Search

PurposeTo compare rates of retinal nerve fiber layer change over time in healthy, eyes with nonprogressing glaucoma and eyes with progressing glaucoma using single wide-field (SWF) and optic nerve head (ONH) cube scan optical coherence tomography (OCT) images.MethodsForty-five eyes of 25 healthy individuals and 263 eyes of 161 glaucoma patients from the Diagnostic Innovations in Glaucoma Study were included. All eyes underwent 24-2 visual field testing and OCT (Spectralis SD-OCT) ONH and macular imaging. SWF images (up to 43° × 28°) were created by stitching together ONH cube scans centered on the optic disc and macular cube scans centered on the fovea. Visual field progression was defined as guided progression analysis likely progression and/or a significant (P < 0.01) mean deviation slope of less than -1.0 dB/year. Mixed effects models were used to compare rates of change. Highly myopic eyes were included.ResultsThirty glaucomatous eyes were classified as progressing. In eyes with glaucoma, mean global rate of change was -1.22 µm/year (P < 0.001) using SWF images and -0.83 µm/year (P = 0.003) using ONH cube scans. Rate of change was significantly greater in eyes with progressing glaucoma compared with eyes with nonprogressing glaucoma (-1.51 µm/year vs. -1.24 µm/year; P = 0.002) using SWF images and was similar using ONH cube scans (P = 0.27).ConclusionsIn this cohort that includes eyes with and without high axial myopia, the mean rate of retinal nerve fiber layer thinning measured using SWF images was faster in eyes with progressing glaucoma than in eyes with nonprogressing glaucoma. Wide-field OCT images including the ONH and macula can be effective for monitoring glaucomatous progression in patients with and without high myopia.

ABSTRACT Objectives Patients and Methods Results Conclusion Development of a prediction model using machine learning (ML) method for tumor progression in oral squamous cell carcinoma (OSCC) patients would provide risk estimation for individual patient outcomes.This predictive modeling study was conducted of 1163 patients with OSCC from Hospital of Stomatology, SYSU and SYSU Cancer Center from March 2009 to October 2021. Clinical, pathological, and hematological features of the patients were collected. Six ML algorithms were explored, and model performance was assessed by accuracy, sensitivity, specificity, f1 score, and AUC. SHAP values were used to identify the variables with the greatest contribution to the model.Among the 1163 patients (mean [SD] age, 55.36 [12.91] years), 563 are from development cohort and 600 are from validation cohort. The Logistic Regression algorithm outperformed all other models, with a sensitivity of 94.7% (68.2%), a specificity of 55.3% (63.7%), and the AUC of 0.76 ± 0.09 (0.723) in the development (validation) cohort. The most predictive feature was neutrophil count.This study demonstrated ML models can improve clinical prediction of oral squamous cell carcinoma progression through basic information of patients. These tools could be used to provide individual risk estimation and may help direct intervention. [ABSTRACT FROM AUTHOR]

Introduction: Historically, Multiple Endocrine Neoplasia type 1 (MEN1)-related pituitary adenomas (PAs) were considered more aggressive and treatmentresistant than sporadic PAs. However, recent studies suggest similarities in their behavior. This study aimed to evaluate the long-term outcomes of MEN1 PAs and identify predictive factors. Methods: Nationwide multicenter retrospective cohort study of MEN1-related PAs with a minimum 1-year follow-up, collecting patient demographics, germline MEN1 pathogenic variants (PV), PA size, secretory profile, radiological characteristics, treatments, and outcomes. Results: We analyzed 84 PAs, 69%in females and 31% in males (P<0.001), diagnosed at a mean age of 35.2±14.9 years, mostly through screening (60.7%). Median follow-up was 9 years (IQR:4-16). Prolactin-secreting PAs (PRLomas) (53.5%) and microadenomas (65.5%) were most common. Dopamine agonist treatment was first line for 16 macroPRLomas and 25 microPRLomas, 60.9% of them achieved PRL normalization. There was no significant association observed with tumor size, sex, treatment duration or MEN1 PV. The risk of progression from micro-PA to invasive macro-PA was 7.2% (4/55), after 8 years (IQR:4-13), all of them were microPRLomas. Kaplan-Meier estimation curve showed significantly higher progression probability in microPRLomas than in other microadenomas subtypes (P=0.017) or microNFPAs (P=0.032). No differences were found between sex, age, or germline MEN1 PV. Conclusion: MEN1-related micro-PAs have a low risk of progressing to invasive macro-PAs, regardless of sex, age at diagnosis, or MEN1 germline PV. The risk is higher for microPRLomas over the long term. Therefore, long-term surveillance with reduced frequency, rather than intensive short-term monitoring, may be appropriate for patients with MEN1-related PAs. [ABSTRACT FROM AUTHOR]

Ferroptosis, a lipid peroxidation- and iron-mediated type of regulated cell death, relates to both neuroinflammation, which is common in relapsing-remitting multiple sclerosis (RRMS), and neurodegeneration, which is prevalent in progressive (P)MS. Currently, findings related to the molecular markers proposed in this paper in patients are scarce. We analyzed circulatory molecular indicators of the main ferroptosis-related processes, comprising lipid peroxidation (malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and hexanoyl–lysine adduct (HEL)), glutathione-related antioxidant defense (total glutathione (reduced (GSH) and oxidized (GSSG)) and glutathione peroxidase 4 (GPX4)), and iron metabolism (iron, transferrin and ferritin) to estimate their contributions to the clinical manifestation of MS and differences between RRMS and PMS disease course. In 153 patients with RRMS and 69 with PMS, plasma/serum lipid peroxidation indicators and glutathione were quantified using ELISA and colorimetric reactions, respectively. Iron serum concentrations were determined using spectrophotometry, and transferrin and ferritin were determined using immunoturbidimetry. Compared to those with RRMS, patients with PMS had decreased 4-HNE (median, 1368.42 vs. 1580.17 pg/mL; p = 0.03). Interactive effects of MS course (RRMS/PMS) and disease-modifying therapy status on MDA (p = 0.009) and HEL (p = 0.02) levels were detected. In addition, the interaction of disease course and self-reported fatigue revealed significant impacts on 4-HNE levels (p = 0.01) and the GSH/GSSG ratio (p = 0.04). The results also show an association of MS course (p = 0.03) and EDSS (p = 0.04) with GSH levels. No significant changes were observed in the serum concentrations of iron metabolism indicators between the two patient groups (p > 0.05). We suggest circulatory 4-HNE as an important parameter related to differences between RRMS and PMS. Significant interactions of MS course and other clinically relevant parameters with changes in redox processes associated with ferroptosis support the further investigation of MS with a larger sample while taking into account both circulatory and central nervous system estimation. [ABSTRACT FROM AUTHOR]

The serine/threonine/tyrosine kinase 1 (STYK1) is a receptor protein-tyrosine kinase (RPTK)-like molecule that is detected in several human organs. STYK1 plays an important role in promoting tumorigenesis and metastasis in various cancers. By analyzing the expression of RTKs in immune cells in the database of 2013 Immunological Genome Project, we found that STYK1 was principally expressed in NK cells. In order to investigate the function of STYK1, we used CRISPR/Cas9 technology to generate STYK1-deleted mice, we found STYK1 deletion mice have normal number, development, and function of NK cells in spleen and bone marrow in tumor-free resting state. To examine the tumor surveillance of STYK1 in vivo, we utilized a variety of tumor models, including NK cell-specific target cell (ß2M and RMA-S) clearance experiments in vivo, subcutaneous and intravenous injection of B16F10 melanoma model, and the spontaneous breast cancer model MMTV-PyMT. Surprisingly, we discovered that deletion of the oncogenic STYK1 promoted the four-model tumor progression, and we observed a reduction of NK cell accumulation in the tumor tissues of STYK1 deletion mice compared to WT mice. In order to study the mechanism of STYK1 in NK, RNA sequence of STYK1−/− and WT NK have unveiled a disparity in the signaling pathways linked to migration and adhesion in STYK1−/− NK cells. Further analysis of chemokine receptors associated with NK cell migration revealed that STYK1-deficient NK cells exhibited a significant reduction in CCR2 expression. The STYK1 expression was negatively associated with tumor progression in glioma patients. Overall, our study found the expression of STYK1 in NK cell mediates NK cell anti-tumor response through regulating CCR2 and infiltrating into tumor tissue. [ABSTRACT FROM AUTHOR]

Background: The search for neuroprotective treatments for Parkinson's disease (PD) still relies largely on motor disability scales. A limitation of these tools is the strong influence of symptomatic dopaminergic treatment effects. Drawing on a wealth of published information, we conducted a systematic review and metaanalysis of motor progression in PD and its relationships with dopaminergic therapy. Methods: We searched Medline, Embase, and Central to identify 84 publications with adequate serial motor scores to calculate progression, expressed as an increase in the percentage of maximum disability. Results: A random-effects model showed motor progression at 2.0% p.a. (95% CI 1.7-2.4%). There were no significant differences by baseline age, sample size, or observation period. However, untreated patients, in 8 publications, progressed at 4.5% p.a. compared to 1.6% p.a. in 76 studies containing individuals on dopaminergic drugs (p = 0.0004, q = 0.003). This was supported by research on phenoconversion in prodromal PD, where motor progression exceeded 5% p.a. in the 2 years before diagnosis. Starting levodopa improved pre-treatment disability by 40.3 ± 15.2%. Practically defined off state measurements increase faster than on scores by a modest degree (p = 0.05). Conclusion: This survey suggests that accurate long-term measurements of motor progression to assess disease-modifying therapies can be conducted despite the sequential commencement of dopaminergic drugs and sample attrition over time. While study designs involving prodromal or untreated PD avoid confounding effects of symptomatic treatment, different assumptions about motor progression may be needed. A defined off state with the levodopa test dose method maximizes information about the medication cycle once dopaminergic therapy has begun. [ABSTRACT FROM AUTHOR]

