Optimizing survival outcomes with post-remission therapy in acute myeloid leukemia.

Optimization of post-remission therapies to maintain complete remission and prevent relapse is a major challenge in treating patients with acute myeloid leukemia (AML). Monitoring patients for measurable residual disease (MRD) is helpful to identify those at risk for relapse. Hypomethylating agents are being investigated as post-remission therapy. Identification of recurrent genetic alterations that drive disease progression has enabled the design of new, personalized approaches to therapy for patients with AML. Emerging data suggest that targeted post-remission therapy, alone or in combination with chemotherapy, may improve outcomes. Results of ongoing clinical trials will further define potential clinical benefits

Predictors and outcomes of sustained, intermittent or never achieving remission in patients with recent onset inflammatory polyarthritis:Results from the Norfolk Arthritis Register

Objectives: Early remission is the current treatment strategy for patients with inflammatory polyarthritis (IP) and RA. Our objective was to identify baseline factors associated with achieving remission: sustained (SR), intermittent (IR) or never (NR) over a 5-year period in patients with early IP.  Methods: Clinical and demographic data of patients with IP recruited to the Norfolk Arthritis Register (NOAR) were obtained at baseline and years 1, 2, 3 and 5. Remission was defined as no tender or swollen joints (out of 51). Patients were classified as NR or PR, respectively, if they were in remission at: no assessment or ⩾3 consecutive assessments after baseline, and IR otherwise. Ordinal regression and a random effects model, respectively, were used to examine the association between baseline factors, remission group and HAQ scores over time.  Results: A total of 868 patients (66% female) were included. Of these, 54%, 34% and 12% achieved NR, IR and SR, respectively. In multivariate analysis, female sex (odds ratio, OR 0.47, 95% CI: 0.35, 0.63), higher tender joint count (OR = 0.94, 95% CI: 0.93, 0.96), higher HAQ (OR = 0.59, 95% CI: 0.48, 0.74), being obese (OR = 0.70, 95% CI: 0.50, 0.99), hypertensive (OR = 0.67, 95% CI: 0.50, 0.90) or depressed (OR = 0.74, 95% CI: 0.55, 1.00) at baseline were independent predictors of being in a lower remission group. IR and SR were associated with lower HAQ scores over time and lower DAS28 at year 5.  Conclusion: Women with higher tender joint count and disability at baseline, depression, obesity and hypertension were less likely to achieve remission. This information could help when stratifying patients for more aggressive therapy

Diabetes mellitus remission in a cat with pituitary-dependent hyperadrenocorticism after trilostane treatment

An 8-year-old male neutered Persian cat was presented with polyuria, polydipsia, polyphagia and muscle weakness associated with a 7 month history of diabetes mellitus (DM). The cat had initially been treated with neutral protamine Hagedorn (NPH) insulin 2 U q12h, followed by porcine lente insulin 2 U q12h and, most recently, 3 U glargine insulin q12h, without improvement of clinical signs. The cat also suffered from concurrent symmetrical bilateral alopecia of thorax and forelimbs, abdominal distension and lethargy. Hyperadrenocorticism (HAC), specifically pituitary-dependent HAC, was suspected and confirmed through abdominal ultrasonography demonstrating bilateral adrenal enlargement, and a low-dose dexamethasone suppression test using 0.1 mg/kg dexamethasone intravenously. Trilostane treatment (initially 10 mg/cat PO q24h then increased to 10 mg/cat PO q12h) was started and insulin sensitivity gradually improved, ultimately leading to diabetic remission after an increased in trilostane dose to 13mg/cat PO q12h, 14 months after the DM diagnosis and 7 months after the initiation of trilostane therapy

The role of stereotactic radiosurgery in the multimodal management of growth hormone–secreting pituitary adenomas

Growth hormone (GH)–secreting pituitary adenomas represent a common source of GH excess in patients with acromegaly. Whereas surgical extirpation of the culprit lesion is considered first-line treatment, as many as 19% of patients develop recurrent symptoms due to regrowth of previously resected adenomatous tissue or to continued growth of the surgically inaccessible tumor. Although medical therapies that suppress GH production can be effective in the management of primary and recurrent acromegaly, these therapies are not curative, and lifelong treatment is required for hormonal control. Stereotactic radiosurgery has emerged as an effective adjunctive treatment modality, and is an appealing alternative to conventional fractionated radiation therapy. The authors reviewed the growing body of literature concerning the role of radiosurgical procedures in the treatment armamentarium of acromegaly, and identified more than 1350 patients across 45 case series. In this review, the authors report that radiosurgery offers true hormonal normalization in 17% to 82% of patients and tumor growth control in 37% to 100% of cases across all series, while minimizing adverse complications. As a result, stereotactic radiosurgery represents a safe and effective treatment option in the multimodal management of primary or recurrent acromegaly secondary to GH-secreting pituitary adenomas

Disparity between General Symptom Relief and Remission Criteria in the Positive and Negative Syndrome Scale (PANSS): A Post-treatment Bifactor Item Response Theory Model.

