Higher Progression Rate Research Articles

Studying Alzheimer’s disease through an integrative serum metabolomic and lipoproteomic approach

BackgroundAlzheimer’s disease (AD) is the most frequent neurodegenerative disorder worldwide. The great variability in disease evolution and the incomplete understanding of the molecular mechanisms underlying AD make it difficult to predict when a patient will convert from prodromal stage to dementia. We hypothesize that metabolic alterations present at the level of the brain could be reflected at a systemic level in blood serum of patients, and that these alterations could be used as prognostic biomarkers.MethodsThis pilot study proposes a serum investigation via nuclear magnetic resonance (NMR) spectroscopy in a consecutive series of AD patients including 57 patients affected by Alzheimer’s disease at dementia stage (AD-dem) and 45 patients with mild cognitive impairment (MCI) due to AD (MCI-AD). As control group, we considered 31 subjects with mild cognitive impairment in whom AD and other neurodegenerative disorders were excluded (MCI). A panel of 26 metabolites and 112 lipoprotein-related parameters was quantified and the logistic LASSO regression algorithm was employed to identify the optimal combination of metabolites-lipoproteins and their ratios to discriminate the groups of interest.ResultsIn the training set, our model classified AD-dem and MCI with an accuracy of 81.7%. These results were reproduced in the validation set (accuracy 75.0%). Evolution of MCI-AD patients was evaluated over time. Patients who displayed a decrease in MMSE < 1.5 point per year were considered at lower progression rate: we obtained a division in 18 MCI-AD at lower progression rate (MCI-AD LR) and 27 at higher progression rate (MCI-AD HR). The model calculated using 4 metabolic features identified MCI-AD LR and MCI-AD HR with an accuracy of 73.3%.ConclusionsThe identification of potential novel peripheral biomarkers of Alzheimer’s disease, as proposed in this study, opens a new prospect for an innovative and minimally invasive method to identify AD in its very early stages. We proposed a novel approach able to sub-stratify MCI-AD patients identifying those associated with a faster rate of clinical progression.

Standardisation of the radiological definition of supramaximal resection in glioblastoma.

Glioblastoma remains the most common and lethal primary malignant brain tumour, with high rates of recurrence and progression despite gross-total resection of the contrast-enhancing region based on T1-weighted MRI. There has been growing interest in exploring "supramaximal" resections that extend beyond contrast-enhancing borders, with initial retrospective data suggesting survival benefit, but there is currently no consensus definition. In this systematic review, we explore the evolution of supramaximal resection in glioblastoma, dissect the incongruencies in the literature regarding its definition, qualitatively appraise each definition and discuss the results of various studies that have explored its impacts on patient outcomes. MEDLINE, EMBASE, SCOPUS, Cochrane Registry of Clinical Trials and Pub-MED were systematically searched for studies of glioblastoma patients who had undergone supramaximal resection. After screening and applying eligibility criteria, 25 studies were included in the final review. Definitions were grouped according to radiological modality and visualisation adjuncts and included various extents of resection of hyperintensity visualised using T2-Fluid-Attenuated Inversion Recovery, various volumetric resections of the non-contrast enhancing region, removal of methionine-uptake areas on PET, complete removal of 5-aminolevulinic acid fluorescent tissue and lobectomies. Our systematic review identified a general trend suggesting a survival benefit from supramaximal resection compared to gross-total resection but, more importantly, demonstrated the limitations of these studies due to selection bias and substantial methodological heterogeneity. Ultimately, our findings demonstrate the need for an applicable, standardised and specific definition for supramaximal resection so that prospective studies can determine prognostically significant clinical data to guide the surgical management of glioblastoma.

The emergence of DNAM-1 as the facilitator of NK cell-mediated killing in ovarian cancer.

