Early Progression Research Articles

Sensitivity of Advanced Magnetic Resonance Imaging to Progression over Six Months in Early Spinocerebellar Ataxia.

Clinical trials for upcoming disease-modifying therapies of spinocerebellar ataxias (SCA), a group of rare movement disorders, lack endpoints sensitive to early disease progression, when therapeutics will be most effective. In addition, regulatory agencies emphasize the importance of biological outcomes. READISCA, a transatlantic clinical trial readiness consortium, investigated whether advanced multimodal magnetic resonance imaging (MRI) detects pathology progression over 6 months in preataxic and early ataxic carriers of SCA mutations. A total of 44 participants (10 SCA1, 25 SCA3, and 9 controls) prospectively underwent 3-T MR scanning at baseline and a median [interquartile range] follow-up of 6.2 [5.9-6.7] months; 44% of SCA participants were preataxic. Blinded analyses of annual changes in structural, diffusion MRI, MR spectroscopy, and the Scale for Assessment and Rating of Ataxia (SARA) were compared between groups using nonparametric testing. Sample sizes were estimated for 6-month interventional trials with 50% to 100% treatment effect size, leveraging existing large cohort data (186 SCA1, 272 SCA3) for the SARA estimate. Rate of change in microstructural integrity (decrease in fractional anisotropy, increase in diffusivities) in the middle cerebellar peduncle, corona radiata, and superior longitudinal fasciculus significantly differed in SCAs from controls (P < 0.005), with high effect sizes (Cohen's d = 1-2) and moderate-to-high responsiveness (|standardized response mean| = 0.6-0.9) in SCAs. SARA scores did not change, and their rate of change did not differ between groups. Diffusion MRI is sensitive to disease progression at very early-stage SCA1 and SCA3 and may provide a >5-fold reduction in sample sizes relative to SARA as endpoint for 6-month-long trials. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The role of VI-RADS scoring criteria for predicting oncological outcomes in bladder cancer

PurposeOur purpose was to evaluate the prognostic value of Vesical Imaging Reporting and Data System (VI-RADS) in bladder cancer (BCa) staging and predicting recurrence or progression.MethodsWe retrospectively analyzed the prospectively collected data from 96 patients with bladder tumors who underwent VI-RADS-based multiparametric magnetic resonance imaging (mpMRI) before endourological treatment from April 2021 to December 2022. Diagnostic performance was evaluated by comparing mpMRI reports with final pathology, using logistic regression for muscle-invasive bladder cancer (MIBC) predictors. Follow-up until May 2023 included Kaplan-Meier and Cox regression analysis to assess VI-RADS predictive roles for recurrence-free survival (RFS) and progression-free survival (PFS).ResultsA total of 96 patients (19.8% women, 80.2% men; median age 68.0 years) were included, with 71% having primary tumors and 29% recurrent BCa. Multiparametric MRI exhibited high sensitivity (92%) and specificity (79%) in predicting MIBC, showing no significant differences between primary and recurrent cancers (AUC: 0.96 vs. 0.92, P = .565). VI-RADS emerged as a key predictor for MIBC in both univariate (OR: 40.3, P < .001) and multivariate (OR: 54.6, P < .001) analyses. Primary tumors with VI-RADS ≥ 3 demonstrated significantly shorter RFS (P = .02) and PFS (P = .04).ConclusionsIn conclusion, mpMRI with VI-RADS has a high diagnostic value in predicting MIBC in both primary and recurrent BCa. A VI-RADS threshold ≥ 3 is a strong predictor for MIBC, and in primary tumors predicts early recurrence and progression.