Background Materials and methods Results Conclusions Kinesin family member C3 (KIFC3), as reported, plays important roles in several tumor types. Nevertheless, it is unknown whether KIFC3 has effects on non–small cell lung cancer (NSCLC) development.KIFC3 expression was detected by RT‐PCR, and its correlation with prognosis was analyzed by GEPIA website. Small interfering RNA against KIFC3 were adopted for modulating KIFC3 expression in NSCLC cells. KIFC3 effects on NSCLC cell proliferation were determined using the MTT and clone formation assay. Matrigel invasion and wound healing assays were adopted for measuring the invasion and migration capability of NSCLC cells. Western blot was applied for measuring the levels of proteins associated with the phosphatidylinositol‐3‐kinase/protein kinase B (PI3K/Akt) pathway in NSCLC cells.KIFC3 was markedly increased in NSCLC samples and cells. KIFC3 knockdown suppressed the proliferation, invasion, and migration in NSCLC. Mechanically, KIFC3 silencing suppressed NSCLC progression through inhibiting the PI3K/Akt pathway.KIFC3 lack suppressed the proliferation, invasion, and migration which works, at least partially, by the PI3K/Akt pathway. These findings suggest that targeting KIFC3 via the PI3K/Akt pathway may offer a novel therapeutic strategy for NSCLC. [ABSTRACT FROM AUTHOR]

Background: It is difficult to distinguish between the brain metastasis progression (BMP) and brain radionecrosis (BRN) on the basis of 18F-3,4-dihydroxyphenylalanine positron emission tomography/computed-tomography (18F-FDOPA PET/CT) data. The advent of silicon photomultiplier (SiPM) PET technology makes it possible to study dynamic volumes and potentially improve diagnostic accuracy. We developed a method for processing 18F-FDOPA PET/CT in the differential diagnosis between BMP and BRN. The method involves a short (3-second) sampling time during a 4-minute acquisition on a SiPM-PET/CT machine. We prospectively included 15 patients and 19 metastases. All acquisitions were performed in list mode acquisition for 25 min on a four-ring SiPM PET/CT system. We calculated the ratios between the maximum activity in the lesion's voxel and the mean activity in the contralateral region (VOImax/CLmean) or the mean activity in the white matter (VOImax/WMmean). Results: Seven lesions were classified as BMP and twelve were classified as BRN. Statistically significant intergroup differences in the VOImax/CLmean and VOImax/WMmean activity ratios were observed for both the clinical volume and the early acquisition. The best performing quantitative variable was the VOImax/CLmean ratio on early acquisition, with a diagnostic accuracy of 94.7%, a sensitivity of 100%, and a specificity of 91.7%. Conclusion: The 18F-FDOPA PET/CT data acquired a few minutes after the bolus injection confirms its value in differentiating between BMP and BRN, compared to the much longer classic clinical protocol. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions To determine the regional and ethnic differences in ocular axial elongation and refractive error progression in myopic and non‐myopic children.A retrospective analysis of 15 longitudinal clinical and population‐based studies was conducted in the UK, Sweden, Australia (classified as European), China, and Vietnam (classified as East Asian) between 2005 and 2021. A total of 14,593 data points from 6208 participants aged 6–16 years with spherical equivalent from +6 to −6 D were analysed. Progression was annualised from longitudinal axial length and cycloplegic spherical equivalent (SE) refraction. Generalised estimating equation models including main effects and interactions were used for model building. Age and region‐specific estimates for myopes and non‐myopes and confidence intervals are reported.Factors affecting axial elongation and SE progression in children included being myopic, followed by age, region/ethnicity and sex. The magnitude of regional/ethnic differences was dependent on myopia and age. Axial elongation and SE progression were lower in European compared with East Asian children, but differences were reduced with increasing age and differences in axial elongation were larger in myopes than non‐myopes. Age‐specific regional/ethnic differences indicated that axial elongation for a 6‐year‐old East Asian myopic child was greater than a European child by 0.15 mm/year (0.58 vs. 0.43 mm/year) and by 0.09 mm/year (0.35 vs. 0.26 mm/year) for a 10‐year‐old myope. SE progression was lower in a 6‐year‐old European myope by 0.48 D/year and at 10 years of age by 0.34 D/year compared with an East Asian myope.There are regional/ethnic differences in age‐specific refractive and axial growth patterns in both myopic and non‐myopic eyes, with more marked differences in younger East Asian children who demonstrated a higher axial growth and greater negative SE shift than their non‐Asian peers. Regional/ethnic differences in progression reflect environmental and ethnic variations. Age and region/ethnicity‐specific estimates could contribute as a reference for future comparisons. [ABSTRACT FROM AUTHOR]

This research investigates the intricate involvement of nuclear Transcription Factor Y Subunit Alpha (NFYA) in the advancement of castration-resistant prostate cancer (CRPC) and its consequential impact on early Growth Response 4 (EGR4) expression. NFYA demonstrates a significant elevation in CRPC tissues and cell lines, displaying robust upregulation in metastatic prostate cancer (mPCa) samples, closely associated with the Gleason score. Immunohistochemistry validates heightened nuclear staining of NFYA in CRPC patients, highlighting its crucial role in the progression of advanced prostate cancer. Silencing NFYA through siRNA in androgen-independent cell lines markedly impedes cell growth and migration, emphasizing NFYA's pivotal role in promoting CRPC behavior. RNA-seq analysis identifies EGR4 as a downstream target of NFYA, with both genes consistently upregulated in CRPC. Validating this finding, heightened expression of EGR4 is observed in CRPC samples. In vivo studies utilizing a mouse model demonstrate that NFYA silencing substantially inhibits LNCaP-AI/22RV1shNFYA xenograft tumor growth, accompanied by reduced expression of EGR4 and Ki67. This comprehensive study reveals the multifaceted role of NFYA in CRPC progression, elucidates its downstream impact on EGR4, and underscores the therapeutic potential of targeting NFYA to inhibit CRPC growth in vivo. These findings contribute valuable insights into potential therapeutic strategies for managing CRPC. [ABSTRACT FROM AUTHOR]

Pediatric low-grade gliomas (PLGG) are commonly treated with a combination of surgery, radiotherapy, and chemotherapy. Recent trends prioritize reducing long-term morbidities, particularly in younger patients. While historically chemotherapy was reserved for cases progressing after radiotherapy, evolving recommendations now advocate for its early use, particularly in younger age groups. The carboplatin and vincristine (CV) combination stands as a standard systemic therapy for PLGG, varying in dosage and administration between North America and Europe. Clinical trials have shown promising response rates, albeit with varying toxicity profiles. Vinblastine has emerged as another effective regimen with minimal toxicity. TPCV, a regimen combining thioguanine, procarbazine, lomustine, and vincristine, was compared to CV in a Children's Oncology Group trial, showing comparable outcomes, but more toxicity. Vinorelbine, temozolomide, and metronomic chemotherapy have also been explored, with varied success rates and toxicity profiles. Around 40–50% of PLGG patients require subsequent chemotherapy lines. Studies have shown varied efficacy in subsequent lines, with NF1 patients generally exhibiting better outcomes. The identification of molecular drivers like BRAF mutations has led to targeted therapies' development, showing promise in specific molecular subgroups. Trials comparing targeted therapy to conventional chemotherapy aim to delineate optimal treatment strategies based on molecular profiles. The landscape of chemotherapy in PLGG is evolving, with a growing focus on molecular subtyping and targeted therapies. Understanding the role of chemotherapy in conjunction with novel treatments is crucial for optimizing outcomes in pediatric patients with low-grade gliomas. [ABSTRACT FROM AUTHOR]

Background: We recently reported an increased risk of Parkinson's disease (PD) in service members who resided at Marine Base Camp Lejeune, North Carolina, when water supplies were contaminated with trichloroethylene and other volatile organic compounds (VOCs). Prior studies suggest that environmental exposures may affect PD phenotype or progression, but this has not been reported for VOCs. Objective: The objective of this study was to test whether PD progression is faster in individuals exposed to VOCs in water at Camp Lejeune. Methods: A cohort of 172,128 marines residing at Camp Lejeune between 1975 and 1985 was previously assembled. We identified individuals with PD in Veterans Health Administration and Medicare databases between 2000 and 2021. Using estimates derived by the US Agency for Toxic Substances and Disease Registry, we classified individuals as exposed or unexposed to VOCs in residential water. We used Kaplan–Meier and Cox regression models to test differences between exposed and unexposed groups in the time from PD diagnosis until psychosis, fracture, fall, or death. Results: Among 270 persons with PD, 177 (65.6%) were exposed to VOCs in residential water. Median cumulative exposure was 4970 μg/L‐months, >50‐fold the permissible level. Time until psychosis, fracture, and fall were all shorter in the exposed group, with adjusted hazard ratios (HRs) exceeding 2: psychosis HR, 2.19 (95% confidence interval [CI]: 0.99–4.83); fracture HR, 2.44 (95% CI: 0.91–6.55); and fall HR, 2.64 (95% CI: 0.97–7.21). A significant dose response was observed for time to fall (P trend, 0.032). No differences were observed for time until death. Conclusions: PD progression may be faster in persons exposed to trichloroethylene and other VOCs in water decades earlier. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA. [ABSTRACT FROM AUTHOR]