Ovarian cancer (OC) is the sixth most common malignancy in women and the poor 5-year survival emphasises the need for novel therapies. NK cells play an important role in the control of malignant disease but the nature of tumour-infiltrating and peripheral NK cells in OC remains unclear. Using flow cytometric analysis, we studied the phenotype and function of NK cells in blood, primary tumour and metastatic tissue in 80 women with OC. The cell type contexture of metastatic OC tissue was explored utilising scRNAseq analysis, with a focus on portraying an immunogenic tumour microenvironment and determining the characteristics of a dysfunctional NK cell population. The proportion of peripheral NK cells was markedly elevated with a highly activated profile and increased cytotoxicity. In contrast, NK cell numbers in primary tumour and metastasis were substantially reduced, with downregulation of activatory receptors together with elevated PD-1 expression. scRNA-Seq identified 5 NK cell subpopulations along with increased exhausted and immature NK cells within tumour tissue compared to normal tissue. These features were attenuated following chemotherapy where higher levels of activated and cytotoxic NK cells associated with improved disease-free survival. Correlation of NK cell phenotype with clinical outcomes revealed high levels of DNAM-1 expression on tissue-localised and peripheral NK cells to be associated with reduced survival. Expression of PVR, the DNAM-1 ligand, was significantly increased on tumours and DNAM-1 mediated NK cell lysis of primary tumour tissue was observed in vitro. These findings reveal profound modulation of the tumour tissue and systemic profile of NK cells which likely contributes to the high rates of local progression and metastasis seen with OC. Immunotherapeutic approaches that overcome local immune suppression and enhance DNAM-1-targeted lysis of OC offer the potential to improve disease control.

Optimizing prone CT use for suspected interstitial lung abnormalities.

We investigated whether supine chest CT alone suffices for diagnosing ILAs, thereby reducing the need for prone chest CT. Patients who underwent prone chest CT for suspected ILAs from January 2021 to July 2023, with matching supine CT within 1 year, were retrospectively evaluated. Five multinational thoracic radiologists independently rated ILA suspicion and fibrosis scores (1 to 5-point) and ILA extent (1-100%) using supine CT first, then combined supine-prone CT after a 1-month washout. We categorized ILA suspicion and fibrosis scores into four diagnostic groups; normal, non-fibrotic, indeterminate-type, and fibrotic ILAs. The areas under the receiver operating characteristic curve (AUCs) of ILA suspicion scores, inter-reader agreement on diagnostic categories, and intra-reader/inter-reader reliability for ILA extent were evaluated. This study included 69 patients (mean age 67.2 ± 7.2 years; 36 women), with 23 age- and sex-matched patients in each group: normal, non-fibrotic ILAs, and fibrotic ILAs. The pooled AUC for ILA suspicion and inter-reader agreement on diagnostic categories improved for non-fibrotic ILAs with prone CT (AUC 0.76 to 0.92, p < 0.001; Fleiss kappa 0.25 to 0.51, p = 0.004), but not for fibrotic ILAs (AUC 0.94 to 0.99, p = 0.06; Fleiss kappa 0.63 to 0.72, p = 0.08). ILA extent was 1-2% smaller with prone CT for both ILA types (p < 0.001). For fibrotic ILAs, supine CT alone exhibited substantial diagnostic accuracy and inter-reader agreement, while the diagnosis of non-fibrotic ILAs benefited from adding prone CT. Supine CT alone slightly overestimated extent regardless of ILA type. Question Prone CT is recommended when interstitial lung abnormalities (ILAs) are suspected on supine CT, but its benefits remain underexplored. Findings Supine CT alone sufficed for diagnosing fibrotic ILAs, while prone CT improved non-fibrotic ILA diagnosis and reduced extent overestimation for both types. Clinical relevance Omitting prone CT reduces extra time, space, and radiation exposure without compromising the diagnosis of fibrotic ILAs, which have higher rates of progression and mortality risks, enhancing patient comfort and simplifying patient management.

RRM2 Is a Putative Biomarker and Promotes Bladder Cancer Progression via PI3K/AKT/mTOR Pathway.

