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Science Translational Medicine Sep 2015Patients with multiply relapsed or refractory chronic lymphocytic leukemia (CLL) have a poor prognosis. Chimeric antigen receptor (CAR)-modified T cells targeting CD19...
Patients with multiply relapsed or refractory chronic lymphocytic leukemia (CLL) have a poor prognosis. Chimeric antigen receptor (CAR)-modified T cells targeting CD19 have the potential to improve on the low complete response rates with conventional therapies by inducing sustained remissions in patients with refractory B cell malignancies. We previously reported preliminary results on three patients with refractory CLL. We report the mature results from our initial trial using CAR-modified T cells to treat 14 patients with relapsed and refractory CLL. Autologous T cells transduced with a CD19-directed CAR (CTL019) lentiviral vector were infused into patients with relapsed/refractory CLL at doses of 0.14 × 10(8) to 11 × 10(8) CTL019 cells (median, 1.6 × 10(8) cells). Patients were monitored for toxicity, response, expansion, and persistence of circulating CTL019 T cells. The overall response rate in these heavily pretreated CLL patients was 8 of 14 (57%), with 4 complete remissions (CR) and 4 partial remissions (PR). The in vivo expansion of the CAR T cells correlated with clinical responses, and the CAR T cells persisted and remained functional beyond 4 years in the first two patients achieving CR. No patient in CR has relapsed. All responding patients developed B cell aplasia and experienced cytokine release syndrome, coincident with T cell proliferation. Minimal residual disease was not detectable in patients who achieved CR, suggesting that disease eradication may be possible in some patients with advanced CLL.
Topics: Aged; Cytokines; Female; Humans; Immunotherapy; Leukemia, Lymphocytic, Chronic, B-Cell; Macrophage Activation; Male; Middle Aged; Receptors, Antigen, T-Cell; Remission Induction; T-Lymphocytes
PubMed: 26333935
DOI: 10.1126/scitranslmed.aac5415 -
Danish Medical Journal Jan 2021The prevalence of severe obesity is increasing and highly associated with co-morbidities such as Type 2 diabetes (T2D). Furthermore, quality of life (QoL) is negatively...
INTRODUCTION
The prevalence of severe obesity is increasing and highly associated with co-morbidities such as Type 2 diabetes (T2D). Furthermore, quality of life (QoL) is negatively affected among patients with severe obesity and T2D. Studies have found that gastric bypass surgery may lead to remission of T2D and improved QoL. The aim of this study was to investigate the association between partial remission of T2D and change in QoL from baseline to a one-year follow-up in severely obese patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB).
METHODS
This cohort study was based on data from patients with T2D undergoing LRYGB at a private hospital in Denmark and included 704 patients among whom 337 (48%) patients with T2D contributed with data in the analysis. Data were collected preoperatively and at a one-year follow-up. Preoperative T2D status was patient-reported and validated through the patient's medical record. At the one-year follow-up, partial remission was defined as an HbA1c concentration less than 7.3% with no use of antidiabetics. Continued T2D was defined as intake of diabetic medication or an HbA1c concentration > 7.3%. QoL was measured by the Moorehead-Ardelt QoL Questionnaire. Multiple linear regression was applied.
RESULTS
At the one-year follow-up, the prevalence of partial remission of T2D was 72.7%. No significant association was seen between partial remission of T2D after LRYGB and change in QoL one year later. Loss to follow-up was 35.8%.
CONCLUSIONS
The majority of patients with T2D experienced partial remission one year after undergoing LRYGB surgery. However, partial remission of T2D was not associated with an improved QoL.
FUNDING
none.
TRIAL REGISTRATION
not relevant.
