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Scientific Reports Jul 2022The rates of early gastric cancer and type 2 diabetes mellitus(T2DM) are sharply increasing in Korea. Oncometabolic surgery in which metabolic surgery is conducted along...
The rates of early gastric cancer and type 2 diabetes mellitus(T2DM) are sharply increasing in Korea. Oncometabolic surgery in which metabolic surgery is conducted along with cancer surgery is a method used to treat gastric cancer and T2DM in one-stage operation. From 2011 to 2019, a total of 48 patients underwent long-limb Roux-en-Y gastrectomy (LRYG) in Inha University Hospital, and all data were reviewed retrospectively. A 75 g oral glucose tolerance test and serum insulin level test were performed before and 1 week and 1 year after surgery. One year after LRYG operation, 25 of 48 patients showed complete or partial remission and 23 patients showed non-remission of T2DM. The preoperative HbA1c level was significantly lower and the change in HbA1c was significantly greater in the T2DM remission group. Insulin secretion indices(insulinogenic index and disposition index) were increased significantly in the T2DM remission group. In contrast, the insulin resistance indices (homeostatic model assessment of insulin resistance (HOMA-IR) and Matsuda index) changed minimal. In the case of LRYG in T2DM patients, remnant β cell function is an important predictor of favorable glycemic control.
Topics: Blood Glucose; Diabetes Mellitus, Type 2; Gastric Bypass; Glycated Hemoglobin; Humans; Insulin Resistance; Obesity, Morbid; Remission Induction; Retrospective Studies; Stomach Neoplasms; Treatment Outcome
PubMed: 35831319
DOI: 10.1038/s41598-022-15404-2 -
World Journal of Gastrointestinal... May 2024A treat-to-target strategy in inflammatory bowel disease (IBD) involves treatment intensification in order to achieve a pre-determined endpoint. Such uniform and tight...
A treat-to-target strategy in inflammatory bowel disease (IBD) involves treatment intensification in order to achieve a pre-determined endpoint. Such uniform and tight disease control has been demonstrated to improve clinical outcomes compared to treatment driven by a clinician's subjective assessment of symptoms. However, choice of treatment endpoints remains a challenge in management of IBD a treat-to-target strategy. The treatment endpoints for ulcerative colitis (UC), recommended by the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) consensus have changed somewhat over time. The latest STRIDE-II consensus advises immediate (clinical response), intermediate (clinical remission and biochemical normalisation) and long-term treatment (endoscopic healing, absence of disability and normalisation of health-related quality of life, as well as normal growth in children) endpoints in UC. However, achieving deeper levels of remission, such as histologic normalisation or healing of the gut barrier function, may further improve outcomes among UC patients. Generally, all medical therapy should seek to improve short- and long-term mortality and morbidity. Hence treatment endpoints should be chosen based on their ability to predict for improvement in short- and long-term mortality and morbidity. Potential benefits of treatment intensification need to be weighed against the potential harms within an individual patient. In addition, changing therapy that has achieved partial response may lead to worse outcomes, with failure to recapture response on treatment reversion. Patients may also place different emphasis on certain potential benefits and harms of various treatments than clinicians, or may have strong opinions re certain therapies. Potential benefits and harms of therapies, incremental benefits of achieving deeper levels of remission, as well as uncertainties of the same, need to be discussed with individual patients, and a treatment endpoint agreed upon with the clinician. Future research should focus on quantifying the incremental benefits and risks of achieving deeper levels of remission, such that clinicians and patients can make an informed decision about appropriate treatment end-point on an individual basis.
PubMed: 38764502
DOI: 10.4292/wjgpt.v15.i2.91591 -
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 -
Frontiers in Endocrinology 2023As diabetes continues to grow as major health problem, there has been great progress in understanding the important role of pancreatic beta-cells in its pathogenesis....
