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Blood Advances Oct 2019Rapid remission by induction therapy has long been recognized as an important predictor for long-time survival in acute leukemia. However, the impact of response... (Review)
Review
Rapid remission by induction therapy has long been recognized as an important predictor for long-time survival in acute leukemia. However, the impact of response kinetics on multiple myeloma (MM) seems to be different and remains unexplored. The relationship between response kinetics and outcome were assessed in 626 patients with newly diagnosed MM who were included in a prospective, nonrandomized clinical trial (BDH 2008/02). Patients were assigned to either immunomodulatory drug- or proteasome inhibitor-based therapy. The response depth, time to best response (T) and duration of best response (D) were collected. Depth of response was associated with superior outcomes, consistent with findings from other studies. However, the early responders (defined as T ≤3 months) showed significantly worse survival compared with late responders. We found that patients with rapid complete remission experienced inferior survivals comparable to those attaining a gradual partial remission. Moreover, 4 distinct response kinetics patterns were identified. Patients with gradual and sustained remission ("U-valley" pattern) experienced superior outcomes, whereas poor outcomes were observed in rapid and transient responders ("roller coaster" pattern) (median overall survival, 126 vs 30 months). The effects of response patterns on survival were confirmed in patients at different stages of disease and cytogenetic risk, including transplant-eligible patients and those attaining different extents of response depth. Collectively, our data indicated that slow and gradual response is a favorable prognostic factor in MM. In addition to response depth, the kinetic pattern of response is a simple and powerful predictor for survival even in the era of novel agents.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Multiple Myeloma
PubMed: 31594763
DOI: 10.1182/bloodadvances.2019000432 -
Therapeutic Advances in Endocrinology... 2023To evaluate the residual effect of partial remission (PR) on immediate post-PR glycemic control according to its occurrence and duration in a cohort of children with...
OBJECTIVE
To evaluate the residual effect of partial remission (PR) on immediate post-PR glycemic control according to its occurrence and duration in a cohort of children with type 1 diabetes mellitus (T1DM).
PATIENTS AND METHODS
Values of glycemic control parameters [i.e. HbA, insulin dose-adjusted hemoglobin A (IDAA), glycemic target-adjusted HbA (GTAA)] and data from glucose monitoring devices from 189 pediatric patients with new-onset type 1 diabetes were collected retrospectively from 24 months. Patients were characterized according to their remission status (PR and PR). PR patients were subdivided into three subgroups regarding PR duration [i.e. short (⩾3-⩽6 months), intermediate (>6-⩽12 months), and long PR (>12-⩽14 months)]. We compared glycemic control data from each PR subgroup at +6 and +12 months post-PR with PR patients at the same postdiagnosis time. Second, PR subgroups were compared with each other.
RESULTS
PR patients showed improved glycemic control (i.e. HbA, IDAA, and GTAA) at + 6 months post-PR when compared with nonremitters (PR), independently of the PR duration subgroups (p < 0.05). Interestingly, patients in long PR subgroup exhibited higher positive residual effect than short PR subgroup with lower GTAA scores (p = 0.02), better time in range (TIR) (p = 0.003), less time in hypoglycemia (10.45 16.13%, p = 0.03) and less glycemic variability (83.1 mg/dl 98.84 mg/dl, p = 0.03). No significant differences were found for glucose control between PR and PR patients at +12 months post-PR.
CONCLUSION
This study supports the positive impact of PR occurrence and duration on short-term metabolic control (better HbA levels, IDAA and GTAA scores, TIR, and less glycemic variability) with the residual effect increasing according to PR duration.
PubMed: 36699944
DOI: 10.1177/20420188221145550 -
Frontiers in Psychiatry 2022This patient case report describes a 45-year old white unmarried man with disability pension due to schizoaffective disorder, diagnosed at the age of 24. He lives in an...
Remission of Persistent Negative Symptoms and Psychosocial Consequences by Combined Clozapine and Cariprazine Treatment in a Patient With Long-Standing Treatment-Resistant Schizoaffective Disorder.
This patient case report describes a 45-year old white unmarried man with disability pension due to schizoaffective disorder, diagnosed at the age of 24. He lives in an apartment and has housing support. Retrospectively, the patient displayed prodromal markers of a disorder within the schizophrenia spectrum many years before the onset of frank psychosis, indeed since childhood. Over the years several symptoms and signs across schizophrenia domains have been manifest: positive, negative, cognitive, and affective, among which the negative and affective symptoms and signs were the earliest to appear. While the positive, disorganized, and catatonic symptoms responded to treatment - when duly tested and complied with - the negative and affective symptoms have been notoriously difficult to handle. We now report on the successful introduction of cariprazine (CAR) to his ongoing clozapine (CLZ) medication, the result of which has been a near-complete remission of his persistent negative and psychosocial issues. We interpret this remarkable alleviation of the patient's disease - and concomitant improvement of his quality of life - in terms of neuroreceptor target complementarity between CLZ and CAR, with particular emphasis on the contributions from the D3 and D2 receptor partial agonist components of the latter agent.