Topics: Body Mass Index; Cohort Studies; Diabetes Mellitus, Type 2; Gastric Bypass; Humans; Laparoscopy; Obesity, Morbid; Quality of Life; Treatment Outcome; Weight Loss
PubMed: 33543699
DOI: No ID Found -
Journal of Psychiatry & Neuroscience :... Jul 2002The goal of treatment of major depression should be full remission. Many patients, however, fail to achieve or maintain symptom-free status. Residual depressive symptoms... (Review)
Review
The goal of treatment of major depression should be full remission. Many patients, however, fail to achieve or maintain symptom-free status. Residual depressive symptoms are common, even where there has been a robust response to antidepressant therapy. In clinical studies, approximately one-third of patients achieve a full remission, one-third experience a response and one-third are nonresponders. Partial remission is characterized by the presence of poorly defined residual symptoms. These symptoms typically include depressed mood, psychic anxiety, sleep disturbance, fatigue and diminished interest or pleasure. It is currently unclear which factors predict partial remission. However, it is clear that residual symptoms are powerful predictors of relapse, with relapse rates 3-6 times higher in patients with residual symptoms than in those who experience full remission. Residual symptoms are also associated with more medical and psychiatric visits, increased public assistance, disability benefits, thoughts of and attempts at suicide and chronicity. The risk of stroke and coronary events is also higher in patients with residual depressive symptoms. The substantial proportion of patients who achieve only partial remission has traditionally been neglected in antidepressant trials. Given that residual symptoms may relate, in part, to an incompatibility between patient and treatment, further research is needed to predict a better match. These symptoms are a clinically relevant state of illness, and the correct choice of initial antidepressant treatment should offer the greatest chance of achieving full remission.
Topics: Adult; Depressive Disorder, Major; Female; Humans; Male; Prevalence; Remission Induction; Treatment Outcome
PubMed: 12174733
DOI: No ID Found -
The Primary Care Companion For CNS... Sep 2022To evaluate the level of disability and identify an association between sociodemographic and clinical variables and disability in patients with bipolar disorder (BD)....
To evaluate the level of disability and identify an association between sociodemographic and clinical variables and disability in patients with bipolar disorder (BD). This cross-sectional study was conducted in a tertiary care general hospital psychiatric unit with 100 patients with BD in partial or full remission ( criteria) from January 2017 to March 2018. Patients were assessed using a semistructured proforma, the Mini-International Neuropsychiatric Interview 5.0-Hindi version, the Hamilton Depression Rating Scale (HDRS) or the Young Mania Rating Scale (YMRS), and the Indian Disability Evaluation and Assessment Scale (IDEAS). All patients with BD had at least mild disability. The mean ± SD IDEAS global score was 5.1 ± 2.59. Of the sample, 66% and 34% had mild or moderate, disability, respectively. The global score of disability was associated with the number of episodes, number of manic episodes, frequency of episodes in the past year, YMRS and HDRS scores, partial remission, and hospitalization. Categories of disability were associated with the type of last episode, type of remission, and treatment setting. Patients with BD had at least a mild level of disability even during remission. Disability worsened with the increasing number, frequency, and severity of episodes; number of manic episodes; partial remission; and hospitalization.
Topics: Bipolar Disorder; Cross-Sectional Studies; Diagnostic and Statistical Manual of Mental Disorders; Humans; Mania; Psychiatric Status Rating Scales
PubMed: 36126938
DOI: 10.4088/PCC.21m03183 -
Cureus Dec 2019Chronic graft-versus host disease (cGVHD) occurs in 30% to 70% of patients undergoing allogeneic hematopoietic cell transplantation (HCT). Cutaneous cGVHD affects 75% of... (Review)
Review
Chronic graft-versus host disease (cGVHD) occurs in 30% to 70% of patients undergoing allogeneic hematopoietic cell transplantation (HCT). Cutaneous cGVHD affects 75% of cGVHD patients, causing discomfort, limiting the range of movement, and increasing the risk of wound infections. Furthermore, systemic immunosuppression is often needed to treat cGVHD and long-term use can lead to adverse events. Optimal use of skin-directed therapies is integral to the management of cutaneous cGVHD and may decrease the amount of systemic immunosuppression required. This study reviewed English-language articles published from 1990 to 2017 that evaluated the effect of skin-directed treatments for cutaneous cGVHD. A total of 201 papers were identified, 164 articles were screened, 46 were read, and 18 publications were utilized in the review. Skin-directed treatments for cGVHD included topical steroids, topical calcineurin inhibitors, psoralen with ultraviolet A (PUVA) irradiation, ultraviolet A1 (UVA1) irradiation, and ultraviolet B (UVB) irradiation. We report the number of complete remissions, partial remissions, and systemic immunosuppression reduction in each study, as available. Twenty-two out of 30 (73.3%) patients experienced overall improvement with topical calcineurin inhibitors. At least 26 out of 76 patients (34.2%) receiving PUVA experienced complete remission, and 30 out of 76 patients (39.5%) experienced partial remission. In UVA1 studies, 44 out of 52 (84.6%) patients experienced overall improvement. In UVB studies, nine out of 14 patients (64.3%) experienced complete remission and four out of 14 patients (28.6%) experienced partial remission. As more HCTs are performed, more individuals will develop cGVHD. Awareness and optimal use of skin-directed therapies for cutaneous cGVHD may help improve patient outcomes and quality of life.