As diabetes continues to grow as major health problem, there has been great progress in understanding the important role of pancreatic beta-cells in its pathogenesis. Diabetes develops when the normal interplay between insulin secretion and the insulin sensitivity of target tissues is disrupted. With type 2 diabetes (T2D), glucose levels start to rise when beta-cells are unable to meet the demands of insulin resistance. For type 1 diabetes (T1D) glucose levels rise as beta-cells are killed off by autoimmunity. In both cases the increased glucose levels have a toxic effect on beta-cells. This process, called glucose toxicity, has a major inhibitory effect on insulin secretion. This beta-cell dysfunction can be reversed by therapies that reduce glucose levels. Thus, it is becoming increasingly apparent that an opportunity exists to produce a complete or partial remission for T2D, both of which will provide health benefit.
Topics: Humans; Blood Glucose; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Insulin Resistance; Glucose; Remission Induction
PubMed: 37409234
DOI: 10.3389/fendo.2023.1213954 -
Inflammatory Intestinal Diseases Dec 2023Ustekinumab is an IgG1 kappa monoclonal antibody directed against the common p40 subunit of interleukin-12 and interleukin-23, which activate Th1- and Th17-mediated...
INTRODUCTION
Ustekinumab is an IgG1 kappa monoclonal antibody directed against the common p40 subunit of interleukin-12 and interleukin-23, which activate Th1- and Th17-mediated immune responses, respectively. It has proven efficacy for the treatment of moderate to severe ulcerative colitis (UC) in the UNIFI phase III clinical trial; however, data on its efficacy in the real world are limited. In this study, we aimed to assess the real-world efficacy of ustekinumab.
METHODS
This observational study included 30 patients with UC who received ustekinumab from April 2020 to April 2022. We examined demographic information, disease type and activity (Mayo score, partial Mayo score [PMS]), use of biologics, concomitant use of predonisolone (PSL), 8-week ustekinumab clinical response rate, remission induction rate, 44- and 152-week remission maintenance rate, continuation rate, and 44-week steroid-free remission rate. The primary outcomes were the short- and long-term efficacy of ustekinumab.
RESULTS
Included patients (53% women; mean age: 41.2 years [16-80 years]) had an average disease duration of 86 weeks. The Mayo score (median) was 7.4 and the PMS was 5.4. Two (7%), 24 (80%), and four (13%) patients had a Mayo endoscopic subscore (MES) of MES1, MES2, and MES3, respectively. The median serum CRP was 1.0 mg/dL. Five patients had no history of biotherapy (naive), while eight and 17 had a history of one and two or more biologic agents, respectively. Eight patients were PSL-resistant and 22 were PSL-dependent. The 8-week clinical response rate was 73% and the clinical remission induction rate was 70%. The remission maintenance rates at 44 and 152 weeks were 67% and 63%, respectively. The ustekinumab retention rate was 67% (86-week mean follow-up period). Regarding biologic failure cases, the clinical response rate in the failure group with up to one biologic agent (including naive cases) was 84.6%, which was higher than the 58.0% rate in the failure group with two or more biologic agents ( = 0.06). Steroid-free remission rates at 44 and 152 weeks were 63% each. In the logistic regression analysis parameters for discontinuation of ustekinumab, only PMS remained significant after multivariate analysis ( = 0.018).
CONCLUSION
Our study showed short-term and long-term ustekinumab effectiveness, especially with comparative low disease activity.
PubMed: 38115909
DOI: 10.1159/000534457 -
The Primary Care Companion For CNS... Sep 2022To evaluate the level of disability and identify an association between sociodemographic and clinical variables and disability in patients with bipolar disorder (BD)....
To evaluate the level of disability and identify an association between sociodemographic and clinical variables and disability in patients with bipolar disorder (BD). This cross-sectional study was conducted in a tertiary care general hospital psychiatric unit with 100 patients with BD in partial or full remission ( criteria) from January 2017 to March 2018. Patients were assessed using a semistructured proforma, the Mini-International Neuropsychiatric Interview 5.0-Hindi version, the Hamilton Depression Rating Scale (HDRS) or the Young Mania Rating Scale (YMRS), and the Indian Disability Evaluation and Assessment Scale (IDEAS). All patients with BD had at least mild disability. The mean ± SD IDEAS global score was 5.1 ± 2.59. Of the sample, 66% and 34% had mild or moderate, disability, respectively. The global score of disability was associated with the number of episodes, number of manic episodes, frequency of episodes in the past year, YMRS and HDRS scores, partial remission, and hospitalization. Categories of disability were associated with the type of last episode, type of remission, and treatment setting. Patients with BD had at least a mild level of disability even during remission. Disability worsened with the increasing number, frequency, and severity of episodes; number of manic episodes; partial remission; and hospitalization.
