Rate Of Progression Research Articles

Early treatment response assessment with [177Lu]PSMA whole-body-scintigraphy compared to interim PSMA-PET

BackgroundProstate-specific membrane antigen positron emission tomography (PSMA-PET) is an essential tool for patient selection before radioligand therapy (RLT). Interim-staging with PSMA-PET during RLT allows for therapy monitoring. However, its added value over post-treatment imaging is poorly elucidated. The aim of this study was to compare early treatment response assessed by post-therapeutic whole-body scans (WBS) with interim-staging by PSMA-PET after 2 cycles in order to prognosticate OS.MethodsMen with metastasized castration-resistant PC (mCRPC) who had received at least two cycles of RLT, and interim PSMA-PET were evaluated retrospectively. PROMISE V2 framework was used to categorize PSMA expression and assess response to treatment. Response was defined as either disease control rate (DCR) for responders or progression for non-responders.ResultsA total of 188 men with mCRPC who underwent RLT between February 2015 and December 2021 were included. The comparison of different imaging modalities revealed a strong and significant correlation with Cramer V test: e.g. response on WBS during second cycle compared to interim PET after two cycles of RLT (cφ = 0.888, P < 0.001, n = 188). The median follow-up time was 14.7 months (range: 3–63 months; 125 deaths occurred). Median overall survival (OS) time was 14.5 months (95% CI: 11.9–15.9). In terms of OS analysis, early progression during therapy revealed a significantly higher likelihood of death: e.g. second cycle WBS (15 vs. 25 months, P < 0.001) with a HR of 2.81 (P < 0.001) or at PET timepoint after 2 cycles of RLT (11 vs. 24 months, P < 0.001) with a HR of 3.5 (P < 0.001). For early biochemical response, a PSA decline of at least 50% after two cycles of RLT indicates a significantly lower likelihood of death (26 vs. 17 months, P < 0.001) with a HR of 0.5 (P < 0.001).ConclusionResponse assessment of RLT by WBS and interim PET after two cycles of RLT have high congruence and can identify patients at risk of poor outcome. This indicates that interim PET might be omitted for response assessment, but future trials corroborating these findings are warranted.

Differences in Clinical Outcomes and Survival Among Primary, Secondary, and Concomitant Carcinoma In Situ of the Bladder.

Carcinoma in situ (CIS) is a flat, high-grade, and aggressive form of urothelial carcinoma with a high risk of progression to muscle-invasive disease and metastasis. This study aimed to investigate differences in clinical outcomes and survival among patients with primary, secondary, and concomitant CIS of the bladder. A total of 209 patients diagnosed with CIS between 2010 and 2022 in our department with a minimum follow-up of 12 months were retrospectively analyzed. Patients with muscle-invasive cancer at diagnosis, those with recurrence within one month after diagnosis, and those with primary malignant melanoma were excluded. The recurrence, progression, and cancer-specific mortality rates of patients receiving Bacillus Calmette-Guérin therapy for CIS were analyzed. A total of 96 patients with primary (n = 18), secondary (n = 29), and concomitant CIS (n = 49) were included in the analysis. The median follow-up was 52.2 months. Patients with secondary CIS had a significantly higher recurrence rate than those with concomitant CIS (58.6% vs. 32.7%, p = 0.016). However, no significant difference in progression rates was observed among the three groups. Furthermore, no significant association was observed between CIS subtypes and recurrence-free survival (RFS) (HR = 1.45, 95% CI 0.96-2.46, p = 0.16) or progression-free survival (PFS) (HR = 2.20, 95% CI 0.99-4.87, p = 0.054). Secondary CIS had a significantly higher recurrence rate than concomitant CIS. However, no statistically significant association was observed between CIS subtypes and RFS or PFS.

