Remission of type 2 diabetes mellitus.

The surge in type 2 diabetes mellitus (T2DM) is tightly linked to obesity, leading to ectopic fat accumulation in internal organs. Weight management has become a cornerstone of T2DM treatment, with evidence suggesting that significant weight loss can induce remission. Remission, defined as sustained hemoglobin (HbA1c) below 6.5% for at least 3 months without medication, can be achieved through various approaches, including lifestyle, medical, and surgical interventions. Metabolic bariatric surgery offers significant remission rates, particularly for patients with severe obesity. Intensive lifestyle modifications, including low-calorie diets and exercise, have also demonstrated significant potential. Medications like incretin-based agents show robust results in improving beta-cell function, achieving glycemic control, and promoting weight loss. While complete remission without medication may not be attainable for everyone, especially those with severe insulin resistance or deficiency, early and aggressive glycemic control remains a crucial strategy. Maintaining HbA1c below 6.5% from the time of diagnosis reduces the risk of long-term complications and mortality. Moreover, considering a broader definition of remission, encompassing individuals with sustained control on medication, could offer a more comprehensive and inclusive approach to managing this chronic disease.

Diabetes remission and nonalcoholic fatty pancreas disease.

This editorial focuses on the relationship between nonalcoholic fatty pancreas disease (NAFPD) and the development and remission of type 2 diabetes (T2D). NAFPD is characterized by intrapancreatic fatty deposition associated with obesity and not associated with alcohol abuse, viral infections, and other factors. Ectopic fat deposition in the pancreas is associated with the development of T2D, and the underlying mechanism is lipotoxic ß-cell dysfunction. However, the results on the relationship between intrapancreatic fat deposition (IPFD) and ß-cell function are conflicting. Regardless of the therapeutic approach, weight loss improves IPFD, glycemia, and ß-cell function. Pancreatic imaging is valuable for clinically monitoring and evaluating the management of T2D.

Obinutuzumab in Refractory Membranous Nephropathy: A Case Series.

Rationale & Objective: Membranous nephropathy (MN), recognized as an autoimmune kidney disease, responds well to anti-CD20 monoclonal antibodies. Obinutuzumab, a type Ⅱ humanized anti-CD20 and immunoglobulin G1 Fc-optimized monoclonal antibody, when compared with rituximab, has demonstrated superior efficacy in B-cell leukemia and lymphoma, especially in rituximab-resistant cases. However, the efficacy and safety of obinutuzumab in MN remain unclear. Study Design: A case series study. Setting & Participants: A total of 18 patients were diagnosed with MN and had received obinutuzumab at our center without secondary MN, undergoing dialysis, having a history of kidney transplantation, or infections requiring treatment. Exposure: Obinutuzumab treatment. Outcomes: Primary outcomes included remission rate, time to first remission, and first relapse-free survival time during the follow-up period. Analytical Approach: Survival analysis was performed with Cox proportional hazards models, log-rank test, and Kaplan-Meier survival analysis. Results: Patients with MN (median age of 52.5 years, 83.3% males) received an average dose of 2.1 ± 0.8 g of obinutuzumab during a median follow-up period of 13.6 months. During the follow-up, 17 patients (94.4%) achieved remission, with 12 patients (66.7%) achieving partial remission, and 5 patients (27.8%) achieving complete remission. The median time to first remission and first relapse-free survival time was 2.7 (1.0-6.1) months and 9.8 (2.6-11.2) months, respectively. Of 12 patients with previous rituximab treatment, all achieved remission successfully, with 8 (66.7%) achieving partial remission and 4 (33.3%) achieving complete remission. Adverse events were mostly mild, and no severe treatment-related adverse events were observed. Limitations: Limited or missing data; risks of selection bias; or recall bias; underestimated first relapse-free survival time because of a limited follow-up period; unmonitored counts of CD19+ B-cells and other lymphocyte subsets. Conclusions: Obinutuzumab demonstrated promising efficacy and safety in inducing remission in MN, particularly in patients with an unsatisfactory response to rituximab.

