction of underlying genetic alterations has been illustrated.

A delphi-based model for prognosis of femoral head collapse in osteonecrosis: a multi-factorial approach

BackgroundOsteonecrosis of the femoral head (ONFH) is a progressive and debilitating condition characterized by the death of bone tissue due to inadequate blood supply. Despite advances in diagnostic imaging and treatment strategies, predicting the risk of femoral head collapse remains a significant clinical challenge. This study seeks to address this gap by developing a robust prognostic model that integrates clinical, imaging, and laboratory data to improve early diagnosis and guide therapeutic decision-making.MethodsWe conducted a qualitative systematic review and employed the Delphi method to select key prognostic factors from clinical data, imaging findings, and laboratory indicators. The study included ONFH patients treated from January 2014 to December 2021. We used univariate and multivariate Cox regression analyses to develop a nomogram for predicting the risk of femoral head collapse. The model’s performance was evaluated using the concordance index (C-index), calibration plots, and decision curve analysis (DCA).ResultsThe study included 297 patients (454 hips) with ONFH. Key prognostic factors identified included pain presence (p < 0.001, RR = 0.185, 95% CI: 0.11–0.31), JIC classification (C1: p < 0.001, RR = 0.096, 95% CI: 0.054–0.171; C2: p < 0.001, RR = 0.323, 95% CI: 0.215–0.487), necrotic area (3 < MNAI < 6: p < 0.001, RR = 0.107, 95% CI: 0.061–0.190; MNAI ≥ 6: p < 0.001, RR = 0.466, 95% CI: 0.314–0.692), weight-bearing reduction (p < 0.001, RR = 0.466, 95% CI: 0.323–0.672), preservation of the anterolateral pillar (p < 0.001, RR = 0.223, 95% CI: 0.223–0.473), and subchondral bone fracture on CT (p < 0.001, RR = 0.32, 95% CI: 0.217–0.472). The nomogram demonstrated a high C-index of 0.88, indicating excellent predictive accuracy. Calibration plots showed good agreement between predicted and observed outcomes, and DCA confirmed the model’s clinical utility.ConclusionsThe prognostic model developed in this study provides a reliable tool for predicting femoral head collapse in ONFH patients. It allows for early identification of high-risk patients, guiding personalized treatment strategies to improve patient outcomes and reduce the need for invasive surgical procedures.

EVALUATING THE EFFICACY OF TRANSCUTANEOUS VERSUS SERUM BILIRUBIN MEASUREMENTS IN MANAGING NEONATAL JAUNDICE IN PRETERM INFANTS

Objective: Managing neonatal jaundice effectively in preterm infants is crucial due to their increased vulnerability to bilirubin-induced neurological disorders. This study evaluates the efficacy of transcutaneous (TcB) versus serum bilirubin (TSB) measurements in this context. Methods: A total of 100 preterm neonates undergoing treatment for jaundice were assessed using both TcB and TSB measurements before, during, and after phototherapy. The study conducted paired t-tests and correlation analyses to evaluate the agreement between these two methods. Results: Before phototherapy, there was a strong positive correlation (r = 0.8319) between TcB and TSB, with a statistically significant mean difference (p = 0.0001). During phototherapy, TcB measurements were consistently lower than TSB, indicating significant discrepancies. The differences highlighted the influence of clinical interventions like phototherapy on the accuracy of TcB readings. Conclusion: The study validates transcutaneous bilirubinometry (TcB) as a non-invasive, effective alternative for jaundice monitoring in preterm infants. Despite some discrepancies with traditional serum bilirubin (TSB) measurements during phototherapy, the integration of TcB can decrease the reliance on invasive procedures. This research supports the potential of TcB to replace serum assessments, promoting a less stressful clinical experience for neonates while maintaining accuracy in therapeutic decisions. Future advancements are encouraged to enhance TcB measurement techniques to align more closely with serum bilirubin levels.

Endothelin-1 receptor blockade impairs invasion patterns in engineered 3D high-grade serous ovarian cancer tumouroids.

High-grade serous ovarian cancer (HG-SOC), accounting for 70-80% of ovarian cancer deaths, is characterized by a widespread and rapid metastatic nature, influenced by diverse cell types, cell-cell interactions, and acellular components of the tumour microenvironment (TME). Within this tumour type, autocrine and paracrine activation of the endothelin-1 receptors (ET-1R), expressed in tumour cells and stromal elements, drives metastatic progression. The lack of three-dimensional models that faithfully recapitulate the unique HG-SOC TME has been the bottleneck in performing drug screening for personalized medicine. Herein, we developed HG-SOC tumouroids by engineering a dense central artificial cancer mass (ACM) containing HG-SOC cells, nested within a compressed hydrogel recapitulating the stromal compartment comprising type I collagen, laminin, fibronectin, and stromal cells (fibroblasts and endothelial cells). ET-1-stimulated HG-SOC cells in the tumouroids showed an altered migration pattern and formed cellular aggregates, mimicking micrometastases that invaded the stroma. Compared with control cells, ET-1-stimulated tumouroids showed a higher number of invasive bodies, which were reduced by treatment with the dual ET-1 receptor (ET-1R) antagonist macitentan. In addition, ET-1 increased the size of the invading aggregates compared with control cells. This study establishes an experimental 3D multicellular model eligible for mechanical research, investigating the impact of matrix stiffness and TME interactions, which will aid drug screening to guide therapeutic decisions in HG-SOC patients.