Dietary inflammatory index is associated with metabolic dysfunction-associated fatty liver disease among United States adults.

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is presently the most prevalent chronic liver disorder globally that is closely linked to obesity, dyslipidemia metabolic syndrome, and type 2 diabetes mellitus (T2DM). Its pathogenesis is strongly associated with inflammation, and diet is a major factor in reducing inflammation. However, current research has focused primarily on exploring the relationship between diet and NAFLD, with less research on its link to MAFLD. Methods: In this research, using dietary inflammatory index (DII) as a measure to assess dietary quality, we analyzed the relationship between diet and MAFLD. Data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018, including 3,633 adults with complete DII and MAFLD, were used to develop cross-sectional analyses. Logistic regression analysis was adapted for investigating the relationship between DII and MAFLD development. Additionally, subgroup analysis and threshold effect analysis were carried out. Results: A positive link between DII and MAFLD was found in the fully adjusted model (OR = 1.05; 95%CI, 1.00-1.11, p < 0.05). Subgroup analysis indicated that there was no significant dependence for the connection between DII and MAFLD except for the subgroup stratified by age. Compared with other age groups, people with MAFLD had 20% higher DII scores than non-MAFLD participants in those aged 20-41 years old (OR = 1.20; 95%CI, 1.08-1.33, p < 0.001). Furthermore, we found a U-shaped curve with an inflection point of 3.06 illustrating the non-linear connection between DII and MAFLD. Conclusion: As a result, our research indicates that pro-inflammatory diet may increase the chance of MAFLD development, thus improved dietary patterns as a lifestyle intervention is an important strategy to decrease the incidence of MAFLD.

Machine learning models with time-series clinical features to predict radiographic progression in patients with ankylosing spondylitis.

Objective: Ankylosing spondylitis (AS) is chronic inflammatory arthritis causing structural damage and radiographic progression to the spine due to repeated and continuous inflammation over a long period. This study establishes the application of machine learning models to predict radiographic progression in AS patients using time-series data from electronic medical records (EMRs). Methods: EMR data, including baseline characteristics, laboratory findings, drug administration, and modified Stoke AS Spine Score (mSASSS), were collected from 1,123 AS patients between January 2001 and December 2018 at a single center at the time of first (T1), second (T2), and third (T3) visits. The radiographic progression of the (n+1)th visit (Pn+1=(mSASSSn+1-mSASSSn)/(Tn+1-Tn)≥1 unit per year) was predicted using follow-up visit datasets from T1 to Tn. We used three machine learning methods (logistic regression with the least absolute shrinkage and selection operation, random forest, and extreme gradient boosting algorithms) with three-fold cross-validation. Results: The random forest model using the T1 EMR dataset best predicted the radiographic progression P2 among the machine learning models tested with a mean accuracy and area under the curves of 73.73% and 0.79, respectively. Among the T1 variables, the most important variables for predicting radiographic progression were in the order of total mSASSS, age, and alkaline phosphatase. Conclusion: Prognosis predictive models using time-series data showed reasonable performance with clinical features of the first visit dataset when predicting radiographic progression.

Endoscopic and clinicopathological features of segmental colitis associated with diverticulosis.

Objectives: Segmental colitis associated with diverticulosis (SCAD) has close endoscopic and pathological similarities to ulcerative colitis (UC) and Crohn's disease. Clinical data on SCAD are limited in Japan. We examined the endoscopic and clinicopathological features of patients with SCAD. Methods: This single-center retrospective study included 13 patients with SCAD between 2012 and 2022. Endoscopic findings were categorized as follows: type A (swollen red patches 5-10 mm at the top of mucosal folds), mild and moderate type B (mild-to-moderate UC-like findings), type C (aphthous ulcers resembling Crohn's disease), and type D (severe UC-like findings). Results: Overall, six, five, and two patients were diagnosed with type A, mild type B, and moderate type B disease, respectively. Among the type A cases, two spontaneously progressed to moderate type B and one escalated to type D, necessitating an emergency sigmoidectomy owing to perforation peritonitis, despite repeated antibiotic treatments. Histopathologically, diffuse neutrophil and lymphocyte infiltration with cryptitis were noted in all type A cases, whereas UC-like alterations were observed in type B and D cases. Seven type B cases were treated with oral 5-aminosalicylic acid and/or salazosulfapyridine. Clinical remission was achieved in three mild type B cases and one moderate type B case, while clinical relapse and remission were noted in three moderate type B cases. No anti-inflammatory treatment was required in three type A and two mild type B cases. Conclusions: Aggressive anti-inflammatory treatment should be considered for SCAD with UC-like findings due to the potential risk of severe ulceration, stenosis, and/or perforation.

