Urinary Soluble CD163 Levels Predict IgA Nephropathy Remission Status

Noninvasive biomarkers of disease activity are needed to predict disease remission status in patients with IgA nephropathy (IgAN). Soluble CD163 (sCD163), shed by monocytes and macrophages, is a potential biomarker in diseases associated with excessive macrophage activation. We investigated the association of urinary sCD163 (u-sCD163) with histopathological activity and clinical manifestations in 349 patients with biopsy-diagnosed IgAN. U-sCD163 was measured via enzyme-linked immunosorbent assay. In patients with IgAN, higher u-sCD163 levels were associated with histological lesions of greater severity, as well as more proteinuria and poorer renal function. Additionally, u-sCD163 was correlated with infiltration of tubulointerstitial CD163+ macrophages. High u-sCD163 levels (>3.57 ng/mg Cr) were associated with a 2.66-fold greater risk for IgAN remission failure in adjusted analyses. Adding u-sCD163 levels to the model containing clinical data at biopsy and MEST-C score significantly improved the risk prediction of IgAN remission status (AUC 0.788). Together, our results suggest that u-sCD163 may be a useful noninvasive biomarker to evaluate disease severity and remission status of IgAN.

Suppressed activity of the rostral anterior cingulate cortex as a biomarker for depression remission

Background Suppression of the rostral anterior cingulate cortex (rACC) has shown promise as a prognostic biomarker for depression. We aimed to use machine learning to characterise its ability to predict depression remission. Methods Data were obtained from 81 15- to 25-year-olds with a major depressive disorder who had participated in the YoDA-C trial, in which they had been randomised to receive cognitive behavioural therapy plus either fluoxetine or placebo. Prior to commencing treatment patients performed a functional magnetic resonance imaging (fMRI) task to assess rACC suppression. Support vector machines were trained on the fMRI data using nested cross-validation, and were similarly trained on clinical data. We further tested our fMRI model on data from the YoDA-A trial, in which participants had completed the same fMRI paradigm. Results Thirty-six of 81 (44%) participants in the YoDA-C trial achieved remission. Our fMRI model was able to predict remission status (AUC = 0.777 [95% confidence interval (CI) 0.638–0.916], balanced accuracy = 67%, negative predictive value = 74%, p < 0.0001). Clinical models failed to predict remission status at better than chance levels. Testing the model on the alternative YoDA-A dataset confirmed its ability to predict remission (AUC = 0.776, balanced accuracy = 64%, negative predictive value = 70%, p < 0.0001). Conclusions We confirm that rACC activity acts as a prognostic biomarker for depression. The machine learning model can identify patients who are likely to have difficult-to-treat depression, which might direct the earlier provision of enhanced support and more intensive therapies.

Role of the Gut in the Temporal Changes of β-Cell Function After Gastric Bypass in Individuals With and Without Diabetes Remission

<i>Objective</i>: The role of the gut in diabetes remission after gastric bypass (RYGB) is incompletely understood. We therefore assessed the temporal change in insulin secretory capacity after RYGB, using oral and intravenous (IV) glucose, in individuals with type 2 diabetes. <p><i>Research Design and Methods:</i> Longitudinal, prospective measures of β-cell function after oral glucose and IV graded glucose infusion in individuals with severe obesity and diabetes studied at 0, 3 (n=29), 12 (n=24) and 24 (n=20) months after RYGB. Data were collected between 2015 and 2019 in an academic clinical research center.</p> <p><i>Results</i>: The decreases in body weight, fat mass, waist circumference and insulin resistance after surgery (all p<0.001 at 12 and 24 months), did not differ according to diabetes remission status. In contrast, both the magnitude and temporal changes in β-cell glucose sensitivity after oral glucose differed by remission status (p=0.04): greater (6.5 fold, p<0.01) and sustained in full remitters, moderate and not sustained past 12 months in partial remitters (3.3 fold, p<0.001), minimal in non-remitters (2.7 fold, p=ns). The improvement in β-cell function after IV glucose was not apparent until 12 months, significant only in full remitters, and only ~1/3 of that observed after oral glucose.</p> <p>Pre-intervention β-cell function and its change after surgery predicted remission; weight loss and insulin sensitivity did not. </p> <p><i>Conclusion</i>: Our data show the time course of changes in β-cell function after RYGB. The improvement in β-cell function after RYGB, but not changes in weight loss or insulin sensitivity, drives diabetes remission.</p>

Role of the Gut in the Temporal Changes of β-Cell Function After Gastric Bypass in Individuals With and Without Diabetes Remission