Sepsis remains a significant contributor to neonatal mortality worldwide. However, the nonspecific nature of sepsis symptoms in neonates often leads to the necessity of empirical treatment, placing a burden of ineffective treatment on patients. Furthermore, the global challenge of antimicrobial resistance is exacerbating the situation. Artificial intelligence (AI) is transforming medical practice and in hospital settings. AI shows great potential for assessing sepsis risk and devising optimal treatment strategies. Background/Objectives: This review aims to investigate the application of AI in the detection and management of neonatal sepsis. Methods: A systematic literature review (SLR) evaluating AI methods in modeling and classifying sepsis between 1 January 2014, and 1 January 2024, was conducted. PubMed, Scopus, Cochrane, and Web of Science were systematically searched for English-language studies focusing on neonatal sepsis. Results: The analyzed studies predominantly utilized retrospective electronic medical record (EMR) data to develop, validate, and test AI models to predict sepsis occurrence and relevant parameters. Key predictors included low gestational age, low birth weight, high results of C-reactive protein and white blood cell counts, and tachycardia and respiratory failure. Machine learning models such as logistic regression, random forest, K-nearest neighbor (KNN), support vector machine (SVM), and XGBoost demonstrated effectiveness in this context. Conclusions: The summarized results of this review highlight the great promise of AI as a clinical decision support system for diagnostics, risk assessment, and personalized therapy selection in managing neonatal sepsis. [ABSTRACT FROM AUTHOR]

Simple Summary: This research aims to identify new protein markers that can help predict the risk of disease progression in patients with follicular lymphoma (FL) at the time of diagnosis. By analyzing a large number of proteins in FL samples, the study found significant differences in protein composition among patients, which may help distinguish those at higher risk of disease progression. These findings could improve our understanding of FL biology and lead to the discovery of new biomarkers or treatment targets, potentially allowing for more personalized and effective treatment strategies for FL patients, improving their outcomes. Background: Follicular lymphoma (FL) is characterized by an indolent nature and generally favorable prognosis, yet poses a particular clinical challenge, since disease progression is observed in a notable subset of patients. Currently, it is not possible to anticipate which patients will be at risk of progression, highlighting the need for reliable predictive biomarkers that can be detected early in the disease. Methods: We applied tandem-mass-tag labelled nano-liquid chromatography tandem mass spectrometry (nLC-MS/MS) on 48 diagnostic formalin-fixed, paraffin-embedded tumor samples from patients with advanced-stage FL. Of these, 17 experienced subsequent progression (subsequently-progressing, sp-FL) while 31 did not (non-progressing, np-FL). Results: We identified 99 proteins that were significantly differentially expressed between sp-FL samples and np-FL samples (p < 0.05; log2-fold changes between 0.2 and −1.3). Based on this subset of proteins, we classified patients into high-risk and low-risk subgroups using unsupervised machine learning techniques. Pathway analyses of the identified proteins revealed aberrancies within the immune system and cellular energy metabolism. In addition, two proteins were selected for immunohistochemical evaluation, namely stimulator of interferon genes 1 (STING1) and isocitrate dehydrogenase 2 (IDH2). Notably, IDH2 retained significantly lower expression levels in sp-FL samples compared with np-FL samples (p = 0.034). Low IDH2 expression correlated with shorter progression-free survival (PFS, p = 0.020). Conclusions: This study provides evidence for some of the biological mechanisms likely to be involved in FL progression and, importantly, identifies potential predictive biomarkers for improvement of risk stratification up-front at time of FL diagnosis. [ABSTRACT FROM AUTHOR]

'Active' and 'non-active' secondary progressive MS (SPMS) have distinct pathophysiological mechanisms and clinical characteristics, but there is still no consensus regarding the frequency of these MS forms in the real-world setting. We aimed to evaluate the frequency of 'active' and 'non-active' SPMS in a large cohort of Italian MS patients and the differences in terms of clinical and MRI characteristics and disease progression. This multicenter study collected data about MS patients who have transitioned to the SP form in the period between 1st January 2014 and 31st December 2019 and followed by the MS centers contributing to the Italian MS Registry. Patients were divided into 'active SPMS' and 'non-active SPMS', based on both reported MRI data and relapse activity in the year before conversion to SPMS. Out of 68,621, 8,316 (12.1%) patients were diagnosed with SPMS. Out of them, 872 (10.5%) were classified into patients with either 'active' or 'non-active' SPMS. A total of 237 were classified into patients with 'active SPMS' (27.2%) and 635 as 'non-active SPMS' (72.8%). 'Non-active SPMS' patients were older, with a longer disease duration compared to those with 'active SPMS'. The percentages of patients showing progression independent of relapse activity (PIRA) at 24 months were similar between 'active' and 'non-active' SPMS patients (67 [27.4%] vs 188 [29.6%]; p = 0.60). In the 'active' group, 36 (15.2%) patients showed relapse-associated worsening (RAW). Comparison of the survival curves to EDSS 6 and 7 according to disease activity did not show significant differences (p = 0.68 and p = 0.71). 'Active' and 'non-active' SPMS patients had a similar risk of achieving disability milestones, suggesting that progression is primarily attributed to PIRA and only to a small extent to disease activity. [ABSTRACT FROM AUTHOR]

Background: Identifying high-risk individuals with mild cognitive impairment (MCI) who are likely to progress to Alzheimer's disease (AD) is crucial for early intervention. Objective: This study aimed to develop and validate a novel clinical score for personalized estimation of MCI-to-AD conversion. Methods: The data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study were analyzed. Two-thirds of the MCI patients were randomly assigned to a training cohort (n = 478), and the remaining one-third formed the validation cohort (n = 239). Multivariable logistic regression was performed to identify factors associated with MCI-to-AD progression within 4 years. A prediction score was developed based on the regression coefficients derived from the logistic model and tested in the validation cohort. Results: A lipidomics-signature was obtained that showed a significant association with disease progression. The MCI conversion scoring system (ranged from 0 to 14 points), consisting of the lipidomics-signature and five other significant variables (Apolipoprotein ɛ4, Rey Auditory Verbal Learning Test immediate and delayed recall, Alzheimer's Disease Assessment Scale delayed recall test, Functional Activities Questionnaire, and cortical thickness of the AD signature), was constructed. Higher conversion scores were associated with a higher proportion of patients converting to AD. The scoring system demonstrated good discrimination and calibration in both the training cohort (AUC = 0.879, p of Hosmer-Lemeshow test = 0.597) and the validation cohort (AUC = 0.915, p of Hosmer-Lemeshow test = 0.991). The risk classification achieved excellent sensitivity (0.84) and specificity (0.75). Conclusions: The MCI-to-AD conversion score is a reliable tool for predicting the risk of disease progression in individuals with MCI. [ABSTRACT FROM AUTHOR]

Objectives: We tested whether the 2012 Briganti nomogram for the risk of pelvic lymph node invasion (PLNI) may represent a predictor of disease progression after surgical management in high-risk (HR) prostate cancer (PCa) patients according to the European Association of Urology. Methods: Between January 2013 and December 2021, HR PCa patients treated with robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND) were identified. The 2012 Briganti nomogram was evaluated as a continuous and categorical variable, which was dichotomized using the median. The risk of disease progression, defined as the event of biochemical recurrence and/or local recurrence/distant metastases was assessed by Cox regression models. Results: Overall, 204 patients were identified. The median 2012 Briganti nomogram score resulted 12.0% (IQR: 6.0–22.0%). PLNI was detected in 57 (27.9%) cases. Compared to patients who had preoperatively a 2012 Briganti nomogram score ≤12%, those with a score >12% were more likely to present with higher percentage of biopsy positive cores, palpable tumors at digital rectal examination, high-grade cancers at prostate biopsies, and unfavorable pathology in the surgical specimen. At multivariable Cox regression analyses, disease progression, which occurred in 85 (41.7%) patients, was predicted by the 2012 Briganti nomogram score (HR: 1.02; 95%CI: 1.00–1.03; p = 0.012), independently by tumors presenting as palpable (HR: 1.78; 95%CI: 1.10.2.88; p = 0.020) or the presence of PLNI in the surgical specimen (HR: 3.73; 95%CI: 2.10–5.13; p = 0.012). Conclusions: The 2012 Briganti nomogram represented an independent predictor of adverse prognosis in HR PCa patients treated with RARP and ePLND. As the score increased, so patients were more likely to experience disease progression, independently by the occurrence of PLNI. The association between the nomogram, unfavorable pathology and tumor behavior might turn out to be useful for selecting a subset of patients needing different treatment paradigms in HR disease. [ABSTRACT FROM AUTHOR]

