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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 -
Cureus Jan 2023Mycophenolate mofetil (MMF) has been long used in the treatment of systemic lupus erythematosus (SLE). Further studies are warranted to investigate its long-term use in...
OBJECTIVES
Mycophenolate mofetil (MMF) has been long used in the treatment of systemic lupus erythematosus (SLE). Further studies are warranted to investigate its long-term use in maintenance treatment of lupus nephritis (LN). The purpose of this study was to describe our practice experience using MMF with regard to its indications, safety, tolerability, and treatment efficacy. We sought to identify rates of renal remission, flare and progression to end-stage renal disease (ESRD).
METHODS
In this retrospective chart review, we identified all patients treated with MMF between 1999 and 2019. Descriptive statistics were used to identify occurrence of remission, occurrence of flares, progression to ESRD, and occurrence of adverse effects.
RESULTS
One hundred and one patients were treated with MMF for a mean duration of 69 months. The most common indication was LN (90%). Among patients with LN, 60% achieved complete remission and 16% achieved partial remission at one-year follow-up. Ten patients flared while on maintenance therapy and seven patients flared after treatment was discontinued. Of the 40 patients who were treated for at least five years, one patient developed a flare. Of the 13 patients who were treated for at least 10 years, none developed a flare. One patient on maintenance therapy progressed to ESRD. The most common adverse effects were leukopenia (9%), nausea (7%) and diarrhea (6%).
CONCLUSION
Maintenance treatment with MMF constitutes an effective long-term treatment for lupus nephritis. Our practice demonstrates its tolerability over many years with few adverse effects, prevention of renal flares, and a low progression rate to ESRD.
PubMed: 36874710
DOI: 10.7759/cureus.34413 -
Pediatric Nephrology (Berlin, Germany) Nov 2019The pathogenesis of steroid-resistant nephrotic syndrome (SRNS) is not completely known. Recent advances in genomics have elucidated some of the molecular mechanisms and... (Review)
Review
The pathogenesis of steroid-resistant nephrotic syndrome (SRNS) is not completely known. Recent advances in genomics have elucidated some of the molecular mechanisms and pathophysiology of the disease. More than 50 monogenic causes of SRNS have been identified; however, these genes are responsible for only a small fraction of SRNS in outbred populations. There are currently no guidelines for genetic testing in SRNS, but evidence from the literature suggests that testing should be guided by the genetic architecture of the disease in the population. Notably, most genetic forms of SRNS do not respond to current immunosuppressive therapies; however, a small subset of patients with monogenic SRNS will achieve partial or complete remission with specific immunomodulatory agents, presumably due to non-immunosuppressive effects of these agents. We suggest a pragmatic approach to the therapy of genetic SRNS, as there is no evidence-based algorithm for the management of the disease.
Topics: DNA Mutational Analysis; Drug Resistance; Genetic Testing; Glucocorticoids; High-Throughput Nucleotide Sequencing; Humans; Immunologic Factors; Inheritance Patterns; Mutation; Nephrotic Syndrome; Precision Medicine; Remission Induction
PubMed: 30280213
DOI: 10.1007/s00467-018-4093-1 -
Frontiers in Endocrinology 2021Risk factors for atherosclerotic cardiovascular disease (ASCVD) are well established in type 2 diabetes (T2D), but not in type 1 diabetes (T1D). The impact of partial...
IMPORTANCE
Risk factors for atherosclerotic cardiovascular disease (ASCVD) are well established in type 2 diabetes (T2D), but not in type 1 diabetes (T1D). The impact of partial clinical remission (PR) on short-term ASCVD risk in T1D is unclear.
AIM
To investigate the impact of PR on the earliest ASCVD risk phenotype in adult T1D using factor analysis to compare the lipid phenotypes of T1D, T2D and controls after stratifying the T1D cohort into remitters and non-remitters.
SUBJECTS AND METHODS
A study of 203 adults subjects consisting of 86 T2D subjects, and 77 T1D subjects stratified into remitters (n=49), and non-remitters (n=28). PR was defined as insulin-dose adjusted HbA1c of ≤9, and obesity as a BMI ≥30 kg/m. Factor analysis was used to stratify the groups by ASCVD risk by factorizing seven lipid parameters (TC, LDL, HDL, non-HDL, TC/HDL, TG, TG/HDL) into 2 orthogonal factors (factor 1: TC*LDL; factor 2: HDL*TG) that explained 90% of the variance in the original seven parameters.