Overview of the immunological mechanisms in hepatitis B virus reactivation: Implications for disease progression and management strategies.

Hepatitis B virus (HBV) reactivation is a clinically significant challenge in disease management. This review explores the immunological mechanisms underlying HBV reactivation, emphasizing disease progression and management. It delves into host immune responses and reactivation's delicate balance, spanning innate and adaptive immunity. Viral factors' disruption of this balance, as are interactions between viral antigens, immune cells, cytokine networks, and immune checkpoint pathways, are examined. Notably, the roles of T cells, natural killer cells, and antigen-presenting cells are discussed, highlighting their influence on disease progression. HBV reactivation's impact on disease severity, hepatic flares, liver fibrosis progression, and hepatocellular carcinoma is detailed. Management strategies, including anti-viral and immunomodulatory approaches, are critically analyzed. The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation. In conclusion, this comprehensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation. With a dedicated focus on understanding its implications for disease progression and the prospects of efficient management strategies, this article contributes significantly to the knowledge base. The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches, ultimately enhancing disease management and elevating patient outcomes. The dynamic landscape of management strategies is critically scrutinized, spanning anti-viral and immunomodulatory approaches. The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

Usefulness of Palliative Prognostic Index, Objective Prognostic Score, and Neutrophil-Lymphocyte Ratio/Albumin Ratio As Prognostic Indicators for Patients Without Cancer Receiving Home-Visit Palliative Care: A Pilot Study at a Community General Hospital.

Background: Although the palliative prognostic index (PPI), objective prognostic score (OPS), and neutrophil-lymphocyte ratio/albumin ratio (NLR/Alb) are well-known prognostic indicators for cancer patients, they do not provide clarity when it comes to predicting prognosis in patients without cancer who receive home-visit palliative care. Objective: The aim of this study was to determine whether PPI, OPS, and NLR/Alb can predict prognosis for patients without cancer who received home-visit palliative care. Design: This is a retrospective study. Setting/Subjects: We recruited 58 patients without cancer who received home-visit palliative care from Tokushima Prefectural Kaifu Hospital, Japan, and died at home or at the hospital within seven days of admission between January 2009 and March 2023. Measurements: The PPI, OPS, and NLR/Alb of the study patients were evaluated at regular intervals, and statistical analysis was performed on the relationship between these indices and the time to death. Results: Simple regression analysis showed that PPI, OPS, and NLR/Alb were negatively correlated with the period until death (p < 0.001). The survival curves of the groups classified according to PPI, OPS, and NLR/Alb were significantly stratified. The predictive capacities of PPI, OPS, and NLR/Alb for death within 21 days were as follows: PPI (area under the curve [AUC]: 0.71; sensitivity: 59%; specificity: 68%), OPS (AUC: 0.73; sensitivity: 88%; specificity: 47%), and NLR/Alb (AUC: 0.72; sensitivity: 72%; specificity: 73%). Conclusions: PPI, OPS, and NLR/Alb were useful in predicting the survival period and short-term prognosis within 21 days for patients without cancer who received home-visit palliative care.

Predictive Models for Assessing Patients' Response to Treatment in Metastatic Prostate Cancer: A Systematic Review.