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 12 months were compared (with vs without progression) and cumulative costs for early versus late progression were predicted over 36 months. Results: A total of 228 patients with EGFRm mNSCLC were included. Patients with progression within 12 months incurred significantly higher total costs despite lower treatment costs (vs without 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. Plain Language Summary Lung cancer is the leading cause of cancer death among both men and women in the US. Among US patients with adenocarcinoma histology, approximately 17% have epidermal growth factor activating mutations (EGFRm) that include exon 19 deletions or L858R mutations. These common mutations make up approximately 85% of all EGFR mutations. The aim of this study was to compare healthcare resource utilization and costs for patients with EGFRm metastatic non-small-cell lung cancer with and without disease progression within the first 12 months following first-line treatment initiation using data from insurance claims. The results suggest that patients with EGFRm metastatic non-small-cell lung cancer with disease progression in the first 12 months (after treatment initiation) have significantly higher costs compared with patients without disease progression in the first 12 months (and highest in the first 6 months). These data may help inform oncology providers aiming to administer high quality cancer care in a cost-efficient way. Article highlights Patients with non-small-cell lung cancer face a high burden of healthcare costs, especially when the disease progresses. This was a retrospective study using administrative claims data of 228 adult patients with epidermal growth factor receptor mutated (EGFRm) metastatic non-small-cell lung cancer (mNSCLC) that initiated a first-line EGFR tyrosine kinase inhibitor (TKI) between 2015 and 2020. Healthcare costs were captured during the first 12 months after treatment initiation in patients with and without disease progression, and cumulative costs were predicted over 36 months for patients with early (post initiation months 0–6) versus late (post initiation months 7–12) disease progression. There were 152 (66.7%) patients whose disease progressed at any time during the 12 months after treatment initiation; 101 (66.4%) patients had early progression and 51 (34.2%) had late progression. Patients with any disease progression had greater healthcare resource utilization compared with patients whose disease did not progress during follow-up. Adjusted mean total healthcare costs were statistically significantly higher for patients with any progression compared with those without progression, mainly driven by inpatient costs. Adjusted monthly predicted cumulative costs were significantly higher among patients who progressed early compared with those that progressed late. Study limitations include lack of biomarker and histology data from claims data, misclassification of metastatic disease status and specific EGFR mutations based on coding errors and limited generalizability. This studies provides real-world costs of patients with EGFRm mNSCLC that initiate a TKI whose disease progresses in a 12-month time period; the cost burden was highest among patients with disease progression in the first 6 months after treatment initiation. This study highlights the importance of delaying EGFRm mNSCLC disease progression in a timely manner. [ABSTRACT FROM AUTHOR]

Copyright of Die Urologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Innere Medizin (2731-7080) is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: MiR-1271-5p and coagulation factor XIII A (F13A1) are reported to be associated with the malignant progression of various types of cancers. The aim of this present research study was to delineate miR-1271-5p and F13A1 functional significance on oral squamous cell carcinoma (OSCC) progression. Methods: MiR-1271-5p and F13A1 expression levels were determined via RT-qPCR and western blot, their overexpression or knockdown effects on OSCC cells were assessed through various in vitro assays, including colony formation, wound healing, transwell and flow cytometry, and their mutual relationship were investigated using an online software and validated confirmed by additional in vitro experiments. Further, mechanistic assays were performed to determine their influence on the PI3K/AKT pathway. Results: Our results indicated downregulation of miR-1271-5p and upregulation of F13A1 in the investigated OSCC cell lines. In addition, upon overexpressing miR-1271-5p or knocking down F13A1, the cell proliferation, migration and invasion were suppressed and apoptotic rate was enhanced. Further investigations showed that the growth and invasive capabilities of OSCC cells were limited by miR-1271-5p through the downregulation of F13A1 mediated PI3K/AKT pathway. Conclusion: MiR-1271-5p could suppress OSCC progression by influencing F13A1 expression to inhibit the PI3K/AKT signaling, indicating the promising potential of targeting miR-1271-5p as a novel approach for treating OSCC. [ABSTRACT FROM AUTHOR]

Low‐grade cervical intraepithelial neoplasia (CIN1) is an early stage of cervical cancer development. Previously, we reported that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of cervical precancerous lesions, especially in females with a high‐risk human papillomavirus (HR‐HPV) infection. However, the effects of PAHs on CIN1 progression remain unclear. A community‐based prospective cohort study was conducted to evaluate the role of exposure to PAHs in the progression of CIN1. A total of 564 patients diagnosed with CIN1 were followed‐up at 6, 12, and 24 months, post‐diagnosis, to determine CIN1 reversion, persistence, and progression. Exposure to PAHs was determined by the urine 1‐hydroxipayrene (1‐OHP) level. Our results showed that the 1‐OHP level was significantly higher in patients with CIN1 persistence/progression than in those with reversion (P <.05). High exposure to PAHs increased the risk of CIN1 persistence/progression, with hazard ratios (HR), 95% confidence intervals (CI) of (1.62, 1.24–2.67), (1.98, 1.42–2.75), and (2.37, 1.61–3.49) at 6, 12, and 24 months, post‐diagnosis, respectively. The effect was enhanced with HR‐HPV positivity, as determined at 6 (1.82, 1.24–2.67), 12 (3.02, 1.74–5.23), and 24 (2.51, 1.48–4.26) months, post‐diagnosis. Moreover, the predictive value of exposure to PAHs for CIN1 persistence/progression was higher in HR‐HPV‐positive patients than in HR‐HPV‐negative patients. The results revealed that exposure to PAHs facilitated the malignant progression of CIN1 and hindered its reversal, particularly in patients with HR‐HPV infection. Our findings provide novel insights into early prevention and intervention targeting the initiation and progression of cervical neoplasia. [ABSTRACT FROM AUTHOR]

Background: This report investigated the expression, prognostic and biological implications of hsa_circ_0079929 in lung adenocarcinoma, which was based on clinical and experimental data. Methods: Patients with lung adenocarcinoma were screened and their clinical data and tissues (including cancerous tissues and adjacent normal tissues) were collected. The total RNA in tissues and cell lines was analyzed to obtained hsa_circ_0079929 level. The clinical significance was examined using the Chi-square test, Multi-variate Cox proportional hazards regression, and Kaplan-Meier curve. Cell malignant features were evaluated from three aspects (proliferation, migration, and invasion), detected by CCK-8 and Transwell methods. Results: Hsa_circ_0079929 raised in expression level in lung adenocarcinoma. This upregulation of hsa_circ_0079929 was correlated with adverse clinical parameters and poor outcome in terms of overall survival, resulting in an independent prognostic purpose molecular for overall survival. Overexpression of hsa_circ_0079929 could contribute to cell proliferation/migration/invasion, whereas its knockdown could inhibit these malignant features. Hsa_circ_0079929 was a molecular decoy for miR-1184 in lung adenocarcinoma cells. Conclusions: Hsa_circ_0079929 could promote the malignant features of lung adenocarcinoma cells and may aid the follow up and therapeutic target discovery of lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) have become the recommended first-line treatment for advanced non-small cell lung cancer (NSCLC) without driver gene mutations. However, data on the failure patterns of first-line ICIs monotherapy is limited, and the optimal strategy for subsequent treatment remains controversial. Methods: Advanced NSCLC patients receiving first-line ICIs monotherapy at Guangdong Lung Cancer Institute between December 2017 and October 2021 were identified. The progressive sites were recorded to analyze failure patterns. Post-progression survival (PPS) was compared between different treatment regimens. Results: A total of 121 patients receiving first-line ICIs monotherapy were identified, with a median progression-free survival of 8.6 months. Sixty-five patients had available imaging at diagnosis as well as progressive disease, with 56.9% showing oligoprogression. For those with progression in existing lesions, the most common sites were the liver (77.8%) and lung parenchyma (62.5%), while progression with new lesions frequently occurred in the liver (32.0%). Fifty patients with recorded subsequent treatment were included in the analysis of subsequent treatment patterns. Patients treated with anti-angiogenesis therapy could get better PPS (HR: 0.275, P = 0.013). Isolated oligoprogression occurred most often in the lung parenchyma and intracranial lesions. More than half of these patients continued immunotherapy after local treatment, with a 2.5-year PPS rate of 51.4%. Conclusion: The liver was the most common site of progression on first-line ICIs monotherapy. Anti-angiogenesis-based therapy might be an optimal regimen at the time of progression. Patients with isolated oligoprogressive could still benefit from immunotherapy after local treatment. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact of ageing on survival outcomes in Bacillus Calmette–Guérin (BCG) treated non-muscle invasive bladder cancer (NMIBC) patients and its synergy with adequate BCG treatment. Method: Patients with NMIBC who received BCG treatment from 2001 to 2020 were divided into group 1 (< = 70 years) and group 2 (> 70 years). Overall Survival (OS), Cancer-Specific Survival (CSS), Recurrence-Free Survival (RFS), and Progression-Free Survival (PFS) were analyzed using the Kaplan–Meier method. Multivariable Cox regression analysis was used to adjust potential confounding factors and to estimate Hazard Ratio (HR) and 95% Confidence Interval (CI). Subgroup analysis was performed according to adequate versus inadequate BCG treatment. Results: Overall, 2602 NMIBC patients were included: 1051 (40.4%) and 1551 (59.6%) in groups 1 and 2, respectively. At median follow-up of 11.0 years, group 1 (< = 70 years) was associated with better OS, CSS, and RFS, but not PFS as compared to group 2 (> 70 years). At subgroup analysis, patients in group 1 treated with adequate BCG showed better OS, CSS, RFS, and PFS as compared with inadequate BCG treatment in group 2, while patients in group 2 receiving adequate BCG treatment had 41% less progression than those treated with inadequate BCG from the same group. Conclusions: Being younger (< = 70 years) was associated with better OS, CSS, and RFS, but not PFS. Older patients (> 70 years) who received adequate BCG treatment had similar PFS as those younger with adequate BCG treatment. [ABSTRACT FROM AUTHOR]