RESULTS
The analysis of individual lipid parameters showed that TC/HDL was similar between the controls and remitters (p=NS) but was significantly higher in the non-remitters compared to the remitters (p=0.026). TG/HDL was equally similar between the controls and remitters (p=NS) but was lower in the remitters compared to the non-remitters (p=0.007). TG was significantly lower in the remitters compared to T2D subjects (p<0.0001) but was similar between T2D subjects and non-remitters (p=NS). Non-HDL was significantly lower in the controls non-remitters (p=0.0003) but was similar between the controls and remitters (p=NS). Factor analysis showed that the means of factor 1 and factor 2 composite scores for dyslipidemia increased linearly from the controls, remitters, non-remitters to T2D, p value 0.0042 for factor 1, and <0.0001 for factor 2, with remitters having similar lipid phenotype as controls, while non-remitters were similar to T2D.
CONCLUSIONS
Partial clinical remission of T1D is associated with a favorable early lipid phenotype which could translate to reduced long-term CVD risk in adults.
Topics: Adolescent; Adult; Aged; Atherosclerosis; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Diabetes Mellitus, Type 1; Dyslipidemias; Female; Follow-Up Studies; Heart Disease Risk Factors; Humans; Lipids; Male; Middle Aged; Prognosis; Remission Induction; Retrospective Studies; Young Adult
PubMed: 34899592
DOI: 10.3389/fendo.2021.705565 -
BMC Nephrology May 2022Tripterygium Wilfordii Hook F (TwHF) preparation has been widely used in the treatments of IgA nephropathy (IgAN) in China. However, the effectiveness and safety of the...
BACKGROUND
Tripterygium Wilfordii Hook F (TwHF) preparation has been widely used in the treatments of IgA nephropathy (IgAN) in China. However, the effectiveness and safety of the new generation of TwHF preparation, KuxXian capsule, on the treatment of IgAN remains unknown.
METHODS
Here, we retrospectively describe our experience treating 55 consecutive IgAN patients with KunXian. We defined complete remission as proteinuria < 0.5 g/24 h and partial remission as proteinuria < 1 g/24 h, each also having > 50% reduction in proteinuria from baseline.
RESULTS
At first follow-up after KunXian treatment (5.7 weeks, IQR 4.7-7.9), all but two patients (96%) showed a reduction in proteinuria. The overall median proteinuria decreased from 2.23 g/day at baseline to 0.94 g/day (P < 0.001) at the first follow-up. During a median follow-up of 28 weeks after KunXian administration, 25(45.5%) patients achieved complete remission, 34 (61.8%) patients achieved complete/partial remission. Of the 12 patients discontinued KunXian treatment during the follow-up, the median proteinuria was increased from 0.97 g/24 h to 2.74 g/24 h after a median of 10.9 weeks (P = 0.004). Multivariable Cox models showed that female, treatment switching from previous generation of TwHF preparation, lower initial KunXian dosage, and higher proteinuria at baseline were independently associated proteinuria remission. Of the 20 pre-menopausal females, 12 of them developed oligomenorrhea or menstrual irregularity and ten of them developed amenorrhea.
CONCLUSION
KunXian is effectiveness and safety for the treatment of IgA nephropathy. Woman of childbearing age to be informed of the risk of ovarian failure after being treated with TwHF preparations.
Topics: Drugs, Chinese Herbal; Female; Glomerulonephritis, IGA; Humans; Male; Proteinuria; Retrospective Studies; Treatment Outcome; Tripterygium
PubMed: 35538439
DOI: 10.1186/s12882-022-02814-7 -
Medicine May 2021To investigate the clinicopathological features and outcomes of primary IgA nephropathy with nephrotic-range proteinuria in Chinese children. Patients with biopsy-proven... (Observational Study)
Observational Study
To investigate the clinicopathological features and outcomes of primary IgA nephropathy with nephrotic-range proteinuria in Chinese children. Patients with biopsy-proven IgA nephropathy and nephrotic-range proteinuria between January 2011 and December 2017 were included, and their proteinuria and renal function were followed up. A total of 90 patients were enrolled, and 21.1% (19/90) of them had decreased renal function at diagnosis. Complete remission, partial remission, and no response of proteinuria occurred in 88.6% (70/79), 10.1% (8/79), and 1.3% (1/79), respectively, of the 79 patients who were followed up for 6 to 104 months. 73.7% (14/19) of the patients with decreased renal function at diagnosis recovered to normal level while 26.3% (5/19) of them did not recover or progressed to end-stage renal disease. Two patients with normal renal function at diagnosis progressed to renal insufficiency during follow-up period. By multivariate analysis, the risk for renal function deterioration was significantly higher in the partial remission and no response groups than in the complete remission group. Remission of proteinuria was important for improving renal prognosis in children with IgA nephropathy and nephrotic-range proteinuria. The outcomes for pediatric patients appeared to be better than that reported in adults.
