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Frontiers in Oncology 2024To assess the impact of different treatment strategies and risk factors on the prognosis of patients with extranodal NK/T-cell lymphoma, nasal type (ENKTL) in a single...
OBJECTIVE
To assess the impact of different treatment strategies and risk factors on the prognosis of patients with extranodal NK/T-cell lymphoma, nasal type (ENKTL) in a single medical center.
METHODS AND ANALYSIS
The clinical features of 266 patients with ENKTL were retrospectively analyzed, among whom those in stages I and II received sandwich therapy, while those in stages III and IV underwent chemotherapy plus autologous hematopoietic stem cell transplantation. The Kaplan-Meier curves, univariate and multivariate Cox regression analyses were employed for survival and prognosis analysis. Statistical significance was set at P<0.05.
RESULTS
Following treatment, the post-intervention outcomes demonstrated a complete remission (CR) rate of 71.05% and a partial remission (PR) rate of 3.76%. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 70.4% and 70.9%, respectively. In addition, the PFS for patients in stage I/II was 79.8%, with an OS of 81.1%, whereas for those in stage III/IV, the PFS was 41.7% and the OS was 40.9%. Notably, the achievement of CR immediately after treatment was an independent prognostic factor (P<0.001). Patients in stage I/II depicted a favorable 5-year OS rate, while those in stage III/IV manifested a less favorable prognosis.
CONCLUSION
Stages of the disease and whether CR was achieved following treatment are important factors determining the survival and prognosis of patients with ENKTL. Further researches focusing on disease onset and mechanisms of drug resistance will contribute to better management of ENKTL.
PubMed: 38634054
DOI: 10.3389/fonc.2024.1388564 -
BMJ Open Apr 2024Characterised by chronic inflammation of the gastrointestinal tract, inflammatory bowel disease (IBD) symptoms including diarrhoea, abdominal pain and fatigue can...
Defining predictors of responsiveness to advanced therapies in Crohn's disease and ulcerative colitis: protocol for the IBD-RESPONSE and nested CD-metaRESPONSE prospective, multicentre, observational cohort study in precision medicine.
INTRODUCTION
Characterised by chronic inflammation of the gastrointestinal tract, inflammatory bowel disease (IBD) symptoms including diarrhoea, abdominal pain and fatigue can significantly impact patient's quality of life. Therapeutic developments in the last 20 years have revolutionised treatment. However, clinical trials and real-world data show primary non-response rates up to 40%. A significant challenge is an inability to predict which treatment will benefit individual patients.Current understanding of IBD pathogenesis implicates complex interactions between host genetics and the gut microbiome. Most cohorts studying the gut microbiota to date have been underpowered, examined single treatments and produced heterogeneous results. Lack of cross-treatment comparisons and well-powered independent replication cohorts hampers the ability to infer real-world utility of predictive signatures.IBD-RESPONSE will use multi-omic data to create a predictive tool for treatment response. Future patient benefit may include development of biomarker-based treatment stratification or manipulation of intestinal microbial targets. IBD-RESPONSE and downstream studies have the potential to improve quality of life, reduce patient risk and reduce expenditure on ineffective treatments.
METHODS AND ANALYSIS
This prospective, multicentre, observational study will identify and validate a predictive model for response to advanced IBD therapies, incorporating gut microbiome, metabolome, single-cell transcriptome, human genome, dietary and clinical data. 1325 participants commencing advanced therapies will be recruited from ~40 UK sites. Data will be collected at baseline, week 14 and week 54. The primary outcome is week 14 clinical response. Secondary outcomes include clinical remission, loss of response in week 14 responders, corticosteroid-free response/remission, time to treatment escalation and change in patient-reported outcome measures.
ETHICS AND DISSEMINATION
Ethical approval was obtained from the Wales Research Ethics Committee 5 (ref: 21/WA/0228). Recruitment is ongoing. Following study completion, results will be submitted for publication in peer-reviewed journals and presented at scientific meetings. Publications will be summarised at www.ibd-response.co.uk.
TRIAL REGISTRATION NUMBER
ISRCTN96296121.
Topics: Humans; Colitis, Ulcerative; Crohn Disease; Inflammatory Bowel Diseases; Multicenter Studies as Topic; Observational Studies as Topic; Precision Medicine; Prospective Studies; Quality of Life
PubMed: 38631839
DOI: 10.1136/bmjopen-2023-073639 -
Clinical Medicine Insights.... 2024An essential process affecting the course of type 1 diabetes (DM1) is the appearance and duration of clinical remission. One of the most important factors promoting the...