Membranous nephropathy (MN), an autoimmune kidney disease, usually responds favorably to rituximab, a chimeric anti-CD20 monoclonal antibody. Nevertheless, certain patients exhibit inadequate responses to rituximab. Obinutuzumab, a novel humanized anti-CD20 monoclonal antibody, has shown enhanced efficacy in cases where rituximab fails to address B-cell leukemias and lymphomas. However, its efficacy and safety in MN treatment remain uncertain. A case series involving 18 patients treated with obinutuzumab at our center demonstrated promising results, suggesting favorable efficacy and safety in inducing and maintaining remission, particularly among patients who did not respond well to rituximab previously. These findings signify a potential alternative for MN treatment, though further research is needed to confirm them.

Worse fibro-inflammatory activity on diagnostic liver biopsy adversely impacts biochemical remission in autoimmune hepatitis.

BACKGROUND: Autoimmune hepatitis (AIH) patients can present with advanced fibrosis at diagnosis or may progress to the same if biochemical remission on treatment is not achieved. METHODS: We conducted a single-center retrospective analysis of 34 pediatrics and 39 adult AIH patients. Three pathologists, blinded to clinical information, reviewed the diagnostic liver biopsy (DLB) slides of AIH patients. We evaluated the impact of clinical, laboratory, and histopathologic parameters on outcomes including biochemical remission (BR). RESULTS: Incidence of advanced (Ludwig stage 3 or 4) fibrosis on DLB was 45.2 %. AIH patients with advanced fibrosis had higher median Ishak score (p < 0.001) and higher IgG level (p = 0.01) at diagnosis. The incidence of BR at 6-month (31.2% vs. 88.6 %, p = 0.001) and 1-year (68.8% vs. 88.6 %, p = 0.04) post-diagnosis was significantly lower in AIH patients with advanced fibrosis. Although not statistically significant, a higher proportion of AIH patients with advanced fibrosis were on high dose of steroids (58% vs. 37.9 %, p = 0.1) at 1 year post diagnosis. Higher serum IgG level at diagnosis was associated with lower odds of achieving BR at 6-month (p = 0.004) and 1-year (p = 0.03) post-diagnosis in multivariate analysis. Pediatric age at diagnosis (p = 0.02) was associated with higher steroid dose at 1-year post-diagnosis in univariate analysis. CONCLUSIONS: Findings of advanced fibrosis on DLB of AIH patients was accompanied by more pronounced necro-inflammatory activity and higher serum IgG level, which translated to lower rates of BR and higher exposure to steroids during the first year after diagnosis.

Prospective study of the effect of rituximab on kidney function in membranous nephropathy.

Background: Patients with membranous nephropathy (MN) and poor kidney function or active disease despite previous immunosuppression are underrepresented in clinical trials. It is unknown how effective rituximab is in this population. Methods: This prospective, multi-centre, single-arm, real-world study of patients with active MN [urine protein-creatinine ratio (uPCR) >350 mg/mmol and serum albumin <30 g/L, or a fall in estimated glomerular filtration rate (eGFR) of at least 20% or more over at least 3 months] evaluated rituximab in those with contraindications to calcineurin inhibitors and cytotoxic therapy. The primary outcome was change in rate of eGFR decline before and after rituximab. Complete or partial remission were defined as uPCR <30 mg/mmol or uPCR <350 mg/mmol with a ≥50% fall from baseline, respectively. Results: A total of 180 patients [median age 59 years, interquartile range (IQR) 48-68] received rituximab and were followed up for a median duration of 17 months. Seventy-seven percent had prior immunosuppression. Median eGFR and uPCR at baseline were 49.2 mL/min/1.73 m2 (IQR 34.4-80.6) and 766 mg/mmol (IQR 487-1057), respectively. The annual rate of decline of eGFR fell from 13.9 to 1.7 mL/min/1.73 m2/year following rituximab (Z score = 2.48, P < .0066). At 18 months 12% and 42% of patients were in complete or partial remission, respectively. Rituximab was well tolerated; patient survival was 95.6% at 2 years and in patients in whom eGFR was available, kidney survival was 93% at 2 years. Conclusion: Rituximab significantly reduced the rate of eGFR decline in active MN including those who had received prior immunosuppression or with poor baseline kidney function.

