-
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 -
Journal of Crohn's & Colitis Mar 2024Although ulcerative proctitis [UP] can dramatically impair quality of life, treatment efficacy has been poorly investigated in UP as it was historically excluded from...
BACKGROUND
Although ulcerative proctitis [UP] can dramatically impair quality of life, treatment efficacy has been poorly investigated in UP as it was historically excluded from phase 2/3 randomised controlled trials in ulcerative colitis. Our aim was to assess the effectiveness and safety of tofacitinib for the treatment of UP.
METHODS
We conducted a retrospective, multicentre study in 17 GETAID centres, including consecutive patients with UP treated with tofacitinib. The primary endpoint was steroid-free remission between Week 8 and Week 14, defined as a partial Mayo score of 2 [and no individual subscore above 1]. Secondary outcomes included clinical response and steroid-free remission after induction and at 1 year.
RESULTS
All the 35 enrolled patients previously received anti-tumour necrosis factor [TNF] therapy and 88.6% were exposed to at least two lines of biologics. At baseline, the median partial Mayo score was 7 (intequartile range [IQR] [5.5-7]). After induction [W8-W14], 42.9% and 60.0% of patients achieved steroid-free remission and clinical response, respectively. At 1 year, the steroid-free clinical remission and clinical response rates were 39.4% and 45.5%, respectively, and 51.2% [17/33] were still receiving tofacitinib treatment. Survival without tofacitinib withdrawal was estimated at 50.4% (95% confidence interval [CI] [35.5-71.6]) at 1 year. Only a lower partial Mayo at baseline was independently associated with remission at induction (0dds ratio [OR] = 0.56 for an increase of 1, (95% CI [0.33-0.95], p = 0.03). Five [14.3%] adverse events were reported, with one leading to treatment withdrawal [septic shock secondary to cholecystitis].
CONCLUSION
Tofacitinib may offer a therapeutic option for patients with refractory UP.
Topics: Humans; Tumor Necrosis Factor Inhibitors; Retrospective Studies; Quality of Life; Proctitis; Piperidines; Pyrimidines
PubMed: 37796025
DOI: 10.1093/ecco-jcc/jjad169 -
American Journal of Kidney Diseases :... Dec 2021B-cell depletion with rituximab has emerged as a first-line therapy for primary membranous nephropathy (MN). However, most patients do not achieve complete remission...
RATIONALE & OBJECTIVE
B-cell depletion with rituximab has emerged as a first-line therapy for primary membranous nephropathy (MN). However, most patients do not achieve complete remission with rituximab monotherapy. In this case series, we report longer-term remission and relapse rates, anti-phospholipase A receptor (PLAR) antibody levels, B-cell levels, and serious adverse events in patients with primary MN who received rituximab combined with an initial short course of low-dose oral cyclophosphamide and a course of rapidly tapered prednisone.
STUDY DESIGN
Single-center retrospective case series.
SETTING & PARTICIPANTS
60 consecutive patients with primary MN treated with the combination of rituximab, low-dose cyclophosphamide, and prednisone at the Vasculitis and Glomerulonephritis Center at the Massachusetts General Hospital.
FINDINGS
After treatment initiation, median follow-up was 38 (interquartile range [IQR], 25-62) months; 100% of patients achieved partial remission, defined as a urinary protein-creatinine ratio (UPCR) < 3 g/g and a 50% reduction from baseline, at a median of 3.4 months. By 2 years after treatment initiation, 83% achieved complete remission, defined as a UPCR < 0.3 g/g. The median time to complete remission was 12.4 months. Immunologic remission (defined by an anti-PLAR titer < 14 RU/mL) was achieved by 86% and 100% of anti-PLAR seropositive patients (n = 29) at 3 and 6 months, respectively, after treatment initiation. After 1 year, the median UPCR fell from 8.4 (IQR, 5.0-10.7) to 0.3 (IQR, 0.2-0.8) g/g (P < 0.001). No patient relapsed throughout the duration of B-cell depletion. Relapse occurred in 10% of patients at 2 years after the onset of B-cell reconstitution following the last rituximab dose. Over a combined follow-up time of 228 patient-years, 18 serious adverse events occurred. One death occurred unrelated to treatment or primary MN, and 1 patient progressed to kidney failure requiring kidney replacement therapy.