Background and objective: The treatment landscape of metastatic prostate cancer (mPCa) has evolved significantly over the past two decades. Despite this, the optimal therapy for patients with mPCa has not been determined. This systematic review identifies available predictive models that assess mPCa patients' response to treatment. Methods: We critically reviewed MEDLINE and CENTRAL in December 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Only quantitative studies in English were included with no time restrictions. The quality of the included studies was assessed using the PROBAST tool. Data were extracted following the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews criteria. Key findings and limitations: The search identified 616 citations, of which 15 studies were included in our review. Nine of the included studies were validated internally or externally. Only one study had a low risk of bias and a low risk concerning applicability. Many studies failed to detail model performance adequately, resulting in a high risk of bias. Where reported, the models indicated good or excellent performance. Conclusions and clinical implications: Most of the identified predictive models require additional evaluation and validation in properly designed studies before these can be implemented in clinical practice to assist with treatment decision-making for men with mPCa. Patient summary: In this review, we evaluate studies that predict which treatments will work best for which metastatic prostate cancer patients. We found that existing studies need further improvement before these can be used by health care professionals.

Deep Learning Enables Automatic Detection of Joint Damage Progression in Rheumatoid Arthritis-Model Development and External Validation.

OBJECTIVES: Although deep learning has demonstrated substantial potential in automatic quantification of joint damage in rheumatoid arthritis (RA), evidence for detecting longitudinal changes at an individual patient level is lacking. Here, we introduce and externally validate our automated RA scoring algorithm (AuRA), and demonstrate its utility for monitoring radiographic progression in a real-world setting. METHODS: The algorithm, originally developed during the Rheumatoid Arthritis 2-Dialogue for Reverse Engineering Assessment and Methods (RA2-DREAM) challenge, was trained to predict expert-curated Sharp-van der Heijde total scores in hand and foot radiographs from two previous clinical studies (n = 367). We externally validated AuRA against data (n = 205) from Turku University Hospital and compared the performance against two top-performing RA2-DREAM solutions. Finally, for 54 patients, we extracted additional radiograph sets from another control visit to the clinic (average time interval of 4.6 years). RESULTS: In the external validation cohort, with a root-mean-square-error (RMSE) of 23.6, AuRA outperformed both top-performing RA2-DREAM algorithms (RMSEs 35.0 and 35.6). The improved performance was explained mostly by lower errors at higher expert-assessed scores. The longitudinal changes predicted by our algorithm were significantly correlated with changes in expert-assessed scores (Pearson's R = 0.74, p< 0.001). CONCLUSION: AuRA had the best external validation performance and demonstrated potential for detecting longitudinal changes in joint damage. Available in https://hub.docker.com/r/elolab/aura, our algorithm can easily be applied for automatic detection of radiographic progression in the future, reducing the need for laborious manual scoring.

Redefining Clinical Hyperprogression: The Incidence, Clinical Implications, and Risk Factors of Hyperprogression in Non-Small Cell Lung Cancer Treated with Immunotherapy.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) may be associated with hyperprogressive disease (HPD). However, there is currently no standardized definition of HPD, with its risk factors and clinical implications remaining unclear. We investigated HPD in lung cancer patients undergoing immunotherapy, aiming to redefine HPD, identify risk factors, and assess its impact on survival. METHODS: Clinical and radiologic data from 121 non-small cell lung cancer (NSCLC) patients with 136 immunotherapy cases were reviewed retrospectively. Three HPD definitions (Champiat et al., HPDc; Saâda-Bouzid et al., HPDs; and Ferrara et al., HPDf) were employed. Additionally, all new measurable lesions on the post-treatment CT scan were incorporated in measuring the sum of longest diameters (SLD) to define modified HPD (mHPD). RESULTS: Among the 121 patients, 4 (3.3%) had HPDc, 11 (9.1%) had HPDs, and none had HPDf. Adding all new measurable lesions increased HPD incidence by 5%-10% across definitions. Multivariate analysis revealed significantly lower progression-free survival (PFS) and overall survival (OS) for patients with HPDc (HR 5.25, P = .001; HR 3.75, P = .015) and HPDs (HR 3.74, P < .001; HR 3.46, P < .001) compared to those without. Patients with mHPD showed similarly poor survival outcomes as HPD patients. Liver metastasis at diagnosis was associated with HPDs, and a high tumor burden correlated with HPDc. CONCLUSIONS: The incidence and risk factors of HPD varied with different definitions, but mHPD identified more cases with poor outcomes. This comprehensive approach may enhance the identification of at-risk patients and lead to a better understanding of HPD in lung cancer during immunotherapy.