Topics: Adolescent; Biopsy; Child; Child, Preschool; China; Drug Therapy, Combination; Female; Follow-Up Studies; Glomerular Mesangium; Glomerulonephritis, IGA; Glucocorticoids; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Male; Proteinuria; Remission Induction; Retrospective Studies; Treatment Outcome
PubMed: 34032732
DOI: 10.1097/MD.0000000000026050 -
Psychological Medicine Jun 2023Serotonin-reuptake inhibitors (SRIs) are first-line pharmacotherapy for the treatment of body dysmorphic disorder (BDD), a common and severe disorder. However, prior... (Clinical Trial)
Clinical Trial
BACKGROUND
Serotonin-reuptake inhibitors (SRIs) are first-line pharmacotherapy for the treatment of body dysmorphic disorder (BDD), a common and severe disorder. However, prior research has not focused on or identified definitive predictors of SRI treatment outcomes. Leveraging precision medicine techniques such as machine learning can facilitate the prediction of treatment outcomes.
METHODS
The study used 10-fold cross-validation support vector machine (SVM) learning models to predict three treatment outcomes (i.e. response, partial remission, and full remission) for 97 patients with BDD receiving up to 14-weeks of open-label treatment with the SRI escitalopram. SVM models used baseline clinical and demographic variables as predictors. Feature importance analyses complemented traditional SVM modeling to identify which variables most successfully predicted treatment response.
RESULTS
SVM models indicated acceptable classification performance for predicting treatment response with an area under the curve (AUC) of 0.77 (sensitivity = 0.77 and specificity = 0.63), partial remission with an AUC of 0.75 (sensitivity = 0.67 and specificity = 0.73), and full remission with an AUC of 0.79 (sensitivity = 0.70 and specificity = 0.79). Feature importance analyses supported constructs such as better quality of life and less severe depression, general psychopathology symptoms, and hopelessness as more predictive of better treatment outcome; demographic variables were least predictive.
CONCLUSIONS
The current study is the first to demonstrate that machine learning algorithms can successfully predict treatment outcomes for pharmacotherapy for BDD. Consistent with precision medicine initiatives in psychiatry, the current study provides a foundation for personalized pharmacotherapy strategies for patients with BDD.
Topics: Humans; Body Dysmorphic Disorders; Machine Learning; Quality of Life; Selective Serotonin Reuptake Inhibitors; Treatment Outcome
PubMed: 35000652
DOI: 10.1017/S0033291721005390 -
Langenbeck's Archives of Surgery Feb 2022Bariatric surgery has proven to be the most efficient treatment for obesity and type 2 diabetes mellitus (T2DM). Despite detailed qualification, desirable outcome after...
PURPOSE
Bariatric surgery has proven to be the most efficient treatment for obesity and type 2 diabetes mellitus (T2DM). Despite detailed qualification, desirable outcome after an intervention is not achieved by every patient. Various risk prediction models of diabetes remission after metabolic surgery have been established to facilitate the decision-making process. The purpose of the study is to validate the performance of available risk prediction scores for diabetes remission a year after surgical treatment and to determine the optimal model.
METHODS
A retrospective analysis comprised 252 patients who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) between 2009 and 2017 and completed 1-year follow-up. The literature review revealed 5 models, which were subsequently explored in our study. Each score relationship with diabetes remission was assessed using logistic regression. Discrimination was evaluated by area under the receiver operating characteristic (AUROC) curve, whereas calibration by the Hosmer-Lemeshow test and predicted versus observed remission ratio.
RESULTS
One year after surgery, 68.7% partial and 21.8% complete diabetes remission and 53.4% excessive weight loss were observed. DiaBetter demonstrated the best predictive performance (AUROC 0.81; 95% confidence interval (CI) 0.71-0.90; p-value > 0.05 in the Hosmer-Lemeshow test; predicted-to-observed ratio 1.09). The majority of models showed acceptable discrimination power. In calibration, only the DiaBetter score did not lose goodness-of-fit in all analyzed groups.
CONCLUSION
The DiaBetter score seems to be the most appropriate tool to predict diabetes remission after metabolic surgery since it presents adequate accuracy and is convenient to use in clinical practice. There are no accurate models to predict T2DM remission in a patient with advanced diabetes.
Topics: Bariatric Surgery; Diabetes Mellitus, Type 2; Gastrectomy; Gastric Bypass; Humans; Obesity, Morbid; Retrospective Studies; Treatment Outcome
PubMed: 34255166
DOI: 10.1007/s00423-021-02260-3 -
Frontiers in Endocrinology 2022To propose a new definition of partial remission (PR) for patients with type 1 diabetes (T1D) of all-ages using insulin dose and glycated albumin (GA), and find the...
OBJECTIVE
To propose a new definition of partial remission (PR) for patients with type 1 diabetes (T1D) of all-ages using insulin dose and glycated albumin (GA), and find the optimal cut-off values for stimulated C-peptide to diagnose PR in different age-groups.
