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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 -
Inflammatory Bowel Diseases Aug 2016Mucosal healing (MH) in inflammatory bowel disease has been associated with improved long-term clinical outcomes. Uncertainty remains as to the magnitude of this effect... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mucosal healing (MH) in inflammatory bowel disease has been associated with improved long-term clinical outcomes. Uncertainty remains as to the magnitude of this effect and to how this association changes with time and degree of healing.
METHODS
PubMed, EMBASE, and Web of Science searches identified 1570 citations. Screening of abstracts identified 155 articles for full-text review, of which 19 met inclusion criteria. For 3 outcomes of interest (surgeries, hospitalizations, remission), weighted random-effects meta-analysis was performed.
RESULTS
In pooled analysis, MH predicted fewer major abdominal surgeries (relative risk [RR], 0.34; 95% confidence interval [CI], 0.26-0.46), increased remission (RR, 1.84; 95% CI, 1.43-2.36), and fewer hospitalizations (RR, 0.58; 95% CI, 0.42-0.78). Complete MH and partial MH both showed significantly higher rates of favorable outcomes. Separate analyses for Crohn's disease and ulcerative colitis showed identical patterns for surgeries and remission. When subjects with no healing were excluded, and complete versus partial healing was compared, rates of surgery were not significantly different (RR, 0.82; 95% CI, 0.46-1.44). However, complete healing was superior in predicting corticosteroid-free remission (RR, 1.71; 95% CI, 1.24-2.34). Meta-regression found that the predictive power of this complete versus partial healing distinction was strongly associated with the duration of follow-up after endoscopy.
CONCLUSIONS
MH is a strong predictor of fewer surgeries, long-term clinical remission, and fewer hospitalizations. Complete healing is not significantly more favorable than partial healing for predicting surgeries or hospitalizations, but it did predict higher rates of clinical remission. This benefit of complete MH over partial healing increases with follow-up time.
Topics: Adrenal Cortex Hormones; Endoscopy, Gastrointestinal; Hospitalization; Humans; Inflammatory Bowel Diseases; Intestinal Mucosa; Prognosis; Remission Induction; Wound Healing
PubMed: 27206015
DOI: 10.1097/MIB.0000000000000816 -
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 -
Terapevticheskii Arkhiv Dec 2018Analysis of etiology, clinical and morphological manifestations, approaches to therapy and prognosis of membranoproliferative glomerulonephritis (MPGN).
AIM
Analysis of etiology, clinical and morphological manifestations, approaches to therapy and prognosis of membranoproliferative glomerulonephritis (MPGN).
MATERIALS AND METHODS
Cases of MPGN were retrospectively identified in the period 2000-2017 with subsequent analysis of etiology, clinical data and morphology (including deposits of immunoglobulins (Ig) and C3 complement fractions). The achievement of complete and partial remissions (PR, CR), overall survival, progression (by composite endpoint: decrease in the estimated GFR (eGFR) ≥50% from the baseline or eGFR <15 ml/min/1.73 m2 or the onset of dialysis).
RESULTS
214 cases of MPGN entered the study with the average age of 44±16 years. Most patients had nephrotic syndrome and significant hematuria. In 58.4% of cases, eGFR was <60 mL/min/1.73 m2, and every fifth patient had CKD 4 or 5 stages. The prevalence of MPGN among all biopsy-confirmed glomerulopathies was 9.3%. Idiopathic MPGN (iMPGN) was detected in 30.4% of cases, secondary MSGN (sMPGN) - in 69.6% (autoimmune diseases - 34.1%, infectious diseases - 16.4%, monoclonal gammopathies - 9.3%, complement-mediated damage - 9.8%). Ig+C3+MPGN was mainly associated with autoimmune diseases and infections; C3-glomerulopathy or thrombotic microangiopathy were most often causes of Ig-C3+MPGN; Ig-C3-/Ig+C3-MPGN had heterogeneous etiology. The median follow-up period was 28 [7; 37] months. The 10-year total cumulative patient and renal survival rates were 71 and 50%, respectively (without differences between sMPGN and iMPGN). The frequency of the PR/CR was 50% (iMPGN - 46.2%, sMPGN - 51.3%) depending on the etiology of the MPGN (p=0.049). The cumulative 10-year progression-free renal survival was nearly 100% in cases with PR/CR and 0% in non-responders.
CONCLUSION
MPGN is a severe variant of glomerular damage with a heterogeneous etiological structure and an unfavorable prognosis. Targeted clinical and morphological diagnostics of MPGN allows to identify the cause of the disease in most cases. This approach is reliable for the adequate treatment choice and improvement of outcomes in MPGN.
Topics: Adult; Complement C3; Glomerulonephritis, Membranoproliferative; Humans; Kidney; Middle Aged; Retrospective Studies; Russia
PubMed: 30701832
DOI: 10.26442/00403660.2018.12.000007 -
Seminars in Arthritis and Rheumatism Oct 2016Both the diagnosis and treatment of the syndrome of synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) remain difficult. We describe a case series of 21...
INTRODUCTION
Both the diagnosis and treatment of the syndrome of synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) remain difficult. We describe a case series of 21 patients with SAPHO and their response to several pharmacological treatments.