Risk factors for chronic kidney disease in middle eastern patients with type 2 diabetes mellitus: A cross-sectional study using the KDIGO classification.

AIMS: Chronic kidney disease (CKD) is prevalent in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate risk factors for CKD progression across the kidney disease-Improving Global Outcomes (KDIGO)categories in a Middle Eastern population beyond hyperglycemia as emphasized by KDIGO guidelines which classifying CKD by cause and severity. METHODS: This cross-sectional study targeted 1603 patients with T2DM. Risk factors for CKD progression were determined using odds ratios (ORs) and 95 % confidence intervals (CIs). RESULTS: Overall, 35.5 %, 31.7 %, and 32.8 % of patients were classified as low-risk, moderate-risk, and high-/very high-/highest-risk, respectively. Several factors were associated with high/very high/highest risk categorization, including being aged >45 years (OR: 1.85, 95 % CI: 1.36-2.49; P < 0.001), male gender (OR: 1.87, 95 % CI: 1.38-2.54; P < 0.001), hypertension (OR: 3.66, 95 % CI: 2.32-5.78; P < 0.001), and T2DM duration of ≥15 years (OR: 3.2, 95 % CI: 2.27-4.5; P < 0.001). Patients with more concurrent risk factors were notably represented in the high/very high/highest risk category. CONCLUSIONS: Male patients, older patients, and those with comorbid hypertension, longstanding T2DM, and additional concurrent risk factors have a significantly higher risk of advanced CKD. Such findings should be considered when planning management approaches for patients with CKD.

Distinct spatiotemporal atrophy patterns in corticobasal syndrome are associated with different underlying pathologies.

Objective: To identify imaging subtypes of the cortico-basal syndrome (CBS) based solely on a data-driven assessment of MRI atrophy patterns, and investigate whether these subtypes provide information on the underlying pathology. Methods: We applied Subtype and Stage Inference (SuStaIn), a machine learning algorithm that identifies groups of individuals with distinct biomarker progression patterns, to a large cohort of 135 CBS cases (52 had a pathological or biomarker defined diagnosis) and 252 controls. The model was fit using volumetric features extracted from baseline T1-weighted MRI scans and validated using follow-up MRI. We compared the clinical phenotypes of each subtype and investigated whether there were differences in associated pathology between the subtypes. Results: SuStaIn identified two subtypes with distinct sequences of atrophy progression; four-repeat-tauopathy confirmed cases were most commonly assigned to the Subcortical subtype (83% of CBS-PSP and 75% of CBS-CBD), while CBS-AD was most commonly assigned to the Fronto-parieto-occipital subtype (81% of CBS-AD). Subtype assignment was stable at follow-up (98% of cases), and individuals consistently progressed to higher stages (100% stayed at the same stage or progressed), supporting the model's ability to stage progression. Interpretation: By jointly modelling disease stage and subtype, we provide data-driven evidence for at least two distinct and longitudinally stable spatiotemporal subtypes of atrophy in CBS that are associated with different underlying pathologies. In the absence of sensitive and specific biomarkers, accurately subtyping and staging individuals with CBS at baseline has important implications for screening on entry into clinical trials, as well as for tracking disease progression.

Dynamic Changes of the Gut Microbiota and Its Functional Metagenomic Potential during the Development of Non-Small Cell Lung Cancer.