Animal Models of Vascular Cognitive Disorder after Myocardial Infarction: Scoping Review

Vascular cognitive disorders (VCD) are one of the most common forms of non-psychotic mental disorders with a variable phenotype and rate of progression, transformation into vascular dementia. VCD is characterized by development against the background of existing cardiovascular diseases (CVD), which explains the importance of an interdisciplinary approach to their diagnosis and treatment. The study of new mechanisms of development of VCD can help in finding the key to the development of innovative diagnostic methods and personalized treatment approaches. The purpose of this thematic review is to search, generalize and systematize domestic and foreign research in the field of fundamental neurology using methods of modeling VCD in experimental animals. The authors conducted a search for publications in the databases PubMed, Springer, Web of Science, Clinical Keys, Scopus, Oxford Press, Cochrane, e-Library using keywords and their combinations. The publications for 2005-2024 were analyzed, including original studies of VCD and vascular dementia.

The role of the cytokinin biosynthesis pathways in the rate of tobacco leaf senescence

The regulation of leaf senescence depends on endogenous and exogenous factors, among them phytohormones like cytokinins (CKs). CKs are key players regulating the senescing process, as their endogenous concentration is linked to the onset and rate of senescence progression. Thus, this study aimed to identify the relationship between the activity of endogenous CKs biosynthesis pathways - the cytosolic mevalonate (MVA) and the plastid methyl-erythritol phosphate (MEP) and the rate of leaf senescence. To this end, three distinct tobacco (Nicotiana tabacum L.) cultivars – Xanthi, Golden Virginia and Monte Calme Yellow were analysed. The study involved treatment with exogenous CK – benzyladenine – and two different CK synthesis inhibitors: lovastatin and clomazone. The progression of senescence was induced by light deprivation and monitored with chlorophyll level (SPAD), photosynthetic activity (PAM) and changes in the Rubisco protein profile (SDS-PAGE). Analyses showed that the Xanthi cultivar was characterized by delayed onset of senescence and stay-green phenotype, while Golden Virginia, and particularly Monte Calme Yellow showed rapid leaf senescence. The studies provided valuable information regarding the role of MEP and MVA pathway of CK synthesis in the regulation of tobacco leaf senescence.

Analysis of Baseline Molecular Factors Associated With the Risk of Central Nervous System Progression Among Alectinib-Treated Patients With ALK–Positive NSCLC

IntroductionDespite receiving alectinib therapy, patients with ALK-positive NSCLC remain at risk of central nervous system (CNS) progression. Our retrospective study aimed to identify baseline clinical and molecular factors associated with the risk of CNS progression in this patient subset. MethodsWe analyzed the clinical, molecular, and imaging data of 318 patients with ALK-positive advanced NSCLC who received alectinib as first-line (1L-alectinib) or second-line (2L-alectinib) therapy at baseline (1L, n = 183; 2L, n = 135) and at disease progression (1L, n = 80; 2L, n = 76). ResultsThe incidence rates of CNS progression were 23.7% after 1L-alectinib treatment and 31.6% after 2L-alectinib treatment. Compared with patients who received 1L-alectinib, CNS progression was similar in patients who received 2L-alectinib (p > 0.05). Oligoprogression was detected in 55.0% (44 of 80) of patients who progressed after first-line alectinib, with the remaining 45.0% (36 of 80) having nonoligoprogression. Univariate and multivariate analyses and stepwise regression analyses consistently identified a higher likelihood of CNS progression among (1) patients who received 2L-alectinib than 1L-alectinib, (2) patients with non-3a/b variant ALK fusion than those with echinoderm microtubule-associated protein-like 4–ALK variant 3a/b, and (3) patients with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 50% or higher than PD-L1 TPS of less than 50%. ConclusionsOur study provided real-world evidence that patients who harbored PD-L1 TPS of 50% or higher were more likely to experience CNS progression during alectinib therapy. The association between CNS progression and breakpoint variants warrants further investigation. Our findings suggest that close monitoring and prompt intervention are crucial in prolonging the quality of life of this patient subset.