Correlation of Pronated Foot Posture and Vertical Jump Measurement in Adolescent Recreational Basketball Players - An Observational Study

Background: Osteoarthritis (OA); a whole joint disorder is a most common and progressive disease that worsens with age. Synovitis and synovial effusion can play important role in early OA diagnosis and progression. Limited Background: Jumping is a significant move commonly performed by basketball players, with an average of 44 jumps completed by each player during a competitive game. The influence of foot pronation on the mechanics of the lower extremities in basketball players' movements, particularly during repeated jumps and various landing techniques, is a significant area under investigation. Methodology: After receiving ethical approval, a total of 250 individuals underwent screening. Out of these, 85 participants were selected for the study on specific criteria and convenience sampling. Prior to the commencement of the study, written consent was obtained from the parents of the participants, along with their assent. The participants were then categorized into different groups based on their navicular drop, with Group 1 (consisting of 42 individuals) exhibiting a pronated foot posture, and Group 2 (comprising 43 individuals) displaying a neutral foot posture. Subsequently, the Sargent jump test was conducted on all participants, and the data obtained was analyzed for both groups. Results: Data from basketball players were examined using SPSS 16.0. After conducting an unpaired t-test (p=0.15, Df= 83, t= 1.43) and a Pearson correlation test (r=0.12 and r=0.08), it was found that there was no statistically significant correlation between pronated foot posture and vertical jump performance. Conclusion: This research study has determined that there is no connection between a pronated foot position and the vertical jump height among young recreational basketball players. Keywords: Pronated foot, Navicular drop, Vertical jump, Adolescent, Basketball players.

Genomic and immune determinants of resistance to daratumumab-based therapy in relapsed refractory multiple myeloma

Targeted immunotherapy combinations, including the anti-CD38 monoclonal antibody (MoAb) daratumumab, have shown promising results in patients with relapsed/refractory multiple myeloma (RRMM), leading to a considerable increase in progression-free survival. However, a large fraction of patients inevitably relapse. To understand this, we investigated 32 relapsed MM patients treated with daratumumab, lenalidomide, and dexamethasone (Dara-Rd; NCT03848676). We conducted an integrated analysis using whole-genome sequencing (WGS) and flow cytometry in patients with RRMM. WGS before and after treatment pinpointed genomic drivers associated with early progression, including RPL5 loss, APOBEC mutagenesis, and gain of function structural variants involving MYC and chromothripsis. Flow cytometry on 202 blood samples, collected every 3 months until progression for 31 patients, revealed distinct immune changes significantly impacting clinical outcomes. Progressing patients exhibited significant depletion of CD38-positive NK cells, persistence of T-cell exhaustion, and reduced depletion of regulatory T cells over time. These findings underscore the influence of immune composition and daratumumab-induced immune changes in promoting MM resistance. Integrating genomics and flow cytometry unveiled associations between adverse genomic features and immune patterns. Overall, this study sheds light on the intricate interplay between genomic complexity and the immune microenvironment driving resistance to Dara-Rd in patients with RRMM.

Deletion of adipocyte Sine Oculis Homeobox Homolog 1 prevents lipolysis and attenuates skin fibrosis.

Dermal fibrosis is a cardinal feature of systemic sclerosis (SSc) for which there are limited treatment strategies. This is in part due to our fragmented understanding of how dermal white adipose tissue (DWAT) contributes to skin fibrosis. We identified elevated sine oculis homeobox homolog 1 (SIX1) expression in SSc skin samples from the GENISOS and PRESS cohorts, the expression of which correlated with adipose-associated genes and molecular pathways. SIX1 localization studies identified increased signals in the DWAT area in SSc and in experimental models of skin fibrosis. Global and adipocyte specific Six1 deletion abrogated end-stage fibrotic gene expression and dermal adipocyte shrinkage induced by SQ bleomycin treatment. Further studies revealed a link between elevated SIX1 and increased expression of SERPINE1 and its protein PAI-1 which are known pro-fibrotic mediators. However, SIX1 deletion did not appear to affect cellular trans differentiation. Taken together these results point at SIX1 as a potential target for dermal fibrosis in SSc.

The burden and care cascade in young and middle-aged patients with diabetes hypertension comorbidity with abdominal obesity in India: A nationally representative cross-sectional survey.