PubMed: 32025391
DOI: 10.7759/cureus.6462 -
Frontiers in Endocrinology 2022A literature search was conducted to identify publications addressing the early phases of lipid phenotypes in children and adults with either type 1 diabetes or type 2...
A literature search was conducted to identify publications addressing the early phases of lipid phenotypes in children and adults with either type 1 diabetes or type 2 diabetes. Medline, EMBASE, and Ovid were searched using the following search terms: Partial clinical remission (PR) of type 1 diabetes (T1D) is characterized by continued endogenous production of insulin and C-peptide following the diagnosis and the introduction of exogenous insulin therapy. PR is associated with improved glycemic control and reduced prevalence of diabetes complications. The theory of hyperglycemic memory was proposed to explain this concept of improved glycemic outcomes in remitters (those who experienced PR) versus non-remitters (those who did not experience PR). However, this theory is incomplete as it does not explain the dichotomy in early lipid phenotypes in T1D based on PR status, which is an understudied area in diabetology and lipidology. To fill this knowledge gap, we propose the Theory of Hyperlipidemic Memory of T1D. This theory is premised on our 5-year research on early post-diagnostic dichotomy in lipid phenotypes between remitters and non-remitters across the lifespan. It provides a more rigorous explanation for the differences in lifelong atherosclerotic cardiovascular disease (ASCVD) risk between remitters and non-remitters. We conducted 4 clinical studies in pediatric and adult subjects with diabetes mellitus to characterize the particulars of the hyperlipidemic memory. In the first investigation, we explored the impact of the presence or absence of PR on lipid parameters in children and adolescents with T1D. In the second, we investigated whether pubertal maturation influenced our findings in T1D; and whether these findings could be replicated in healthy, non-diabetic children and adolescents. In the third, we leveraged our findings from T1D and controls to investigate the mechanisms of early lipid changes in T2D by comparing the earliest lipid phenotype of subjects with type 2 diabetes (T2D) to those of remitters, non-remitters, and controls. In the fourth, we investigated the impact of PR on the earliest lipid phenotypes in adults with T1D and compared these early lipid data to those of T2D subjects and controls. This body of work across the lifespan in children, adolescents, and adults supports the Theory of Hyperlipidemic Memory. This new theory clarifies why PR largely determines the risks for early-phase dyslipidemia, mid-term microvascular disease risk, and long-term ASCVD risk in subjects with T1D.
Topics: Adolescent; Atherosclerosis; C-Peptide; Child; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Insulin; Lipids; Remission Induction
PubMed: 35432186
DOI: 10.3389/fendo.2022.819544 -
Clinical Journal of the American... Mar 2014Membranous nephropathy (MN) is an autoimmune disease usually associated with a nephrotic syndrome and it may progress to ESRD in the long term. Its etiology is often... (Review)
Review
Membranous nephropathy (MN) is an autoimmune disease usually associated with a nephrotic syndrome and it may progress to ESRD in the long term. Its etiology is often unknown (idiopathic MN), whereas other cases have a recognizable etiology (secondary MN). In idiopathic MN, the glomerular lesions are mainly caused by autoantibodies against a podocyte membrane protein, the M-type of phospholipase A2 receptor 1. The natural course of idiopathic MN is quite varied with spontaneous complete or partial remissions a relatively common occurrence. Patients with asymptomatic non-nephrotic proteinuria seldom progress and need only conservative management. Those with persistent full-blown nephrotic syndrome and those with declining renal function are candidates for specific treatment with any of several regimens. Cyclical therapy with alternating monthly intravenous and oral glucocorticoids combined with a cytotoxic agent can induce remission and preserve renal function in the long term. Cyclosporine or tacrolimus can induce remission, but relapses are frequent after the drug withdrawal. Mycophenolate mofetil monotherapy seems to be ineffective, but may be beneficial when administered together with steroids. The experience with adrenocorticotropic hormone, natural or synthetic, is limited to a few studies with short-term follow-up, but high rates of remission can be seen after prolonged treatment. A high rate of remission and good tolerance have also been reported with rituximab. Patients with moderate renal insufficiency may also benefit from treatment, but at a price of frequent and serious side effects. With these limitations in mind, idiopathic MN may be considered a treatable disease in many patients.