METHODS
Clinical and biochemical data, along with medical imaging, were collected from the medical records of 21 patients, diagnosed as SAPHO during follow-up between 2005 and 2013. Symptoms and inflammatory markers were recorded twice, once at first patient presentation, and once at the end of follow-up. Synovitis, acne, pustulosis, hyperostosis, and osteitis were labeled as defining features. All treatment options were categorized according to their respective responses (full remission, partial remission, and no disease control).
RESULTS
There was a female predominance and a median age of 32 years (range: 12-54 years). Median follow-up duration was 45 months (range: 0-188 months). Total prevalence of defining features in this cohort increased for each defining feature during follow-up, except for acne. All patients reached full or partial remission at the end of follow-up. A total of 14 patients were treated with bisphosphonates. Of which 8 of them went into full or partial remission.
DISCUSSION AND CONCLUSION
In our case series, none of the patients had the full presentation of SAPHO at the first consultation. Some presented with symptoms suggestive for psoriatic arthritis. This explains why diagnosis of SAPHO can be challenging. Full remission was induced in the majority of individuals. Bisphosphonates seem to be a noteworthy treatment option. We suggest a prospective placebo-controlled clinical trial with bisphosphonates to confirm this observation.
Topics: Acquired Hyperostosis Syndrome; Adolescent; Adult; Bone Density Conservation Agents; Child; Diphosphonates; Female; Humans; Male; Middle Aged; Retrospective Studies; Sex Factors; Treatment Outcome; Young Adult
PubMed: 27369452
DOI: 10.1016/j.semarthrit.2016.04.004 -
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 -
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 -
Frontiers in Endocrinology 2022Despite advances in the characterization of partial clinical remission (PR) of type 1 diabetes, an accurate definition of PR remains problematic. Two recent studies in... (Review)
Review
Despite advances in the characterization of partial clinical remission (PR) of type 1 diabetes, an accurate definition of PR remains problematic. Two recent studies in children with new-onset T1D demonstrated serious limitations of the present gold standard definition of PR, a stimulated C-peptide (SCP) concentration of >300 pmol/L. The first study employed the concept of insulin sensitivity score (ISS) to show that 55% of subjects with new-onset T1D and a detectable SCP level of >300 pmol/L had low insulin sensitivity (IS) and thus might not be in remission when assessed by insulin-dose adjusted A1c (IDAA1c), an acceptable clinical marker of PR. The second study, a randomized controlled trial of vitamin D (ergocalciferol) administration in children and adolescents with new-onset T1D, demonstrated no significant difference in SCP between the ergocalciferol and placebo groups, but showed a significant blunting of the temporal trend in both A1c and IDAA1c in the ergocalciferol group. These two recent studies indicate the poor specificity and sensitivity of SCP to adequately characterize PR and thus call for a re-examination of current approaches to the definition of PR. They demonstrate the limited sensitivity of SCP, a static biochemical test, to detect the complex physiological changes that occur during PR such as changes in insulin sensitivity, insulin requirements, body weight, and physical activity. These shortcomings call for a broader definition of PR using a combination of functional markers such as IDAA1c and ISS to provide a valid assessment of PR that reaches beyond the static changes in SCP alone.
Topics: Adolescent; Biomarkers; Body Weight; C-Peptide; Child; Diabetes Mellitus, Type 1; Ergocalciferols; Exercise; Glycated Hemoglobin; Health Status Indicators; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Randomized Controlled Trials as Topic; Remission Induction
PubMed: 35592786
DOI: 10.3389/fendo.2022.884219 -
Frontiers in Pharmacology 2021Some encouraging findings of Chinese herbal medicine (CHM) in management of idiopathic membranous nephropathy (IMN) obtained in the setting of clinical trials are hard... (Review)
Review
Some encouraging findings of Chinese herbal medicine (CHM) in management of idiopathic membranous nephropathy (IMN) obtained in the setting of clinical trials are hard to validate in the daily clinical practice due to a complicated treatment scenario of CHM in practice. The primary objective of this registry is to provide a description of treatment patterns used in management of IMN and assess clinical remission in daily practice in a Chinese population sample with IMN. This is a prospective, multicenter cohort which will comprise 2000 adults with IMN regardless of urinary protein levels that will be recruited from 11 nephrology centers across China. The participants will be followed for up to at least 2 years. Primary outcome is composite remission (either complete remission or partial remission) 24 months after enrolment. The secondary outcomes are complete remission, partial remission, time to remission, no response, relapse, proteinuria, annual change of glomerular filtration rate, antibodies against PLA2R, and composite endpoint of 40% reduction of glomerular filtration rate, doubling of serum creatinine, end-stage renal disease, and death. Propensity score analysis will be used for matching and adjustment. This study has been approved by the Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine (BF2020-094-01). Results of the study will be published in both national and international peer-reviewed journals, and presented at scientific conferences. Investigators will inform the participants as well as other IMN patients of the findings via health education. : ChiCTR2000033680 (prospectively registered).
PubMed: 35046805
DOI: 10.3389/fphar.2021.760482