The gut microbiota plays a significant role in tumor pathogenesis by regulating the host metabolism and immune response, and there are few studies focused on tracking changes in the gut microbiota from the onset of lung cancer. Therefore, the aim of our study is combining preclinical and clinical research to thoroughly analyze the signatures of fecal microbiota in lung cancer, which will be useful for early diagnosis and predicting the therapeutic efficacy of lung cancer. The first part of this study analyzed the fecal metagenomic differences between patients with non-small cell lung cancer and healthy subjects, and the second part of this work constructed a murine lung cancer model to monitor changes in mouse fecal metagenomics and T cell immunology during lung cancer progression. We found that the fecal microbiota was altered in both humans and mice with lung cancer, characterized by a significantly reduced microbial diversity and number of beneficial microbes, with increases in potential pathogens. The fecal level of Akkermansia muciniphila and the gut metabolic module of the secondary bile acid metabolism were diminished in both humans and mice with lung cancer compared with healthy subjects. Splenomegaly was observed in the lung cancer mice. Flow cytometer analysis of the splenocytes revealed substantial alterations in the proportions of T cell subsets in the lung cancer mice, characterized by significant increases in CD4+Foxp3+CD25+ T regulatory cells (p < 0.05) while significant decreases in CD3+ T cells (p < 0.001), CD4+ T cells (p < 0.001), and the CD4+/CD8+ ratio (p < 0.01). Vertical and longitudinal analyses of the fecal microbiota of the two mouse groups identified some lung cancer biomarkers (including Acutalibacter timonensis, Lachnospiraceae bacterium NSJ-38 sp014337195, etc.). The fecal microbiota of the lung cancer mice had a reduced metagenomic potential for neurotransmitters (melatonin, γ-aminobutyric acid, and histamine) compared with healthy mice. In summary, this study found that the diversity, structure, and composition of gut microbiota vary between cancer and healthy conditions, ultimately leading to changes in the potential for functional metagenomics.

Risk of diabetes and expected years in life without diabetes among adults from an urban community in India: findings from a retrospective cohort.

BACKGROUND: Diabetes prevalence has increased over the past few decades, and the shift of the burden of diabetes from the older population to the younger population has increased the exposure of longer durations in a morbid state. The study aimed at ascertaining the likelihood of progression to diabetes and to estimate the onset of diabetes within the urban community of Mumbai. METHODS: This study utilized an observational retrospective non-diabetic cohort comprising 1629 individuals enrolled in a health security scheme. Ten years of data were extracted from electronic medical records, and the life table approach was employed to assess the probability of advancing to diabetes and estimate the expected number of years lived without a diabetes diagnosis. RESULTS: The study revealed a 42% overall probability of diabetes progression, with age and gender variations. Males (44%) show higher probabilities than females (40%) of developing diabetes. Diabetes likelihood rises with age, peaking in males aged 55-59 and females aged 65-69. Males aged 30-34 exhibit a faster progression (10.6 years to diagnosis) compared to females (12.3 years). CONCLUSION: The study's outcomes have significant implications for the importance of early diabetes detection. Progression patterns suggest that younger cohorts exhibit a comparatively slower rate of progression compared to older cohorts.

Sleep deprivation: A risk factor for the pathogenesis and progression of Alzheimer's disease.

Sleep deprivation refers to an intentional or unintentional reduction in sleep time, resulting in insufficient sleep. It is often caused by sleep disorders, work demands (e.g., night shifts), and study pressure. Sleep deprivation promotes Aß deposition and tau hyperphosphorylation, which is a risk factor for the pathogenesis and progression of Alzheimer's disease (AD). Recent research has demonstrated the potential involvement of sleep deprivation in both the pathogenesis and progression of AD through glial cell activation, the glial lymphatic system, orexin system, circadian rhythm system, inflammation, and the gut microbiota. Thus, investigating the molecular mechanisms underlying the association between sleep deprivation and AD is crucial, which may contribute to the development of preventive and therapeutic strategies for AD. This review aims to analyze the impact of sleep deprivation on AD, exploring the underlying pathological mechanisms that link sleep deprivation to the initiation and progression of AD, which offers a theoretical foundation for the development of drugs aimed at preventing and treating AD.