We ascertained the burden, determinants, and care cascade in the young and middle-aged patients having co-existing hypertension (HTN), Diabetes Mellitus (DM), and abdominal obesity in India from a secondary data analysis of nationally representative data. The study examined cross-sectional data from the National Family Health Survey (NFHS-5) conducted in India from 2019 to 2021 in 788974 individuals aged 15-49 years including 695707 women and 93267 men. The weighted prevalence of DM-HTN comorbidity with high waist circumference in the sample was 0.75% (95% CI: 0.71 to 0.79) including 46.33% (95% CI: 44.06 to 48.62) newly diagnosed cases detected for HTN and high blood sugars. The weighted prevalence of Metabolic syndrome as per NCEP ATPIII criteria was found to be 1.13% (95% CI: 1.08 to 1.17). Only 46.16% existing cases were treated with both anti-diabetes and antihypertensive medication (full treatment), while 34.71% cases were untreated. On adjusted analysis, increasing age, females, higher wealth index, high fat diet, obesity and comorbidities were significantly associated with having DM-HTN comorbidity along with high-waist circumference. More than half of young and middle aged-population in India with DM-HTN-abdominal obesity triad are not initiated on treatment for DM and HTN comorbidities, while a majority of the previously diagnosed cases have uncontrolled blood pressure and poor glycemic control. The poor cascade of care for DM and HTN in these high-risk group of patients may substantially increase their risk for early progression and severity of microvascular and macrovascular complications especially cardiovascular disease.

Cost of early progression: patients with epidermal growth factor receptor mutated metastatic non-small-cell lung cancer.

Aim: Compare healthcare costs for patients with epidermal growth factor receptor mutated (EGFRm) metastatic non-small-cell lung cancer (mNSCLC) with and without progression and estimate costs of progression.Materials & methods: Retrospective claims analysis (2015-2020) from adults with EGFRm mNSCLC initiating EGFR tyrosine kinase inhibitors. Adjusted costs for 12months were compared (with vswithout progression) and cumulative costs for early versus late progression were predicted over 36months.Results: A total of228 patients with EGFRm mNSCLC were included. Patients with progression within 12months incurred significantly higher total costs despite lower treatment costs (vswithout progression). Medical costs were significantly higher among early versus late progressors.Conclusion: These data may aid providers aiming to administer quality care in a cost-efficient way.

Intraperitoneal Nivolumab after Debulking Surgery and Hyperthermic Intraperitoneal Chemotherapy in Advanced Ovarian Cancer: A Phase I Study with Expansion Cohort.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are expected to be synergistic with intraperitoneal (IP) immunotherapy by increasing tumor antigen expression and mutational load. We assessed the feasibility and safety of IP nivolumab following complete CRS and HIPEC in pretreated patients with recurrent ovarian cancer (ClinicalTrials.gov identifier: NCT03959761). Patients received IP nivolumab (0.5, 1, or 3 mg/kg) using a 3 + 3 dose-escalation design, starting 5 to 7 days after CRS and HIPEC. Four IP Q2W (once every 2 weeks) nivolumab infusions were planned. The primary objective was to demonstrate the feasibility of IP nivolumab based on dose-limiting toxicity. Secondary objectives were to assess changes in tolerance of CRS and HIPEC. A total of 17 patients were enrolled including 10 patients in the dose escalation and 7 patients in the expansion phase. No dose-limiting toxicity was observed at any dose level in the 9 evaluable patients. Six of the 17 patients (35%) did not complete all planned infusions: 4 (23.5%) due to peritoneal catheter complications and 2 (11.8%) due to early progression. No procedure-related deaths occurred. Eleven patients (65%) experienced serious adverse events (SAE), mainly transitory grade 3 to 4 transaminase elevations (6/11) and surgery-related (9/11). Four SAEs were related to the peritoneal catheter and two to HIPEC. No SAEs/grade 3 to 4 adverse events related to IP nivolumab occurred. This is the first study demonstrating the feasibility of IP nivolumab in patients with relapsed advanced ovarian cancer. Further investigation at 3 mg/kg is warranted.

