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Inflammatory Bowel Diseases Jan 2021This study addresses whether existing specific transcriptional profiles can improve and support the current status of the definition of ulcerative colitis (UC) remission... (Comparative Study)
Comparative Study
BACKGROUND
This study addresses whether existing specific transcriptional profiles can improve and support the current status of the definition of ulcerative colitis (UC) remission apart from the existing endoscopic, histologic, and laboratory scoring systems. For that purpose, a well-stratified UC patient population in remission was compared to active UC and control patients and was investigated by applying the next-generation technology RNA-Seq.
METHODS
Mucosal biopsies from patients in remission (n = 14), patients with active UC (n = 14), and healthy control patientss (n = 16) underwent whole-transcriptome RNA-Seq. Principal component analysis, cell deconvolution methods, gene profile enrichment, and pathway enrichment methods were applied to define a specific transcriptional signature of UC in remission.
RESULTS
Analyses revealed specific transcriptional signatures for UC in remission with increased expression of genes involved in O-glycosylation (MUC17, MUC3A, MUC5AC, MUC12, SPON1, B3GNT3), ephrin-mediated repulsion of cells (EFNB2E, EFNA3, EPHA10, EPHA1), GAP junction trafficking (TUBA1C, TUBA4A, TUBB4B, GJB3, CLTB), and decreased expression of several toll-like receptors (TLR1, TLR3, TLR5, TLR6).
CONCLUSIONS
This study reveals specific transcriptional signatures for remission. Partial restoration and improvement of homeostasis in the epithelial mucus layer and revival of immunological functions were observed. A clear role for bacterial gut flora composition can be implied. The results can be useful for the development of treatment strategies for UC in remission and may be useful targets for further investigations aiming to predict the outcome of UC in the future.
Topics: Adult; Case-Control Studies; Colitis, Ulcerative; Colon; Connexins; Ephrins; Female; Glycosylation; High-Throughput Nucleotide Sequencing; Humans; Intestinal Mucosa; Male; Middle Aged; Mucins; Principal Component Analysis; Remission Induction; Toll-Like Receptors; Transcriptome
PubMed: 32322884
DOI: 10.1093/ibd/izaa075 -
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 -
Colorectal Disease : the Official... Jan 2024Remission rates of medically and surgically treated complex perianal fistulas in Crohn's disease are low. Recently, trials have demonstrated the potential for long-term...
AIM
Remission rates of medically and surgically treated complex perianal fistulas in Crohn's disease are low. Recently, trials have demonstrated the potential for long-term remission with local injection of allogeneic adipose-derived mesenchymal stem cells (darvadstrocel). Our aim was to analyse outcomes from our real-world experience with this new treatment.
METHODS
All patients with Crohn's disease suffering complex perianal fistulas who consecutively underwent administration of darvadstrocel at two centres were followed up and evaluated. Patients were assessed for clinical remission, response, failure, and any complications during follow-up. The results of all patients with a minimum of 3 months' follow-up are presented.
RESULTS
Thirty-three patients with Crohn's disease and complex perianal fistulas were included. Of these, 20 (61%) experienced clinical remission that was maintained for a mean follow-up of 14 (3-32) months. A total of 24 of 33 (73%) experienced at least 3 months of clinical remission, with four later having recurrence (3-12 months). Among the remaining nine patients who did not experience clinical remission, two (6%) had partial remission (such as one of two fistulas closing), two (6%) showed signs of response but not remission, and five (15%) showed no signs of healing. The mean time to maintained clinical remission was 6 weeks (range 2 weeks to 6 months), and there were no severe adverse events.
CONCLUSION
In this real-world experience, treatment of Crohn's disease complex perianal fistulas with darvadstrocel had a 61% success rate for maintained clinical remission.
Topics: Humans; Crohn Disease; Treatment Outcome; Mesenchymal Stem Cell Transplantation; Rectal Fistula; Immunosuppressive Agents; Mesenchymal Stem Cells
PubMed: 38095303
DOI: 10.1111/codi.16830 -
European Journal of Pediatrics Mar 2020The aim of this study was to evaluate rates of clinical remission, endoscopic remission, and mucosal healing after a 6-week treatment period with partial enteral...