PubMed: 35664491
DOI: 10.3389/fpsyt.2022.887547 -
Cureus Apr 2022A compelling intervention to maintain healthy gut microbiota in graft-versus-host-disease (GVHD) is fecal microbial transplantation (FMT). To examine its role in GVHD,... (Review)
Review
A compelling intervention to maintain healthy gut microbiota in graft-versus-host-disease (GVHD) is fecal microbial transplantation (FMT). To examine its role in GVHD, we conducted a systemic literature search using multiple electronic databases. Upon pooling of data, 79 patients from six studies and five case reports were included. Complete remission (CR) occurred in 55.9% of patients, and partial remission (PR) occurred in 26.5% of patients (82.4% overall response rate). A limited number of patients had treatment-related mortality (TRM), while few showed mild gastrointestinal (GI)-related and non-GI adverse effects. None of the studies directly examined the role of FMT in the prevention of GVHD. In conclusion, FMT seems to be a safe and effective strategy for the management of GVHD based on the current evidence. Due to the small number of patients evaluated and the absence of randomized data, one cannot portray FMT as a standard of care yet; however, the low toxicity along with the clinical improvement justifies this modality to be tested in a randomized fashion.
PubMed: 35530905
DOI: 10.7759/cureus.23873 -
Annals of Gastroenterology 2023A new subcutaneous (SC) formulation exists for infliximab (CT-P13 SC). The aim of this study was to assess the durability of clinical and endoscopic responses after a...
BACKGROUND
A new subcutaneous (SC) formulation exists for infliximab (CT-P13 SC). The aim of this study was to assess the durability of clinical and endoscopic responses after a switch from intravenous (IV) to SC infliximab.
METHODS
Patients were transitioned on maintenance infliximab, including those with dose-optimized therapy. The primary outcome was clinical, biochemical and overall remission at 6 months, as defined by a Harvey-Bradshaw Index <5 for Crohn's disease or a partial Mayo score <3 for ulcerative colitis, C-reactive protein less than 10 mg/L, and fecal calprotectin less than 100 μg/g.
RESULTS
Forty patients were switched from IV to SC infliximab. Twenty-seven (68%) had a diagnosis of Crohn's disease and 13 (33%) had ulcerative colitis. Twenty-three (58%) were on 5 mg/kg of IV infliximab every 8 weeks and 15 (38%) 5 mg/kg every 6 weeks. There were 2 patients (4%) on 10 mg/kg every 6 weeks. At the time of their switch, 37 (93%) patients were in clinical remission, 25 (76%) were in biochemical remission, and 25 (76%) were in both biochemical and clinical remission. At 6 months the proportion of patients in clinical remission decreased from 93% to 82%, with an overall relapse rate of 11%. Treatment persistence at 6 months was 77.5%.
CONCLUSION
Switching patients from IV infliximab to 120 mg fortnightly SC injections is a safe and effective option for the treatment of inflammatory bowel disease, including for those patients on dose-escalated infliximab or with active disease at the time of switch.
PubMed: 37664232
DOI: 10.20524/aog.2023.0816 -
Pediatric Nephrology (Berlin, Germany) May 2023The aim of the current PodoNet registry analysis was to evaluate the outcome of steroid-resistant nephrotic syndrome (SRNS) in children who were not treated with...
BACKGROUND
The aim of the current PodoNet registry analysis was to evaluate the outcome of steroid-resistant nephrotic syndrome (SRNS) in children who were not treated with intensified immunosuppression (IIS), focusing on the potential for spontaneous remission and the role of angiotensin blockade on proteinuria reduction.
METHODS
Ninety-five pediatric patients who did not receive any IIS were identified in the PodoNet Registry. Competing risk analyses were performed on 67 patients with nephrotic-range proteinuria at disease onset to explore the cumulative rates of complete or partial remission or progression to kidney failure, stratified by underlying etiology (genetic vs. non-genetic SRNS). In addition, Cox proportional hazard analysis was performed to identify factors predicting proteinuria remission.
RESULTS
Eighteen of 31 (58.1%) patients with non-genetic SRNS achieved complete remission without IIS, with a cumulative likelihood of 46.2% at 1 year and 57.7% at 2 years. Remission was sustained in 11 children, and only two progressed to kidney failure. In the genetic subgroup (n = 27), complete resolution of proteinuria occurred very rarely and was never sustained; 6 (21.7%) children progressed to kidney failure at 3 years. Almost all children (96.8%) received proteinuria-lowering renin-angiotensin-aldosterone system (RAAS) antagonist treatment. On antiproteinuric treatment, partial remission was achieved in 7 of 31 (22.6%) children with non-genetic SRNS and 9 of 27 children (33.3%) with genetic SRNS.