Efficacy and safety of probiotics in IBD: An overview of systematic reviews and updated meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: Probiotics show promise in inflammatory bowel disease (IBD), yet knowledge gaps persist. We performed an overview of systematic reviews and an updated metanalysis of randomized controlled trials (RCT) assessing the effect of probiotics on Crohn's disease (CD) and ulcerative colitis (UC). METHODS: MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched up to September 2023. Primary outcomes were clinical remission and recurrence; secondary outcomes included endoscopic response and remission, and adverse events. We calculated odds ratios (OR) using a random-effects model in R. The quality of systematic reviews was assessed using the AMSTAR-2; the trials' risk of bias was evaluated using the Cochrane Collaboration tool. Evidence certainty was rated using the GRADE framework. RESULTS: Out of 2613 results, 67 studies (22 systematic reviews and 45 RCTs) met the eligibility criteria. In the updated meta-analysis, the OR for clinical remission in UC and CD was 2.00 (95% CI 1.28-3.11) and 1.61 (95% CI 0.21-12.50), respectively. The subgroup analysis suggested that combining 5-ASA and probiotics may be beneficial for inducing remission in mild-to-moderate UC (OR 2.35, 95% CI 1.29-4.28). Probiotics decreased the odds of recurrence in relapsing pouchitis (OR 0.03, 95% CI 0.00-0.25) and trended toward reducing clinical recurrence in inactive UC (OR 0.65, 95% CI 0.42-1.01). No protective effect against recurrence was identified for CD. Multi-strain formulations appear superior in achieving remission and preventing recurrence in UC. The use of probiotics was not associated with better endoscopic outcomes. Adverse events were similar to control. However, the overall certainty of evidence was low. CONCLUSION: Probiotics, particularly multi-strain formulations, appear efficacious for the induction of clinical remission and the prevention of relapse in UC patients as well as for relapsing pouchitis. Notwithstanding, no significant effect was identified for CD. The favorable safety profile of probiotics was also highlighted.

The effect of solid food diet therapies on the induction and maintenance of remission in Crohn's disease: a systematic review.

BACKGROUND: The efficacy of highly restrictive dietary therapies such as exclusive enteral nutrition (EEN) in the induction of remission in Crohn's disease (CD) are well established, however, ongoing issues exist with its poor palatability, restrictions, and adherence. The primary aim of this review is to evaluate the current evidence for the efficacy of exclusively solid food diets on the induction and maintenance of clinical and biochemical remission in CD. Secondary aims include impact on endoscopic healing and quality of life. METHODS: A systematic review of all randomised controlled trials (RCTs), open-label randomised trials and head-to-head clinical trials assessing solid food diet intervention in patients with active or inactive Crohn's disease was conducted. Studies included adult and paediatric patients with a verified disease activity index at baseline and follow up (Harvey Bradshaw Index, HBI; Crohn's disease activity index, CDAI and paediatric CDAI, PCDAI). Additional secondary endpoints varied between studies, including endoscopic and biochemical responses, as well as quality of life measures. Two authors independently performed critical appraisals of the studies, including study selection and risk of bias assessments. RESULTS: 14 studies were included for review, with several studies suggesting clinically significant findings. Clinical remission was achieved in a paediatric population undertaking the Mediterranean diet (MD) (moderate risk of bias). In adults, the Crohn's disease exclusion diet (CDED) was comparable to the CDED with partial enteral nutrition (PEN) diet in induction of remission (moderate risk of bias). A low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet was also shown to decrease symptoms in patients with quiescent or mildly active CD (high risk of bias), however, this was not corroborated by other low FODMAP diet studies. CONCLUSIONS: There are promising outcomes for the MD and CDED in inducing clinical remission in mild to moderate CD. The results need to be interpreted with caution due to design limitations, including issues with combining outcomes among CD and UC patients, and small sample size. The current evidence for solid food dietary therapy in CD is limited by the lack of high quality studies and moderate to high bias. Future well designed studies are needed to confirm their efficacy.