Nutritional disorders as a predictor of rapid diagnosis and disease progression in patients with amyotrophic lateral sclerosis

Background: One of the symptoms of amyotrophic lateral sclerosis (ALS) is progressive loss of body weight. Moreover, in various forms of ALS, regardless of the presence of dysphagia at the onset of the disease, there are similar changes in nutritional status. The problem of nutritional support in patients with ALS, as well as monitoring nutritional status over time in this group of patients remains relevant. Purpose: to evaluate the severity and rate of increase in nutritional disorders in patients with ALS and their relationship with the rate of disease progression, as well as the life expectancy of these patients. Materials and methods: The study included 49 patients diagnosed with ALS who died from 2018 to 2023. All participants underwent a neurological examination, measurement of anthropometric parameters, and laboratory blood tests; 61 % (n=30) of the patients underwent bioimpedance analysis of body composition over time. Results: The highest rate of body weight loss was recorded in the group of patients with quickly diagnosed ALS: it accounted for 1.9 (1.6; 2.2) kg/month. The highest rate of loss of skeletal muscle mass was noted in the same group of patients at 0.4 (0.38;0.46) kg/month. In the group with a quickly diagnosed disease, only 20 % of the patients underwent gastrostomy insertion; in the group with a slow diagnosis rate, 25 % of the patients underwent gastrostomy; only 50 % of the patients received special therapeutic nutrition. Conclusions: Patients with rapid disease progression have a short period of ALS diagnosis and rapidly increasing nutritional disorders, reflected in higher rates of losing weight and skeletal muscle mass. However, patients with rapid diagnosis of the disease had the lowest level of nutritional support. Lack of time to make the difficult decision to insert a gastrostomy tube and perform the necessary preoperative examination is the main reason for the low rate of gastrostomy tube placement in patients with rapidly progressing disease. In this regard, the development of new measures and algorithms for dynamic monitoring of the nutritional status of patients with ALS, as well as increasing awareness of the need for timely gastrostomy, is required. Bioimpedance analysis of body composition can be one of the methods for monitoring the patient’s nutritional status, allowing one to assess the dynamics of decrease in skeletal muscle mass as the most labile component of body composition in patients with ALS.

The use of a clinical calculator to determine the rate of development of chronic kidney disease in elderly patients with type 2 diabetes mellitus

Aim – to develop an applied prognostic calculator for the rate of progression of CKD in elderly patients with type 2 diabetes, which makes it possible to identify a group of high rate of GFR reduction in conditions of routine outpatient admission. Material and methods. 69 clinical indicators were studied, the interrelationships and significance of differences in parameters in the groups identified according to the original diagnostic parameter, the glomerular filtration rate reduction index with a threshold value of 3.83 ml/min/1.73 m2 per year, above which the rate of progression of CKD was considered high. Results. By using regression analysis, significant factors for the prognostic calculator were identified: the duration of diabetes and insulin therapy, concomitant diagnosis of obesity, pulse in the ankle artery, severe stage of polyneuropathy, risk group IV of hypertension, treatment with sulfonylureas, the number of antihypertensive drugs taken. When evaluating the information capacity and predictive ability of the calculator, the area under the AUC ROC curve was 0.89 (0.80; 0.99) p 0.001, which characterizes the quality of the diagnostic technique as high. Conclusion. The presented calculator gives the doctor the opportunity to identify a group of patients with the risk of rapid progression of CKD directly on an outpatient basis.

Assessing potato cultivars for resistance against late blight under high altitudinal conditions of North Western Himalayas

Different stages in plant development significantly influence the incidence of potato late blight disease in India. In the present study, the disease progression was monitored weekly in five selected potato cultivars viz. Kufri Jyoti, Kufri Giriraj, Gulmarg Special, Shalimar Potato-I, and Gurez local, during the 2018 and 2019 cropping seasons. The severity of potato late blight, caused by Phytophthora infestans, increased with fluctuations in weather variables. Calculations for the area under the disease progress curve (AUDPC) and the rate of disease spread (r-value) at different growth stages of potatoes were used to track disease progression. Notably, the Kufri Jyoti cultivar demonstrated resistance compared to the other cultivars, with lower severity values and susceptibility scale values (48.40%; 5.6 and 4.9) in 2018 and 2019, respectively. The average rate of disease progress was also lower in Kufri Jyoti (0.064 and 0.060) compared to the local cultivar (0.076 and 0.074) in 2018 and 2019, respectively. These observations indicate that weather parameters have a strong positive impact on the incidence of potato late blight.