Bladder cancer (BLCA) is the tenth most common cancer worldwide, characterized by its high recurrence and progression rates. Thus, identifying prognostic biomarkers and understanding its underlying mechanisms are imperative to enhance patient outcomes. In this study, we aimed to investigate the prognostic significance, expression, functional activity, and underlying mechanisms of RRM2 in BLCA. RRM2 expression and its association with pathological grading and survival were investigated in samples from TCGA dataset and BLCA tissue microarray. CCK8 assays, colony formation assays, wound healing, and transwell assays were performed to assess the role of RRM2 in BLCA cell proliferation and migration. Western blot was employed to investigate alterations in markers associated with epithelial-to-mesenchymal transition (EMT), apoptosis, and cell cycle regulation. Gene set enrichment analysis was performed to investigate the biological processes associated with RRM2, which were subsequently validated. The expression of RRM2 was significantly elevated in both BLCA tissues and cells. Our results also indicated a positive correlation between RRM2 expression and high tumor stage, high tumor grade, and poor survival. Knockdown of RRM2 inhibited cell proliferation and migration of BLCA. RRM2 knockdown significantly induced apoptosis and arrested the cell cycle at the G0/G1 phase. Opposite results were observed in the RRM2 overexpression cells. Additionally, our study demonstrates that RRM2 promotes BLCA progression by activating the PI3K/AKT/mTOR pathway. RRM2 is remarkably correlated with poor prognosis in BLCA and facilitate its progression via PI3K/AKT/mTOR pathway. It is suggested that RRM2 might become an effective prognostic biomarker and potential therapeutic target for BLCA.

A blastocyst's implantation potential is linked to its originating oocyte cohort's blastulation rate: evidence for a cohort effect.

To investigate if blastocysts originating from different follicular cohorts have variable implantation rates, adjusted for oocyte age, morphology and/or ploidy DESIGN: Retrospective cohort SETTING: Academic center SUBJECTS: Patients who underwent one or more cycles of autologous ovarian stimulation and in vitro fertilization/intracytoplasmic sperm injection, followed by elective single frozen blastocyst transfer EXPOSURE: Blastocyst progression rate of a follicular cohort; defined as the total number of expanded blastocyst, euploid blastocyst, Day 5 blastocyst, or Day 5 euploid blastocyst(s) divided by the number of 2 pronuclei (2PN) zygote(s) MAIN OUTCOME MEASURES: Implantation, defined as serum human chorionic gonadotropin >5mIU/ml following elective single embryo transfer (eSET) RESULTS: A total of 4,292 blastocysts were tracked from their follicular cohort origin to their outcome following eSET. The mean age±standard deviation of the study population was 36.2±3.6 years old. The median (interquartile range; IQR) number of oocytes and 2PN zygotes per cohort was 17 (12-24) and 11 (8-16), respectively. The median (IQR) number of total expanded blastocysts and Day 5 blastocysts per cohort was 6 (4-9) and 2 (1-4), respectively. Preimplantation genetic testing for aneuploidy (PGT-A) utilization rate was 63.0%. The median (IQR) number of total euploid blastocysts and Day 5 euploid blastocysts were 2 (1-4) and 1 (0-2), respectively. Median (IQR) overall blastocyst progression rate was 60.0% (43.5-75.0%), euploid blastocyst progression rate 21.4% (13.3-33.3%), Day 5 blastocyst progression rate 20.0% (8.7-35.2%), and Day 5 euploid blastocyst progression rate 9.1% (0.0-18.2%). All blastocyst progression parameters inversely correlated with increasing age. Multivariable mixed-effects logistic regression analyses, adjusting for oocyte age, number of oocytes retrieved, embryo morphology, and PGT-A status, showed a positive association between overall blastocyst progression (adjusted OR 1.04 [95% CI 1.01-1.08], p=0.02), Day 5 blastocyst progression (adjusted OR 1.05 [95% CI 1.01-1.09], p=0.01), and Day 5 euploid blastocyst progression (adjusted OR 1.10 [95% CI 1.03-1.18], p=0.01) and implantation rates. Adjusting for age, oocytes retrieved, morphology, and ploidy status, blastocysts from follicular cohorts with high blastocyst progression rates demonstrate superior implantation potential compared to those from cohorts with lower blastocyst progression rates. This observation suggests the presence of a cohort effect, and offers valuable information for patient counseling on an embryo's implantation potential beyond ploidy/morphology.

Construction of a disulfidptosis-associated lncRNA signature to predict prognosis in bladder cancer.