The transition from tube feeding to oral feeding algorithm in preterm infants: case-control study

BackgroundOral feeding is a complex sensorimotor process influenced by many variables, making it challenging for healthcare providers to introduce and manage it. Feeding practice guided by tradition or a trial-and-error approach may be inconsistent and potentially delay the progression of oral feeding skills.AimTo apply a new feeding approach that assesses early oral feeding independence skills of preterm infants in the neonatal intensive care unit (NICU). To prove its effectiveness, compare two approaches of oral feeding progression based on clinical outcomes in preterm infants, the traditional approach used in the NICU of Mansoura University Children Hospital (MUCH) versus the newly applied approach.MethodsA quasi-experimental, exploratory, and analytical design was employed using two groups, control and intervention groups, with 40 infants for the first group and 41 infants for the second one. The first group (the control) was done first and included observation of the standard practice in the NICU of MUCH for preterm oral feeding, in which oral feeding was dependent on post-menstrual age (PMA) and weight for four months. The second group (the intervention) included early progression to oral feeding depending on early assessment of Oral Feeding Skills (OFS) and early supportive intervention and/or feeding therapy if needed using the newly developed scoring system, the Mansoura Early Feeding Skills Assessment “MEFSA” for the other four months. Infants in both groups were studied from the day of admission till discharge.ResultsIn addition to age and weight criteria, other indicators for oral feeding readiness and oral motor skills were respected, such as oral feeding readiness cues, feeding practice, feeding maintenance, and feeding techniques. By following this approach, preterm infants achieved earlier start oral feeding (SOF) and full oral feeding (FOF) and were discharged with shorter periods of tube feeding. Infants gained weight without increasing their workload to the NICU team.ConclusionThe newly applied approach proved to be a successful bedside scoring system scale for assessing preterm infants’ early oral feeding independence skills in the NICU. It offers an early individualized experience of oral feeding without clinical complications.

Metabolic bone imaging and its relationship with biomechanics

ObjectiveThis mini review delves into the mechanisms of [18F]Sodium Fluoride positron emission tomography ([18F]NaF PET), which, by interrogating areas of newly mineralizing bone, provides a valuable tool to study the joint response to loading and areas of altered whole-joint function in osteoarthritis (OA). DesignThe review consolidates and discusses findings from both preclinical and clinical studies that utilize [18F]NaF PET to evaluate the bone response to various loading paradigms. It also briefly reviews technical considerations for PET imaging and discusses its strong potential as a tool in the quest to understand bone metabolism in the context of loading and osteoarthritis. ResultsWhile considering previous studies, technical considerations and potential new applications of this methodology are also discussed. [18F]NaF PET/MRI reveals localized, load-related bone responses after exercise, providing insights into early OA progression. In human studies, significant increases in tracer uptake are observed in areas affected by OA pathology, driven by bone perfusion and blood volume. Future work to examine the relationship between metabolic bone response to exercise and the bone loading environment is needed. ConclusionsIntegrating [18F]NaF PET/MRI with advanced biomechanical modeling holds promise for guiding clinical management of OA, primarily by examining the relationship between bone, soft tissues of the joint, and loading forces.

Associations between serum metabolites and female cancers: A bidirectional two-sample mendelian randomization study