Assessing Bronchiectasis Progression in Low-dose Screening for Lung Cancer: Frequency and Predictors.

Bronchiectasis is associated with loss of lung function, substantial use of health care resources, and increased morbidity and mortality in people with cardiopulmonary diseases. We assessed the frequency of progression or new development of bronchiectasis and predictors of progression in participants in low-dose computed tomography (CT) screening programs. We reviewed our prospectively enrolled screening cohort in the Early Lung and Cardiac Action Program cohort of smokers, aged 40 to 90, between 2010 and 2019, and medical records to assess the progression of bronchiectasis after five or more years of follow-up after baseline low-dose CT. Logistic and multivariate-analysis-of-covariance regression analyses were used to examine factors associated with bronchiectasis progression. Among 2182 baseline screening participants, we identified 534 (mean age: 65±9y; 53.6% women) with follow-up screening of 5+ years (median follow-up: 103.2mo). Of the 534 participants, 34 (6.4%) participants had progressed (25/126, 19.8%) or newly developed (9/408, 2.2%) bronchiectasis. Significant predictors of progression (progressed+newly developed) were: age (P=0.03), pack-years of smoking (P=0.004), baseline components of the ELCAP Bronchiectasis Score, including the severity of bronchial dilatation (P=0.01), its extent (P=0.01), bronchial wall thickening (P=0.04), and mucoid impaction (P<0.001). Assuming similar progression rates, ~136 out of 2182 participants are expected to progress on follow-up screening. This study sheds light on bronchiectasis progression and its significant predictors in a low-dose CT screening program. We recommend reporting bronchiectasis as participants who have smoked are at increased risk, and continued assessment over the entire period of participation in the low-dose CT screening program would allow for the identification of possible causes, early warning, and even early treatment.

Surgical management and outcomes of T4a papillary thyroid carcinoma: a single-centre study of 602 cases.

This study aimed to investigate the clinical characteristics and risk factors associated with the disease progression of T4a papillary thyroid carcinoma (PTC). In all, 602 patients (230 males; 372 females), aged 8-82 years, with T4a PTC who were admitted for initial surgery between April 2010 and September 2022 were retrospectively analysed. Tracheal invasion was observed in 271 (45.0%), oesophageal invasion in 190 (31.6%), recurrent laryngeal nerve (RLN) invasion in 516 (85.7%), and larynx invasion in 22 (3.7%) patients. The 5-year progression-free survival was 89.8%, and disease-specific survival was 96.0%, with a postoperative disease progression rate of 9.6% (54 patients) and mortality rate of 5.17% (29 patients). Disease recurrence was most likely to occur at the initial surgical site. Age ≥55 years, preoperative vocal cord paralysis, microvascular invasion, trachea invasion, and metastases to >5 cervical lymph nodes were independent risk factors for disease progression in patients with M0 stage. Male sex, preoperative vocal cord paralysis, microvascular invasion, specific pathological type, and laryngeal invasion were associated with an increased risk of disease progression for all T4a patients, while lobectomy, total thyroidectomy, tumour shaving on the RLN surface, total RLN resection, and absence of radioactive iodine therapy were not. Surgery was the primary treatment for patients with stage T4a PTC and most patients had a satisfactory prognosis. Surgeons should comprehensively evaluate each patient before deciding the surgical approach.

Descriptive study showing the effect of small differences in entry scores on retention and success in six courses in nursing