Bladder cancer (BCa) is the most common neoplasm of the urinary system, and its high rates of progression and recurrence contribute to a generally poor prognosis, especially in advanced cases. It is reported that disulfidptosis is closely related with tumor proliferation. We aimed to construct a disulfidptosis-associated long non-coding RNA (lncRNA) signature that can predict prognosis and immune microenvironment in BCa. We obtained RNA-seq data, clinical information, and mutation data of BCa patients from The Cancer Genome Atlas (TCGA) database. Based on Pearson correlation and uni-Cox regression analysis, we identified disulfidptosis-associated lncRNAs related with overall survival (OS). Then a prognosis signature based on seven disulfidptosis-associated lncRNAs was constructed by least absolute shrinkage and selection operator (LASSO) Cox regression analysis and multi-Cox regression analysis. We performed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) analyses to examine biological functional of differentially expressed genes related to the risk model. We assessed the immune microenvironment and chemotherapeutic response of several drugs. Finally, the quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression level of the disulfidptosis-associated lncRNAs. We established a prognosis signature based on seven disulfidptosis-associated lncRNAs (AP003419.3, AL161891.1, AC234917.3, LINC00536, AL021707.6, AL445649.1 and AC104785.1). According to the signature, all patients were divided in high- and low-risk group and patients in low-risk group showed a significantly better prognosis. Moreover, the risk model was confirmed to be an independent prognostic factor with high accuracy. Immune cells and several immune checkpoints were more active in high-risk group and patients in this group had a higher tumor mutation burden (TMB) that those in low-risk group. The results of qRT-PCR demonstrated that expression level of the lncRNAs were all significantly different between BCa cell lines and normal urinary epithelial cells. The disulfidptosis-associated lncRNA signature is a promising biomarker for predicting prognosis and characterizing the immune landscape in BCa, potentially guiding personalized treatment strategies.

SLC12A9 is an immunological and prognostic biomarker for glioma

BackgroundGlioma is one of the most common malignant brain tumors. It has a high rate of progression and a poor prognosis, and effective biomarkers still need to be identified. The solute carrier family 12 (SLC12) family has been reported to be involved in various physiological and pathological processes, but their functional roles in glioma remain unclear. MethodsUsing public datasets, we studied the mutation and expression level of SLC12 family genes in glioma and identified the significantly differentially expressed member solute carrier family 12 member 9 (SLC12A9). We further predicted the prognostic role of SLC12A9 in glioma by using the Kaplan–Meier method and Cox regression analysis. Then, we performed biological functional enrichment analysis. We focused on the relationships between SLC12A9 expression and immune infiltration in glioma. Meanwhile, we conducted in vitro experiments to evaluate the effect of SLC12A9 expression on glioma cells. ResultsAmong the members of the SLC12 family, SLC12A9 had the highest mutation rate in glioma, with gene amplification as the major mutation type, and its expression was significantly upregulated in glioma. Higher SLC12A9 expression was significantly associated with older age, higher grade, wild-type isocitrate dehydrogenase (IDH), and a worse prognosis. The functional enrichment analysis indicated that SLC12A9 is mainly related to ion channel annotation. Gene set enrichment analysis (GSEA) revealed that SLC12A9 was mainly related to the DNA replication pathway. Furthermore, we found that SLC12A9 correlated with tumor-infiltrating immune cells and immune checkpoints. Thus, SLC12A9 may be involved in regulating the immune response of glioma. Finally, our in vitro experiments revealed that silencing SLC12A9 dramatically inhibited glioma cell growth and migration. ConclusionsWe showed that SLC12A9 may be a new predictive biomarker for glioma diagnosis, prognosis, and immunotherapy response, offering helpful guidelines to advance glioma treatment.

Distinct clinical features of urothelial carcinoma with low-expressing human epidermal growth factor receptor 2 status.

Some urothelial carcinoma patients are ineligible for platinum-based chemotherapy, necessitating exploration of other effective therapeutic strategies. Human epidermal growth factor receptor 2 (HER2) protein overexpression, gene amplification or mutations exist in urothelial carcinoma. Our study is to investigate the correlation of three-tier assessment of HER2 expression with clinical pathological characteristics and prognosis of urothelial carcinoma. HER2 expression in 75 urothelial carcinomas from Jiangsu Cancer Hospital was re-scored by immunohistochemistry and fluorescence in situ hybridization according to HER2 three-tier assessment standards. Its relationship with various pathological parameters of urothelial carcinoma and its correlation with prognosis were analyzed. And validate in The Cancer Genome Atlas (TCGA) cohort. HER2 expression was observed in 82.7% (62/75) of urothelial carcinoma patients, of which HER2-low expression accounted for 61.3% (46/75). HER2 expression was significantly correlated with the tumor-nodes-metastasis (TNM) stage of urothelial carcinoma (P=0.043) and HER2-low was an independent poor prognostic factor for patients with urothelial carcinoma (P=0.04). Follow-up showed that HER2-low patients had the worst prognosis compared with HER2-negative (P=0.02) and HER2 positive (P=0.02) and also had the highest progression rate in TCGA cohort (P=0.02); receiver operator characteristic (ROC) model suggested HER2-low could effectively predict prognosis. HER2 expression is closely related to the TNM stage of urothelial carcinoma; HER2 three-tier assessment can effectively predict clinical prognosis of urothelial carcinoma.