Female cancers, especially breast, ovarian, cervical, and endometrial cancers, constitute a major threat to women's health worldwide. In view of the complex genetic background of cancers cannot be fully explained with current genetic information, we used a bidirectional two-sample mendelian randomization approach to explore the causal associations between serum metabolites and four major female cancers—breast, ovarian, cervical, and endometrial cancers. We analyzed the metabolites dataset from the Canadian Longitudinal Study of Aging and cancer datasets from the 10th round of the Finngen project. Replication analyses was performed with Cancer Association Consortium and Leo’s studies. Instrumental variables were analyzed using methods including the Wald ratio, inverse-variance weighted, MR-Egger, and weighted median. To ensure robustness, sensitivity analyses were performed using Cochrane’s Q, Egger’s intercept, MR-PRESSO, and leave-one-out methods. After meticulous analysis, we obtained levels of 3-hydroxyoleoylcarnitine, hexadecanedioate, tetradecanedioate, and carnitine C14 with robust causal associations with breast cancer, levels of 5alpha-androstan-3alpha,17beta-diol monosulfate (1), androstenediol (3beta,17beta) monosulfate (1), androsterone sulfate, and 5alpha-androstan-3beta,17beta-diol disulfate causal associations with endometrial cancer. The reverse analysis showed that breast, ovarian, and endometrial cancer and survival of breast and ovarian cancer were found to have causal relationships with 8, 5, 2, 6, and 3 metabolites, respectively. These insights underscore the potential roles of specific metabolites in the etiology of female cancers, providing new biomarkers for early detection, risk stratification, and disease progression monitoring. Further research could elucidate how these metabolites influence specific pathways in cancer development, offering theoretical foundations for prevention and treatment strategies.

Grade C Molar-Incisor Pattern Periodontitis in Young Adults: What Have We Learned So Far?

Grade C molar-incisor pattern periodontitis (C-MIP) is a disease that affects specific teeth with an early onset and aggressive progression. It occurs in systemically healthy patients, mostly African descendants, at an early age, with familial involvement, minimal biofilm accumulation, and minor inflammation. Severe and rapidly progressive bone loss is observed around the first molars and incisors. This clinical condition has been usually diagnosed in children and young adults with permanent dentition under 30 years of age. However, this disease can also affect the primary dentition, which is not as frequently discussed in the literature. Radiographic records have shown that most patients diagnosed in the permanent dentition already presented disease signs in the primary dentition. A hyperresponsive immunological profile is observed in local (gingival crevicular fluid-GCF) and systemic environments. Siblings have also displayed a heightened inflammatory profile even without clinical signs of disease. A. actinomycetemcomitans has been classified as a key pathogen in C-MIP in both dentitions. Scaling and root planning associated with systemic antibiotics is the current gold standard to treat C-MIP, leading to GCF biomarker reduction, some systemic inflammatory response modulation and microbiome profile changes to a healthy-site profile. Further studies should focus on other possible disease-contributing risk factors.

Deep Cascade of Convolutional Neural Networks for Quantification of Enlarged Perivascular Spaces in the Basal Ganglia in Magnetic Resonance Imaging.

In this paper, we present a cascaded deep convolution neural network (CNN) for assessing enlarged perivascular space (ePVS) within the basal ganglia region using T2-weighted MRI. Enlarged perivascular spaces (ePVSs) are potential biomarkers for various neurodegenerative disorders, including dementia and Parkinson's disease. Accurate assessment of ePVS is crucial for early diagnosis and monitoring disease progression. Our approach first utilizes an ePVS enhancement CNN to improve ePVS visibility and then employs a quantification CNN to predict the number of ePVSs. The ePVS enhancement CNN selectively enhances the ePVS areas without the need for additional heuristic parameters, achieving a higher contrast-to-noise ratio (CNR) of 113.77 compared to Tophat, Clahe, and Laplacian-based enhancement algorithms. The subsequent ePVS quantification CNN was trained and validated using fourfold cross-validation on a dataset of 76 participants. The quantification CNN attained 88% accuracy at the image level and 94% accuracy at the subject level. These results demonstrate significant improvements over traditional algorithm-based methods, highlighting the robustness and reliability of our deep learning approach. The proposed cascaded deep CNN model not only enhances the visibility of ePVS but also provides accurate quantification, making it a promising tool for evaluating neurodegenerative disorders. This method offers a novel and significant advancement in the non-invasive assessment of ePVS, potentially aiding in early diagnosis and targeted treatment strategies.

Evaluating the Urinary Exosome microRNA Profile of von Hippel Lindau Syndrome Patients with Clear Cell Renal Cell Carcinoma.