BackgroundUndergraduate enrolments and completions in nursing are declining at the same time as requirements for registered nurses in the workforce is increasing. One way to increase enrolments is to lower entry requirements into nursing programs. This study determined the effect of a small lowering of entry scores on the retention and success rates. The study was undertaken at Griffith University, where identical bioscience and clinical courses run at three campuses, one with a lower- than normal-entry score and two with the normal-entry requirements.MethodsA comparison of the 62–148 students enrolled in the courses at the lower- than normal- (lesser) entry requiring campus with the 197–288 students enrolled in the courses in one normal-entry requiring campuses. For individual courses (4 bioscience and 2 clinical courses) retention rates were measured and compared between campuses/cohorts. For completing students, we measured success as (i) Academic outcomes; overall marks and marks for the exam and coursework and (ii) Failure rates in the examination and coursework. Data analysis was by Student’s t-test and Odds ratio.ResultsFor all courses, there were few significant differences in measures of retention and success between the lower- and normal-entry campuses, and all differences were small.Comparing the campuses; (a) For all courses, progression rates were similar. (b) For completing students, passing rates were similar in the bioscience courses, but higher in the normal- than lower-entry campus for the clinical courses. (c) In the bioscience courses, the overall marks were similar, but in the clinical courses, the overall mark was slightly higher in the normal- than lower-entry campus. (d) The overall failure rates were similar for the biosciences, but higher for the lower- than normal-entry cohort in the clinical courses. (e) The failure rates in exams were similar between cohorts in all courses.ConclusionsThis study shows that small changes in entry requirements for a nursing program had minimal effects on retention. The differences in entry requirements also did not affect the success of students in the bioscience courses. Decreasing entry requirement for nursing programs may be a way to increase nursing graduates.

Medical costs in the peridiagnosis period of various biopsy-confirmed kidney diseases in South Korea.

In-depth investigation is imperative to scrutinize medical costs associated with the periods before and after biopsies for diverse kidney diseases in South Korea. Long-term epidemiological data, including follow-up information, is essential for comparing risks linked to various kidney diseases and their adverse outcomes. Patients diagnosed with glomerulonephritis (GN), tubulointerstitial nephritis (TIN), and acute tubular necrosis (ATN) at Seoul National University Hospital between 2012 and 2018 were included. We linked the prospective cohort data of biopsy-confirmed kidney disease patients (KORNERSTONE) from our study hospital to the national claims database of Korea, covering both medical events and insured costs. We analyzed medical costs during the periods before and after kidney biopsies, categorized by specific diagnoses, and delved into adverse prognostic outcomes. Our study involved 1,390 patients with biopsy-confirmed GN, TIN, and ATN. After diagnosis, monthly average medical costs increased for most kidney diseases, excluding membranous nephropathy, Henoch-Schönlein purpura, and amyloidosis. The most substantial yearly average medical cost increase was observed in the ATN, acute TIN (ATIN), and chronic TIN (CTIN) groups. Costs rose for most kidney disease categories, except for amyloidosis. Higher myocardial infarction, stroke, and death rates were noted in CTIN, ATIN, and ATN compared to other types, with lupus nephritis displaying the highest end-stage kidney disease progression rate. In South Korea, medical costs for the majority of GN, TIN, and ATN patients increased following kidney biopsy diagnosis. This current data provides valuable epidemiological insights into the medical costs and prognosis of various kidney diseases in the country.

GPR37 processing in neurodegeneration: a potential marker for Parkinson’s Disease progression rate

The orphan G protein-coupled receptor 37 (GPR37), widely associated with Parkinson’s disease (PD), undergoes proteolytic processing under physiological conditions. The N-terminus domain is proteolyzed by a disintegrin and metalloproteinase 10 (ADAM-10), which generates various membrane receptor forms and ectodomain shedding (ecto-GPR37) in the extracellular environment. We investigated the processing and density of GPR37 in several neurodegenerative conditions, including Lewy body disease (LBD), multiple system atrophy (MSA), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and Alzheimer’s disease (AD). The presence of ecto-GPR37 peptides in the cerebrospinal fluid (CSF) of PD, MSA, CBD and PSP patients was assessed through an in-house nanoluciferase-based immunoassay. This study identified increased receptor processing in early-stage LBD within the PFC and striatum, key brain areas in neurodegeneration. In MSA only the 52 kDa form of GPR37 appeared in the striatum. This form was also significantly elevated in the striatum of AD necropsies. On the contrary, GPR37 processing remained unchanged in the brains of CBD and PSP patients. Furthermore, while CSF ecto-GPR37 increased in PD patients, its levels remained unchanged in MSA, CBD, and PSP subjects. Importantly, patients with PD with rapid progression of the disease did not have elevated ecto-GPR37 in the CSF, while those with slow progression showed a significant increase, suggesting a possible prognostic use of ecto-GPR37 in PD. This research underscores the distinctive processing and density patterns of GPR37 in neurodegenerative diseases, providing crucial insights into its potential role as an indicator of PD progression rates.