AbstractBackground: The rate of disease progression, measured by the decline of ALS Functional Rating Scale-Revised (ALSFRS-R) from symptom onset to diagnosis (ΔFS) is a well-established prognostic biomarker for predicting survival. Objectives: This study aims to categorize a large patient cohort based on the initial ΔFS and subsequently investigate survival deviations from the expected prognosis defined by ΔFS. Methods: 1056 ALS patients were stratified into three progression categories based on their ΔFS: slow progressors (below 25th percentile), intermediate progressors (between 25th and 75th percentiles), and fast progressors (above 75th percentile). Survival outcomes were classified as short survivors (<2 years), average survivors (2–5 years), and long survivors (>5 years). Clinical and demographic characteristics within each subgroup were then analyzed. Results: ΔFS stratification yielded cutoff values of <0.29, 0.29–1.03, and >1.03 points/month. Long survivors comprised 26% and 21% were short survivors. Six percent of the fast progressors had a life expectancy of more than 5 years, and none of the clinical and demographic characteristics analyzed could fully explain this discrepancy. Conversely, 13% of intermediate progressors lived less than 2 years, according to a short-diagnostic delay in these patients. Discussion: Our study reaffirms ΔFS as a prognostic biomarker for ALS. We disclosed outliers defying anticipated patterns. The observed shift in progression categories underscores the non-linear nature of disease progression. Genetic and unknown biological reasons may explain these deviations. Further research is needed to fully understand modulation of ALS survival. [ABSTRACT FROM AUTHOR]

AbstractObjective: A high glycemic index and high glycemic load diet has been associated with slower progression of amyotrophic lateral sclerosis (ALS), suggesting a benefit from high blood glucose levels. We examined the association between average blood glucose level and ALS progression in two independent cohorts. Methods: Sporadic ALS patients enrolled in the ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS) who completed a 3-month follow-up visit and had available blood samples were included. Hemoglobin A1c (HbA1c) was measured from whole blood collected at the 3-month follow-up. From the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database, we included ALS patients with one or more HbA1c measurements at enrollment and available death information. Associations between HbA1c with revised ALS functional rating scale (ALSFRS-R)/ALSFRS total score change, and tracheostomy-free survival/survival were examined in these cohorts using linear regression, linear mixed-effects models, and Cox proportional hazard models, adjusted for covariates. Results: In the ALS COSMOS cohort (n = 193), HbA1c level was not significantly associated with the change in the ALSFRS-R total score from baseline to the 3-month follow-up (p = 0.8) nor baseline to the 6-month follow-up (p = 0.4). No significant association was found between HbA1c level and tracheostomy-free survival (p = 0.8). In the PRO-ACT cohort (n = 928), no significant association was found between HbA1c level and the rate of ALSFRS decline in the first 200 days (p = 0.81 for interaction) nor between HbA1c level and survival (p = 0.45). Interpretation: We did not find convincing evidence that mean blood glucose level is associated with disease progression among ALS patients. [ABSTRACT FROM AUTHOR]

Background: Eating disorders (EDs) are serious, often chronic, conditions associated with pronounced morbidity, mortality, and dysfunction increasingly affecting young people worldwide. Illness progression, stages and recovery trajectories of EDs are still poorly characterised. The STORY study dynamically and longitudinally assesses young people with different EDs (restricting; bingeing/bulimic presentations) and illness durations (earlier; later stages) compared to healthy controls. Remote measurement technology (RMT) with active and passive sensing is used to advance understanding of the heterogeneity of earlier and more progressed clinical presentations and predictors of recovery or relapse. Methods: STORY follows 720 young people aged 16–25 with EDs and 120 healthy controls for 12 months. Online self-report questionnaires regularly assess ED symptoms, psychiatric comorbidities, quality of life, and socioeconomic environment. Additional ongoing monitoring using multi-parametric RMT via smartphones and wearable smart rings ('Ōura ring') unobtrusively measures individuals' daily behaviour and physiology (e.g., Bluetooth connections, sleep, autonomic arousal). A subgroup of participants completes additional in-person cognitive and neuroimaging assessments at study-baseline and after 12 months. Discussion: By leveraging these large-scale longitudinal data from participants across ED diagnoses and illness durations, the STORY study seeks to elucidate potential biopsychosocial predictors of outcome, their interplay with developmental and socioemotional changes, and barriers and facilitators of recovery. STORY holds the promise of providing actionable findings that can be translated into clinical practice by informing the development of both early intervention and personalised treatment that is tailored to illness stage and individual circumstances, ultimately disrupting the long-term burden of EDs on individuals and their families. [ABSTRACT FROM AUTHOR]

Background: Post-translational modification pathway of protein ubiquitination is intricately associated with tumorigenesis. We previously reported elevated ubiquitin-conjugating enzyme 2T (UBE2T) as an independent risk factor in stage I lung adenocarcinoma and promoting cellular proliferation. However, its underlying mechanisms needed further investigation. Methods: Immunohistochemistry was used to assess the expression of UBE2T and retinoic acid receptor-related orphan receptor α (RORA) in stage I LUAD. Cell proliferation, migration, and invasion of LUAD cell lines were measured by Cell Counting Kit-8 assay (CCK-8), Colony-forming assay and Transwell assay, respectively. Western blot analysis was performed to determine the expression of epithelial-mesenchymal transition (EMT) markers. A xenograft model was established to evaluate the proliferative capacity of UBE2T and its interaction with RORA in promoting LUAD. Mechanistic insights into the promotion of early-stage LUAD by UBE2T were obtained through luciferase reporter assay, chromatin immunoprecipitation and co-immunoprecipitation. Results: UBE2T and RORA expression was significantly up- and down-regulated in early-stage LUAD patients which's proved to be associated with unfavorable outcomes, strengthened cell proliferation, migration, EMT and invasion through its interaction with RORA both in vivo and in vitro. The growth NSCLC xenografts was reduced by down-expression of UBE2T but was suppressed by RORA knockout. Mechanistically, UBE2T mediated the ubiquitination of the intermediate transcription factor PBX1, which played a transcriptional role in downstream regulation of RORA. Conclusion: The oncogenic role of UBE2T and the UBE2T-PBX1-RORA axis in driving malignant progression in Stage I LUAD had been established. UBE2T might be a novel and promising therapeutic target for LUAD treatment. [ABSTRACT FROM AUTHOR]

Background: The entorhinal cortex is the very earliest involvement of Alzheimer's disease (AD). Grid cells in the medial entorhinal cortex form part of the spatial navigation system. Objective: We aimed to determine whether path integration performance can be used to detect patients with mild cognitive impairment (MCI) at high risk of developing AD, and whether it can predict cognitive decline. Methods: Path integration performance was assessed in 71 patients with early MCI (EMCI) and late MCI (LMCI) using a recently developed 3D virtual reality navigation task. Patients with LMCI were further divided into those displaying characteristic brain imaging features of AD, including medial temporal lobe atrophy on magnetic resonance imaging and posterior hypoperfusion on single-photon emission tomography (LMCI+), and those not displaying such features (LMCI–). Results: Path integration performance was significantly lower in patients with LMCI+than in those with EMCI and LMCI–. A significantly lower performance was observed in patients who showed progression of MCI during 12 months, than in those with stable MCI. Path integration performance distinguished patients with progressive MCI from those with stable MCI, with a high classification accuracy (a sensitivity of 0.88 and a specificity of 0.70). Conclusions: Our results suggest that the 3D virtual reality navigation task detects prodromal AD patients and predicts cognitive decline after 12 months. Our navigation task, which is simple, short (12–15 minutes), noninvasive, and inexpensive, may be a screening tool for therapeutic choice of disease-modifiers in individuals with prodromal AD. [ABSTRACT FROM AUTHOR]

Background: Disease progression is observed across the spectrum of people with multiple sclerosis (MS) and identification of effective treatment strategies to halt progression remains one of the greatest unmet clinical needs. Objectives: The Canadian Prospective Cohort Study to Understand Progression in MS (CanProCo) was designed to evaluate a wide range of factors associated with the onset and rate of clinical disease progression in MS and to describe the interplay between these factors. Design: A prospective cohort study. Methods: CanProCo is a national, prospective, observational cohort study that has recruited 944 individuals from 5 large academic MS centers in Canada. Participants include people with radiologically isolated syndrome (RIS), early relapsing-remitting and primary progressive MS (RRMS, PPMS), and healthy controls (HCs). Annually, participants complete self-reported questionnaires, undergo clinical evaluation and, if clinically indicated, magnetic resonance images (MRIs) of the brain and cervical spinal cord; in a subset of participants (n = 399), blood, and research MRIs of the brain and cervical spinal cord are collected. Linkages to health administrative databases are available at three sites. Results: Overall, 944 participants were recruited (53 HCs, 63 RIS, 751 RRMS, 77 PPMS). RIS and MS participants had a mean age of 39.0 years and 70.5% female. The mean time since diagnosis was 2.7 years. There were differences observed in the Expanded Disability Status Scale score and components of the MS performance test (walking speed test, manual dexterity test, processing speed test, and low-contrast visual acuity) between RIS and MS subtypes. Questionnaires revealed more symptoms of depression and anxiety and impaired physical and mental quality of life in people with RIS/MS versus HCs and differences across RIS/MS subtypes. Conclusion: Physical and mental neurological disability is prevalent even in the earliest stages of MS. Transdisciplinary approaches such as those used in CanProCo are needed to better characterize clinical progression in MS. Additional CanProCo results, including MRI, biological, and pharmaco-economic data will be forthcoming. Going forward, CanProCo's data sharing and collaborative vision will facilitate numerous global collaborations, which will inform the development and implementation of effective interventions for people with MS around the world. [ABSTRACT FROM AUTHOR]