Unveiling the arthritis divide: Exploring treatment response and impact in late-onset vs. young-onset rheumatoid arthritis.

OBJECTIVES: Impact of osteoarthritis (OA) on the initial treatment response of rheumatoid arthritis (RA) by treat to target (T2T) practice was compared between the patients with an onset age ≥65 years old (late-onset RA [LORA]) and those with an onset age <65 years old (young-onset RA [YORA]). METHODS: A retrospective study was conducted on the patients with RA, who were referred to our clinic without treatment between January 2021 and July 2022. Patients with grade ≥3 OA according to the Kellgren-Lawrence (K-L) classification either in the knee or hand were classified in the OA(+) group and others were in the OA(-) group. The clinical data were compared at the diagnosis and one year after the initial treatment between the groups for 74 LORA and 59 YORA patients, respectively. RESULTS: One year after starting treatment in the LORA patients, the OA(+) group had poorer disease activity control and greater disability in the several activities of daily living (ADL) than the OA(-) group. In the YORA patients, there were no differences in ADL disability between the groups. CONCLUSIONS: In the initial treatment of the LORA patients, the prevalence of OA was high, and impact of OA on LORA was larger than on YORA.

Cognitive Alterations Associated with Remission and Alcohol Dependence Severity in Ethnically Diverse Patients of Siberia.

Background: Impaired cognition in individuals with alcohol dependence may be associated with increased relapse risk. It has been recorded in more than half of patients during six months after treatment. In certain ethnic groups, for example, Tuvinians, the indigenous people of Siberia, relapses occur in extremely short periods of one to three months after treatment. An approach currently used to alcohol dependence treatment may be less effective for these patients. Objective: The study aimed to investigate cognitive sequelae in indigenous Tuvinian patients with alcohol dependence. Methods: The sample included 166 patients, 74 of indigenous ethnicity (Tuvinians) and 92 non-indigenous white patients. Data on inhibitory control, cognitive flexibility, attention, and working memory were collected from all the patients and processed using cluster analysis. The clustering data were then complemented by indicators of disorder dynamics, impulsivity, and emotion regulation. Results: The clustering procedure revealed groups with severe cognitive sequelae. More than four-fold attention decrease was found in 43.5% of non-indigenous patients, and more impaired cognitive flexibility was revealed among 60.8% of indigenous patients. Groups with severe cognitive sequelae had higher impulsivity, maladaptive emotion regulation, more hospitalizations, faster disease progression, and shorter remissions. The latter was significantly reduced to 90 days on average in the severe group of indigenous patients versus 135 days of remission in the non-indigenous severe group. Conclusion: Results obtained may advance tailored intervention in alcohol-dependent patients of the indigenous Tuvinian ethnicity. While little is still known about the alcohol dependence course and consequences in the indigenous Tuvinians of Siberia, this study contributes to the global mental health data on alcohol abuse and dependence in indigenous communities.

Spontaneous Cushing's Disease Remission Induced by Pituitary Apoplexy.

Spontaneous remission of Cushing's disease (CD) is uncommon and often attributed to pituitary tumor apoplexy. We present a case involving a 14-year-old female who exhibited clinical features of Cushing's syndrome. Initial diagnostic tests indicated CD: elevated 24h urinary cortisol (235 µg/24h, n < 90 µg/24h), abnormal 1 mg dexamethasone overnight test (cortisol after 1 mg dex 3.4 µg/dL, n < 1.8 µg/dL), and elevated adrenocorticotropic hormone concentrations (83.5 pg/mL, n 10-60 pg/mL). A pituitary adenoma was suspected, so a nuclear MRI was performed, with findings suggestive of a pituitary microadenoma. The patient was referred for a transsphenoidal resection of the microadenoma. While waiting for surgery, the patient presented to the emergency department with a headache and clinical signs of meningism. A computed axial tomography of the central nervous system was performed, and no structural alterations were found. The symptoms subsided with analgesia. One month later, she presented again to the emergency department with clinical findings of acute adrenal insufficiency (cortisol level of 4.06 µg/dL), and she was noted to have spontaneous biochemical remission associated with the resolution of her symptoms of hypercortisolism. For that reason, spontaneous CD remission induced by pituitary apoplexy (PA) was diagnosed. The patient has been managed conservatively since the diagnosis and remains in clinical and biochemical remission until the present time, after 10 months of follow-up. There are three unique aspects of our case: the early age of onset of symptoms, the spontaneous remission of CD due to PA, which has been rarely reported in the medical literature, and the fact that the patient presented a microadenoma because there are fewer than 10 clinical case reports of PA associated with microadenoma.