Association of mean platelet volume (MPV), MPV/PLATELET (PLT) ratio, and lymphocyte/monocyte ratio (LMR) as poor prognostic factor in EGFR-mutant lung adenocarcinoma treated with EGFR tyrosine kinase inhibitor.

Platelets (PLT) and host systemic inflammatory response (SIR) are known to be effective in the aggregation of cancer cells and the formation of metastasis. There are studies pointing out to the prognostic efficacy of lymphocyte-monocyte ratio (LMR) showing SIR activation and mean platelet volume (MPV) values indicating platelet activation in various cancer types. We predict that easy-to-access hemogram parameters such as MPV, MPV/PLT, and LMR can be guiding in the clinical follow-up period of patients with epidermal growth factor receptor (EGFR) positive mutation and who received EGFR, tyrosine kinase inhibitor (TKI) in the first-line treatment in predicting the progression of the disease, predicting the survival time of the patients, and evaluating the response to treatment. The study is retrospective and included patients with stage III and stage IV pulmonary adenocarcinoma with positive EGFR mutations and for whom TKI was used in the first-line treatment between January 2011 and January 2021. MPV, MPV/PLT, and LMR values of the patients were calculated before treatment. Age, sex, comorbidity, smoking history, TNM stage, metastasis localizations, EGFR mutation types, TKI treatments used in first-line treatment, and MPV, MPV/PLT, and LMR values at the 1st month of treatment were recorded. With Kaplan-Meier, six-month, one-year, three-year, and five-year survival rates, average life expectancy, and 95% confidence intervals for these periods were calculated. Variables that may affect progression and overall survival (OS) were determined by performing univariate and multivariate Cox regression analysis. One hundred and two patients were included in the study. The mean age of the patients was 64.30 ± 12.6 years. Eighty-four patients were in stage IV at the time of diagnosis. The expected mean progression-free survival (PFS) period of the cases was found to be 13.3 months. The mean life expectancy of the cases was found to be 35.1 months. Web-based Cutoff Finder algorithm written in the R program (http://molpath.charite.de/cutoff) was used to determine the ideal cut points for MPV, MPV/PLT, and LMR. The cut-off values were found to be 7.55 fL for MPV, 0.251 for MPV/PLT, and 2.615 for LMR, respectively. In univariate Cox regression analysis, LMR level lower than 2.615 increased the rate of progression 1.747 times (95% confidence interval: 1.129-2.705) and the death rate 2.056 times (95% confidence interval: 1.217-3.475) (p= 0.012, p= 0.007). The mean PFS LMR cut-off value was 10.3 months, and 15.3 months, and mean OS durations were 25.1 months and 40.8 months for the groups with low and high cut-off values respectively (p= 0.011, p= 0.006 log-rank test). According to the results of multivariate Cox regression analysis, MPV/PLT < 0.251, smoking, presence of pleural and adrenal metastases, and gefitinib treatment were independent factors in determining PFS. The independent factors determining OS in multivariate Cox regression analysis were being male, platelet increase, MPV > 7.55, gefitinib treatment, and smoking. MPV, MPV/PLT, and LMR are potential biomarkers that can be used for the clinical follow-up of lung ADC patients receiving EGFR-TKI treatment.

Time wears on everyone, but not equally quickly

In 30 patients (average age 38 ± 8 years, 77% male, 23% female) with intra-oral scans made at intake and after 3 years, tooth wear progression was measured. With the aid of GeoMagic to superimpose the scans, the maximum difference in height of 64 surfaces was measured per surface. A large variation was found in progression rates between patients, between various teeth in a single mouth, and between surfaces on a single tooth. Tooth wear progression rates are therefore highly individual and can even be very localized. Treatment must therefore be individualized, with an essential role for measuring tooth wear when deciding on the need for restorative treatment.