RESEARCH DESIGN AND METHODS
Patients with newly diagnosed T1D (n=301) were included. GA/insulin dose was used to diagnose PR, and insulin dose-adjusted glycated albumin (IDAGA) was proposed to facilitate clinical application. The optimal diagnostic levels of IDAGA and stimulated C-peptide were determined in different age-groups (≤ 12y, 12-18y and ≥ 18y). Furthermore, the diagnostic consistency between different PR definitions was studied.
RESULTS
GA≤ 23%/insulin dose ≤ 0.5u/kg/day was used to define PR, and IDAGA (GA (%) + 40 * insulin dose(u/kg/day)) ≤ 40 was feasible in all age-groups. Whereas, the optimal diagnostic level showed difference for stimulated C-peptide (265.5, 449.3 and 241.1 pmol/L for the ≤ 12y, 12-18y and ≥ 18y age-group, respectively). About 40% of patients met the PR definition by stimulated C-peptide but not GA/insulin dose or IDAGA, who showed dyslipidemia and higher insulin resistance.
CONCLUSIONS
A new definition of the PR phase is proposed using GA/insulin dose, and the calculated IDAGA≤ 40 applies to all age-groups. The stimulated C-peptide to diagnose PR is the highest in the 12-18y age-group, which reflects the effect of puberty on metabolism. For patients with insulin resistance, it is not recommended to use stimulated C-peptide alone to diagnose PR.
Topics: C-Peptide; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Glycation End Products, Advanced; Humans; Insulin; Insulin Resistance; Serum Albumin; Glycated Serum Albumin
PubMed: 35928900
DOI: 10.3389/fendo.2022.938059 -
Journal of Clinical Medicine Jan 2024Nowadays, highly selective biological drugs offer the possibility of treating severe type 2 asthma. However, in the real-life setting, it is crucial to confirm the...
Nowadays, highly selective biological drugs offer the possibility of treating severe type 2 asthma. However, in the real-life setting, it is crucial to confirm the validity of the chosen biological treatment by evaluating the achievement of clinical remission. The main aims of this real-life study were to evaluate the efficacy of dupilumab in terms of clinical, functional, and inflammatory outcomes at 6, 12, 18, and 24 months of treatment and to estimate the percentage of patients achieving partial or complete clinical remission at 12 and 24 months of treatment. In addition, we attempted to identify whether baseline clinical characteristics of patients could be associated with clinical remission at 24 months of treatment. In this observational prospective study, 20 outpatients with severe uncontrolled eosinophilic asthma were prescribed dupilumab and followed-up after 6, 12, 18, and 24 months of treatment. At each patient visit, need for oral corticosteroids (OCS) and corticosteroid required dose, number of exacerbations during the previous year or from the previous visit, asthma control test (ACT) score, pre-bronchodilator forced expiratory volume in the 1st second (FEV), fractional exhaled nitric oxide at a flow rate of 50 mL/s (FeNO), and blood eosinophil count were assessed. The number of OCS-dependent patients was reduced from 10 (50%) at baseline to 5 (25%) at one year (T12) and 2 years (T24). The average dose of OCS required by patients demonstrated a significant reduction at T12 (12.5 ± 13.75 mg vs. 2.63 ± 3.94 mg, = 0.015), remaining significant even at T24 (12.5 ± 13.75 mg vs. 2.63 ± 3.94 mg, = 0.016). The number of exacerbators showed a statistically significant decrease at T24 (10 patients, 50% vs. 3 patients, 15%, = 0.03). The mean number of exacerbations demonstrated a statistically significant reduction at T24 (1.45 ± 1.58 vs. 0.25 ± 0.43, = 0.02). The ACT score improved in a statistically significant manner at T12 (15.30 ± 4.16 vs. 21.40 ± 2.35, < 0.0001), improving further at T24 (15.30 ± 4.16 vs. 22.10 ± 2.59, < 0.0001). The improvement in pre-bronchodilator FEV values reached statistical significance at T24 (79.5 ± 14.4 vs. 87.7 ± 13.8, = 0.03). The reduction in flow at the level of the small airways (FEF) also demonstrated an improvement, although it did not reach statistical significance either at T12 or T24. A total of 11 patients (55%) showed clinical remission at T12 (6 complete + 5 partial) and 12 patients (60%) reached clinical remission at T24 (9 complete + 3 partial). Only obesity was associated with a negative odds ratio (OR) for achieving clinical remission at T24 (OR: 0.03, 95% CI: 0.002-0.41, = 0.004). No other statistically significant differences in baseline characteristics emerged between patients who reached clinical remission at T24 and the group of patients who did not achieve this outcome. Dupilumab appears to be an effective drug in promoting achievement of clinical remission in patients with severe uncontrolled eosinophilic asthma. The achievement of clinical remission should be continuously evaluated during treatment. Further studies are needed to clarify whether certain baseline clinical characteristics can help predict dupilumab favorable outcomes.
PubMed: 38202298
DOI: 10.3390/jcm13010291