Primary Central Nervous System Vasculitis Mimicking Susac Syndrome and Multiple Sclerosis With Long-Term Remission and Spontaneous Resolution of Lesions: A Case Report.

Primary central nervous system vasculitis (PCNSV) is an angiitis localized to the central nervous system (CNS), with various manifestations and no specific biomarkers. Herein, we report a case of PCNSV that presented with an unusual course. A 40-year-old Japanese male developed inner ear symptoms and visual field disturbances. Later, at 42 years of age, the patient developed right hemiparesis and was diagnosed with multiple sclerosis (MS). He received methylprednisolone pulse therapy, which improved his symptoms and resolved most brain lesions. Subsequently, he did not visit the hospital for 13 years, during which time he experienced no relapse. At 55 years of age, he presented to our hospital with fatigue and dizziness. Susac syndrome was suspected because of sensorineural hearing loss and snowball lesions in the corpus callosum. Some of the brain lesions resolved spontaneously. A biopsy was performed on a right frontal lobe lesion, which revealed vasculitis with fibrinoid necrosis, no demyelinating lesions, no amyloid positivity, and no infiltration of atypical lymphocytes. With no evidence of vasculitis in other organs, the patient was diagnosed with PCNSV. The patient was treated with methylprednisolone pulse therapy, followed by oral prednisolone (1 mg/kg/day). The prednisolone was tapered off, and no relapse of symptoms or new lesions on magnetic resonance imaging (MRI) were noted. As observed in this case, even in a scenario suggestive of Susac syndrome or multiple sclerosis, PCNSV should be considered a differential diagnosis and confirmed via brain biopsy.

Definitions of and Instruments for Disease Activity, Remission, and Relapse in Polymyalgia Rheumatica: A Systematic Literature Review.

OBJECTIVE: To perform a systematic literature review on definitions and instruments used to measure remission, relapse, and disease activity in polymyalgia rheumatica (PMR), to inform an OMERACT project to endorse instruments for these outcomes. METHODS: A search of Pubmed/MEDLINE, EMBASE, CINAHL, Cochrane, and Epistemonikos was performed May 2021 and updated August 2023. Qualitative and quantitative studies published in English were included if they recruited people with isolated PMR regardless of treatment. Study selection and data extraction was performed independently by two investigators and disagreement was resolved through discussion. Data extracted encompassed definitions of disease activity, remission and relapse, and details regarding the instruments used to measure these outcomes. RESULTS: From the 5,718 records, we included 26 articles on disease activity, 36 on remission, and 53 on relapse; 64 studies were observational and 15interventional, and none used qualitative methods. Some heterogeneity was found regarding definitions and instruments encompassing the domains pain, stiffness, fatigue, laboratory markers (mainly acute phase reactants), and patient and physician global assessment of disease activity. However, instruments for clinical signs were often poorly described. Whilst measurement properties of the polymyalgia rheumatica activity score (PMR-AS) have been assessed, data to support its use for measurement of remission and relapse is limited. CONCLUSION: Remission, relapse, and disease activity have been defined heterogeneously in clinical studies. Instruments to measure these disease states still need to be validated. Qualitative research is needed to better understand the concepts of remission and relapse in PMR. REVIEW REGISTRATION: PROSPERO identification: CRD42021255925.

"It means almost forgetting that you've got a disease": An OMERACT study to define independence in the context of rheumatoid arthritis remission from the patient perspective.