CONCLUSION
Our results demonstrate that spontaneous complete remission can occur in a substantial fraction of children with non-genetic SRNS and milder clinical phenotype. RAAS blockade increases the likelihood of partial remission of proteinuria in all forms of SRNS. A higher resolution version of the Graphical abstract is available as Supplementary information.
Topics: Child; Humans; Nephrotic Syndrome; Immunosuppressive Agents; Proteinuria; Immunosuppression Therapy; Renal Insufficiency; Drug Resistance
PubMed: 36315273
DOI: 10.1007/s00467-022-05762-4 -
Frontiers in Pharmacology 2023Advancing age is a risk factor for treatment-related side effects and mortality in membranous nephropathy (MN) patients treated with traditional immunosuppressive...
Advancing age is a risk factor for treatment-related side effects and mortality in membranous nephropathy (MN) patients treated with traditional immunosuppressive regimens. This study aimed to determine the efficacy and safety of rituximab (RTX) in the treatment of elderly patients with MN. We performed a single center retrospective review of 37 consecutive MN patients aged 70 and older at the time of RTX infusion. We also enrolled 76 young patients (<70 years old) with MN as the control group. We assessed clinical and laboratory indices, remission rates, and adverse events at RTX infusion, 3 months, and last visit. A total of 37 elderly patients with MN were included, with a median follow-up period of 15.50 (10.00, 24.40) months. Of the 37 patients, 75.68% were male, and mean age was 71.89 ± 2.47 years. At last visit, 7 (18.92%) patients achieved complete remission, and 26 (70.27%) patients achieved complete or partial remission. There were no differences in the complete remission rate and complete or partial remission rate at last visit compared to young patients (26.32% vs 18.92%, = 0.387; 85.53% vs 70.27%, = 0.055). After RTX treatment, three of 6 elderly patients with pneumonia died due to ineffective treatment of the infection in RTX therapy courses. The results of multivariant regression analysis showed that elderly patients have an increased risk of serious infection, compared with patients younger than 70 years (OR = 32.874, 95% CI 1.300-831.490, = 0.034). For each increase of 1 g/L in serum albumin, the risk of serious infection would decrease by 43.2% (OR = 0.568, 95% CI 0.334-0.969, = 0.038). This study demonstrates that RTX is effective in the treatment of elderly patients with MN. However, we also observed a high incidence of infectious complications. Our experience was limited by its retrospective design and relatively small sample size, and further randomized controlled studies with large sample size are needed to confirm our preliminary findings.
PubMed: 38186651
DOI: 10.3389/fphar.2023.1323334 -
Journal of the Endocrine Society Jan 2022The effect of the anti-inflammatory and immunomodulatory actions of vitamin D on the duration of partial clinical remission (PR) in youth with type 1 diabetes (T1D) is...
CONTEXT
The effect of the anti-inflammatory and immunomodulatory actions of vitamin D on the duration of partial clinical remission (PR) in youth with type 1 diabetes (T1D) is unclear.
OBJECTIVE
This work aimed to determine the effect of adjunctive ergocalciferol on residual β-cell function (RBCF) and PR in youth with newly diagnosed T1D who were maintained on a standardized insulin treatment protocol. The hypothesis was that ergocalciferol supplementation increases RBCF and prolongs PR.
METHODS
A 12-month, randomized, double-blind, placebo-controlled trial was conducted of 50 000 IU of ergocalciferol per week for 2 months, and then once every 2 weeks for 10 months, vs placebo in 36 individuals aged 10 to 21 years, with T1D of less than 3 months and a stimulated C-peptide (SCP) level greater than or equal to 0.2 nmol/L (≥ 0.6 ng/mL). The ergocalciferol group had 18 randomly assigned participants (10 male/8 female), mean age 13.3 ± 2.8 years, while the control group had 18 participants (14 male/4 female), aged 14.3 ± 2.9 years.
RESULTS
The ergocalciferol treatment group had statistically significantly higher serum 25-hydroxyvitamin D at 6 months ( = .01) and 9 months ( = .02) than the placebo group. At 12 months, the ergocalciferol group had a statistically significantly lower serum tumor necrosis factor α (TNF-α) concentration ( = .03). There were no statistically significant differences between the groups at each time point from baseline to 12 months for SCP concentration ( = .08), glycated hemoglobin A (HbA) ( = .09), insulin dose-adjusted A (IDAA), or total daily dose of insulin. Temporal trends for rising HbA ( = .04) and IDAA ( = .02) were statistically significantly blunted in the ergocalciferol group.
CONCLUSION
Ergocalciferol statistically significantly reduced serum TNF-α concentration and the rates of increase both in A and IDAA, suggesting a protection of RBCF and PR in youth with newly diagnosed T1D.