<i>Objective</i>: The role of the gut in diabetes remission after gastric bypass (RYGB) is incompletely understood. We therefore assessed the temporal change in insulin secretory capacity after RYGB, using oral and intravenous (IV) glucose, in individuals with type 2 diabetes. <p><i>Research Design and Methods:</i> Longitudinal, prospective measures of β-cell function after oral glucose and IV graded glucose infusion in individuals with severe obesity and diabetes studied at 0, 3 (n=29), 12 (n=24) and 24 (n=20) months after RYGB. Data were collected between 2015 and 2019 in an academic clinical research center.</p> <p><i>Results</i>: The decreases in body weight, fat mass, waist circumference and insulin resistance after surgery (all p<0.001 at 12 and 24 months), did not differ according to diabetes remission status. In contrast, both the magnitude and temporal changes in β-cell glucose sensitivity after oral glucose differed by remission status (p=0.04): greater (6.5 fold, p<0.01) and sustained in full remitters, moderate and not sustained past 12 months in partial remitters (3.3 fold, p<0.001), minimal in non-remitters (2.7 fold, p=ns). The improvement in β-cell function after IV glucose was not apparent until 12 months, significant only in full remitters, and only ~1/3 of that observed after oral glucose.</p> <p>Pre-intervention β-cell function and its change after surgery predicted remission; weight loss and insulin sensitivity did not. </p> <p><i>Conclusion</i>: Our data show the time course of changes in β-cell function after RYGB. The improvement in β-cell function after RYGB, but not changes in weight loss or insulin sensitivity, drives diabetes remission.</p>

Autologous Haematopoietic Stem Cell Transplantation in Waldenström Macroglobulinemia: A Single-Centre 18-Year Experience

BACKGROUND The role of autologous stem cell transplantation (ASCT) in Waldenström Macroglobulinaemia (WM) is not well established, largely due to the paucity of evidence. It remains unclear where ASCT should be placed in the sequence of treatment lines. The debate is stronger in the era of targeted therapies that can achieve prolonged progression free survival (PFS) intervals and expected treatment-free intervals of approximately 4 to 8 years. The goal of this real world analysis was to review response and survival outcomes, and relapse risk factors in WM patients who underwent ASCT in a single WM referral centre. METHODS A retrospective cohort analysis was undertaken of consecutive WM patients treated with ASCT at a single specialist centre between 2003 and 2020. Baseline demographic/biological data, number/types of prior therapies, and pre- and post-ASCT depth of response, were collected from patient records and the WMUK Rory Morrison Registry. The primary aims were to determine depth of response, overall survival (OS), progression free survival (PFS), transplant related mortality (TRM) and relapse-associated mortality. RESULTS A total of 32 patients received ASCT, with a median age at time of ASCT of 57 years (range 40-68 years) and median interval from diagnosis to ASCT of 2.3 years (range 0.5-16.8 years); 14 (43.7%) were male. Prior to ASCT, 11 patients (34%) had received one therapy, 11 patients had 2 lines of treatment (excluding mobilisation), and 10 patients (31%) had received 3 or more therapies. The disease status pre-ASCT was complete remission (CR)/very good partial response (VGPR) in 14 patients (43.7%) and partial response (PR) in 18 patients (56.2%). Conditioning therapy comprised LEAM (Lomustine, Etoposide, Cytarabine, Melphalan; 18 patients, 56.2%), BEAM (Carmustine substituted for Lomustine; 12 patients, 37.5%), or Melphalan only (2, 6.2%). All patients had successful engraftment. Median time from stem cell reinfusion to hospital discharge was 15.5 days (range 13-187 days) in the 24 patients for whom these data were available; 5/24 patients (21%) were discharged &gt;25 days after stem cell reinfusion. Restaging at 100 days post-ASCT showed deepening of response by ASCT in 17 patients (53.1%). CR/VGPR was achieved by 26 patients (81.2%) and PR by 4 patients (12.5%). Two patients (6.2%) experienced disease progression before day 100 post-ASCT (both receiving ASCT in second remission/PR2). At a median follow up of 8.9 years (range 0.1-18 years), the estimated median PFS was 4.5 years (95% confidence interval [CI] 3.2-5.7 years), with estimated 2-year and 5-year PFS rates of 75% and 35.9%, respectively (Figure 1A). In this small cohort, there was no significant difference in PFS based on age, number of prior lines of treatment, pre-ASCT remission status (CR/VGPR vs PR) or post-ASCT response achieved. At time of analysis, 14/32 patients (43.7%) had died: TRM rate was 6.2% (2 patients died during inpatient admission of ASCT complications), 4 patients (12.5%) died of PD, and 1 patient died of unknown causes. Another 7 patients (21.9%) died of infective causes after the immediate post-ASCT period: the median time from ASCT to death among these patients was 5.5 years (range 0.8-10.8 years). Estimated median OS for the unstratified cohort was 10.8 years (95% CI 7.3-14.3 years), with estimated 2- and 5-year OS rates of 87.5% and 77.5%, respectively (Figure 1B). Overall survival did not differ significantly based on age at time of ASCT, number of therapy lines prior to ASCT, pre-ASCT remission status (CR/VGPR vs PR) or post-ASCT response achieved. One patient (3.1%) underwent ASCT after BTK inhibitor therapy, achieving deepening of response (PR to VGPR) with ASCT and progression free interval of 11 months. CONCLUSION ASCT is a feasible treatment option for patients with relapsed WM, producing deeper responses following salvage therapy and resulting in PFS intervals comparable to other currently available therapeutic options. With the benefit of a long follow up period, performing ASCT at later stages in the treatment course (i.e. following 3 or more prior therapy lines) did not appear to result in inferior survival outcomes; timing of ASCT should therefore be considered on an individual patient basis and in light of other available therapy options for relapsed disease. Figure 1 Figure 1. Disclosures Yong: Sanofi: Honoraria, Research Funding; GSK: Honoraria; Amgen: Honoraria; Autolus: Research Funding; BMS: Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria. Wechalekar: Amgen: Research Funding; Alexion, AstraZeneca Rare Disease: Consultancy; Caelum Biosciences: Other: Clinical Trial Funding; Takeda: Honoraria; Celgene: Honoraria; Janssen: Consultancy. D'Sa: Sanofi: Honoraria; Janssen Cilag: Honoraria, Research Funding; BeiGene: Honoraria, Research Funding.