Post-transplant IgA nephropathy: a rapidly evolving field of kidney transplant medicine.

IgA nephropathy is the commonest pattern of primary glomerular disease in the world, with high rates of progression to kidney failure. As IgA nephropathy commonly causes kidney failure at a young age, kidney transplantation is commonly used to treat kidney failure. However, high rates of recurrent disease in the allograft remain a common management challenge. The prevalence of post-transplant recurrence approaches 15% at ten years post-transplant and is associated with poor allograft function and high rates of allograft loss. Post-transplant IgA nephropathy has also been described de novo in some case series. Treatment of recurrent IgA nephropathy has been challenging but with the rapid growth of new treatments for IgA nephropathy it is likely that many of these treatments will, over time, transition to the treatment of recurrent disease. In this narrative review, our aim is to evaluate post-transplant IgA nephropathy in terms of epidemiology, risk factors, underlying pathophysiology, diagnosis and management strategies.

Limited Effectiveness in Early Human Clinical Experience with Pulsed Electrical Field Ablation

PurposeTo evaluate oncological outcomes, abscopal effect, and adverse events (AEs) of pulsed electrical field (PEF) ablation of tumors in the chest, abdomen, and pelvis. Materials and MethodsPEF ablations performed at an academic medical center between May 2023 and January 2024 were retrospectively analyzed. Eleven patients (4 males and 7 females; age, 58 years ± 19) underwent 11 PEF sessions targeting 13 tumors (lung metastasis from solitary fibrous tumor [n = 3] and colorectal carcinoma [CA; n = 1], osteosarcoma pleural metastases [n = 2], hepatocellular CA [n = 2], liver metastasis from colorectal CA [n = 1] and leiomyosarcoma [n = 1], metastatic melanoma to the pancreas [n = 1], metastatic retroperitoneal lymph node from endometrial CA [n = 1], and recurrence of endometrial CA in the vaginal cuff [n = 1]) with the goal of complete coverage (n = 11/13) or debulking (n = 2/13). The mean tumor diameter was 1.9 cm (SD ± 1.0; range, 0.4–3.3 cm). Cross-sectional imaging follow-up was 5.3 months (SD ± 2.2; range, 1.9–7.9 months). Oncological outcomes, abscopal effect, and AEs categorized according to the Society of Interventional Radiology (SIR) guidelines were analyzed. ResultsOf 11 tumors that underwent ablation for complete coverage, complete coverage was achieved for 1 (9%), and residual was detected in 9 (81%). Ten (91%) of 11 patients showed either residual, local, or distant progression within a median of 3 months. No abscopal effect was observed. There were 2 mild and 2 severe AEs. ConclusionsPEF ablation showed a low rate of complete coverage (9%) and a high rate (91%) of residual, local, or distant progression. No abscopal effect was observed within a median of 5.1 months after the ablation.

High expression of LINC00467 promotes proliferation and metastasis of lung adenocarcinoma cells by suppressing autophagy via inhibiting the AMPK/mTOR pathway