PubMed: 34913020
DOI: 10.1210/jendso/bvab179 -
Therapeutic Advances in Gastroenterology 2022Endoscopic and histological activity scores in ulcerative colitis (UC) are associated with clinical outcomes and have become important targets of clinical trials....
BACKGROUND
Endoscopic and histological activity scores in ulcerative colitis (UC) are associated with clinical outcomes and have become important targets of clinical trials. However, these endpoints have been scarcely investigated in patients receiving only conventional treatment.
OBJECTIVE
We aimed to assess the deep and complete remission rates after 3 months of conventional treatment in patients with newly diagnosed UC with moderate to severe endoscopic activity. We also aimed to investigate whether selected clinical and biochemical variables at baseline were associated with complete remission status after 3 months.
DESIGN
This was a prospective cohort study.
METHODS
Newly diagnosed patients with active UC commencing 5-aminosalicylate, corticosteroid, and/or azathioprine treatment were consecutively included. Clinical, biochemical, endoscopic, and histological data were collected at baseline and after 3 months. Rates of (Partial Mayo Score ⩽ 2), (Mayo Endoscopic Score ⩽ 1), and (Nancy Index ⩽ 1) were determined. was assessed as clinical remission plus mucosal healing and as deep remission plus histologic healing. Predictors of complete remission were identified by logistic regression.
RESULTS
A total of 180 patients were included in the study. Deep remission and complete remission occurred in 62.8% and 42.2% of patients, respectively. Thus, of patients in deep remission one-third had persistent histologic activity. Histologic activity in mucosally healed patients was associated with higher symptom scores and faecal calprotectin levels. Of baseline variables, less endoscopic distribution and disease activity showed strongest association with achieving complete remission, and limited distribution in combination with moderate activity gave highest odds for complete remission (odds ratio: 4.1, 95% confidence interval: 7.69-2.18).
CONCLUSION
In patients with mucosal healing, persistent histologic activity was a common finding and was associated with increased disease activity. Pancolitis and severe inflammatory activity at baseline were associated with lower complete remission rates.
PubMed: 36506747
DOI: 10.1177/17562848221140659 -
Signal Transduction and Targeted Therapy Dec 2020Advanced natural killer/T cell lymphoma (NKTL) has demonstrated poor prognosis with currently available therapies. Here, we report the efficacy of anti-programmed death... (Clinical Trial)
Clinical Trial
Advanced natural killer/T cell lymphoma (NKTL) has demonstrated poor prognosis with currently available therapies. Here, we report the efficacy of anti-programmed death 1 (PD-1) antibody with the P-GEMOX (pegaspargase, gemcitabine, and oxaliplatin) regimen in advanced NKTL. Nine patients underwent six 21-day cycles of anti-PD-1 antibody (day 1), pegaspargase 2000 U/m (day 1), gemcitabine 1 g/m (days 1 and 8) and oxaliplatin 130 mg/m (day 1), followed by anti-PD-1 antibody maintenance every 3 weeks. Programmed death-ligand 1 (PD-L1) expression and genetic alterations were determined in paraffin-embedded pretreatment tissue samples using immunohistochemistry and next-generation sequencing (NGS) analysis. Responses were assessed using F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography or magnetic resonance imaging. Eight patients exhibited significant responses, comprising of seven complete remissions and one partial remission (overall response rate: 88.9%). After a median follow-up of 10.6 months, 6/9 patients (66.7%) remained in complete remission. The most common grade 3/4 adverse events were anemia (33.3%), neutropenia (33.3%), and thrombocytopenia (33.3%); all of which were manageable and resolved. Immunochemotherapy produced a high response rate in patients with positive PD-L1 expression (5/6, 83.3%). NGS analysis suggested that STAT3/JAK3/PD-L1 alterations and ARID1A mutation were associated with immunochemotherapy efficacy. Mutation in DDX3X and alteration in epigenetic modifiers of KMT2D, TET2, and BCORL1 might indicate a poor response to immunochemotherapy. In conclusion, the anti-PD-1 antibody plus P-GEMOX regimen demonstrated promising efficacy in advanced NKTL. PD-L1 expression combined with specific genetic alterations could be used as potential biomarkers to predict therapeutic responses to immunochemotherapy.
Topics: Adult; Aged; Antibodies, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Deoxycytidine; Disease-Free Survival; Female; Fluorodeoxyglucose F18; Follow-Up Studies; Humans; Lymphoma, Extranodal NK-T-Cell; Male; Middle Aged; Neoplasm Proteins; Oxaliplatin; Polyethylene Glycols; Positron-Emission Tomography; Programmed Cell Death 1 Receptor; Survival Rate; Gemcitabine
PubMed: 33376237
DOI: 10.1038/s41392-020-00331-3