LIMITATIONS
Absence of a comparison group.
CONCLUSIONS
All patients with primary MN treated with combination therapy achieved partial remission and most achieved a durable complete remission with an acceptable safety profile.
Topics: Cyclophosphamide; Follow-Up Studies; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Prednisone; Receptors, Phospholipase A2; Retrospective Studies; Rituximab; Treatment Outcome
PubMed: 34174365
DOI: 10.1053/j.ajkd.2021.04.014 -
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 -
Frontiers in Physiology 2023To explore the clinical value of fecal calprotectin (FC) for evaluating disease activity in patients with Crohn's disease (CD) and its relationship with disease...
To explore the clinical value of fecal calprotectin (FC) for evaluating disease activity in patients with Crohn's disease (CD) and its relationship with disease location. Patients with CD were enrolled retrospectively, and clinical data, including FC levels, were collected. Clinical activity was assessed using the Crohn's disease activity index (CDAI). Endoscopic activity was assessed using a simple endoscopic score for Crohn's disease (SES-CD). The partial SES-CD (pSES-CD) was scored for the size of ulcers in each segment as defined by the SES-CD and was calculated as the sum of segmental ulcer scores. This study included 273 CD patients. The FC level was significantly positively correlated with the CDAI and SES-CD, with correlation coefficients of 0.666 and 0.674, respectively. The median FC levels in patients with clinical remission and mildly active and moderately-severely active disease were 41.01, 164.20, and 444.45 μg/g. These values were 26.94, 66.77, and 327.22 μg/g during endoscopic remission and mildly and moderately-severely active stages, respectively. Compared with c-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), and other biomarker parameters, FC was better at predicting disease activity for CD patients. For an FC <74.52 μg/g, the area under the curve (AUC) for predicting clinical remission was 0.86, with a sensitivity of 89.47% and a specificity of 71.70%. Moreover, endoscopic remission was predicted with a sensitivity of 68.02% and a specificity of 85.53%. The AUC was 0.83, and the cutoff value was 80.84 μg/g. In patients with ileal and (ileo) colonic CD, FC was significantly correlated with the CDAI, SES-CD, and pSES-CD. The correlation coefficients were 0.711 (CDAI), 0.473 (SES-CD), and 0.369 (pSES-CD) in patients with ileal CD and 0.687, 0.745, and 0.714 in patients with (ileo) colonic CD, respectively. For patients in remission, those in the active stage, and those with large or very large ulcers, differences in FC levels were not significant between patients with ileal and (ileo) colonic CD. FC is a reliable predictor of disease activity in patients with CD, including those with ileal CD. FC is thus recommended for the routine follow-up of patients with CD.
PubMed: 37324392
DOI: 10.3389/fphys.2023.1186665 -
Frontiers in Immunology 2023Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal non-Hodgkin lymphoma with a poor prognosis. We aimed to evaluate the prognostic impact of...
BACKGROUND
Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal non-Hodgkin lymphoma with a poor prognosis. We aimed to evaluate the prognostic impact of circulating NK cells in PCNSL.
MATERIALS AND METHODS
Patients diagnosed with PCNSL who were treated at our institution between December 2018 and December 2019 were retrospectively screened. Patient variables including age, sex, Karnofsky performance status, diagnostic methods, location of lesions, lactate dehydrogenase, cerebrospinal fluids (CSF), and vitreous fluids involvement or not were documented. NK cell count and NK cell proportion (NK cell count/lymphocyte count) in the peripheral blood were evaluated by flow cytometry. Some patients underwent two consecutive NK cell tests before and three weeks after chemotherapy (before the next chemotherapy). The fold change in NK cell proportion and NK cell counts were calculated. CD56-positive NK cells in tumor tissue were assessed by immunohistochemistry. NK cell cytotoxicity assay was performed using flow cytometry.