Prognostic implication of 1-year decline in diffusing capacity in newly diagnosed idiopathic pulmonary fibrosis.

The progression of idiopathic pulmonary fibrosis (IPF) is assessed through serial monitoring of forced vital capacity (FVC). Currently, data regarding the clinical significance of longitudinal changes in diffusing capacity for carbon monoxide (DLCO) is lacking. We investigated the prognostic implications of a 1-year decline in DLCO in 319 patients newly diagnosed with IPF at a tertiary hospital between January 2010 and December 2020. Changes in FVC and DLCO over the first year after the initial diagnosis were reviewed; a decline in FVC ≥ 5% and DLCO ≥ 10% predicted were considered significant changes. During the first year after diagnosis, a significant decline in FVC and DLCO was observed in 101 (31.7%) and 64 (20.1%) patients, respectively. Multivariable analysis showed that a 1-year decline in FVC ≥ 5% predicted (aHR 2.74, 95% CI 1.88-4.00) and 1-year decline in DLCO ≥ 10% predicted (aHR 2.31, 95% CI 1.47-3.62) were independently associated with a higher risk of subsequent mortality. The prognostic impact of a decline in DLCO remained significant regardless of changes in FVC, presence of emphysema, or radiographic indications of pulmonary hypertension. Therefore, serial monitoring of DLCO should be recommended because it may offer additional prognostic information compared with monitoring of FVC alone.

Is Quadriceps-Strengthening Exercises (QSE) in Medial-Compartment Knee Osteoarthritis with Neutral and Varus Malalignment a Paradox? - A Risk-Appraisal of Strength-Training on Disease Progression.

Introduction: The present inquiry seeks to investigate whether the current regimens of QSEs (Quadriceps-Strengthening Exercises) aggravate the disease while mitigating symptoms. Materials and methods: A comparative study was conducted on 32 patients with medial compartment osteoarthritis of knees. While the neutral group of 16 patients was constituted of those with an anatomical-lateral-femoro-tibial-angle (aFTA) 176-180º, varus group comprised an equal number of patients with an aFTA >180º. A home-based 12-week strength-training program involving weekly visits to hospital for supervised sessions was administered. The outcome measures were visual-analog-scale (VAS), medial patello-femoral joint tenderness (MPFJT), time-up-and-go-test (TUGT), stair-climb test, step test, WOMAC, IKDC scores, aFTA, hip-knee-ankle (HKA) angle, lateral-tibio-femoral-joint-separation (LTFJS), and horizontal-distance-from-centre-of-knee-to-Mikulicz-line. Results: There was a significant increase in quadriceps strength (p<0.01) in both groups. Values for neutral group with VAS score (p=0.01), MPFJT (p=0.01), TUGT (p=0.01), timing of the stair climb test (p=0.01), WOMAC (p<0.01), and IKDC (p=0.03) were better compared to varus group with VAS score (p=0.13), MPFJT (p=0.03), TUGT (p=0.90), timing of stair climb test (p=0.68), WOMAC (p<0.02), and IKDC (p=0.05). Varus group also showed an increase in aFTA and LTFJS in 12 patients, increase in HKA in 11, and increase in horizontal distance from the centre of knee to the Mikulicz line in 7 patients. Conclusion: The present study brings to the fore the paradoxical role played by QSEs in management of medial knee OA. While there is a radiological progression of the disease in both neutral and varus mal-aligned knees more so in the latter than the former.

Penile carcinoma: A retrospective analysis of 93 patients at a tertiary care center in Jakarta, Indonesia.