Plasma NfL, GFAP, amyloid, and p-tau species as Prognostic biomarkers in Parkinson’s disease

IntroductionThe prognostic role of plasma neurofilament light chain (NfL), phospho-tau, beta-amyloid, and GFAP is still debated in Parkinson’s disease (PD).MethodsPlasma p-tau181, p-tau231, Aβ1-40, Aβ1-42, GFAP, and NfL were measured by SIMOA in 136 PD with 2.9 + 1.7 years of follow-up and 76 controls. Differences in plasma levels between controls and PD and their correlation with clinical severity and progression rates were evaluated using linear regression analyses.ResultsPatients exhibited similar distribution of plasma biomarkers but higher P-tau181, P-tau231 and lower Aβ1-42 compared with controls. NfL and GFAP correlated with baseline motor and non-motor severity measures. At follow-up, NfL emerged as the best predictor of progression with marginal effect of GFAP and p-tau181 adjusting for age, sex, disease duration, and baseline motor severity.ConclusionThe present findings confirmed plasma NfL as best predictor of progression in PD, with a marginal role of p-tau181 and GFAP.

C4d Is an Independent Predictor of the Kidney Failure in Primary IgA Nephropathy.

Background: C4d deposits are present in a substantial proportion of patients with IgA nephropathy (IgAN), indicating the activation of the lectin pathway (LP) of the complement system. It seems that patients with activated LP have worse renal prognosis. The aim of this study was to investigate the prevalence and prognostic significance of C4d in our cohort of patients with primary IgA nephropathy (pIgAN). Methods: Patients with pIgAN were recruited from a hospital register of kidney biopsies of the Department of Nephrology and Dialysis, Dubrava University Hospital, Zagreb. Additional immunohistochemistry staining for C4d was performed on paraffin-embedded kidney tissue, and patients were stratified into being C4d positive or C4d negative. The clinical and histologic features of patients were analyzed and compared regarding C4d positivity. The primary outcome was defined as kidney failure (KF), and predictor variables of KF and renal survival were analyzed. Results: Of a total of 95 patients with pIgAN included in the study, C4d was present in 43 (45.3%). C4d-positive patients had a higher value of systolic (p = 0.039) and diastolic (p = 0.006) blood pressure at diagnosis as well as higher 24 h proteinuria (p = 0.018), serum urate (p = 0.033), and lower eGFR (p < 0.001). C4d-positive patients had worse renal survival (p < 0.001), higher rates of disease progression to KF (p < 0.001), and higher proteinuria (p < 0.001) and lower eGFR (p < 0.001) at the last follow-up. Glomerular C4d was an independent predictor of disease progression to KF (HR = 5.87 [0.95 CI 1.06-32.44], p = 0.032). Conclusions: C4d is an independent predictor of disease progression in patients with pIgAN. C4d may be used as an additional marker of progressive disease course in IgAN. The therapeutic implications of C4d status in IgAN, particularly in terms of complement inhibitors application, are not yet known.

MOY 2 - ‘Cachexia Index’ for Prognostication in Surgical Patients with Locally Advanced Oesophageal or Gastric Cancer: A Multicentre Cohort Study