RESULTS
A total of 161 patients with PCNSL were included in this study. The median NK cell count of all NK cell tests was 197.73/μL (range 13.11-1889.90 cells/μL). The median proportion of NK cells was 14.11% (range 1.68-45.15%) for all. Responders had a higher median NK cell count (<0.0001) and NK cell proportion (<0.0001) than non-responders. Furthermore, Responders had a higher median fold change in NK cell proportion than non-responders (=0.019) or patients in complete remission/partial remission (<0.0001). A higher median fold change in NK cell count was observed in responders than in non-responders (=0.0224) or patients in complete remission/partial remission (=0.0002). For newly diagnosed PCNSL, patients with a high NK cell count (>165 cells/μL) appeared to have a longer median overall survival than those with a low NK cell count (=0.0054). A high fold change in the proportion of NK cells (>0.1957; =0.0367) or NK cell count (>0.1045; =0.0356) was associated with longer progression-free survival. Circulating NK cells from newly-diagnosed PCNSL demonstrated an impaired cytotoxicity capacity compared to those from patients with PCNSL in complete remission or healthy donors.
CONCLUSION
Our study indicated that circulating NK cells had some impact on the outcome of PCNSL.
Topics: Humans; Prognosis; Retrospective Studies; Lymphoma, Non-Hodgkin; Killer Cells, Natural; Central Nervous System
PubMed: 37426647
DOI: 10.3389/fimmu.2023.1191033 -
Frontiers in Pharmacology 2023The effectiveness and safety of vedolizumab (VDZ) against ulcerative colitis (UC) have been validated in several randomized controlled trials and real-world studies in...
The effectiveness and safety of vedolizumab (VDZ) against ulcerative colitis (UC) have been validated in several randomized controlled trials and real-world studies in Western countries. However, there are few studies on VDZ in Asia, and the follow-up period for these studies is generally short. Therefore, this study evaluates the long-term effectiveness and safety of VDZ in Chinese patients with UC. This retrospective study included patients with moderate to severe UC treated with VDZ between September 2019 and April 2022 at Sir Run Run Shaw Hospital, College of Medicine Zhejiang University. Clinical response and remission were assessed using the patient reported outcomes and the partial Mayo Score, and mucosal remission and healing were assessed using the Mayo Endoscopy Score. The primary endpoint was defined as clinical remission at week 14, and secondary endpoints included clinical response and steroid-free clinical remission at week 14, clinical response, clinical remission, and steroid-free clinical remission at week 52, and mucosal remission and healing at weeks 14 ± 8 and 52 ± 8. Overall, 64 patients with moderate to severe UC were enrolled. The clinical response, clinical remission, and steroid-free clinical remission rates at week 14 were 73.4% (47/64), 65.6% (42/64), and 54.7% (35/64), respectively. Mucosal remission and healing rates at week 14 ± 8 were 64.7% (22/34) and 38.2% (13/34), respectively. A total of 48 patients were treated with VDZ for 52 weeks. Based on intention-to-treat analysis, the clinical response, clinical remission, and steroid-free clinical remission rates at week 52 were 68.8% (44/64), 64.1% (41/64), and 64.1% (41/64), respectively. Mucosal remission and healing rates at week 52 ± 8 were 70.6% (12/17) and 35.3% (6/17), respectively. During the follow-up period, the most common adverse event was skin rash (6/64). No cases of acute infusion reactions, delayed allergic reactions, new hepatitis B infections, active tuberculosis, or malignant tumors were reported. In this single-center retrospective real-world study, the effectiveness of long-term use of VDZ for Chinese patients with UC was similar to the outcomes previously reported in other geographical regions and populations; no new safety signals were found compared with other registered studies.