Better Cardiorespiratory Fitness Defined as VOmax Increases the Chance of Partial Clinical Remission and Prolongs Remission Duration in People with Newly Diagnosed Type 1 Diabetes.
INTRODUCTION
An essential process affecting the course of type 1 diabetes (DM1) is the appearance and duration of clinical remission. One of the most important factors promoting the occurrence of remission is physical activity, due to increased activity of antioxidants, reduces insulin resistance and improves glucose transport. Maximal oxygen capacity (VOmax) is an objective measure of the body's aerobic capacity. To assess VOmax, oxygen uptake should be measured directly during the exercise test. The aim of the study was to evaluate the physical capacity in adults with DM1 and its relationship with the occurrence of partial clinical remission (pCR) during 2 years follow-up.
METHODS
The pCR was assessed by the following mathematical formula: A1c (%) + [4 × insulin dose (U/kg/d)]. The result ⩽9 indicates pCR. VOmax was assessed between 6th and 24th month of diabetes duration using an ergospirometer (COSMED K5 System), during an exercise test carried out on a cycloergometer (RAMP incremental exercise test).
RESULTS
The study group consisted of 32 adults with DM1. People with pCR were proved to have higher VOmax level [36.0 (33.0-41.5) vs 30.9 (26.5-34.4) ml/min/kg, = .009. Univariate and multivariate regression confirmed a significant association between VOmax and presence of pCR [AOR 1.26 (1.05-1.52), = .015]. Duration of remission was longer among group with higher VOmax results [15 (9-24) vs 9 (0-12) months, = .043]. The positive relationship was observed between diabetes duration and VOmax (rs = 0.484, = .005). Multivariate linear regression confirms a significant association between remission duration and VOmax (ml/min/kg) (β = 0.595, = .002).
CONCLUSION
The higher VOmax, the better chance of partial clinical remission at 2 years of DM1 and longer duration of remission.
PubMed: 38628617
DOI: 10.1177/11795514241244872 -
Surgical Neurology International 2024Standalone coil embolization is often less effective for partially thrombosed intracerebral aneurysms (PTIA) because of the risk of frequent recurrence if the coil...
BACKGROUND
Standalone coil embolization is often less effective for partially thrombosed intracerebral aneurysms (PTIA) because of the risk of frequent recurrence if the coil migrates into the thrombus. This report describes a case of PTIA at the basilar tip in which simple coil embolization using a Target 3D Coil resulted in sustained remission without recurrence during long-term follow-up.
CASE DESCRIPTION
The patient was a 63-year-old male who presented with right oculomotor nerve palsy after having undergone direct surgery for a basilar artery aneurysm 15 years earlier. Recurrence with partial thrombosis of the basilar artery aneurysm was diagnosed. Target 3D Coil embolization with frame construction in the aneurysmal sac was performed, resulting in the complete disappearance of the aneurysm and improvement of the oculomotor nerve palsy. Magnetic resonance imaging at five years postoperatively confirmed that the thrombus had completely disappeared, and there was no recurrence of the aneurysm. The closed loops in the Target 3D Coil may have contributed to the cohesive mass of coils remaining in the sac of the PTIA, potentially leading to healing.
CONCLUSION
The characteristics of the Target 3D Coil may have prevented migration of the coil into the thrombus, potentially contributing to the successful resolution of the aneurysm.
PubMed: 38628531
DOI: 10.25259/SNI_44_2024 -
Annals of Saudi Medicine 2024Multiple myeloma (MM) represents the second most common hematologic malignancy (15%). Induction with bortezomib, cyclophosphamide, and dexamthasone VCd (d: low dose...
Improved long-term survival rate in the responders to bortezomib, cyclophosphamide, dexamethasone induction therapy in a transplant-eligible cohort of predominantly middle-age multiple myeloma patients.
BACKGROUND
Multiple myeloma (MM) represents the second most common hematologic malignancy (15%). Induction with bortezomib, cyclophosphamide, and dexamthasone VCd (d: low dose dexamthasone) regimen is widely used due to its high effectiveness, low toxicity and good tolerability, particularly with renal impairment. Real-world data on the use of VCD in clinical practice is lacking.
OBJECTIVES
Evaluate the real-world experience of the VCD regimen.
DESIGN
Retrospective.
SETTING
Tumor registry database of tertiary cancer care center.