Renal cell carcinoma is one of the ten more common malignant tumors worldwide, with a high incidence and mortality rate. Kidney cancer frequently presents at an advanced stage, and it is almost invariably fatal. Much progress has been made in identifying molecular targets for therapy in the hope of improving survival rates, but still, we have no good markers for early detection or progression of the disease. Von Hippel Lindau syndrome (VHL) is an autosomal dominant cancer hereditary syndrome in which affected individuals are at risk of developing bilateral and multifocal renal cell carcinomas (RCC) as well as other tumors. These patients provide an ideal platform to investigate the potential of urinary exosomal miRNA biomarkers in the early development of ccRCC, as these patients are regularly imaged and tumors are actively monitored until the tumor reaches 3 cm before surgical excision. This allows for pre- and post-surgical urine collection and comparison to excised tumor tissues. Studying different biomarkers in urine can provide comprehensive molecular profiling available to patients and physicians and can be a great source of additional tumor genetic information. Pre- and postoperative urine samples were obtained from a cohort of VHL patients undergoing surveillance and surgical excision of ccRCCs, and exosomes were extracted. MicroRNA-Seq analysis was performed on miRNA extracted from both urine-derived exosomes and FFPE material from excised ccRCCs. MicroRNA-Seq analysis highlighted a significant difference in the urinary exosome-derived miRNA expression profiles between VHL patients and normal control individuals. This included decreased expression of the miR-320 family, such as miR-320a, known to be decreased in sporadic ccRCC and suppressed by the HIF1α transcription factor activated by the loss of the VHL gene. MiR-542-5p represented a potential marker of VHL-associated ccRCC that was lowly expressed in normal control urinary exosomes, significantly increased in the preoperative urinary exosomes of tumor-bearing VHL patients, and subsequently reduced to normal levels of expression after tumor excision. In concordance with this, the expression of miR-542-5p was increased in the VHL-associated ccRCC in comparison to the normal kidney. This study shows the potential for miRNA profiling of exosomes from readily available biofluids to both distinguish VHL patient urine from normal control urine microRNAs and to provide biomarkers for the presence of VHL syndrome-associated ccRCC. Further validation studies are necessary to demonstrate the utility of urinary exosome-derived miRNAs as biomarkers in kidney cancer.

Locoregional Radiotherapy in Patients with Advanced Breast Cancer Treated with Cyclin-Dependent Kinase 4/6 Inhibitors Based on Real-World Data.

The use of locoregional radiotherapy (RT) in patients with advanced ER-positive, HER2-negative breast cancer remains a topic of ongoing debate. In this study, we aimed to evaluate the efficacy of locoregional RT in advanced breast cancer patients treated with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in a first-line setting. We conducted a retrospective analysis of patients diagnosed with advanced breast cancer between 2018 and 2023 who received treatment with CDK4/6i and underwent locoregional radiotherapy. Among the 371 patients treated with CDK4/6i as part of their first-line therapy, 23 received locoregional RT either concurrently or sequentially with CDK4/6 inhibitors. Disease progression within the breast occurred in 19 patients (5.1%). Among these cases, five patients had previously undergone breast RT (5/23, 21.7%), while 14 did not (14/348, 4.0%, p = 0.004). All cases of local progression after RT followed palliative doses and were accompanied by early systemic progression. The 2-year PFS in the entire cohort of patients treated with locoregional RT was 65.7% (95% CI: 40.5-82.3%). Notably, patients who received higher RT doses had longer 2-year PFS (83.3%, 95% CI: 27.3-97.5%) than those with palliative RT doses (59.3%, 95% CI: 30.7-79.3%); however, the results were not statistically significant (p = 0.58). Furthermore, the 2-year local control in the entire cohort with locoregional RT was 73.0% (95% CI: 46.5-87.9%). Importantly, no local progression was observed after RT when using high doses. The addition of locoregional radiotherapy to first-line CDK4/6 inhibitors warrants further investigation across various clinical scenarios in advanced breast cancer. Palliative radiation regimens delivered early in breast oligoprogression may not always suffice, emphasizing the need for comprehensive studies in this context.