To investigate the regulatory effects of LINC00467 on proliferation and metastasis of lung adenocarcinoma cells and the involvement of autophagy in its regulatory mechanism. LINC00467 expression levels in lung adenocarcinoma tissues and their correlation with the patients' survival outcomes were analyzed using data from TCGA database. LINC00467 expression was also examined using qRT-PCR in human bronchial epithelial cells 16HBE and lung adenocarcinoma cell lines A549 and H1299. In A549 and H1299 cells transfected with a short hairpin RNA targeting LINC00467 (shLINC00467), the effects of 3-methyladenine (3-MA, an autophagy inhibitor) and BML-275 (an AMPK inhibitor) treatment on cell proliferation, migration, and expressions of LC3 and the AMPK/mTOR pathway proteins were tested using colony formation assay, wound-healing and Transwell assays, immunofluorescence staining and Western blotting. GSEA enrichment analysis was conducted to analyze the correlation between LINC00467 and the autophagy pathway. The expression level of LINC00467 was significantly higher in lung adenocarcinoma tissues than in the adjacent tissues (P < 0.001) and increased progressively with the clinical stage (P < 0.05), and its high expression was associated with a poor overall survival (P= 0.049) and a high first progression rate (P=0.026) of the patients. LINC00467 expression was also significantly higher in A549 and H1299 cells than in 16HBE cells. In A549 and H1299 cells, LINC00467 knockdown significantly decreased colony-forming, migration and invasion abilities of the cells, lowered p-mTOR/mTOR and p62 expressions, and increased p-AMPK/AMPK expressions and LC3Ⅱ/Ⅰ ratio, and these effects were strongly attenuated by application of either 3-MA or BML-275. GSEA analysis suggested an inhibitory effect on LINC00467 on the autophagy pathway (|NES| > 1, P < 0.05, FDR < 0.25). High expressions of LINC00467 promote proliferation and metastasis of lung adenocarcinoma cells possibly by inhibiting cell autophagy mediated by the AMPK/mTOR signaling pathway.

Whole Exome Sequencing of Intracranial Epidermoid Cysts Reveals Immune-Associated Mechanistic and Potential Targets.

Background/Objectives: Intracranial Epidermoid Cysts (IECs) are rare intracranial tumors primarily treated through surgery. Cyst adherence complicates complete removal, leading to high rates of tumor progression after subtotal resection. The molecular drivers of IEC remain unknown. Consequently, advances in treatment have fallen short. Tumor genetic profiling has revealed potential targets for drug development, including FDA-approved options and reshaping treatment. The genetic landscape of IECs has not been explored. We applied Whole Exome Sequencing (WES) to IECs to gain insights into the mechanisms of oncogenesis and identify potential therapeutic targets. Methods: We performed WES on tumor tissue and matched blood samples, when available. Following GATK best practices, we conducted read processing, quality control, somatic variant calling, and copy-number inference. Data analyses and visualization were conducted in R. Results: Top altered genes are associated with the immune system and tumor microenvironment, suggesting a mechanism of immune evasion. Gene and pathway enrichment revealed a high mutation burden in genes associated with Extracellular Matrix (ECM) and PI3K-AKT-mTOR cascades. Recurrent and deleterious alterations in NOTCH2 and USP8 were identified in 50% and 30% of the cohort, respectively. Frequent amplifications in deubiquitinases and beta-defensins strengthened the involvement of immune mechanisms for oncogenic transformation. Conclusions: Top altered genes and recurrent mutations may play a role in shaping the microenvironment and modulating immune evasion in IECs. USP8 and NOTCH2 may serve as clinically relevant target for IECs. Finally, we present evidence that the crosstalk between the PI3K-Akt-mTOR and ECM signaling pathways may play a role in modulating the immune escape mechanism in IECs.

Strategies to Improve Clinical Outcomes and Patient Experience Undergoing Transurethral Resection of Bladder Tumor.

To describe patient experiences of transurethral resection of bladder tumor (TURBT) and review recent advances in enhancing clinical outcomes. High rates of recurrence and progression of non-muscle invasive bladder tumors expose patients to multiple TURBT procedures throughout their disease process. Understanding the impact of TURBT on quality of life and patient experiences is crucial for shared decision-making, thus enhanced recovery protocol trials are being explored to improve patient outcomes. The variability in TURBT practices worldwide contributes to differing bladder tumor recurrence rates, prompting efforts to standardize practices by evaluating the impact of patient, hospital, and surgeon factors. For select cases, less intensive surveillance regimens have reduced toxicities and costs without compromising oncologic outcomes. New innovative approaches such as en bloc- and stratified resection techniques may reduce perioperative complications and improve clinical outcomes. Finally, neoadjuvant and ablative treatments have shown to be promising alternatives to TURBT, necessitating further investigation in this setting. TURBT is essential for diagnosing and treating bladder cancer. Reducing associated morbidities and improving surgical outcomes involve multifaceted approaches, including standardizing surgical practices, exploring innovative techniques, and optimizing surveillance regimens, all while promoting patient quality of life. Neoadjuvant therapies as alternative treatments are on the horizon and may ultimately change the landscape of bladder cancer care.

