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Balkan Medical Journal Jul 2023Conventional regimens for refractory idiopathic membranous nephropathy (IMN) still have limitations. Rituximab (RTX) has a good effect in the treatment of refractory...
BACKGROUND
Conventional regimens for refractory idiopathic membranous nephropathy (IMN) still have limitations. Rituximab (RTX) has a good effect in the treatment of refractory IMN. However, whether RTX single or combined with immunosuppressive therapy is more effective and whether adverse events will increase are still inconclusive.
AIMS
To investigate the efficacy and safety of RTX combined with low-dose tacrolimus (TAC) versus RTX alone in the treatment of refractory IMN.
STUDY DESIGN
A retrospective cohort study.
METHODS
We retrospectively studied 91 cases of refractory IMN diagnosed between January 2018 and June 2021, all of which immunosuppressive regimens had failed. Thirty-four patients received RTX combined with TAC (RTX + TAC group), and 57 patients were treated with RTX alone (RTX group). The RTX + TAC group was given RTX 1 g once every 2 weeks, two times, and TAC 0.03 mg/kg/day orally. In the RTX group, RTX was given at the same dosage as the RTX + TAC group. Clinical data were collected at 12 months of follow-up to compare the complete and partial remission rates and the incidence of adverse reactions between the two groups.
RESULTS
The overall effectiveness rate of RTX + TAC in the treatment of refractory IMN was 87.14%, of which the partial and complete remission rates were 50.01% and 37.13%, respectively, and the median time to complete remission was 9 (interquartile range [IQR] 6.0, 12.0) months. The overall effectiveness rate of RTX was 65.87%, of which the partial and complete remission rates were 39.48% and 26.39%, respectively, and the median time to complete remission was 10.5 (IQR 6.0, 12.0) months. Adverse events occurred in 6 (17.65%) patients in the RTX + TAC group and in 11 (19.30%) in the RTX group ( = 0.473). Proteinuria and high titer of PLA2R are risk factors for non-remission.
CONCLUSION
The complete and partial remission rates of RTX combined with low-dose TAC in the treatment of refractory IMN are higher than those of RTX alone, and no significant increase in adverse events was noted.
Topics: Humans; Tacrolimus; Glomerulonephritis, Membranous; Rituximab; Retrospective Studies; Drug Therapy, Combination
PubMed: 37260416
DOI: 10.4274/balkanmedj.galenos.2023.2022-9-7 -
European Archives of Psychiatry and... Aug 2023Many individuals with major depression disorder (MDD) who achieve remission of depressive symptoms, do not perceive themselves as fully recovered. This study explores...
Many individuals with major depression disorder (MDD) who achieve remission of depressive symptoms, do not perceive themselves as fully recovered. This study explores whether clinical remission is related to functional remission and to patient's perception of recovery, as well as, which factors are associated with their functional and subjective remission. 148 patients with MDD in partial clinical remission were included. Demographics and clinical variables were collected through semi-structured interviews. Objective cognition was evaluated through a neuropsychological battery and subjective cognition through a specific questionnaire. The patient's psychosocial functioning and the perception of their remission were also assessed. Apart from descriptive analysis, Pearson correlations and backward stepwise regression models explored the relationship between demographic, clinical, and cognitive factors with patients' functional and self-perceived remission. From the whole sample, 57 patients (38.5%) were considered to achieve full clinical remission, 38 patients (25.7%) showed functional remission, and 55 patients (37.2%) perceived themselves as remitted. Depressive symptoms and objective and subjective executive function were the factors associated with psychosocial functioning. Besides, depressive symptoms, objective and subjective attention, and subjective executive function were the significant explanatory variables for self-perception of remission. The concept of full recovery from an episode of MDD should not only include the clinician's perspective but also the patient's psychosocial functioning along with their self-perceived remission. As residual depressive symptoms and cognition (objective and subjective) are factors with great contribution to a full recovery, clinicians should specifically address them when choosing therapeutic strategies.
Topics: Humans; Depressive Disorder, Major; Cognition; Executive Function; Attention; Surveys and Questionnaires
PubMed: 36085532
DOI: 10.1007/s00406-022-01487-5 -
World Journal of Gastrointestinal... May 2024A treat-to-target strategy in inflammatory bowel disease (IBD) involves treatment intensification in order to achieve a pre-determined endpoint. Such uniform and tight...