PATIENTS AND METHODS
newly diagnosed MM patients who received VCD induction and underwent autologous stem cell transplant (ASCT) from July 2007 to July 2020.
MAIN OUTCOME MEASURES
response evaluation, progression-free survival (PFS) and overall survival (OS).
SAMPLE SIZE
87 patients.
RESULTS
Of 102 patients who started induction with VCd, 87 patients experienced a partial response or more overall response rate of 85%). The median age of these 87 patients at diagnosis was 52 years, of which 29.9% presented with renal impairment and 60.3% of patients had stage 2 by the Revised International Staging System (R-ISS). Patients with a standard cytogenetic risk achieved a better response compared to those with a poor cytogenetic risk (=.044). The post-induction response rates were 6.9% stringent complete remission (sCR), 35% complete remission (CR); 41.4% very good partial response (VGPR), and 16.1% partial response (PR), respectively; the response rates became greater for sCR and CR post-transplantation at day 100 with 16.1% sCR, 35.6% CR, 32.2% VGPR and 16.1% PR, respectively. The median PFS was 49 months and 5 years OS was 84%. PFS was better in patients who achieved sCR vs PR (83 vs 35 months, =.037). High LDH, high-risk cytogenetic and stage 3 R-ISS showed a worse median PFS and OS.
CONCLUSIONS
VCD induction in newly diagnosed MM is highly effective, convenient, tolerable and affordable regimen, especially in low and middle-income countries with limited resources, also with favorable outcomes and survival. while those who did not respond successfully shifted to VRD or VTD.
LIMITATIONS
The usual limitations of a retrospective analysis using registry-level data, no data on quality of life.
Topics: Middle Aged; Humans; Multiple Myeloma; Bortezomib; Induction Chemotherapy; Quality of Life; Retrospective Studies; Survival Rate; Cyclophosphamide
PubMed: 38615184
DOI: 10.5144/0256-4947.2024.93 -
Nutrients Mar 2024Crohn's disease (CD) is an inflammatory bowel disease. Previous research has explored the impact of diet on CD, as specific dietary components can influence gut... (Review)
Review
Crohn's disease (CD) is an inflammatory bowel disease. Previous research has explored the impact of diet on CD, as specific dietary components can influence gut microbiota and immune responses, contributing to damage in the gastrointestinal tract. The Crohn's Disease Exclusion Diet (CDED) is based on an exclusion diet; it is a recent dietary approach that is often used alongside partial enteral nutrition (PEN) and aims to induce disease remission by excluding certain dietary components. This study assesses the current evidence for the effectiveness of the CDED + PEN in achieving remission in both children and adults with active CD. Our systematic review followed PRISMA recommendations and was registered in PROSPERO with CRD number 42022335076. The searched databases were PubMed/MEDLINE, Cochrane Library, Scopus, and Web of Science. The included studies were analyzed using Rayyan software, and the risk of bias was assessed with Cochrane RevMan 5.0 software. The primary assessed outcome was clinical remission, evaluated with validated questionnaire scores such as PCDAI, CDAI, or HBI. All analyzed papers yielded promising results. Notably, the CDED + PEN demonstrated better tolerance than exclusive enteral nutrition (EEN), resulting in higher adherence rates. Therefore, the CDED + PEN appears to be a viable alternative for induction remission in active disease for both children and adults with CD.
Topics: Adult; Child; Humans; Crohn Disease; Inflammatory Bowel Diseases; Causality; Databases, Factual
PubMed: 38613020
DOI: 10.3390/nu16070987 -
Cancers Mar 2024Azacitidine (AZA) is recognized as a vital drug used in the therapy of myelodysplastic syndromes (MDS) due to its beneficial effect on survival and quality of life....