The aim of this study was to evaluate rates of clinical remission, endoscopic remission, and mucosal healing after a 6-week treatment period with partial enteral nutrition (PEN) and to compare them to those obtained by standard exclusive enteral nutrition (EEN) treatment in children with active Crohn's disease (CD). Twenty-five patients with active CD (median age 13.6 years, range 3.6-18.0) were recruited to either PEN (n = 12) or EEN (n = 13) treatment groups. The PEN group received 75% of their dietary needs from a polymeric formula plus one meal per day from an anti-inflammatory diet (AID). Patients were assessed at weeks 0, 1, 3, and 6 using clinical and laboratory parameters. Endoscopic assessment was performed at induction and week 6. On intention to treat analysis, clinical remission (Pediatric CD Activity Index < 10) was achieved in 69.2% and 75.0% of EEN and PEN patients, respectively (p = 0.999). The endoscopic remission (Simple Endoscopic Score for CD (SES-CD) ≤ 2) rates were 45.5% in both groups, while mucosal healing rates (SES-CD = 0) were 45.5% with EEN and 27.3% with PEN (p = 0.659).Conclusion: The results of our prospective pilot study suggest that PEN, allowing one meal from AID, could be as effective as EEN in inducing clinical and endoscopic remission in children with active CD. However, larger randomized controlled studies are warranted to confirm our findings.Trial registration: This clinical trial was registered under the number ClinicalTrials.govidentifier: NCT03176875.What is Known:• Exclusive enteral nutrition is a first-line treatment in active pediatric Crohn's disease; however, patients often find it difficult to adhere to.• Exclusive enteral nutrition is more effective than corticosteroids in achieving mucosal healing.What is New:• This is the first prospective study on partial enteral nutrition in active pediatric Crohn's disease, evaluating not only clinical, but also endoscopic remission.• A novel approach of partial enteral nutrition that allows one meal per day from an anti-inflammatory diet was as effective as exclusive enteral nutrition in inducing clinical and endoscopic remission in active Crohn's disease.
Topics: Adolescent; Child; Child, Preschool; Crohn Disease; Endoscopy; Enteral Nutrition; Female; Humans; Male; Pilot Projects; Remission Induction
PubMed: 31781933
DOI: 10.1007/s00431-019-03520-7 -
Diabetologia Aug 2023Notwithstanding the irreversible beta cell failure seen in type 1 diabetes, some individuals may experience a special phase named 'partial remission' or 'the honeymoon...
AIMS/HYPOTHESIS
Notwithstanding the irreversible beta cell failure seen in type 1 diabetes, some individuals may experience a special phase named 'partial remission' or 'the honeymoon period', in which there is a transient recovery of beta cell function. Importantly, this stage of partial remission shows spontaneous immune downregulation, although the exact mechanisms are unclear. Intracellular energy metabolism is crucial for the differentiation and function of T cells, and provides promising targets for immunometabolic intervention strategies, but its role during partial remission is unknown. In this study, we aim to investigate the association between T cell intracellular glucose and fatty acid metabolism and the partial remission phase.
METHODS
This is a cross-sectional study with a follow-up component. Intracellular uptake of glucose and fatty acids by T cells was detected in participants with either new-onset type 1 diabetes or type 1 diabetes that was already in partial remission, and compared with heathy individuals and participants with type 2 diabetes. Subsequently, the participants with new-onset type 1 diabetes were followed up to determine whether they experienced a partial remission (remitters) or not (non-remitters). The trajectory of changes in T cell glucose metabolism was observed in remitters and non-remitters. Expression of programmed cell death-1 (PD-1) was also analysed to investigate possible mechanisms driving altered glucose metabolism. Partial remission was defined when patients had convalescent fasting or 2 h postprandial C-peptide >300 pmol/l after insulin treatment.
RESULTS
Compared with participants with new-onset type 1 diabetes, intracellular glucose uptake by T cells decreased significantly in individuals with partial remission. The trajectory of these changes during follow-up showed that intracelluar glucose uptake in T cells fluctuated during different disease stages, with a decreased uptake during partial remission that rebounded after remission. This dynamic in T cell glucose uptake was only detected in remitters and not in non-remitters. Further analysis demonstrated that changes of intracellular glucose uptake were found in subsets of CD4 and CD8 T cells, including Th17, Th1, CD8 naive T cells (Tn) and CD8 terminally differentiated effector memory T cells (Temra). Moreover, glucose uptake in CD8 T cells was negatively related to PD-1 expression. The intracellular metabolism of fatty acids was not found to be different between new-onset participants and those in partial remission.
CONCLUSIONS/INTERPRETATION
Intracellular glucose uptake in T cells was specifically decreased during partial remission in type 1 diabetes and may be related to PD-1 upregulation, which may be involved in the down-modulation of immune responses during partial remission. This study suggests that altered immune metabolism could be a target for interventions at the point of diagnosis of type 1 diabetes.