Disparities in Rotator Cuff Tear Progression Definitions and Rates: A Systematic Review.

While rotator cuff tears are prevalent in the general population, the natural history of this disease is unclear. Understanding rotator cuff tear progression is crucial for refining surgical indications and evaluating the necessity of early interventions. This study presents an in-depth analysis of the existing literature on the definitions and progression rates of rotator cuff tears, aiming to enhance clinical decision making and patient outcomes. A systematic literature search was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using Medline (PubMed), Embase (Elsevier), and Web of Science databases on January 12, 2023. Articles were identified as relevant to the natural history and progression of asymptomatic and symptomatic partial-thickness (PT) and full-thickness (FT) rotator cuff tears. Those written in English reporting rotator cuff progression rates of tears in adults, based on magnetic resonance imaging (MRI) or ultrasound, were included. After reviewing the articles, the data on the rates of tear progression and associated risk factors were extracted, compiled, and analyzed. The risk of bias was determined using the Newcastle-Ottawa Scale. Twenty-one articles met the inclusion criteria, with 1,831 tears included. The progression rate for all partial thickness tears was 26.7% ± 12.8% at an average follow-up of 2.2 ± 0.9 years, with 5 definitions for tear progression. For FT tears, the progression rate was 54.9% ± 18.6% at a follow-up time of 3.0 ± 2.0 years, with 8 definitions for tear enlargement. A significant difference (p < 0.0001) was found between the progression rates of PT and FT tears. Patients who were initially asymptomatic and became symptomatic had higher progression rates (33%-63%) than those who remained asymptomatic (4%-38%). Further research would benefit by identifying a clinically relevant and standardized definition of rotator cuff tear progression, to describe the natural history of rotator cuff disease, making results more comparable and optimizing treatment planning. Level II. See Instructions for Authors for a complete description of levels of evidence.

Microfracture for medium size to large knee chondral defects has limited long-term efficacy: A systematic review.

To evaluate clinical and radiographic outcomes, return to sport, failure rate, operations and complications in patients undergoing microfracture of the knee, including the femoral condyle, tibial plateau, patella and trochlea, at a mean 10-year or greater follow-up. A literature search was performed by querying SCOPUS, PubMed, Medline and the Cochrane Central Register for Controlled Trials from database inception through May 2023 according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Inclusion criteria were level I-IV human studies reporting on outcomes, reoperations and complications following microfracture of the knee at a mean 10-year or greater follow-up. Biomechanical and epidemiological studies, including patients undergoing concomitant realignment procedures, and studies with patients under 18 years old were excluded. Data regarding failure, as defined by each study, as well as reoperations were gathered. Study quality was assessed via the Methodological Index for Nonrandomized Studies criteria. Nine studies from 2003 to 2018, consisting of 727 patients (mean age 38.9 ± 8.1 years; range 25.8-47.6) undergoing microfracture for chondral defects in the knee were identified. Mean follow-up ranged from 10 to 17 years. Males composed 56.5% of patients, with a mean defect size ranging from 2.3 to 4.01 cm2. Based on radiographs at follow-up, osteoarthritis progression occurred in 40%-48% of patients. Magnetic Resonance Observation of Cartilage Repair Tissue scores were low. Patient-reported outcome measures showed significant improvement in postoperative scores at final follow-up. Return-to-sport rate ranged from 17.2% to 20%. Longitudinal analysis revealed declining clinical outcomes and return-to-sport rates from short- and mid- to long-term follow-up. There was high variability in failure definition and reoperations, with 2.9%-41% of patients requiring total knee arthroplasty. At a mean 10-year or greater follow-up, microfracture for chondral defects of the knee 2-4 cm2 in size demonstrated a high rate of osteoarthritis progression with poor healing of the chondral defect and low overall return-to-sport rates. Failure and reoperation rates ranged from 2.9% to 41%, with declining outcomes from short- and mid- to long-term follow-up. The advantages of microfracture relating to availability, complexity, and cost should be weighed against concerns about long-term success, particularly with medium-size and larger lesions. Level IV systematic review.

The Efficacy of Prismatic Bifocal Spectacle Lenses in Controlling Myopia Progression in Children.