Multimodal Technologies for Remote Assessment of Neurological and Mental Health.

Automated remote assessment and monitoring of patients' neurological and mental health is increasingly becoming an essential component of the digital clinic and telehealth ecosystem, especially after the COVID-19 pandemic. This review article reviews various modalities of health information that are useful for developing such remote clinical assessments in the real world at scale. We first present an overview of the various modalities of health information-speech acoustics, natural language, conversational dynamics, orofacial or full body movement, eye gaze, respiration, cardiopulmonary, and neural-which can each be extracted from various signal sources-audio, video, text, or sensors. We further motivate their clinical utility with examples of how information from each modality can help us characterize how different disorders affect different aspects of patients' spoken communication. We then elucidate the advantages of combining one or more of these modalities toward a more holistic, informative, and robust assessment. We find that combining multiple modalities of health information allows for improved scientific interpretability, improved performance on downstream health applications such as early detection and progress monitoring, improved technological robustness, and improved user experience. We illustrate how these principles can be leveraged for remote clinical assessment at scale using a real-world case study of the Modality assessment platform. This review article motivates the combination of human-centric information from multiple modalities to measure various aspects of patients' health, arguing that remote clinical assessment that integrates this complementary information can be more effective and lead to better clinical outcomes than using any one data stream in isolation.

The role of tumor-associated neutrophils in early luminal HER2-negative breast cancer progression

BACKGROUND: Luminal HER2-negative breast cancer is the most common type of tumor in women diagnosed with early-stage breast cancer. Stromal cells and immune cells in tumor microenvironment have been reported to play a significant role in cancer prognosis. The prognostic role of tumor-associated neutrophils in early breast cancer remains mostly unclear. AIM: To study predictive role tumor-associated neutrophils in early luminal HER2-negative breast cancer. MATERIALS AND METHODS: The dataset consisted of 60 patients with early luminal HER2-negative breast cancer treated in S.P. Botkin City Clinical Hospital (Moscow, Russia). We first estimated basic morphological signs: tumor size, tumor grade (by Nottingham Histologic Score), tumor-infiltrating lymphocytes, lymphovascular invasion, hormonal receptors status, proliferative index, regional lymph nodes status. The expression of intratumoral neutrophils was studied using immunohistochemistry with CD15. RESULTS: High tumor-associated neutrophils concentration was correlated with tumor size, high grade tumors, proliferative index, tumor-infiltrating lymphocytes, lymphovascular invasion and positive regional lymph nodes. CONCLUSION: Tumor-associated neutrophils predicted a worse prognosis in early luminal HER2-negative breast cancer.

Cylindrical TGR as early radiological predictor of RLT progression in GEPNETs: a proof of concept

This study aims to assess the predictive capability of cylindrical Tumor Growth Rate (cTGR) in the prediction of early progression of well-differentiated gastro-entero-pancreatic tumours after Radio Ligand Therapy (RLT), compared to the conventional TGR. Fifty-eight patients were included and three CT scans per patient were collected at baseline, during RLT, and follow-up. RLT response, evaluated at follow-up according to RECIST 1.1, was calculated as a percentage variation of lesion diameters over time (continuous values) and as four different RECIST classes. TGR between baseline and interim CT was computed using both conventional (approximating lesion volume to a sphere) and cylindrical (called cTGR, approximating lesion volume to an elliptical cylinder) formulations. Receiver Operating Characteristic (ROC) curves were employed for Progressive Disease class prediction, revealing that cTGR outperformed conventional TGR (area under the ROC equal to 1.00 and 0.92, respectively). Multivariate analysis confirmed the superiority of cTGR in predicting continuous RLT response, with a higher coefficient for cTGR (1.56) compared to the conventional one (1.45). This study serves as a proof of concept, paving the way for future clinical trials to incorporate cTGR as a valuable tool for assessing RLT response.