Topics: Bipolar Disorder; Cross-Sectional Studies; Diagnostic and Statistical Manual of Mental Disorders; Humans; Mania; Psychiatric Status Rating Scales
PubMed: 36126938
DOI: 10.4088/PCC.21m03183 -
The Turkish Journal of Gastroenterology... Oct 2022Vedolizumab, which is a monoclonal antibody that selectively binds to α4β7 integrin in the gastrointestinal system, may be an effective and safe treatment alternative...
BACKGROUND
Vedolizumab, which is a monoclonal antibody that selectively binds to α4β7 integrin in the gastrointestinal system, may be an effective and safe treatment alternative in those with anti-tumor necrosis factor-resistant inflammatory bowel disease.
METHODS
Patients administered vedolizumab due to anti-tumor necrosis factor resistant or anti-tumor necrosis factor side effects between August 2017 and November 2020 were included in the study. Crohn's patients were evaluated using the Harvey-Bradshaw index and Simple Endoscopic Score for Crohn's Disease, whereas ulcerative colitis patients were evaluated with the Partial Mayo Score Index and Rachmilewitz score. All patients were followed up for 3 months and their blood samples were taken every 3 months. Hemoglobin, white blood cell, leukocyte, lymphocyte, and platelet counts of the patients were performed. Albumin, C-reactive protein, and erythrocye sedimentation rate values were recorded. The side effect profile for vedolizumab was evaluated for all patients. Among the side effects, arthralgia and flu-like symptoms were observed.
RESULTS
A total of 48 patients (18 ulcerative colitis and 30 Crohn's disease) were included in the study. Vedolizumab therapy was initi- ated in the patients due to anti-tumor necrosis factor resistance (17 ulcerative colitis and 26 Crohn's disease) or anti-tumor necrosis factor side effects (1 ulcerative colitis and 4 Crohn's disease). A total of 30 (63%) patients, including 15 (83%) ulcerative colitis and 15 (50%) Crohn's disease, responded to treatment (both response and remission). The mean duration of response to treatment was 4.5 ± 1.5 months. A total of 20 (42%) patients in the vedolizumab therapy subgroup (10/10, ulcerative colitis/Crohn's disease) went into remission. The mean Harvey-Bradshaw Index value was 9.8 ± 2.8 in the Crohn's disease patients at the time of initial treatment. The mean Simple Endoscopic Score for Crohn's disease value was 11.2 ± 3.1 at the time of initial treatment. The mean Harvey-Bradshaw Index value was 6.5 ± 3.0 and the mean Simple Endoscopic Score for Crohn's disease value was 4.9 ± 3.6 at 6 months post-treatment. The mean Ulcerative Colitis Endoscopic Index (Rachmilewitz) value was 9.3 ± 1.2 at the time of initial treatment. In addition, the mean Partial Mayo Scoring Index was 6.4 ± 1.5 at the time of initial treatment. The mean Ulcerative Colitis Endoscopic Index (Rachmilewitz) value was 0 (0-6.0), and the mean Partial Mayo Scoring Index was 1.5 (0.3-4.0) at 6 months post-treatment.
CONCLUSION
Vedolizumab therapy is effective in both induction and maintenance of remission in inflammatory bowel disease patients who are resistant to anti-tumor necrosis factor or who can not receive anti-tumor necrosis factor therapy due to side effects. No signifi- cant side effect was observed in the patients during follow-up.
Topics: Antibodies, Monoclonal, Humanized; C-Reactive Protein; Colitis, Ulcerative; Crohn Disease; Drug-Related Side Effects and Adverse Reactions; Gastrointestinal Agents; Humans; Inflammatory Bowel Diseases; Integrins; Necrosis; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 35946879
DOI: 10.5152/tjg.2022.21684 -
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 -
Inflammatory Bowel Diseases May 2023Both the Crohn's disease exclusion diet combined with partial enteral nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) can induce remission in mild-to-moderate... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Both the Crohn's disease exclusion diet combined with partial enteral nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) can induce remission in mild-to-moderate pediatric Crohn's disease and are associated with a marked decrease in fecal kynurenine levels. This suggests a link between clinical outcome of dietary therapy and changes in tryptophan metabolism pathways. Here, we characterize the changes in several fecal tryptophan metabolites induced by CDED+PEN or EEN and their association with remission.