Topics: Humans; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; CD8-Positive T-Lymphocytes; Cross-Sectional Studies; Programmed Cell Death 1 Receptor; Glucose
PubMed: 37300581
DOI: 10.1007/s00125-023-05938-z -
Biomedicines Nov 2021Development of targeted therapies in recent years revealed several nonchemotherapeutic options for patients. Chief among targeted therapies is small molecule kinase... (Review)
Review
Development of targeted therapies in recent years revealed several nonchemotherapeutic options for patients. Chief among targeted therapies is small molecule kinase inhibitors targeting key oncogenic signaling proteins. Through competitive and noncompetitive inhibition of these kinases, and therefore the pathways they activate, cancers can be slowed or completely eradicated, leading to partial or complete remissions for many cancer types. Unfortunately, for many patients, resistance to targeted therapies, such as kinase inhibitors, ultimately develops and can necessitate multiple lines of treatment. Drug resistance can either be de novo or acquired after months or years of drug exposure. Since resistance can be due to several unique mechanisms, there is no one-size-fits-all solution to this problem. However, combinations that target complimentary pathways or potential escape mechanisms appear to be more effective than sequential therapy. Combinations of single kinase inhibitors or alternately multikinase inhibitor drugs could be used to achieve this goal. Understanding how to efficiently target cancer cells and overcome resistance to prior lines of therapy became imperative to the success of cancer treatment. Due to the complexity of cancer, effective treatment options in the future will likely require mixing and matching these approaches in different cancer types and different disease stages.
PubMed: 34829820
DOI: 10.3390/biomedicines9111591 -
Acta Bio-medica : Atenei Parmensis May 2021Cutaneous infiltration by Chronic Lymphocytic Leukemia (CLL) is a rare complication. The clinical presentation, impact of it on disease prognosis, and the proper... (Review)
Review
BACKGROUND AND OBJECTIVE
Cutaneous infiltration by Chronic Lymphocytic Leukemia (CLL) is a rare complication. The clinical presentation, impact of it on disease prognosis, and the proper treatment choice are not clear. Here in our review, we try to answer these questions. Acquisition of evidences: A systematic search of PubMed, and Google Scholar for English language articles published from Jan 2000 to June 2019. Synthesis of evidences: A total of 56 cases were identified, with a median age of 66 years. Of these cases 43 were males and 12 were females, and one missing data, with a ratio of 3,6:1. Head and neck were most commonly involved. The commonest clinical presentation was papulonodular lesions, and the majority were diagnosed at an early stage. CLL skin involvement at the site of old herpetic lesions was common. Because of the rarity of the disease, treatment modalities varied widely, and there are no consensus on treatment. The majority were treated with chemotherapy. In general, 35 (77.8% - of the non-missing data) patients responded to treatment (25 patients had a complete remission and 10 a partial remission). All patients ≤60 years had an early-stage disease, on the other hand, all patients with advanced-stage were >60 years.
CONCLUSION
Patients with early-stage and localized leukemia cutis can benefit from observation alone strategy, while intervention in young patients with advanced disease is warranted. Skin infiltration by CLL does not affect prognosis, as most patients attained complete or partial remission with a very low progression rate.
Topics: Aged; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Prognosis; Skin; Skin Neoplasms
PubMed: 33988158
DOI: 10.23750/abm.v92i2.10763 -
Depression and Anxiety Mar 2021Little data exist on remission rates following psychotherapy for body dysmorphic disorder (BDD).
Rates of remission, sustained remission, and recurrence in a randomized controlled trial of cognitive behavioral therapy versus supportive psychotherapy for body dysmorphic disorder.
BACKGROUND
Little data exist on remission rates following psychotherapy for body dysmorphic disorder (BDD).
METHODS
Using data from a large study of therapist-delivered cognitive behavior therapy (CBT) versus supportive psychotherapy (SPT) for BDD (N = 120), we estimated remission rates at treatment endpoint, and rates of delayed remission, sustained remission, and recurrence at 6-month follow-up. We also examined improvement in broader mental health outcomes among remitters.
RESULTS
Full or partial remission rates at end-of-treatment were significantly higher following CBT (68%) than SPT (42%). At 6-month follow-up, an additional 10% (CBT) and 14% (SPT) experienced delayed remission, 52% (CBT) and 27% (SPT) experienced sustained remission, and 20% (CBT) and 14% (SPT) experienced recurrence. Remission was never achieved by 18% (CBT) and 45% (SPT). Participants in remission at end-of-treatment experienced significant improvements in functional impairment, depression severity, BDD-related insight, and quality of life compared to nonremitters.