A treat-to-target strategy in inflammatory bowel disease (IBD) involves treatment intensification in order to achieve a pre-determined endpoint. Such uniform and tight disease control has been demonstrated to improve clinical outcomes compared to treatment driven by a clinician's subjective assessment of symptoms. However, choice of treatment endpoints remains a challenge in management of IBD a treat-to-target strategy. The treatment endpoints for ulcerative colitis (UC), recommended by the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) consensus have changed somewhat over time. The latest STRIDE-II consensus advises immediate (clinical response), intermediate (clinical remission and biochemical normalisation) and long-term treatment (endoscopic healing, absence of disability and normalisation of health-related quality of life, as well as normal growth in children) endpoints in UC. However, achieving deeper levels of remission, such as histologic normalisation or healing of the gut barrier function, may further improve outcomes among UC patients. Generally, all medical therapy should seek to improve short- and long-term mortality and morbidity. Hence treatment endpoints should be chosen based on their ability to predict for improvement in short- and long-term mortality and morbidity. Potential benefits of treatment intensification need to be weighed against the potential harms within an individual patient. In addition, changing therapy that has achieved partial response may lead to worse outcomes, with failure to recapture response on treatment reversion. Patients may also place different emphasis on certain potential benefits and harms of various treatments than clinicians, or may have strong opinions re certain therapies. Potential benefits and harms of therapies, incremental benefits of achieving deeper levels of remission, as well as uncertainties of the same, need to be discussed with individual patients, and a treatment endpoint agreed upon with the clinician. Future research should focus on quantifying the incremental benefits and risks of achieving deeper levels of remission, such that clinicians and patients can make an informed decision about appropriate treatment end-point on an individual basis.
PubMed: 38764502
DOI: 10.4292/wjgpt.v15.i2.91591 -
Primary Care Diabetes Jun 2023Obesity is a global concern with several health-related complications. Bariatric surgeries are major treatment options in patients with obesity and other comorbidities....
BACKGROUND AND AIM
Obesity is a global concern with several health-related complications. Bariatric surgeries are major treatment options in patients with obesity and other comorbidities. This study aims to investigate the effects of sleeve gastrectomy on metabolic indexes, hyperechogenic liver changes, inflammatory state, diabetes, and other obesity-related comorbidities remission after the sleeve gastrectomy.
METHODS
This prospective study was conducted on patients with obesity candidates for laparoscopic sleeve gastrectomy. Patients were followed for one year after the surgery. Comorbidities, metabolic and inflammatory parameters were assessed before and one- year after the surgery.
RESULTS
137 patients (16 males, 44 in the DM group) underwent sleeve gastrectomy. One year after the study, obesity-related comorbidities improved significantly; diabetes had complete remission in 22.7% and partial remission in 63.6% of patients. Hyper-cholesterolemia, hyper-triglyceridemia, and hyper-uricemia also improved in 45.6%, 91.2%, and 69% of the patients. Metabolic syndrome indexes improved in 17.5% of the patients. Also, the prevalence of hyperechogenic changes in the liver has declined from 21% before the surgery to 1.5% after that. Based on logistic regression analysis, increased levels of HbA1C reduced the chance of diabetes remission by 0.9%. In comparison, every unit of increased BMI before the surgery improved the case of diabetes remission by 16%.
CONCLUSION
Laparoscopic sleeve gastrectomy is a safe and effective treatment option in patients with obesity and diabetes. Laparoscopic sleeve gastrectomy alleviates BMI and insulin resistance and effectively improves other obesity-related comorbidities such as Hypercholesterolemia, hyper-triglyceridemia, hyper-uricemia, and hyperechogenic changes of the liver. HbA1C and BMI before the surgery are notable predictors of diabetes remission within the first year after the surgery.
Topics: Male; Humans; Cohort Studies; Glycated Hemoglobin; Prospective Studies; Obesity; Treatment Outcome; Diabetes Mellitus, Type 2; Gastrectomy; Body Mass Index; Retrospective Studies
PubMed: 36894485
DOI: 10.1016/j.pcd.2023.03.001 -
HIV Medicine Sep 2023People living with HIV have a higher risk of developing lymphoma. Outcomes for people living with HIV with relapsed or refractory (r/r) lymphoma remain poor. For this... (Review)
Review
People living with HIV have a higher risk of developing lymphoma. Outcomes for people living with HIV with relapsed or refractory (r/r) lymphoma remain poor. For this group of patients, chimeric antigen receptor (CAR) T-cell therapy represents a new successful treatment strategy. However, people living with HIV were not included in pivotal trials, so data are limited to case reports. We searched the PubMed and Ovid technologies databases for literature until 1 November 2022 using the terms 'HIV and CAR-T', 'HIV and lymphoma' and 'HIV and CAR-T and lymphoma'. Six cases with sufficient information were included in the review. The mean CD4 T-cell count before CAR T-cell therapy was 221 cells/μL (range 52-629). The viral load was below the limit of detection in four patients. All patients had diffuse large B-cell lymphoma (DLBCL) and were treated with gamma-retroviral-based axicabtagene ciloleucel. Four patients developed cytokine-release syndrome (CRS) grade 2 or less or immune effector-cell-associated neurotoxicity syndrome (ICANs) grade 3-4. Four of six patients responded to CAR T-cell therapy (three complete remissions, one partial remission). In summary, there are no clinical reasons to restrict the use of CAR T-cell therapy in people living with HIV with r/r DLBCL. According to the current data, CAR T-cell therapy was safe and effective. In people who meet the standard criteria for CAR T-cell therapy, this treatment approach could significantly improve the unmet need for more effective treatment options for people living with HIV with r/r lymphoma.