PubMed: 37214457
DOI: 10.3389/fphar.2023.1188751 -
Scientific Reports Apr 2023To evaluate the efficacy and safety of rituximab (RTX) in the treatment of primary focal segmental glomerulosclerosis (FSGS) in adults. The clinical data of patients...
To evaluate the efficacy and safety of rituximab (RTX) in the treatment of primary focal segmental glomerulosclerosis (FSGS) in adults. The clinical data of patients with primary FSGS who received RTX treatment in the First Affiliated Hospital of Zhengzhou University were analyzed retrospectively. The selected patients received RTX twice or four times, with a single dose of 375 mg/m, and the interval between two times of administration of RTX was 2-4 weeks. The treatment target is to achieve the clearance of B cells (peripheral blood B cell count < 5/μl). The primary outcome measures were remission and recurrence of renal disease, and the secondary outcome measures were adverse events and renal outcomes. A total of 14 FSGS patients were included, including 12 males, 9 with glucocorticoid-dependent or frequently relapsing nephrotic syndrome, and 3 with newly diagnosed nephrotic syndrome. After RTX treatment, 7 patients with glucocorticoid-dependent/recurrent nephrotic syndrome were completely relieved. At 6 months of follow-up, glucocorticoids were discontinued in all patients except 1 patient. The other 5 patients achieved partial remission (PR), of which 1 patient relapsed after PR, and 1 initial patient achieved complete remission. One patient progressed to end-stage renal disease (ESRD) after 4 months of follow-up. RTX in the treatment of adult glucocorticoid-dependent/relapsing FSGS can reduce the risk of recurrence and help to decline or discontinue the use of glucocorticoid and immunosuppressants.
Topics: Male; Humans; Adult; Rituximab; Glomerulosclerosis, Focal Segmental; Nephrotic Syndrome; Glucocorticoids; Retrospective Studies; Recurrence; Treatment Outcome
PubMed: 37185370
DOI: 10.1038/s41598-023-33678-y -
Renal Failure Dec 2022This study aims to analyze the characteristics of idiopathic membranous nephropathy (iMN) with nondiabetic urine glucose during the follow-up. We retrospectively...
This study aims to analyze the characteristics of idiopathic membranous nephropathy (iMN) with nondiabetic urine glucose during the follow-up. We retrospectively analyzed the data of 1313 patients who were diagnosed iMN. The prevalence of nondiabetic urine glucose during follow-up was 10.89%. There were significant differences between the patients with nondiabetic urine glucose and those without urine glucose in gender, hypertension ratio, proteinuria, N-acetyl-β-glucosaminidase, retinol binding protein, serum albumin, serum creatinine (Scr), cholesterol, triglyceride and positive anti-phospholipase A2 receptor antibody ratio, glomerular sclerosis ratio, acute and chronic tubular injury lesion at baseline. To exclude the influence of the baseline proteinuria and Scr, case control sampling of urine glucose negative patients was applied according to gender, baseline proteinuria and Scr. The proteinuria nonremission (NR) ratio was 45.83 versus 12.50% of the urine glucose positive group and case control group. Partial remission (PR) ratio of the two groups was 36.46 versus 23.96% and complete remission (CR) ratio was 19.79% versus 63.54%, respectively. Patients with urine glucose had higher risk of 50% estimated glomerular filtration rate (eGFR) reduction. Cox regression showed that urine glucose and baseline Scr were risk factors of 50% reduction of eGFR. Urine glucose remission ratio of the patients with proteinuria NR, PR, and CR was 13.33, 56.25, and 94.73% ( < 0.005). Patients who got urine glucose remission also had better renal survival. In conclusion, non-diabetic urine glucose was closely related to proteinuria. It could be applied as a tubular injury marker to predict renal function.
Topics: Glomerulonephritis, Membranous; Glucose; Glycosuria; Humans; Proteinuria; Receptors, Phospholipase A2; Retrospective Studies
PubMed: 35820795
DOI: 10.1080/0886022X.2022.2094806 -
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