METHODS
A total of 21 tryptophan metabolites were quantified in fecal samples from a 12-week prospective randomized trial with CDED+PEN or EEN for induction of remission in mild to moderate pediatric Crohn's disease. Tryptophan metabolites at week 0 (W0), W6, and W12 of 73 samples were quantitatively measured by liquid chromatography coupled with triple quadrupole mass spectrometry, and data were analyzed according to clinical groups of baselines (W0), induced remission at W6, no remission, sustained remission at W12, and nonsustained remission.
RESULTS
Reduction in components of the kynurenine pathway, such as kynurenine and quinolinic acid, were strongly associated with induced remission with both CDED+PEN and EEN, which were maintained in sustained remission. Specific serotonin pathway metabolites, such as melatonin, N-acetylserotonin, and 5-OH-tryptophan, were significantly increased in fecal samples from patients maintaining remission at W12 with both CDED+PEN and EEN. Importantly, in samples from patients failing to sustain remission, no changes were observed. Remission induction with EEN differs from CDED+PEN, particularly the moderate effects on indole pathway metabolites. The ratios of kynurenine and melatonin and quinolinic acid and melatonin perform well as markers for sustained remission.
CONCLUSIONS
The reduction in specific kynurenine pathway compounds and the increase in serotonin pathway compounds are associated with diet-induced and sustained remission. Further studies are warranted to assess causality and the association of these metabolites with specific diet and lifestyle factors, affecting sustained clinical remission.
Topics: Child; Humans; Crohn Disease; Kynurenine; Tryptophan; Prospective Studies; Melatonin; Quinolinic Acid; Serotonin; Diet; Remission Induction
PubMed: 36637175
DOI: 10.1093/ibd/izac262 -
PloS One 2023Colonoscopy is necessary for diagnosing and surveilling patients with ulcerative colitis, though it may cause disease flares. Colonoscopy with carbon dioxide (CO2)... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND AIM
Colonoscopy is necessary for diagnosing and surveilling patients with ulcerative colitis, though it may cause disease flares. Colonoscopy with carbon dioxide (CO2) insufflation decreases abdominal discomfort; however, its effect on exacerbation incidence in ulcerative colitis remains unclear. Therefore, this study aimed to evaluate the colonoscopy effects using CO2 insufflation in patients with ulcerative colitis.
METHODS
Overall, 96 remissive patients with ulcerative colitis (partial Mayo score ≤ 2) who underwent total colonoscopy between March 2015 and December 2019 at Osaka University Hospital were enrolled and blindly randomized to the CO2 (n = 45) and air (n = 51) insufflation group (UMIN-CTR, number: UMIN000018801). The post-procedural abdominal discomfort and the clinical relapse (partial Mayo score ≥ 3) rate within 8 weeks were evaluated.
RESULTS
Baseline backgrounds did not differ between the groups. The mean abdominal fullness and pain scores were significantly lower in the CO2 group than in the Air group immediately (p = 0.0003, p = 0.0003) and 30 min (p < 0.0001, p < 0.0001) after colonoscopy. While the overall clinical relapse rate remained unchanged between the groups, the clinical relapse rate at 8 weeks after colonoscopy was significantly lower in the CO2 group than in the Air group in patients not in complete remission (Mayo endoscopic subscore ≥ 1, p = 0.049; or partial Mayo score ≥ 1, p = 0.022).
CONCLUSIONS
CO2 insufflation can reduce abdominal discomfort in remissive patients with ulcerative colitis and decrease clinical relapse at 8 weeks after colonoscopy for those not in complete remission.
Topics: Humans; Colitis, Ulcerative; Carbon Dioxide; Insufflation; Colonoscopy; Chronic Disease; Fabaceae
PubMed: 37590283
DOI: 10.1371/journal.pone.0290329