Identification of novel prognostic biomarkers for bladder cancer in Egyptian patients using mass spectrometry

BackgroundProteomic biomarkers are considered a central analytical method that improves the outcome of early progression and diagnosis with high accuracy in bladder cancer (BC). Currently, several proteins are detected in plasma and tissues using proteomic techniques, making it challenging to compare and identify common pathways and proteins. MethodUsing mass spectrometry, which can analyze multiple proteins with specific biological considerations and technical implications with high sensitivity and specificity, we identified clinically relevant protein biomarkers in tissue and plasma samples from healthy controls and patients with bladder cancer. The results were analyzed using bioinformatics to evaluate several proteins in the tissue and plasma. ResultsWe identified six candidate biomarkers (GSN, HP, SERPINA1, A2M, HBB, and HBD) that were correlated with increased tumor progression in the Egyptian population. ConclusionOur research focused on genes that are upregulated or downregulated. This indicated that A2M and SERPINA1 could serve as more specific upregulated biomarkers for plasma cancer samples, while GSN, HBB, HBD, and HP could be the downregulated ones for tissue cancer samples. Among patients with bladder cancer, different proteins have been reported to be under different regulations as compared to healthy controls. Thus, there is still a need for further studies in order to ascertain their functionality and treatment prospects, as well as to underscore their significance in pathogenesis as early predictor biomarkers.

Clinical Validation of the Somatic FANCD2 Mutation (c.2022-5C>T) as a Novel Molecular Biomarker for Early Disease Progression in Chronic Myeloid Leukemia: A Case-Control Study.

Background: Chronic myeloid leukemia (CML) results from chromosomal translocation t(9;22) leading to the formation of the BCR-ABL fusion oncogene. CML has three stages: the chronic phase (CP), the accelerated phase (AP), and the blast crisis (BC). Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of CML. TKIs work well in CP-CML, and these patients have a survival rate similar to the normal population, but TKIs are less effective in advanced-phase CML. Even with current advances in treatment, BC-CML patients have an average overall survival of less than a year. Early recognition of CML patients at risk of disease progression can help in timely interventions with appropriate TKIs or other therapeutic modalities. Although some markers of disease progression like BCR-ABL kinase domain, ASXL1, and GATA2 mutations are available, no universal and exclusively specific molecular biomarkers exist to early diagnose CML patients at risk of CML progression for timely therapeutic interventions to delay or minimize blast crisis transformation in CML. A recent study found that all BC-CML patients harbored the FANCD2 (c.2022-5C>T) mutation. Therefore, the current study was designed to detect this FANCD2 mutant in AP-CML (early progression phase) and to clinically validate its potential as a novel molecular biomarker of early CML progression from CP to AP. Methods: Our study comprised 123 CP-CML (control group) and 60 AP-CML patients (experimental group) from 2 oncology centers, from January 2020 to July 2023. Mean hemoglobin level, WBC count, platelet count, treatment type, hepatomegaly, splenomegaly, and survival status of AP-CML patients were significantly different from those of CP-CML patients. However, as these clinical parameters cannot help in the early detection of patients at risk of CML progression, there was a need for a clinically validated biomarker of AP-CML. DNA was extracted from the patients' blood samples, and the FANCD2 gene was sequenced using an Illumina NextSeq500 next-generation sequencer (NGS). Results: The NGS analysis revealed a unique splice-site mutation in the FANCD2 gene (c.2022-5C>T). This mutation was detected in the majority (98.3%) of AP-CML patients but in none of the CP-CML patients or healthy control sequences from genomic databases. The mutation was confirmed by Sanger sequencing. FANCD2 is a member of the Fanconi anemia pathway genes involved in DNA repair and genomic stability, and aberrations of this gene are associated with many cancers. Conclusions: In conclusion, our study shows that the somatic FANCD2 (c.2022-5C>T) mutation is a new molecular biomarker for early CML progression. We recommend further clinical validation of this biomarker in prospective clinical trials.