Topics: Autoantibodies; Biomarkers; Biopsy; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Kidney Glomerulus; Predictive Value of Tests; Recurrence; Remission Induction; Treatment Outcome
PubMed: 23813556
DOI: 10.2215/CJN.04160413 -
Journal of Clinical Medicine Jun 2021(1) Background: We sought to investigate the clinical outcome and to identify the independent predictors of clinical remission in a prospectively followed cohort of...
(1) Background: We sought to investigate the clinical outcome and to identify the independent predictors of clinical remission in a prospectively followed cohort of patients with primary membranous nephropathy (pMN). (2) Methods: We conducted a prospective, observational, non-interventional study that included 65 consecutive patients diagnosed with pMN between January 2015 and December 2019 at our department and followed for at least 24 months. The primary outcomes evaluated during the follow-up period were the occurrence of immunological and clinical remission (either complete or partial remission). Univariate and multivariate Cox proportional hazard regression analyses were performed to identify independent predictors of clinical remission. (3) Results: In the study cohort, 13 patients had a PLA2R-negative pMN, while, of those with PLA2R-associated pMN, 27 patients had a low anti-PLA2R antibody titer (<200 RU/mL), and 25 patients had a high anti-PLA2R antibody titer at baseline (≥200 RU/mL). The clinical outcome was better in patients with PLA2R-negative pMN compared to patients with PLA2R-positive pMN. These patients had a higher percentage of complete remissions (46.2%, compared to 33.3% in those with low anti-PLA2R antibody titer or 24% in those with high anti-PLA2R antibody titer), a faster decline of 24 h proteinuria and lower time to complete remission. In multivariate Cox regression analysis, patients with PLA2R-negative pMN had a 3.1-fold and a 2.87-fold higher chance for achieving a complete or partial remission compared to patients with high anti-PLA2R antibody titer or to all PLA2R-positive patients, respectively. Additionally, patients with a baseline 24 h proteinuria of less than 8 g/day and with an immunological remission at 24 months had a 2.4-fold (HR, 2.4; 95%CI, 1.19-4.8) and a 2.2-fold (HR, 2.26; 95%CI, 1.05-4.87), respectively, higher chance of achieving a clinical response. By contrary, renal function at diagnosis, type of therapeutic intervention or anti-PLA2R antibody titer did not predict the occurrence of clinical remission. (4) Conclusions: We identified a different clinical phenotype between PLA2R-positive and PLA2R-negative pMN. Additionally, we have shown that baseline proteinuria seems to be a more important predictor of clinical outcome than anti-PLA2R-ab titer.
PubMed: 34203607
DOI: 10.3390/jcm10122624 -
Blood Jul 2018Mature T- and natural killer (NK)-cell neoplasms comprise a group of morphologically, immunophenotypically, molecularly, and clinically heterogeneous disorders with... (Review)
Review
Mature T- and natural killer (NK)-cell neoplasms comprise a group of morphologically, immunophenotypically, molecularly, and clinically heterogeneous disorders with generally unfavorable outcome. Results of first-line chemotherapy are unsatisfactory for the most common T-cell lymphomas (peripheral T-cell lymphoma, not otherwise specified; angioimmunoblastic T-cell lymphoma; anaplastic large cell lymphomas; anaplastic lymphoma tyrosine kinase-negative) as well as for many other entities. High-dose therapy followed by autologous hematopoietic stem cell transplantation (HSCT) is widely recommended for consolidation after a complete or partial remission is achieved. However, about one-third of patients never reach transplantation because of early relapse or refractoriness. Targeted therapies have recently been developed; combinations with chemotherapy may improve outcomes, but long-term results from prospective studies are largely missing. In this situation, allogeneic HSCT remains a valuable treatment option inducing long-lived remissions in about 30% to 50% of patients with relapsed and refractory T-cell lymphoma able to proceed to transplantation. Results of allogeneic transplantation for consolidation in first remission are less defined and its indications remain controversial. With growing evidence that haploidentical HSCT also works in lymphoma, more patients can be brought to transplantation. Decreasing the morbidity and mortality of allogeneic transplantation is a continuous challenge. Integrating new drugs into transplant concepts and setting up prospective studies involving allogeneic transplantation remain unmet needs that warrant urgent study in a group of disorders in which classical chemotherapy and new drugs have generated results, which are far from optimal until today.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Disease Management; Drug Resistance, Neoplasm; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, T-Cell; Prognosis; Recurrence; Transplantation, Homologous; Treatment Outcome
PubMed: 29699989
DOI: 10.1182/blood-2018-01-791335 -
Computational and Mathematical Methods... 2021The pathogenesis of nephrotic syndrome (NS) is complex, and there are differences between regions. This study attempted to collect clinicopathological data of patients...