OBJECTIVES: Penile carcinoma (PC) is a rare disease with considerable physical and psychological impact. To date, there is no data regarding PC prevalence and characteristics in Indonesia. This study aimed to analyze the characteristics of patients with PC in Indonesia and determine cumulative survival rates and time to disease progression. METHODS: This was a retrospective study of all patients diagnosed with PC at Cipto Mangunkusumo General Hospital from 1995 to 2014, with a minimum of 1 year follow-up. The outcomes of the study were cumulative survival rates and time-to-disease progression. RESULTS: Ninety-three subjects were recruited, with a mean age of 49.44 ± 13.62. Inguinal lymph node dissection (ILND) was performed in 49 (53%) patients. The mean survival in the ILND group was better compared to the non-ILND group (80.7 months vs. 67.1 months; p = 0.032). Time-to-progression in the ILND group was significantly longer than in the non-ILND group (71.7 months vs. 54.3 months; p = 0.022). No significant difference in survival between the total and partial penectomy (PP) groups was observed (p = 0.701). Time-to-progression in total penectomy (TP) was significantly longer than in PP (68 months vs. 56.0 months; p = 0.023). In Cox-regression analysis, after adjustment of other variables, history of ILND, higher stage of cancer, and older age were found to affect the survival of patients. CONCLUSION: ILND in PC led to better survival and reduced disease progression. The type of penectomy is only associated with progression but not survival. TP had a longer time to disease progression compared to PP.

Conventional Cytogenetic Analysis and Array CGH + SNP Identify Essential Thrombocythemia and Prefibrotic Primary Myelofibrosis Patients Who Are at Risk for Disease Progression.

The Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-MPNs) are a heterogeneous group of clonal hematopoietic malignancies that include polycythemia vera (PV), essential thrombocythemia (ET), and the prefibrotic form of primary myelofibrosis (prePMF). In this study, we retrospectively reviewed the karyotypes from conventional cytogenetics (CC) and array Comparative Genomic Hybridization + Single Nucleotide Polymorphism (aCGH + SNP) in patients with ET or prePMF to determine whether the combined analysis of both methodologies can identify patients who may be at a higher risk of disease progression. We performed a comprehensive genomic review on 169 patients with a clinical diagnosis of ET (154 patients) or prePMF (15 patients). Genomic alterations detected by CC or array-CGH + SNP were detected in 36% of patients. In patients who progressed, 68% had an abnormal genomic finding by either technology. There was a shorter progression-free survival (PFS) among patients who were cytogenetically abnormal or who were cytogenetically normal but had an abnormal aCGH + SNP result. Leveraging the ability to detect submicroscopic copy number alterations and regions of copy neutral-loss of heterozygosity, we identified a higher number of patients harboring genomic abnormalities than previously reported. These results underscore the importance of genomic analysis in prognostication and provide valuable information for clinical management and treatment decisions.

Therapeutic lag: Is treatment effect delayed in progressive MS?

BACKGROUND: Randomized clinical trials (RCTs) in progressive multiple sclerosis (MS) often revealed non-significant treatment effects on disability progression. OBJECTIVES: To investigate whether the failure to detect a significant benefit from treatment may be motivated by a delay in treatment effect, possibly related to baseline characteristics. METHODS: We re-analyzed data from two RCTs testing interferon-beta and glatiramer-acetate versus placebo in progressive MS with no significant effect on EDSS progression. We first designed a time-dependent Cox model with no treatment effect up to time = t0, and constant hazard ratio (HR) after time = t0. We selected the best-fitting t0 from 0 (standard Cox model) to 2.5 years. Furthermore, we modeled the delay as a function of baseline EDSS and fitted the resulting Cox model to the merged dataset. RESULTS: The time-dependent Cox model revealed a significant benefit of treatment delayed by t0 = 2.5 years for the SPECTRIMS study (HR = 0.65 (0.43-0.98), p = 0.041), and delayed by t0 = 2 years for the PROMISE study (HR = 0.65, (0.42-0.99), p = 0.044). In the merged dataset, the HR for the EDSS-dependent delayed effect was 0.68 (0.56, 0.82), p < 0.001. CONCLUSION: The assumption of a delayed treatment effect improved the fit to the data of the two examined RCTs, uncovering a significant, although shifted, benefit of treatment.