Objective: Progression of myopia can lead to vision impairment and increase the risk of sight-threatening complications. Various strategies were described to control the progression of myopia, including the use of specialized spectacle. This retrospective study aimed to analyze the efficacy of prismatic bifocal spectacle lenses in controlling the progression of myopia in pediatric patients. Materials and Methods: Fifty-two eyes of 26 patients using prismatic bifocal spectacle lenses were retrospectively analyzed. Both eyes of each patient with a cycloplegic objective refraction measurement of ≥-2.00 D were included. Demographic data of the patients such as age and gender were investigated. The increase in objective spherical equivalent and axial length over the one year of single-vision spectacle use was compared with the increase observed one year after the prescription of bifocal prismatic spectacle. Results: The mean age of the patients was 11.65 ± 2.70 years. Sixteen patients were male, and 10 patients were female. The increase in mean spherical equivalent in eyes using single vision spectacles over one year was 1.25 ± 0.76 D, compared to 0.24 ± 0.14 D with prismatic bifocal spectacles, which was statistically significant). Similarly, the increase in mean axial length was 0.66 ± 0.31 mm with single vision spectacles and 0.014 ± 0.015 mm with bifocal spectacle, also statistically significant Multiple linear regression analysis revealed that baseline higher myopia and baseline shorter axial length were significantly associated with the treatment effect. Conclusion: The findings suggest that bifocal prismatic lenses have the potential to be an effective intervention for managing myopia in children, particularly those with high rates of progression. However, further research with larger sample sizes and longer follow-up periods is needed to fully understand the long-term impacts of this treatment approach.

Improve clinical feature-based bladder cancer survival prediction models through integration with gene expression profiles and machine learning techniques

BackgroundBladder cancer (BCa), one of the most common cancers worldwide, is characterized by high rates of recurrence, progression, and mortality. Machine learning algorithms offer promising advancements in enhancing predictive models. This study aims to develop robust machine learning models for predicting BCa survival using clinical and gene expression data. MethodsClinical data from BCa patients were obtained from the Surveillance, Epidemiology, and End Results database. Cox proportional hazards regression models assessed the association between clinical variables and overall survival. Machine learning algorithms, including logistic regression, random forest, XGBoost, decision tree, and LightGBM, were employed to predict survival at 1, 3, and 5 years. The TAGO database, combined with the data from The Cancer Genome Atlas and four databases from the Gene Expression Omnibus, which have available genomic data and clinical data, were selected. Gene expression data were transformed into gene sets data, and the performance of models based on clinical data and gene sets data and their combination were compared. Furthermore, the impact of model-derived scores on overall survival was evaluated. ResultsAmong 138,741 BCa patients with available clinical data, key independent predictors of survival included age, race, marital status, surgery, chemotherapy, radiation, and TNM stages. Clinical data machine learning (CML) models used these clinical predictors to achieve AUC values of 0.860, 0.821, and 0.804 in the testing sets for predicting survival at 1, 3, and 5 years, respectively. In the TAGO database, which has 863 patients with clinical and genomic data, the integrated clinical and gene expression machine learning model (IML) outperformed the CML and gene expression machine learning (GML) models in survival prediction. Patients with higher IML and GML model scores exhibited poorer survival outcomes. ConclusionsThis study successfully identifies key clinical and genomic predictors, a significant step forward in BCa research. The development of predictive models for BCa survival underscores the potential of integrated data approaches in improving BCa management and treatment strategies.

MPN-100 High Rate of Disease Progression in Patients With Low-Risk Myelofibrosis (MF) Enrolled in the Prospective Myelofibrosis and Essential Thrombocythemia Observational Study (MOST)

MPN-100 High Rate of Disease Progression in Patients With Low-Risk Myelofibrosis (MF) Enrolled in the Prospective Myelofibrosis and Essential Thrombocythemia Observational Study (MOST)

High Rate of Disease Progression in Patients With Low-Risk Myelofibrosis (MF) Enrolled in the Prospective Myelofibrosis and Essential Thrombocythemia Observational Study (MOST)

High Rate of Disease Progression in Patients With Low-Risk Myelofibrosis (MF) Enrolled in the Prospective Myelofibrosis and Essential Thrombocythemia Observational Study (MOST)