AIMS: Our previous work identified pain, fatigue, and independence as missing from the ACR/EULAR rheumatoid arthritis (RA) remission criteria from the patient perspective. Validated measures exist for pain and fatigue, but not for independence. As a first step towards developing such a measure, this study aimed to understand 'Independence' in the context of RA remission from the patient perspective. METHODS: International qualitative research study comprising five focus groups of 19 participants with RA. Data were analysed using reflexive thematic analysis. RESULTS: Five overarching themes were identified, underpinned by a construct of "stages of independence". Independence means at least being 'physically and functionally able' but may go beyond this and enable 'participation beyond function', 'cognitive independence', and 'having or taking control'. There was no agreement on whether assistance is an aid to independence or undermines ability to achieve independence ('assistance is complicated'). The construct "Stages of independence" acknowledges that Independence may mean different things to different patients and there may be other factors beyond disease activity that hold patients in each of these stages. CONCLUSION: These novel data suggest a desirable definition of independence includes full active participation without the need to consider or work around disease activity, and cognitive independence from thoughts of RA. Independence in RA remission is a complex concept and next steps will be to seek patient and professional agreement on the most important issues raised in these focus groups to take forward to developing a measure for independence in the context of RA remission from the patient perspective.

Assessing Psychological Remission in Adolescent Anorexia Nervosa: A Comparison of Patient and Parent Report.

OBJECTIVE: The definition and assessment of remission in anorexia nervosa (AN) needs greater consensus. Particularly in adolescents, the use of patient-reported composite indices (such as the Eating Disorder Examination [EDE] Global Score) as the sole measure of psychological remission has the potential to obscure patients' true clinical status, given developmental factors and the propensity towards symptom minimization in AN. METHOD: End of treatment (EOT) data from a randomized controlled trial comparing two formats of manualized family-based treatment for adolescents with AN (N = 106) were analyzed. Participants completed the EDE, and their parents completed a parent-as-informant version of the EDE (Parent Eating Disorder Examination; PEDE). Rates of remission were compared across indices (i.e., EDE Global Score vs. diagnostic item analysis) and informant (i.e., adolescent vs. parent), both independently and in combination with the achievement of a percent median body mass index (% mBMI) greater than or equal to 95%. RESULTS: For both adolescent and parent reports, there were higher rates of remission when defined by Global Score than when defined by EDE or PEDE diagnostic items. There were no significant differences in remission rates based on informant. DISCUSSION: In the assessment of remission in AN, the EDE Global Score may not detect some adolescents who continue to exhibit clinically significant psychological symptoms. This study supports a detailed, multidimensional approach to assessing remission in adolescent AN to optimize sensitivity to patients' diagnostic profile. Future research should explore whether parent-child concordance on measures of ED psychopathology varies over the course of treatment.

A randomised, two-arm (1:1 ratio), double blind, placebo controlled phase III trial to assess the efficacy, safety, cost and cost-effectiveness of Rituximab in treating de novo or relapsing NS in patients with MCD/FSGS (TURING).

BACKGROUND: Minimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS) are a spectrum of disease causing the nephrotic syndrome (NS), characterised by proteinuria with debilitating oedema, as well as a high risk of venous thromboembolic disease and infection. Untreated, 50-60% patients with FSGS progress to end stage kidney disease after 5 years. These diseases respond to immunosuppression with high dose glucocorticoids, but 75% will relapse as the glucocorticoids are withdrawn, leading to significant morbidity associated with prolonged use. In children, the B cell depleting monoclonal antibody rituximab reduces relapse risk, but this drug has not been tested in randomised controlled trial in adults. METHODS: 130-150 adults with new or relapsing MCD/FSGS, from UK Renal Units, are being randomised to receive either rituximab (two 1 g infusions two weeks apart) or placebo. Partipicipants are recruited when they present with nephrosis, and all are treated with glucocorticoids as per KDIGO guidelines. Once in remission, prednisolone is withdrawn according to a pre-specified regimen. If in remission at 6 months, participants receive a further dose of trial drug. If they relapse, they are unblinded, and if they have received placebo, they are offered open label rituximab with protocolised prednisolone as in the main phase of the trial. The primary end point is time from remission to relapse. A number of secondary endpoints will be assessed including the effect of rituximab on: (1) NHS and societal resource use and hence cost: (2) safety: (3) other measures of efficacy, such as achievement of partial and complete remission of NS and the preservation of renal function: (4) health status of participant. TRIAL REGISTRATION: TURING received ethical approval on 14 Jun 2019 - REC reference: 19/LO/0738. It is registered on EudraCT, with ID number: 2018-004611-50, with a start date of 2019-06-14.