Daily dynamics of negative affect: indicators of rate of response to treatment and remission from depression?

More instability (MSSD) and variability (SD) of negative affect (NA) have been related to current and future depressive symptoms. We investigated whether MSSD and SD of NA were predictive of the rate of symptom improvement during treatment and of reaching remission status. Forty-six individuals with major depressive disorder completed six days of ecological momentary assessments (10 beeps per day) before starting a combination of pharmacotherapy and supportive therapy. During and after treatment, the Hamilton Depression Rating Scale (HDRS) diagnostic interview was performed monthly for 18 months. Using multilevel modeling and logistic regression, a linear decrease in HDRS scores as well as reaching remission status (HDRS of ≤7 within or after five months) were predicted by the mean, SD and MSSD of NA in momentary assessments, and relevant baseline predictors. Mean NA, but not the SD or MSSD of NA, predicted rates of depressive symptom reduction over five months. The odds of remitting during treatment were not associated with any predictors. Our results suggest that pre-treatment assessments of NA instability and variability may not give an indication of the treatment response over time. Clinically, the mean of NA may be more promising as a baseline indicator of response potential.

Assessment of the prognostic impact of serum level of soluble cluster of differentiation (sCD155) in newly diagnosed Low grade cell Non Hodgjen Lymphoma in Adult Egyptian patients

Background CD155-dependent signals not only influenced net tumor growth but also responsiveness to immune checkpoint therapies. Thus, blocking CD155 could be a rational strategy to improve current immunotherapeutic Aim of the work To assess CD155 in newly diagnosed Low grade B non Hodgkin Lymphomas as prognostic marker for remission Patients and methods CD 155 measured by Ellisa at the time of diagnosis of 50 patients newly diagnosed low grade B non Hodgjen Lymphomas and the remission status followed up prospectively at 3 and 6 months in hematology unit at Ain Shams University Hospital Results there were high statistically significant difference between CD155 level and cytogenetic risk and Eligibility for auto transplantation, there were statistically significant difference between CD155 level and B symptoms, there were high statistically significant difference between CD155 level and Radiology stage, BM infiltation, protocol after 3months, There were high statistically significant difference between CD155 level and Radiology stage, BM infiltration, CBC after 6 months There were high statistically significant difference between CD155 level and non Remission and CD155 had Sensitivity88.46% and Specificity75% as poor predictor of remission Conclusion The CD155 level is prognostic factors for remission in Low grade B non Hodgkin Lymphomas as high CD155 level is poor prognostic factors for response and remission with Sensitivity 88.46%and Specificity75. %

The role of autologous stem cell transplantation (ASCT) in aggressive B-cell lymphomas: real-world data from a retrospective single-center analysis

Patients with high-risk or relapsed aggressive B-cell lymphomas are characterized by poor prognosis. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) can induce durable remissions in these patients and is potentially curative. Two hundred forty-seven patients with aggressive B-cell lymphomas treated with high-dose chemotherapy and ASCT, either as consolidation after first-line therapy or after salvage therapy for relapsed disease, between 2002 and 2019 at the University Hospital Muenster, were analyzed. The median follow-up of surviving patients was 36 months (range 0–163). Progression-free survival (PFS) and overall survival (OS) after 3 years was 63% and 68%, respectively. After ASCT, 28% of all patients experienced a relapse. The cumulative incidence of non-relapse mortality at day 100 after ASCT was 4%. Multivariate analysis identified remission status at ASCT, age at ASCT, and the numbers of infused CD34+ cells as independent prognostic factors for both PFS and OS. Patients with mantle cell lymphoma (MCL) or primary CNS lymphoma (PCNSL) treated with ASCT in first-line had a superior OS and PFS when compared to patients treated with ASCT in relapsed disease. For patients with diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL), early relapse (< 12 months) after first-line therapy showed a trend towards an inferior PFS and OS. Deaths after ASCT were predominantly caused by lymphoma relapse and/or progression (64%) or due to infections (23%). In conclusion, high-dose chemotherapy followed by ASCT in the era of novel targeted agents remains a feasible and effective approach for patients with high-risk or relapsed aggressive B-cell lymphomas. Remission status and age at ASCT, and the number of infused stem cells were of prognostic relevance.