Topics: Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Receptors, Antigen, T-Cell; HIV Infections; Lymphoma, Large B-Cell, Diffuse
PubMed: 37322863
DOI: 10.1111/hiv.13514 -
Nephron 2021Membranous nephropathy (MN) is an immune-mediated glomerular disease that can lead to nephrotic syndrome and progressive kidney function loss. The cyclic...
Membranous nephropathy (MN) is an immune-mediated glomerular disease that can lead to nephrotic syndrome and progressive kidney function loss. The cyclic steroid-cyclophosphamide regimen (the modified Ponticelli protocol) and the monoclonal anti-CD20 antibody rituximab have been advocated as effective therapies to improve renal outcomes, but a direct comparison of these treatments had never been carried out in a prospective study. Subject of Review: Scolari et al. [J Am Soc Nephrol. 2021;32:972-82] recently reported the results of a pilot randomized controlled trial (RI-CYCLO) designed to provide direct estimates of the effect of rituximab (1 g × 2) compared to the cyclic steroid-cyclophosphamide regimen in 74 patients with MN. The proportion of patients with complete remission at 12 months was higher in the cyclic regimen arm than that of rituximab (32 and 16%, respectively), but the difference was not statistically significant in intention-to-treat analyses. Interestingly, differences in the cumulative incidence of complete and partial remissions between treatment arms progressively reduced over the follow-up and became virtually nonexistent from 24 months (>80% in both groups). The frequency of serious and nonserious adverse events was similar between the 2 treatment arms. Infusion reactions and drug discontinuation were more common with rituximab, while infections and leukopenia were more frequently observed with the cyclic regimen. The risk of cancer was similar in the 2 allocation groups, but the limited follow-up length did not allow to draw definitive conclusions. Independent of treatment allocation, 18% of patients experienced at least 1 relapse after achieving complete or partial remission. Second Opinion: Notwithstanding the intrinsic limitations of a pilot study, the RI-CYCLO trial represents an important milestone in the treatment of MN. Findings from this study support the hypothesis that the cyclic regimen and rituximab may have comparable efficacy in inducing disease remission over the long term. Considering its potentially better-albeit not yet formally proven-long-term safety profile, rituximab could be considered as a first-line therapy for most patients with MN. Several questions remain to be addressed, including rituximab ideal dose and its efficacy in patients with a significant reduction in glomerular filtration rate. In light of RI-CYCLO results, a large-scale trial to assess rituximab noninferiority to the cyclic regimen would require the enrollment of thousands of patients, and it would be probably unfeasible within a reasonable time frame. In our opinion, resources should be allocated to provide an answer to the pressing matter of treatment nonresponse and intolerance, which may be addressed in the near future with novel therapeutic strategies.
Topics: Adrenal Cortex Hormones; Autoimmunity; Cyclophosphamide; Female; Glomerulonephritis, Membranous; Humans; Male; Remission Induction; Rituximab
PubMed: 34225270
DOI: 10.1159/000516984 -
International Journal of Rheumatic... Aug 2022The goal of treatment in palindromic rheumatism (PR) is to control the attacks and prevent disease evolution to chronic arthritis. Conventional synthetic...
OBJECTIVE
The goal of treatment in palindromic rheumatism (PR) is to control the attacks and prevent disease evolution to chronic arthritis. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) including antimalarial and methotrexate cannot control attacks in all patients.
METHODS
In this retrospective study, we assessed the efficacy of leflunomide in patients with PR who had an inadequate response to DMARDs. In this study, patients who had a diagnosis of PR and were treated with leflunomide because of active disease despite treatment with csDMARDs for at least 6 months were included. Remission was defined as no attacks for 3 months and prednisolone dose ≤5 mg/d. Leflunomide treatment failure was defined as failure to achieve remission, the need to add other DMARDs for controlling attacks and disease progression to chronic arthritis during treatment with leflunomide.