Absence of Paneth Cell Metaplasia to Predict Clinical Relapse in Ulcerative Colitis with Endoscopically Quiescent Mucosa.

BACKGROUND: Paneth cells play multiple roles in maintaining intestinal homeostasis. However, the clinical role of Paneth cell metaplasia (PCM) in ulcerative colitis (UC) remains unclear. We aimed to investigate the relationship between PCM and relapse in patients with UC and compare the usefulness of PCM with other histological indexes, including mucin depletion (MD) and basal plasmacytosis (BP). METHODS: Patients with UC in clinical remission (CR) who underwent colonoscopy to confirm a Mayo endoscopic subscore (MES) ≦1 with biopsies from the distal colon were enrolled into this retrospective cohort study. Biopsy samples were evaluated for histological findings of PCM, MD, and BP. Clinical relapse was defined as partial Mayo score ≧3 or medication escalation. Multivariate analysis was performed to determine independent predictors of relapse among the three histological findings, MES, and patient background, and relapse prediction models were generated. RESULTS: Eighty-three patients were enrolled in this study (MES 0, n = 47; MES 1, n = 36). The number of PCM cases was significantly higher in patients with prolonged CR than that in those with relapse (p = 0.01). Multivariate analysis showed that the absence of PCM and MD were related to relapse in all the patients. In patients with MES 1, the absence of PCM was the only risk factor significantly and independently associated with relapse (hazard ratio, 4.51 [1.15-17.7]; p = 0.03). CONCLUSION: The absence of PCM was a histological risk factor for relapse in patients with MES 1, implying a protective role for PCM in remission and a new index for mucosal healing.

The clinical influence of complete remission with incomplete count recovery (CRi) on single-unit umbilical cord blood transplantation in patients with acute leukemia.

BACKGROUND: Recent evidence has indicated that measurable residual disease (MRD) markedly affects the prognosis of patients with acute leukemia post-transplantation. However, the prognostic relevance of complete remission with incomplete count recovery (CRi) before transplantation has not been extensively explored. METHODS: In this single-center, longitudinal study, we assessed the outcomes of 466 MRD-negative acute leukemia patients who underwent single-unit unrelated cord blood transplantation (sUCBT), including 117 patients with CRi. RESULTS: We observed that acute myeloid leukemia (AML) patients with CRi had a significantly lower cumulative incidence of both neutrophil (90.8% vs. 96.5%) and platelet engraftment (67.2% vs. 85.3%) and experienced increased transplant-related mortality (TRM) (100-day TRM: 14.2% vs. 5.3%; 1-year TRM: 20.6% vs. 11.3%; P = 0.024 and 0.063, respectively), mainly due to infection-related deaths, compared to those in complete remission (CR). Multivariate analysis revealed that CRi was an independent adverse predictor of both neutrophil and platelet engraftment and increased 100-day TRM in AML patients. However, CRi status did not affect relapse or reduce 5-year overall survival (OS), leukemia-free survival (LFS), or GVHD-free relapse-free survival (GRFS) in the AML cohort. Conversely, for patients with acute lymphoblastic leukemia (ALL), CRi did not impact engraftment, TRM, relapse or survival after sUCBT. CONCLUSIONS: Our findings underscore that CRi status before sUCBT portends poorer engraftment outcomes and a greater TRM in AML patients, although it does not significantly affect the prognosis of ALL patients.

Effects of Very Low-Calorie Diet versus Roux-en-Y Gastric Bypass Surgery on Body Composition in Patients with Obesity.