Objective: There are very few reports on the prevalence of diabetic retinopathy (DR) in children and youth with type-1 diabetes (T1D). Studies have also found very low rates of referral for DR screening in children and youth with T1D. We conducted this study to determine the prevalence of DR, to study the reliability of ISPAD screening recommendations and to identify predictors of DR, its progression and regression in Indian children and youth with T1D. Methods: This study included 882 children and youth with T1D. Demographic data, anthropometry, blood pressure, sexual maturity rating, ophthalmological examination (slit lamp for cataract) and biochemical measurements were performed using standard protocols. Fundus images were captured using the Forus Health 3netra classic digital non-mydriatic fundus camera by the same experienced operator. De-identified images were assessed by a senior grader and ophthalmologist (Belfast Ophthalmic Reading Center). Severity of DR was graded as per the UK National Health Service (NHS) DR classification scale. Result: We report 6.4% and 0.2% prevalence of DR and cataract in Indian children and youth with T1D, respectively. All the subjects with DR had early non-proliferative DR. We report that amongst subjects with DR, only 2 subjects were aged less than 11 years and had duration of illness less than 2 years. Presence of hypertension and older age were significant predictors of DR (P <.05). Subjects with DR had significantly higher triglyceride concentrations (P <.05), of these, 6.9% had progression and 2.9% had regression at 1 year follow up; the change in glycaemic control was a significant positive predictor of progression of DR (P <.05). None of the participants included in the study progressed to develop sight-threatening DR. Conclusion: DR is not uncommon in Indian children and youth with T1D, thus screening for DR needs to be initiated early, particularly in older individuals with higher disease duration. Controlling blood pressure and triglyceride concentrations may prevent occurrence of DR. Improving glycaemic control may prevent progression of DR in Indian children and youth with T1D. Plain Language Summary: Diabetic retinopathy in Indian children with Type 1 Diabetes We found that 6.4% and 0.2% Indian children and youth with type-1 diabetes had diabetic retinopathy and cataract respectively. We report that amongst subjects with DR, only 2 subjects were aged less than 11 years and had duration of illness less than 2 years. Thus, International Society for Paediatric and Adolescent Diabetes (ISPAD) screening criteria must be implemented by all centres to avoid missing cases. Presence of high blood pressure, high triglyceride levels and older age were significant predictors of DR. Of the subjects with DR, 6.9% had progression and 2.9% had regression at 1 year follow up; the change in glycaemic control was a significant positive predictor of progression of DR. None of the participants included in the study progressed to develop sight-threatening DR. DR is not uncommon in Indian children and youth with T1D, hence, screening for DR needs to be initiated early, particularly in older individuals with higher disease duration. Controlling blood pressure and triglyceride concentrations may prevent occurrence of DR. Improving glycaemic control may prevent progression of DR in Indian children and youth with T1D. [ABSTRACT FROM AUTHOR]

Background: Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive breast cancer (IBC). Studies have indicated differences in DCIS outcome based on race or ethnicity, but molecular differences have not been investigated. Methods: We examined the molecular profile of DCIS by self-reported race (SRR) and outcome groups in Black (n = 99) and White (n = 191) women in a large DCIS case-control cohort study with longitudinal follow up. Results: Gene expression and pathway analyses suggested that different genes and pathways are involved in diagnosis and ipsilateral breast outcome (DCIS or IBC) after DCIS treatment in White versus Black women. We identified differences in ER and HER2 expression, tumor microenvironment composition, and copy number variations by SRR and outcome groups. Conclusions: Our results suggest that different molecular mechanisms drive initiation and subsequent ipsilateral breast events in Black versus White women. [ABSTRACT FROM AUTHOR]

Background/aim: Idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) are two entities categorized as fibrotic lung diseases. With a similar clinical presentation and treatment modalities in many cases, the line differentiating these two diseases may not be evident. Hence, it was aimed herein to evaluate the effectiveness of antifibrotic treatment and the course of fibrotic lung diseases. Materials and methods: The study included patients diagnosed with IPF and PPF who were given antifibrotic treatment and followed-up for 12 months at our clinic. At the final follow-up, treatment response and radiological evaluation were investigated via high-resolution computed tomography. Results: Eighty-seven patients were included in the study (57 with IPF and 30 with PPF). Under antifibrotic treatment, there were no statistically significant decreases in the six-minute walking test, forced vital capacity, and diffusing capacity of the lungs for carbon monoxide values at 6 and 12 months posttreatment. The most common side effects were photosensitivity for patients under the pirfenidone regimen, while diarrhea was predominantly observed in the PPF group. Radiological progression was observed in 22.9% of the patients at 12 months posttreatment. Hospitalization requirements were more evident in the PPF group, with at least one hospitalization history present in 60% (n = 18) of the PPF patients compared to 12.3% (n = 7) of the IPF patients. Conclusion: A personalized approach is preferred with similar clinical profiles for both treatment modalities, with specific side effects considered. [ABSTRACT FROM AUTHOR]

Integrating sodium-glucose co-transporter 2 inhibitors (SGLT2i) into the treatment for chronic kidney disease (CKD) has marked a significant therapeutic advance in nephrology. Clinical trials such as DAPA-CKD and EMPA-KIDNEY have demonstrated the beneficial effects of SGLT2i in slowing CKD progression and reducing proteinuria. However, the applicability of these results to patients with glomerulonephritis is still unresolved due to various limitations. This manuscript combines the evidence supporting the use of SGLT2i in glomerular diseases, highlights the limitations and strikes a conclusive balance on their role in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Diabetic retinopathy (DR) may worsen during pregnancy, but its course in the postpartum remains poorly understood. Understanding the natural history of DR during and after pregnancy can help determine when sight‐threatening DR treatment should be administered. Methods: A prospective longitudinal cohort study recruited pregnant women with pre‐existing type 1 (T1D) or type 2 diabetes from two tertiary Diabetes Antenatal Clinics in Melbourne, Australia. Eye examination results in early pregnancy, late pregnancy, and up to 12‐months postpartum were compared to determine DR changes. Two‐field fundus photographs and optical coherence tomography scans were used to assess DR severity. Results: Overall, 105 (61.4%) women had at least two eye examinations during the observation period. Mean age was 33.5 years (range 19–51); 54 women (51.4%) had T1D; 63% had HbA1c <7% in early pregnancy. DR progression rate was 23.8% (95% CI 16.4–32.6). Having T1D (RR 4.96, 95% CI 1.83–13.46), pre‐existing DR in either eye (RR 4.54, 95% CI 2.39–8.61), and elevated systolic blood pressure (adjusted RR 2.49, 95% CI 1.10–5.66) were associated with increased risk of progression. Sight‐threatening progression was observed in 9.5% of women. Among the 19 eyes with progression during pregnancy, 15 eyes remained stable, three eyes progressed, and only one eye regressed in the postpartum. Conclusions: Nearly 1 in 4 women had DR progression from conception through to 12‐months postpartum; almost half of these developing sight‐threatening disease. DR progression occurring during pregnancy was found to predominantly remain unchanged, or worsen, after delivery, with very few eyes spontaneously improving postpartum. [ABSTRACT FROM AUTHOR]

Introduction: This consensus paper provides recommendations for oral health professionals on why and how to assess caries activity and progression with special respect to the site of a lesion. Methods: An expert panel was nominated by the executive councils of the European Organization for Caries Research (ORCA) and the European Federation of Conservative Dentistry (EFCD). The steering committee built three working groups that were asked to provide recommendations on (1) caries detection and diagnostic methods, (2) caries activity and progression assessment, and (3) obtain individualized caries diagnoses. The experts of work group 2 phrased and agreed on provisional general and specific recommendations on caries lesion activity and progression, based on a review of the current literature. These recommendations were then discussed and refined in a consensus workshop followed by an anonymous Delphi survey to determine the agreement on each recommendation. Results: The expert panel agreed on general (n = 7) and specific recommendations (n = 6). The specific recommendations cover coronal caries on pits and fissures, smooth surfaces, proximal surfaces, as well as root caries and secondary caries/caries adjacent to restorations and sealants. 3/13 recommendations yielded perfect agreement. Conclusion: The most suitable method for lesion activity assessment is the visual-tactile method. No single clinical characteristic is indicative of lesion activity; instead, lesion activity assessment is based on assessing and weighing several clinical signs. The recall intervals for visual and radiographic examination need to be adjusted to the presence of active caries lesions and recent caries progression rates. Modifications should be based on individual patient characteristics. [ABSTRACT FROM AUTHOR]