Abstract Background Features of cancer cachexia are known to adversely influence patient outcomes, yet few currently inform clinical decision-making. This study assessed the value of ‘cachexia index’ (CXI), a novel prognostic marker, in patients planned for curative multimodal therapy (neoadjuvant chemotherapy (NAC) and surgery) for oesophagogastric cancer. Methods Consecutive patients newly diagnosed with locally advanced (T3/4 or ≥N1) oesophagogastric cancer were identified through the West of Scotland and South-East Scotland Cancer Networks. CXI was calculated as (L3 skeletal muscle index) x (serum albumin) / (neutrophil-lymphocyte-ratio). Sex-stratified cut-off values were determined based on area under the curve (AUC), and patients were divided into low and normal CXI groups. Primary outcomes of interest were disease progression during NAC and overall survival (≥5-years follow-up). Results Overall, 385 patients (72% male, median 66 years) were treated with NAC for oesophageal (n=274) or gastric (n=111) cancer across the study period. While patients with a low CXI (males: &amp;lt;52 [AUC: 0.691] and females: &amp;lt;41 [AUC: 0.759]) were older and more comorbid, disease characteristics were comparable to those with a normal CXI. Rates of disease progression during neoadjuvant chemotherapy, leading to inoperability, were higher in patients with low CXI (28% vs. 12%, aOR: 3.07 (95% CI: 1.67-5.64), p&amp;lt;0.001). Moreover, low CXI was associated with worsened post-operative mortality (p=0.019) and decreased overall survival (median: 14.9 vs. 56.9 months, aHR: 1.85 (95% CI: 1.42-2.42), p&amp;lt;0.001). Conclusion CXI represents a valuable marker of ‘host stage’, and a potential adjunct to routine tumour staging. This could improve prognostication and decision-making in patients with locally advanced oesophagogastric cancer.

The causal relationship between CSF metabolites and GBM: a two-sample mendelian randomization analysis

BackgroundGlioblastoma multiforme (GBM) is a highly aggressive primary malignant brain tumor characterized by rapid progression, poor prognosis, and high mortality rates. Understanding the relationship between cerebrospinal fluid (CSF) metabolites and GBM is crucial for identifying potential biomarkers and pathways involved in the pathogenesis of this devastating disease.MethodsIn this study, Mendelian randomization (MR) analysis was employed to investigate the causal relationship between 338 CSF metabolites and GBM. The data for metabolites were obtained from a genome-wide association study summary dataset based on 291 individuals, and the GBM data was derived from FinnGen included 91 cases and 174,006 controls of European descent. The Inverse Variance Weighted method was utilized to estimate the causal effects. Supplementary comprehensive assessments of causal effects between CSF metabolites and GBM were conducted using MR-Egger regression, Weighted Median, Simple Mode, and Weighted Mode methods. Additionally, tests for heterogeneity and pleiotropy were performed.ResultsThrough MR analysis, a total of 12 identified metabolites and 2 with unknown chemical properties were found to have a causal relationship with GBM. 1-palmitoyl-2-stearoyl-gpc (16:0/18:0), 7-alpha-hydroxy-3-oxo-4-cholestenoate, Alpha-tocopherol, Behenoyl sphingomyelin (d18:1/22:0), Cysteinylglycine, Maleate, Uracil, Valine, X-12,101, X-12,104 and Butyrate (4:0) are associated with an increased risk of GBM. N1-methylinosine, Stachydrine and Succinylcarnitine (c4-dc) are associated with decreased GBM risk.ConclusionIn conclusion, this study sheds light on the intricate interplay between CSF metabolites and GBM, offering novel perspectives on disease mechanisms and potential treatment avenues. By elucidating the role of CSF metabolites in GBM pathogenesis, this research contributes to the advancement of diagnostic capabilities and targeted therapeutic interventions for this aggressive brain tumor. Further exploration of these findings may lead to improved management strategies and better outcomes for patients with GBM.

Onset and progression of dental erosion in a mouse model.

Purpose of this research was to examine the onset, progression and wear rates of dental erosion in an established mouse model. Dental erosion in mice was experimentally induced, and the acidic effects of cola drink on their teeth after 2, 4 and 6-weeks were closely analysed by scanning electron microscopy. The tooth height and enamel or dentin loss were established. Results: The dental erosion on the molars showed clear progression from 2 to 6 weeks. By the 2-week mark, a significant portion of enamel was already eroded, revealing the dentin on the lingual cusps. When adjusted for attritional wear, molars exposed to cola for 2 weeks showed a 35% drop in lingual tooth height compared to controls (533 μm vs. 818 μm). At 4 and 6 weeks, the cola-exposed group continued to display decreased lingual tooth heights by 40% (476 μm vs. 799 μm) and 43% (440 μm vs. 767 μm), respectively. This study revealed significant acidic effects of cola drink on mouse molars as early as 2 weeks. These findings highlight the challenge of monitoring dental erosion clinically and underscore the importance of early preventive and intervention measures.