RESULTS
Ten cases with active disease despite treatment with hydroxychloroquine and methotrexate and low-dose prednisolone treated with leflunomide were included in the study. During the 12.6 ± 7.5 months of treatment with leflunomide, the frequency of attacks significantly decreased. Complete and partial remission were achieved in 90% of patients.
CONCLUSION
Our results indicate that leflunomide controls PR attacks and it might be a new option for patients with PR.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Drug Therapy, Combination; Humans; Leflunomide; Methotrexate; Prednisolone; Retrospective Studies; Treatment Outcome
PubMed: 35666009
DOI: 10.1111/1756-185X.14364 -
Frontiers in Endocrinology 2023As diabetes continues to grow as major health problem, there has been great progress in understanding the important role of pancreatic beta-cells in its pathogenesis....
As diabetes continues to grow as major health problem, there has been great progress in understanding the important role of pancreatic beta-cells in its pathogenesis. Diabetes develops when the normal interplay between insulin secretion and the insulin sensitivity of target tissues is disrupted. With type 2 diabetes (T2D), glucose levels start to rise when beta-cells are unable to meet the demands of insulin resistance. For type 1 diabetes (T1D) glucose levels rise as beta-cells are killed off by autoimmunity. In both cases the increased glucose levels have a toxic effect on beta-cells. This process, called glucose toxicity, has a major inhibitory effect on insulin secretion. This beta-cell dysfunction can be reversed by therapies that reduce glucose levels. Thus, it is becoming increasingly apparent that an opportunity exists to produce a complete or partial remission for T2D, both of which will provide health benefit.
Topics: Humans; Blood Glucose; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Insulin Resistance; Glucose; Remission Induction
PubMed: 37409234
DOI: 10.3389/fendo.2023.1213954 -
Endocrinology and Metabolism Clinics of... Mar 2023Type 1 diabetes is a chronic autoimmune disorder that results in destruction of insulin-producing cells in the pancreas. The autoimmune process is thought to be waxing... (Review)
Review
Type 1 diabetes is a chronic autoimmune disorder that results in destruction of insulin-producing cells in the pancreas. The autoimmune process is thought to be waxing and waning resulting in variable endogenous insulin secretion ability. An example of this is the honeymoon phase or partial remission phase of type 1 diabetes, during which optimal control of blood glucoses can be maintained with significantly reduced exogenous insulin, and occasionally exogenous insulin can be temporarily discontinued altogether. Understanding this phase is important because even fairly small amounts of endogenous insulin secretion is associated with reduced risk of severe hypoglycemia and microvascular complications.
Topics: Humans; Diabetes Mellitus, Type 1; Insulin; Blood Glucose; Hypoglycemia; Pancreas
PubMed: 36754493
DOI: 10.1016/j.ecl.2022.08.001 -
Psychological Medicine Jan 2021The number of clinical trials in body dysmorphic disorder (BDD) has steadily increased in recent years. As the number of studies grows, it is important to define the...
BACKGROUND
The number of clinical trials in body dysmorphic disorder (BDD) has steadily increased in recent years. As the number of studies grows, it is important to define the most empirically useful definitions for response and remission in order to enhance field-wide consistency and comparisons of treatment outcomes across studies. In this study, we aim to operationally define treatment response and remission in BDD.
METHOD
We pooled data from three randomized controlled trials of cognitive-behavior therapy (CBT) for BDD (combined n = 153) conducted at four academic sites in Sweden, the USA, and England. Using signal detection methods, we examined the Yale-Brown Obsessive Compulsive Scale modified for BDD (BDD-YBOCS) score that most reliably identified patients who responded to CBT and those who achieved remission from BDD symptoms at the end of treatment.
RESULTS
A BDD-YBOCS reduction ⩾30% was most predictive of treatment response as defined by the Clinical Global Impression (CGI) - Improvement scale (sensitivity 0.89, specificity 0.91, 91% correctly classified). At post-treatment, a BDD-YBOCS score ⩽16 was the best predictor of full or partial symptom remission (sensitivity 0.85, specificity 0.99, 97% correctly classified), defined by the CGI - Severity scale.
CONCLUSION
Based on these results, we propose conceptual and operational definitions of response and full or partial remission in BDD. A consensus regarding these constructs will improve the interpretation and comparison of future clinical trials, as well as improve communication among researchers, clinicians, and patients. Further research is needed, especially regarding definitions of full remission, recovery, and relapse.
Topics: Adolescent; Adult; Aged; Body Dysmorphic Disorders; Child; England; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Remission Induction; Sweden; Terminology as Topic; Treatment Outcome; United States; Young Adult
PubMed: 31662124
DOI: 10.1017/S0033291719003003