Roux-en-Y gastric bypass (RYGB) is the most effective treatment for severe obesity. A very low-calorie diet (VLCD) is another effective dietary intervention to treat obesity. This study evaluated the effect of a VLCD versus RYGB on weight reduction, changes in body composition and the resolution of comorbidities during a 12-week period. Individuals with obesity at the obesity clinic, Ramathibodi Hospital, Mahidol University, Thailand with a body mass index (BMI) ≥ 37.5 kg/m2 or ≥32.5 kg/m2 with obesity-related complications were recruited. Treatment options, either RYGB or VLCD, were assigned depending on patients' preferences and physicians' judgment. The analysis included 16 participants in the RYGB group and 15 participants in the VLCD group. Baseline characteristics were similar between groups; nevertheless, the participants in the VLCD group were significantly younger than those in the RYGB group. The number of patients with type 2 diabetes (T2D) was slightly higher in the RYGB group (43.8% vs. 33.3%, p = 0.552). Additionally, patients in the RYGB group had a longer duration of T2D and were treated with anti-diabetic agents, while VLCD patients received only lifestyle modifications. At 12 weeks, total and percentage weight loss in the RYGB and VLCD groups, respectively, were as follows: -17.6 ± 6.0 kg vs. -15.6 ± 5.1 kg (p = 0.335) and -16.2% ± 4.3% vs. -14.1% ± 3.6% (p = 0.147). Changes in biochemical data and the resolution of comorbidities were similar between the groups at 12 weeks. A 12-week VLCD resulted in similar weight loss and metabolic improvement compared with RYGB. Large-scale studies with long follow-up periods are needed to elucidate whether VLCD is a viable alternative treatment to bariatric surgery.

Managing patients' reports of abdominal pain and irritable bowel syndrome-like symptoms during quiescent inflammatory bowel disease: a role for shared sensemaking.

Background: Patients with inflammatory bowel disease (IBD) are often faced with distressing and confusing abdominal pain during remission. Some people respond adversely to healthcare professionals' (HCPs) suggestions that this pain and related symptoms are due to secondary irritable bowel syndrome (IBS). Exploring how HCPs view, manage, and explain pain during quiescent disease may provide insights into how communication can be improved to increase understanding and mitigate negative responses. Methods: In-depth semi-structured interviews were conducted with 12 IBD-nurses (n = 4) and gastroenterologists (n = 8) working in the United Kingdom or the Netherlands. Reflexive thematic analysis was used to analyse interviews. Results: Findings suggest that HCPs pay relatively little attention to pain when there is no underlying pathology and prefer to concentrate on objectifiable causes of symptoms and treating disease activity (Theme 1: Focus on disease activity, not pain and associated symptoms). Explanations of abdominal pain and IBS-like symptoms during remission were not standardised (Theme 2: Idiosyncratic and uncertain explanations for pain during remission). Processes of shared decision-making were outlined and shared sensemaking was reported as a strategy to enhance acceptance of IBS explanations (Theme 3: Shared decision making versus shared sensemaking). Conclusion: Future work should focus on establishing how pain during remission may be best defined, when to diagnose IBS in the context of IBD, and how to explain both to patients. The formulation of standardised explanations is recommended as they might help HCPs to adopt practices of shared sensemaking and shared decision-making. Explanations should be adaptable to specific symptom presentations and different health literacy levels.

Successful rechallenge with azacytidine and venetoclax after sustained treatment-free remission in a relapsed acute myeloid leukemia patient: a case report.

Combined therapy with venetoclax and hypomethylating agents has significantly improved the outcome of unfit patients ineligible for intensive chemotherapy. A recently published exploratory analysis of the VIALE-A trial reported that up to 51% of patients achieving remission survived more than 2 years. These data along with those from reallife settings, lead to questioning how long it is appropriate to continue treatment in long-term survivors. Accordingly, recent retrospective studies suggested the feasibility of suspending therapy in selected patients while maintaining prolonged responses. Also, these studies showed that retreatment may induce a second remission in almost a third of patients. We report the case of a patient who received salvage therapy with venetoclax and azacytidine, that was discontinued few cycles after blasts clearance because of severe hematological toxicity. Despite suspension, he maintained a sustained response lasting almost one year and was successfully retreated with the same combination when a second relapse occurred.