CONCLUSIONS
Full or partial remission rates are high following CBT for BDD and higher than after SPT.
PubMed: 33724643
DOI: 10.1002/da.23148 -
Surgery For Obesity and Related... Oct 2020Laparoscopic sleeve gastrectomy (SG) achieves type 2 diabetes (T2D) remission to various extents, and reasons for such variations are unknown.
BACKGROUND
Laparoscopic sleeve gastrectomy (SG) achieves type 2 diabetes (T2D) remission to various extents, and reasons for such variations are unknown.
OBJECTIVES
We assessed patients' characteristics associated with T2D remission 1 year post SG.
SETTING
University hospital.
METHODS
Retrospective study of 230 T2D patients (18-64 yr) who underwent SG at our institution. We examined pre- and postoperative demographic, anthropometric, biochemical, and clinical characteristics associated with T2D complete remission, partial remission, improvement, or unchanged status. Independent predictors of T2D complete remission were assessed by binary logistic regression and then included in 7 predictive models. Logistic regression assessed the pre- and postoperative predictors of T2D complete remission and their predictive performance was measured with the area under the curve of the receiver operating characteristic curve.
RESULTS
A total of 230 patients were included in the study, females comprised 69%, and mean age was 45.66 ± 8.84 years. Mean preoperative weight and body mass index were 115.69 ± 20.76 kg and 43.53 ± 6.98 kg/m, respectively. Approximately two thirds (64.4%) of the sample had diabetes for >5 years. Insulin therapy users comprised 36.9% of the sample and 29.6% of patients were on ≥2 oral hypoglycemic agents (OHA). At 1 year, mean body mass index was 32.77 ± 6.09 kg/m, percent excess weight loss (%EWL) was 62.29 ± 23.60% and glycosylated hemoglobin (HbA1C) improved from 8.1% to 6.18%. Approximately 42.2% of the sample achieved T2D complete remission. Compared with those with no remission, patients with complete remission were significantly younger, had shorter duration of diabetes, were not on insulin therapy, took fewer OHA, had higher C-peptide, lower preoperative HbA1C, were less likely to have had hypertension or dyslipidemia, and more likely to have achieved higher %EWL. Seven proposed models for prediction of complete remission showed the most useful model comprised diabetes duration + pre-HbA1C + %EWL + insulin therapy + age + OHA (area under the curve = .81). Independent predictors of complete remission were preoperative HbA1C, %EWL, insulin therapy, age, and OHA (but not diabetes duration).
CONCLUSION
SG results in significant weight reduction and various extents of T2D remission. HbA1C, %EWL, insulin therapy, age, and OHA were independent predictors of complete remission. Assessing these factors before bariatric surgery is important to identify any modifiable characteristics that can be altered to increase the likelihood of remission.
Topics: Adult; Body Mass Index; Diabetes Mellitus, Type 2; Female; Gastrectomy; Humans; Laparoscopy; Male; Middle Aged; Obesity; Obesity, Morbid; Remission Induction; Retrospective Studies; Treatment Outcome
PubMed: 32680788
DOI: 10.1016/j.soard.2020.05.013 -
Frontiers in Psychiatry 2022This patient case report describes a 45-year old white unmarried man with disability pension due to schizoaffective disorder, diagnosed at the age of 24. He lives in an...
Remission of Persistent Negative Symptoms and Psychosocial Consequences by Combined Clozapine and Cariprazine Treatment in a Patient With Long-Standing Treatment-Resistant Schizoaffective Disorder.
This patient case report describes a 45-year old white unmarried man with disability pension due to schizoaffective disorder, diagnosed at the age of 24. He lives in an apartment and has housing support. Retrospectively, the patient displayed prodromal markers of a disorder within the schizophrenia spectrum many years before the onset of frank psychosis, indeed since childhood. Over the years several symptoms and signs across schizophrenia domains have been manifest: positive, negative, cognitive, and affective, among which the negative and affective symptoms and signs were the earliest to appear. While the positive, disorganized, and catatonic symptoms responded to treatment - when duly tested and complied with - the negative and affective symptoms have been notoriously difficult to handle. We now report on the successful introduction of cariprazine (CAR) to his ongoing clozapine (CLZ) medication, the result of which has been a near-complete remission of his persistent negative and psychosocial issues. We interpret this remarkable alleviation of the patient's disease - and concomitant improvement of his quality of life - in terms of neuroreceptor target complementarity between CLZ and CAR, with particular emphasis on the contributions from the D3 and D2 receptor partial agonist components of the latter agent.
PubMed: 35664491
DOI: 10.3389/fpsyt.2022.887547