Azacitidine (AZA) is recognized as a vital drug used in the therapy of myelodysplastic syndromes (MDS) due to its beneficial effect on survival and quality of life. Nevertheless, many patients fail to respond to AZA treatment, as prognostic factors still are not identified. The present retrospective analysis included 79 patients with MDS treated with AZA as first-line therapy in a real-life setting. The percentage of patients with good, intermediate, and poor cytogenetics was 46.8%, 11.4%, and 34.2%, respectively. The overall response rate (complete remission [CR], partial remission [PR], and hematological improvement [HI]) was 24%. The CR, PR, and HI rates were 13.9%, 2.5%, and 7.6%, respectively. Stable disease (SD) was documented in 40.5% of patients. The median overall survival (OS) and progression-free survival (PFS) were 17.6 and 14.96 months, respectively. Patients with ORR and SD had a significantly longer median OS (23.8 vs. 5.7 months, = 0.0005) and PFS (19.8 vs. 3.5 months, < 0.001) compared to patients who did not respond to AZA. In univariate analysis, only an unfavorable cytogenetic group was a prognostic factor of a lower response rate ( = 0.03). In a multivariate model, older age ( = 0.047), higher IPSS (International Prognostic Scoring System) risk ( = 0.014), and higher IPSS-R cytogenetic risk ( = 0.004) were independent factors of shorter OS. Independent prognostic factors for shorter PFS were age ( = 0.001), IPSS risk ( = 0.02), IPSS cytogenetic risk ( = 0.002), and serum ferritin level ( = 0.008). The safety profile of AZA was predictable and consistent with previous studies. In conclusion, our study confirms the efficacy and safety of AZA in a real-world population and identifies potential biomarkers for response and survival.
PubMed: 38611011
DOI: 10.3390/cancers16071333 -
Journal For Immunotherapy of Cancer Apr 2024Autologous stem cell transplantation (ASCT) after induction therapy improves disease-free survival for patients with multiple myeloma (MM). While the goal of ASCT is to...
BACKGROUND
Autologous stem cell transplantation (ASCT) after induction therapy improves disease-free survival for patients with multiple myeloma (MM). While the goal of ASCT is to render a minimal disease state, it is also associated with eradication of immunosuppressive cells, and we hypothesize that early introduction of immunotherapy post-ASCT may provide a window of opportunity to boost treatment efficacy.
METHODS
We conducted a phase 1 clinical trial to investigate the application of autologous lymphocyte infusion and anti-SLAMF7 monoclonal antibody, elotuzumab, after ASCT in patients with newly diagnosed MM previously treated with induction therapy. In addition to CD34+ stem cells, peripheral blood mononuclear cells were harvested prior to transplant and infused on day 3 after stem cell infusion to accelerate immune reconstitution and provide autologous natural killer (NK) cells that are essential to the mechanism of elotuzumab. Elotuzumab was administered starting on day 4 and then every 28 days after until 1 year post-ASCT. Cycles 4-12 were administered with standard-of-care lenalidomide maintenance.
RESULTS
All subjects were evaluated for safety, and 13 of 15 subjects completed the treatment protocol. At 1 year post-ASCT, the disease status of enrolled subjects was as follows: five stringent complete responses, one complete response, six very good partial responses, one partial response, and two progressive diseases. The treatment plan was well tolerated, with most grade 3 and 4 AEs being expected hematologic toxicities associated with ASCT. Correlative analysis of the immune microenvironment demonstrated a trend toward reduced regulatory T cells during the first 3 months post-transplant followed by an increase in NK cells and monocytes in patients achieving a complete remission.
CONCLUSIONS
This phase 1 clinical trial demonstrates that early introduction of immunotherapy after ASCT is well tolerated and shows promising disease control in patients with MM, accompanied by favorable changes in the immune microenvironment.
TRIAL REGISTRATION NUMBER
NCT02655458.
Topics: Humans; Lenalidomide; Multiple Myeloma; Hematopoietic Stem Cell Transplantation; Leukocytes, Mononuclear; Transplantation, Autologous; Stem Cell Transplantation; Tumor Microenvironment; Antibodies, Monoclonal, Humanized
PubMed: 38609316
DOI: 10.1136/jitc-2023-008110 -
Heliyon Apr 2024Idiopathic membranous nephropathy (IMN) is a rare autoimmune disorder that causes nephrotic syndromes in adults. Conventional immunosuppressive therapies often exhibit...
BACKGROUND
Idiopathic membranous nephropathy (IMN) is a rare autoimmune disorder that causes nephrotic syndromes in adults. Conventional immunosuppressive therapies often exhibit limited efficacy in achieving remission and may result in notable adverse reactions, warranting the exploration of novel therapeutic approaches for IMN treatment. Traditional Chinese medicine (TCM), which is extensively used for kidney disease management, is a promising alternative.
OBJECTIVE
This study aimed to examine the safety and efficacy of TCM alone or in combination with Western medicine for the management of patients diagnosed with IMN.
METHODS
This study employed a systematic search of English and Chinese electronic databases to identify randomized controlled trials (RCTs) that examined the application of TCM in the treatment of IMN. RCTs that met the predetermined inclusion and exclusion criteria and assessed the safety and efficacy of TCM alone or in combination with Western medicine in patients with IMN were included in the analysis. The methodological quality of the included studies was evaluated by using a risk-of-bias tool. All statistical analyses were performed using the RevMan software (version 5.4.2). The evidence was evaluated on the https://www.gradepro.org/website.