Population-based study of disease trajectory after radical treatment for high-risk prostate cancer.

OBJECTIVES: To investigate long-term disease trajectories among men with high-risk localized or locally advanced prostate cancer (HRLPC) treated with radical radiotherapy (RT) or radical prostatectomy (RP). MATERIAL AND METHODS: Men diagnosed with HRLPC in 2006-2020, who received primary RT or RP, were identified from the Prostate Cancer data Base Sweden (PCBaSe) 5.0. Follow-up ended on 30 June 2021. Treatment trajectories and risk of death from prostate cancer (PCa) or other causes were assessed by competing risk analyses using cumulative incidence for each event. RESULTS: In total, 8317 men received RT and 4923 men underwent RP. The median (interquartile range) follow-up was 6.2 (3.6-9.5) years. After RT, the 10-year risk of PCa-related death was 0.13 (95% confidence interval [CI] 0.12-0.14) and the risk of death from all causes was 0.32 (95% CI 0.31-0.34). After RP, the 10-year risk of PCa-related death was 0.09 (95% CI 0.08-0.10) and the risk of death from all causes was 0.19 (95% CI 0.18-0.21). The 10-year risks of androgen deprivation therapy (ADT) as secondary treatment were 0.42 (95% CI 0.41-0.44) and 0.21 (95% CI 0.20-0.23) after RT and RP, respectively. Among men who received ADT as secondary treatment, the risk of PCa-related death at 10 years after initiation of ADT was 0.33 (95% CI 030-0.36) after RT and 0.27 (95% CI 0.24-0.30) after RP. CONCLUSION: Approximately one in 10 men with HRLPC who received primary RT or RP had died from PCa 10 years after diagnosis. Approximately one in three men who received secondary ADT, an indication of PCa progression, died from PCa 10 years after the start of ADT. Early identification and aggressive treatment of men with high risk of progression after radical treatment are warranted.

MicroRNA-130b Suppresses Malignant Behaviours and Inhibits the Activation of the PI3K/Akt Signaling Pathway by Targeting MET in Pancreatic Cancer.

There has been interested in the microRNAs' roles in pancreatic cancer (PC) cell biology, particularly in regulating pathways related to tumorigenesis. The study aimed to explore the hub miRNAs in PC and underlying mechanisms by bioinformatics and fundamental experiments. RNA datasets collected from the Gene Expression Omnibus were analysed to find out differentially expressed RNAs (DERNAs). The miRNA-mRNA and protein-protein interaction (PPI) networks were built. The clinicopathological features and expressions of hub miRNAs and hub mRNAs were explored. Dual-luciferase reporter gene assay was performed to assess the interaction between microRNA and target gene. RT-qPCR and western blot were employed to explore RNA expression. The roles of RNA were detected by CCK-8 test, wound healing, transwell, and flow cytometry experiment. We verified 40 DEmiRNAs and 1613 DEmRNAs, then detected a total of 69 final functional mRNAs (FmRNAs) and 23 DEmiRNAs. In the miRNA-mRNA networks, microRNA-130b (miR-130b) was the hub RNA with highest degrees. Clinical analysis revealed that miR-130b was considerably lower expressed in cancerous tissues than in healthy ones, and patients with higher-expressed miR-130b had a better prognosis. Mechanically, miR-130b directly targeted MET in PC cells. Cell functional experiments verified that miR-130b suppressed cell proliferation, migration, promoted apoptosis, and inhibited the PI3K/Akt pathway by targeting MET in PC cells. Our findings illustrated the specific molecular mechanism of miR-130b regulating PC progress. The miR-130b/MET axis may be an alternative target in the therapeutic intervention of PC and provide an opportunity to deepen our understanding of the pathogenesis of PC.