Background: Tapping speed (TS) correlates with baseline disability scales in people with multiple sclerosis (pwMS) Objective: The study aimed to address if progression independent of relapse activity (PIRA) could be predicted by first-month measurement of TS. Methods: Prospective study including pwMS in one referral MS center. Consecutive patients were included and keys/second (Keys/s) were passively measured each day using an in-house smartphone application for 1 month. Median, mean, and maximum keys/s were obtained. Multivariate logistic regression models (including keys/s, age, sex, and baseline disability scores) were obtained for prediction of a PIRA event after 1 year. Results: Overall, 59 patients were included in the final analysis (64.4% women, median age of 44.5 years). However, 10 patients presented a PIRA event, without differences regarding baseline characteristics between PIRA and no-PIRA groups. PIRA group presented lower median keys/s (2 vs 4 keys/s, p = 0.002) and mean keys/s (2.8 vs 4.6, p = 0.008), while maximum keys/s were similar (p = 0.32). A median ⩽ 3 keys/s was independently associated with PIRA (aOR = 16.8, p = 0.03), as did a mean ⩽ 3.7 keys/s (aOR = 17, p = 0.02). These differences were not detected regarding other variables analyzed. Conclusion: Low median or mean keys/s obtained during initial month of assessment were indicative of a PIRA event within the next year. [ABSTRACT FROM AUTHOR]

Background: Facial nerve paralysis is a severe dysfunction after vestibular schwannoma (VS) surgery. Methods: This monocentric study analyzed 61 patients who underwent sporadic VS surgery in a standardized manner. The primary endpoint was the facial nerve outcome (FNO) at 3 months after VS surgery. FNO was dichotomized into "good" (House–Brackmann (HB) score ≤ 2) and "poor" (HB > 2). Results: Poor FNO was observed in 11 patients (18.0%) at 3 months after VS surgery. Radiomic tumor shape features were analyzed, and the AUC of elongation in the prediction of a poor HB at 3 months was 0.70 (95% CI: 0.56–0.85, p = 0.03) and the optimum threshold value (≤/>0.35) yielded a sensitivity and specificity of 64.0% and 75.4%, respectively. Multivariable logistic regression analyses considering the extent of resection (0.35) revealed that more elongated VSs (≤0.35; OR: 5.8; 95%CI: 1.2–28.2; p = 0.03) and those with an increased EoR (≥93.4%; OR: 6.5; 95%CI: 1.0–42.5; p = 0.05) are independently associated with poorer FNO at 3 months after surgery. Conclusions: Highly elongated VS shape seems to be a risk factor for worsened facial nerve outcome at 3 months after surgery for Koos grade 3 and 4 tumors. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is an important extra-articular manifestation of rheumatoid arthritis (RA). Identifying patients at risk of progression and death is crucial for improving RA-ILD management and outcomes. This paper explores current evidence on prognostic factors in RA-ILD. Methods: We conducted a systematic literature review to examine the impact of clinical, radiological, and histological factors on lung function decline and the survival of RA-ILD patients. We searched electronic databases, including Medline and EMBASE, from inception to date. The incidence and prognosis of predictors were qualitatively analyzed, and univariate results were combined when feasible. Following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)" guidelines, our systematic literature review involved a five-step algorithm. Out of 2217 records, 48 studies were eligible. These studies reported various prognostic factors, including demographic variables, clinical risk factors, serum markers, and preexisting treatments. Results: Lung function declined over time in 1225 subjects, with significant variability in smoking history and radiological/pathological UIP patterns. Severe lung fibrosis and abnormal pulmonary function tests (PFTs) were key univariate prognostic indicators, while age at initial presentation, RA disease activity, predicted DLCO percentage, and UIP pattern were the most reliable multivariate risk factors for ILD progression. Age, male gender, disease duration, RA activity, acute phase reactants, and specific serum biomarkers (Krebs vin den Lungen 6, surfactant protein D, and interleukin 6) were significantly associated with all-cause mortality. Conclusions: RA-ILD is a severe complication of RA characterized by significant prognostic variability. Key prognostic factors include extensive fibrosis observed on imaging, a marked decline in lung function, high RA disease activity, and specific biomarkers. These factors can guide treatment strategies and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Lung cancer treatment and detection can be improved by the identification of new biomarkers. Novel approaches in investigating circular RNAs (circRNAs) as biomarkers have yielded promising results. A circRNA molecule circHIPK3 was found to be widely expressed in non-small-cell lung cancer (NSCLC) cells, where it plays a crucial role in lung cancer tumorigenesis. CircHIPK3 promotes lung cancer progression by sponging oncosuppressive miRNAs such as miR-124, miR-381-3p, miR-149, and miR-107, which results in increased cell proliferation, migration, and resistance to therapies. Inhibiting circHIPK3 has been demonstrated to suppress tumour growth and induce apoptosis, which suggests its potential use in the development of new lung cancer treatment strategies targeting circHIPK3-related pathways. As a biomarker, circHIPK3 shows promise for early detection and monitoring of lung cancer. CircHIPK3 increased expression levels in lung cancer cells, and its potential link to metastasis risk highlights its clinical relevance. Given the promising preliminary findings, more clinical trials are needed to validate circHIPK3 efficacy as a biomarker. Moreover, future research should determine if the mechanisms discovered in NSCLC apply to small cell lung cancer (SCLC) to investigate circHIPK3-targeted therapies for SCLC. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence indicates a higher prevalence of polyneuropathy (PNP) in Parkinson's disease (PD). However, the involvement of large fiber neuropathy in PD still remains poorly understood. Given the lack of longitudinal data, we investigated the course of PNP associated with PD. Methods: In total, 41 PD patients underwent comprehensive clinical evaluation including motor and non-motor assessments as well as nerve conduction studies at baseline and at 2 years of follow-up. The definition of PNP was based on electrophysiological standard criteria. Common causes of PNP were excluded. Results: At baseline, PNP was diagnosed in 65.85% of PD patients via electroneurography. Patients with PNP presented with higher age (p = 0.019) and PD motor symptom severity (UPDRS III; p < 0.001). Over the course of 2 years, PNP deteriorated in 21.95% of cases, and 26.83% remained without PNP. Deterioration of nerve amplitude was most prevalent in the median sensory nerve affecting 57.58% of all PD cases with an overall reduction of median sensory nerve amplitude of 45.0%. With regard to PD phenotype, PNP progression was observed in 33.33% of the tremor dominant and 23.81% of the postural instability/gait difficulties subtype. Decrease of sural nerve amplitude correlated with lower quality of life (PDQ-39, p = 0.037) and worse cognitive status at baseline (MoCA, p = 0.042). Conclusion: The study confirms the high PNP rate in PD, and demonstrates a significant electrophysiological progression also involving nerves of the upper extremities. Longitudinal studies with larger cohorts are urgently needed and should elucidate the link between PD and PNP with the underlying pathomechanisms. [ABSTRACT FROM AUTHOR]

Tricuspid annular enlargement in patients with atrial fibrillation (AF) can induce tricuspid regurgitation (TR). However, risk factors associated with TR progression in patients with AF have not been defined. This study aimed to clarify an association between tricuspid annular diameter (TAD) and TR progression in patients with longstanding persistent AF. We retrospectively analyzed data from 228 patients who had longstanding persistent AF for > 1 year and mild or less TR on baseline echocardiograms. We defined significant TR as moderate or greater TR, graded according to the jet area and vena contracta. The optimal cut-off value of the TAD index (TADI), based on body surface area for predicting progression to significant TR, was estimated using receiver operating characteristic (ROC) curves. The independence and incremental value of the TADI were evaluated using multivariate Cox proportional hazard regression analysis and likelihood ratio tests. Over a median follow-up of 3.7 years, 55 (24.1%) patients developed significant TR. The optimal cut-off value of 21.1 mm/m2 for the TADI at baseline and ROC curves predicted TR progression with 70.4% sensitivity and 86% specificity. Furthermore, TADI was an independent predictor of TR progression (hazard ratio, 1.32; 95% confidence interval, 1.17–1.49, P < 0.001) and had a significant incremental value that exceeded that of models constructed using clinical parameters. In conclusion, TADI was significantly associated with TR progression and was an independent predictor of TR progression in longstanding persistent AF. [ABSTRACT FROM AUTHOR]

Aim: Prospective studies suggest that sleep‐disordered breathing enhances the risk of diabetes. However, it remains unclear whether diabetes could worsen sleep‐disordered breathing. Methods: The participants from Sleep Heart Health Study underwent two polysomnograms at a 5‐year interval. The relationship of baseline diabetes to change in the apnoea‐hypopnoea index (AHI) was examined based on general linear models, adjusting for demographics, lifestyles, history of hypertension, pulmonary function, length of follow‐up and baseline AHI. Results: In total, 161 of the 2603 participants were diagnosed with diabetes at the first polysomnograms. Compared with participants without diabetes, those with diabetes had a higher baseline and larger increases in follow‐up AHI and obstructive apnoea index (oAI). Diabetes increased 2.52 events per hour (95% confidence interval 0.45‐4.59; p =.017) for AHI change and 1.13 events per hour (95% confidence interval 0.04‐2.23; p =.042) for oAI change, respectively. In addition, subgroup analysis suggested that the association was consistent across baseline obstructive sleep apnoea severity and body mass index groups. Conclusions: Baseline diabetes was associated with worsening sleep‐disordered breathing over 5 years, which mainly increased the change in AHI and oAI. [ABSTRACT FROM AUTHOR]