RESULTS
This study included 29 randomized controlled trials (RCTs) involving 1982 patients with moderate methodological quality that met the inclusion criteria. The results showed that, compared to Western medicine alone therapy, the use of TCM alone or in combination with Western medicine significantly improved total remission (TR) rate (risk ratios [RR] 1.38, 95% confidence interval [CI] 1.29-1.46, I = 0%, P < 0.00001), complete remission (CR) rate (RR 1.78, 95% CI 1.48-2.15, I = 0, P < 0.00001), partial remission (PR) rate (RR 1.27, 95% CI 1.161.40, I = 0%, P < 0.00001), and serum albumin (ALB) levels (MD: 4.05, 95% CI: 3.02-5.09, I = 91%, P < 0.00001). TCM alone or in combination with Western medicine also reduced proteinuria levels (mean difference [MD]: 1.05, 95% CI: 1.30 to -0.79, I = 95%, P < 0.00001), serum creatinine (SCr) levels (MD: 7.47, 95% CI: 13.70 to -1.24, I = 97%, P = 0.02), and serum antibodies against M-type phospholipase A2 receptor levels (aPLA2Rab) (MD: 19.24, 95% CI: 33.56 to -4.93, I = 87%, P = 0.008). Moreover, the efficacy of combined TCM and Western medicine is superior to that of Western medicine alone in reducing the incidence of infection, hepatotoxicity, and thrombosis. Although the primary and secondary outcomes were consistent, the evidence was generally moderate.
CONCLUSION
The results of this study suggest that TCM alone or in combination with Western medicine may be a feasible alternative therapeutic approach for the treatment of IMN. Nevertheless, additional, rigorously designed, high-quality, and extensive clinical trials are imperative to provide substantial evidence regarding the effectiveness of TCM in managing IMN.
PubMed: 38596093
DOI: 10.1016/j.heliyon.2024.e28836 -
JPMA. the Journal of the Pakistan... Mar 2024To determine the clinico-pathological features and long-term outcome of secondary steroid-resistant nephrotic syndrome treated with steroids and calcineurin inhibitors.
OBJECTIVE
To determine the clinico-pathological features and long-term outcome of secondary steroid-resistant nephrotic syndrome treated with steroids and calcineurin inhibitors.
METHODS
The retrospective cohort study was conducted at the Sindh Institute of Urology and Transplant, Karachi, in June and July 2023, and comprised data from January 1, 2008, to December 31, 2020, of children aged 1-18 years who developed steroid resistance after initial sensitivity to steroids with at least 1-year of follow-up. Demographics as well as time taken to secondary steroid response were documented. Renal biopsy of all patients with secondary steroid resistance had been performed. Eventual outcomes after treatment with calcineurin inhibitors based on the degree of proteinuria and serum albumin levels were used to categorise complete remission, partial remission and no response. Kidney function, as determined by estimated glomerular filtration rate, was recorded. Data was analysed using SPSS 22.
RESULTS
Of the 1,000 patients who underwent renal biopsy for steroid resistance, 48(4.8%) had idiopathic steroid-resistant nephrotic syndrome; 32(66.7%) males, 16(33.3%) females and median age of 5 years (interquartile range: 4-7.3 years). Median age at diagnosis of nephrotic syndrome was 5 years (interquartile range: 3.6-7.3 years). The median time from nephrotic syndrome to secondary steroid-resistant nephrotic syndrome was 23 months (interquartile range: 8.75-44.5 months). Biopsy results at diagnosis showed that 27(56.3%) had minimal change disease. The mean follow-up time was 6.1±3.2 years. Of the 43(89.5%) patients who received cyclosporin for 1 year, 29(67%) obtained complete remission, 5(12%) attained partial remission and no response was seen in 9(21%) patients.
CONCLUSION
Majority of the children had minimal change disease at the time of diagnosis of secondary steroid-resistant nephrotic syndrome. The long-term response with calcineurin inhibitors was favourable at 1 year.
Topics: Child; Male; Female; Humans; Child, Preschool; Nephrotic Syndrome; Immunosuppressive Agents; Retrospective Studies; Calcineurin Inhibitors; Nephrosis, Lipoid; Steroids; Treatment Outcome
PubMed: 38591291
DOI: 10.47391/JPMA.10584