BACKGROUNDS
The pathogenesis of nephrotic syndrome (NS) is complex, and there are differences between regions. This study attempted to collect clinicopathological data of patients diagnosed with NS in Xinjiang and Heilongjiang in the past 2 years, so as to explore the onset features of NS and treatment and prognosis of patients in the two regions.
METHODS
Clinical data of 375 patients diagnosed with NS using renal biopsy in Xinjiang and Heilongjiang from March 2019 to March 2021 were collected. Clinical data of patients before treatment were collected, and the chi-square test was utilized to compare the differences in the sex distribution of two groups. The test was utilized to compare abnormal distribution continuous data between two groups, such as age, hemoglobin, plasma albumin, proteinuria, and triglycerides. Independent sample -test was utilized to compare normal distribution continuous data between two groups, such as serum total protein, serum creatinine, blood urea nitrogen, glomerular filtration rate, and total cholesterol. The independent sample -test was also used to compare the immunoglobulin levels and complement levels between the two groups after treatment, including IgA, IgG, IgM, C3, and C4. Kaplan-Meier method was used to analyze and plot the cumulative curves of complete remission rate and partial remission rate.
RESULTS
For 275 NS patients from Xinjiang, the male-to-female ratio was 0.81 : 1. For 84 patients from Heilongjiang, the male-to-female ratio was 1.05 : 1. The onset ages of patients in Xinjiang and Heilongjiang were 22-45 years old and 22-47 years old, respectively. Respectively, there were 221 cases (80.36%) and 66 cases (78.57%) of primary NS in Xinjiang and Heilongjiang. There were 54 cases (19.64%) and 18 cases (21.43%) of secondary NS in Xinjiang and Heilongjiang, respectively. There was no statistically significant difference in cause distribution between the two regions ( = 0.756). After treatment, immunoglobulin levels (IgA ( = 0.009), IgG ( = 0.002), IgM ( < 0.001)) and complement C3 ( < 0.001) and C4 ( < 0.001) levels in Xinjiang and Heilongjiang were statistically significant. 129 cases in Xinjiang (46.91%) and 55 cases in Heilongjiang (65.48%) were treated with glucocorticoid (GC) combined with immunosuppressive therapy, respectively. After receiving treatment, 67 (24.36%) of 275 patients in Xinjiang achieved complete remission, 166 (60.36%) achieved partial remission, 22 (26.19%) of 84 patients in Heilongjiang achieved complete remission, and 56 (66.67%) achieved partial remission, and there was no statistically significant difference in remission rate between the two regions ( = 0.159). Patients in Xinjiang and Heilongjiang achieved complete remission at an average of 10.34 weeks (9.98-10.70) and 9.95 weeks (9.26-10.65), respectively. There was no significant difference in complete remission rates between the two regions ( = 0.663). Patients in Xinjiang and Heilongjiang achieved partial remission at an average of 8.76 weeks (8.38-9.14) and 7.99 weeks (7.33-8.65), respectively. There was no significant difference in the partial remission rate between the two regions ( = 0.065).
CONCLUSION
The causes of NS in Xinjiang and Heilongjiang were similar. After treatment, there were differences in immunoglobulin levels (IgA, IgG, IgM) and complement levels (C3, C4) in the two regions. The main treatment methods used in the two regions were GC combined with immunosuppressive therapy. The prognosis of patients in the two regions was similar. The complete remission rate and partial remission rate after treatment in the two regions were similar, and the average time required to achieve complete remission and partial remission was also similar.
Topics: Adult; Antigen-Antibody Complex; China; Complement System Proteins; Computational Biology; Ethnicity; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Middle Aged; Nephrotic Syndrome; Prognosis; Remission Induction; Socioeconomic Factors; Young Adult
PubMed: 34868346
DOI: 10.1155/2021/8802670