Study Design This study was a retrospective study conducted from October 2020 to October 2022 on 106 posttraumatic patients with acute extradural hematomas (EDHs) who were initially planned for conservative treatment. 74 patients had spontaneous EDH regression (EDHR), while 32 patients developed EDH progression (EDHP) and were shifted for surgery. The two groups were statistically compared regarding the different demographic, clinical, and radiographic factors to identify the significant predictors for regression versus progression of acute posttraumatic EDH. Objectives Conventionally, urgent evacuation is the accepted management for EDH. However, several recent reports have described successful conservative management in selected patients. There are no adequate clues to verify patients who will have spontaneous EDHR from those at risk for EDHP and delayed surgery. The main objective of this study was to identify the significant predictors for possible regression versus progression of acute posttraumatic EDH initially planned for nonsurgical treatment. Materials and Methods A retrospective study conducted over 2 years, included 106 head trauma patients with acute EDH, who were admitted to our department and were initially planned for conservative treatment. Various demographic, clinical, and radiographic factors were analyzed to verify the significant predictors for spontaneous EDHR (EDHR group) versus EDHP and subsequent surgical evacuation (EDHP group). Results The mean age was 20.37 ± 12.712 years and the mean Glasgow Coma Scale score (GCS) was 12.83 ± 2.113. Total 69.8% of patients showed spontaneous EDHR, while 30.2% developed EDHP and were shifted for surgical evacuation. Statistical comparison showed that higher GCS (p = 0.002), frontal location (p = 0.022), and concomitant fissure fracture (p = 0.014) were the significant predictors for EDHR, while younger age (p = 0.006), persistent nausea/vomiting (p = 0.046), early computed tomography (CT) after trauma (p = 0.021), temporal location (p < 0.001), and coagulopathy (p = 0.001) were significantly associated with EDHP. Conclusion Patients with traumatic EDH fitting the criteria of initial nonsurgical treatment necessitates 48 hours of close observation and serial CT scans at 6, 12, 24, and 48 hours to confirm the regression or early detect the EDHP. Patients with high GCS, frontal hematomas, and associated fissure fracture are at low risk for EDHP. Increased alertness is mandatory for young age and patients with persistent nausea/vomiting, early CT scan, temporal hematomas, or coagulopathy. [ABSTRACT FROM AUTHOR]

The clinical course of nontuberculous mycobacterial pulmonary disease (NTM-PD) is varied, and a watchful waiting management strategy is appropriate for a subset of patients. Understanding disease progression and risk factors for progression is essential for deciding on an appropriate follow-up strategy. What is the rate of NTM-PD progression, and what are the predictors of progression? Patients with NTM-PD who were enrolled in a prospective observational cohort study between July 1, 2011, and December 31, 2022, were included in this analysis. Clinical, bacterial, laboratory, and radiographic data were collected at enrollment and then regularly during follow-up. NTM-PD progression was defined as either the initiation of treatment or the clinician's intention to treat. The rate of progression was calculated and the predictors for progression were analyzed. Of the 477 patients enrolled, NTM-PD progressed in 192 patients over a median follow-up of 5.4 years. The incidence of NTM-PD progression was 11.0 cases per 100 person-years (95% CI, 9.5-12.7 cases per 100 person-years). The proportion of patients experiencing disease progression was 21.4% at 1 year, 33.8% at 3 years, and 43.3% at 5 years. The final multivariable analysis model identified female sex (adjusted hazard ratio [aHR], 1.69; 95% CI, 1.19-2.39), elevated erythrocyte sedimentation rate (aHR, 1.79; 95% CI, 1.31-2.43), FEV 1 % predicted (aHR, 0.89; 95% CI, 0.82-0.96), and the presence of a cavity (aHR, 2.78; 95% CI, 2.03-3.80) as predictors of progression. About one-half of patients with NTM-PD experienced progression during an observation period of > 5 years. Patients with risk factors for progression should be observed closely. ClinicalTrials.gov ; No.: NCT01616745 ; URL: www.clinicaltrials.gov [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Peritoneal infiltrating and fibrotic endometriosis, also known as deep endometriosis, is the most severe manifestation of the disease that can cause severe complications including bowel and ureteral stenosis. The natural history of these lesions and the possible effect of hormonal treatments on their progression are undefined. Therefore, we conducted a systematic review and meta‐analysis to investigate whether and how frequently deep endometriosis progresses over time without or with ovarian suppression. This could inform management decisions in asymptomatic and mildly symptomatic patients. Material and Methods: For this pre‐registered systematic review (CRD42023463518), the PubMed and Embase databases were screened, and studies published between 2000 and 2023 that serially evaluated the size of deep endometriotic lesions without or with hormonal treatment were selected. Data on the progression, stability, or regression of deep endometriotic lesions were recorded as absolute frequencies or mean volume variations. Estimates of the overall percentage of progression and corresponding 95% confidence intervals were calculated using a random‐effect model. When studies reported lesion progression as pre‐ and post‐treatment volume means, the delta of the two‐volume means was calculated and analyzed using the inverse variance method. Results: A total of 29 studies were identified, of which 19 studies with 285 untreated and 730 treated patients were ultimately selected for meta‐analysis. The overall estimate of the percentage of lesion progression in untreated individuals was 21.4% (95% CI, 6.8–40.8%; I2 = 90.5%), whereas it was 12.4% during various hormonal treatments (95% CI, 9.0–16.1%; I2 = 0%). Based on the overall meta‐analysis estimates, the odds ratio of progression in treated vs untreated patients was 0.52 (95% CI, 0.41–0.66). During hormonal suppression, the mean volume of deep endometriotic lesions decreased significantly by 0.87 cm3 (95% CI, 0.19–1.56 cm3; I2 = 0%), representing −28.5% of the baseline volume. Conclusions: Untreated deep endometriotic lesions progressed in about one in five patients. Medical therapy reduced but did not eliminate this risk. Given the organ function failure potentially caused by these lesions, the decision whether to use hormonal treatments in asymptomatic or mildly symptomatic women should always be shared, carefully weighing the potential benefits and harms of the two alternatives after extensive counseling. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea (OSA), due to its high prevalence, has been associated with a number of comorbidities, frequently impacting the overall course of these other diseases if left untreated. Recent studies highlight a potential association between OSA and cancer. This study investigates how OSA severity and hypoxia affect cancer prognosis, aiming to elucidate how they interplay. Retrospective study including patients with a diagnosis of OSA after any cancer type followed up in a tertiary center during a 10-year period. OSA was mainly diagnosed after level III polysomnographic studies. Nocturnal hypoxia was significantly more prevalent in patients presenting lung cancer versus other malignancies and was associated with higher rates of oncologic disease progression. Overall survival was significantly lower in severe OSA patients and also in patients presenting nocturnal hypoxia. A composite hypoxia score considering both OSA severity and significant hypoxia was an independent predictor of mortality regardless of clinical cancer staging and treatment. Shorter time between cancer and OSA diagnosis was also associated with worse prognosis. This study suggests an association between OSA severity and nocturnal hypoxia and increased cancer mortality independently from possible confounding factors such as age, cancer clinical staging at diagnosis, treatment modality and also progression. Neoplastic patients with severe OSA and/or complex hypoxia seem to have lower overall survival rates than those with less severe OSA and nocturnal hypoxia. • OSA severity significantly impacts the overall prognosis of oncologic disease. • Nocturnal hypoxia is associated with higher mortality regardless of cancer type. • Hypoxic burden associated with worse prognosis irrespective of staging and treatment. [ABSTRACT FROM AUTHOR]

Copyright of Nefrologia is the property of Revista Nefrologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: There exists a dearth of research concerning non-small cell lung cancer (NSCLC) patients experiencing overall progressive disease concomitant with shrinking lesions after immunotherapy. This is a special type of mixed response. We aim to evaluate the clinical characteristics and treatment options of these patients during immunotherapy. Patients and Methods: We categorized patients into two groups: Progressive Disease with Mixed Responses (PDMR) (n = 31) and Progressive Disease with None Mixed Responses (PDNMR) (n = 144), depending on whether at least one target lesion had shrunk by ≥ 30% at the point of overall progression. Computed tomography scans and magnetic resonance imaging were utilized to evaluate the clinicopathological significance of these patients, and a multivariate analysis was conducted to scrutinize the clinical characteristics and prognosis-influencing factors in these patients. Results: Patients in the PDMR group had worse staging and a greater proportion of previous radiotherapy. The median overall survival (mOS 22 vs 36.4 months; P = 0.019) and median progression-free survival (mPFS 5.83 vs 9.03 months; P = 0.031) of the PDMR group were shorter than PDNMR group. Longer subsequent OS with continued immunotherapy after PDMR compared with patients who do not continue with immunization after PDMR (mOS 23.9 vs 6.5 months; P = 0.024). Conclusion: PDMR was primarily observed in stage IV patients and previously irradiated patients. OS and PFS were inferior in patients with PDMR compared to patients with PDNMR. The continuation of immunotherapy in PDMR patients could extend their survival. [ABSTRACT FROM AUTHOR]