Objective: Total scale scores derived by summing ratings from the 30-item PANSS are commonly used in clinical trial research to measure overall symptom severity, and percentage reductions in the total scores are sometimes used to document the efficacy of treatment. Acknowledging that some patients may have substantial changes in PANSS total scores but still be sufficiently symptomatic to warrant diagnosis, ratings on a subset of 8 items, referred to here as the "Remission set," are sometimes used to determine if patients' symptoms no longer satisfy diagnostic criteria. An unanswered question remains: is the goal of treatment better conceptualized as reduction in overall symptom severity, or reduction in symptoms below the threshold for diagnosis? We evaluated the psychometric properties of PANSS total scores, to assess whether having low symptom severity post-treatment is equivalent to attaining Remission. Design: We applied a bifactor item response theory (IRT) model to post-treatment PANSS ratings of 3,647 subjects diagnosed with schizophrenia assessed at the termination of 11 clinical trials. The bifactor model specified one general dimension to reflect overall symptom severity, and five domain-specific dimensions. We assessed how PANSS item discrimination and information parameters varied across the range of overall symptom severity (θ), with a special focus on low levels of symptoms (i.e., θ<-1), which we refer to as "Relief" from symptoms. A score of θ=-1 corresponds to an expected PANSS item score of 1.83, a rating between "Absent" and "Minimal" for a PANSS symptom. Results: The application of the bifactor IRT model revealed: (1) 88% of total score variation was attributable to variation in general symptom severity, and only 8% reflected secondary domain factors. This implies that a general factor may provide a good indicator of symptom severity, and that interpretation is not overly complicated by multidimensionality; (2) Post-treatment, 534 individuals (about 15% of the whole sample) scored in the "Relief" range of general symptom severity, but more than twice that number (n = 1351) satisfied Remission criteria (37%). 2 in 3 Remitted patients had scores that were not in a low symptom range (corresponding to Absent or Minimal item scores); (3) PANSS items vary greatly in their ability to measure the general symptom severity dimension; while many items are highly discriminating and relatively "pure" indicators of general symptom severity (delusions, conceptual disorganization), others are better indicators of specific dimensions (blunted affect, depression). The utility of a given PANSS item for assessing a patient depended on the illness level of the patient. Conclusion: Satisfying conventional Remission criteria was not strongly associated with low levels of symptoms. The items providing the most information for patients in the symptom Relief range were Delusions, Preoccupation, Suspiciousness Persecution, Unusual Thought Content, Conceptual Disorganization, Stereotyped Thinking, Active Social Avoidance, and Lack of Judgment and Insight. Lower scores on these items (item scores ≤2) were strongly associated with having a low latent trait θ or experiencing overall symptom relief. The inter-rater agreement between Remission and Relief subjects suggested that these criteria identified different subsets of patients. Alternative subsets of items may offer better indicators of general symptom severity and provide better discrimination (and lower standard errors) for scaling individuals and judging symptom relief, where the "best" subset of items ultimately depends on the illness range and treatment phase being evaluated

Switching from reference infliximab to CT-P13 in patients with inflammatory bowel disease: 12 months results

Background: Biological agents, such as infliximab, have transformed the outcomes of patients with immune-mediated inflammatory diseases. The advent of biosimilar treatment options such as CT-P13 promises to improve the availability of biological therapy, yet real-world switching data are currently limited. Here, we assess the effectiveness and safety of switching to CT-P13 from infliximab reference product (RP) in patients with inflammatory bowel disease. Materials and methods: This was a prospective single-center observational study in patients with moderate to severe Crohn’s disease (CD) and ulcerative colitis (UC). All patients were switched from infliximab RP (Remicade) to CT-P13 treatment and followed up for up to 12 months. The efficacy endpoint was the change in clinical response assessed at 3-monthly intervals, according to the Harvey–Bradshaw score and partial Mayo score for patients with CD and UC, respectively. C-reactive protein (CRP) was also measured. Adverse events were monitored and recorded throughout the study. Results: A total of 98 patients with inflammatory bowel disease (67 CD/31 UC) were included. A total of 83.6% (56/67) of patients with CD were in remission at the time of the switch and 62.7% were in remission at 12 months. The Harvey–Bradshaw score showed a significant change at 12 months (P =0.007) but no significant change was observed in median CRP at this timepoint (P= 0.364). A total of 80.6% (25/31) of patients with UC were in remission at the time of the switch and 65.3% (18/28) were in remission at 12 months. No significant changes in the median partial Mayo score (P=0.058) or CRP (P =0.329) were observed at 12 months. Serious adverse events related to medication were reported in 11 (11.2%) patients. Conclusion: Switching from infliximab RP to CT-P13 is efficacious and well tolerated in patients with CD or UC for up to 12 months

Endoscopic and clinical evaluation of treatment and prognosis of Cronkhite-Canada syndrome: a Japanese nationwide survey.

BackgroundFirst reported in 1955, Cronkhite-Canada syndrome (CCS), a rare syndrome characterized by ectodermal abnormalities and inflammatory changes of the gastrointestinal tract mucosa, has been associated with a poor prognosis and life-threatening malignant complications. In a large population survey, we endeavored to characterize the course and treatment outcome of CCS through clinical and endoscopic assessment, and to explore its optimal treatment and surveillance strategy.MethodsA retrospective analysis of 210 patients with CCS was conducted via a questionnaire-based nationwide survey of 983 teaching hospitals located throughout Japan. We assessed clinical features, endoscopic findings, treatments used, and short- and long-term outcomes.ResultsThe average age at diagnosis was 63.5 years. In all cases, upper or lower gastrointestinal tract polyposis was confirmed, accompanied by characteristic ectodermal abnormalities. Of the treatments used, oral corticosteroids (30-49 mg/day) were the most effective treatment for active disease, with adjunctive nutritional support considered beneficial. With corticosteroid treatment, abdominal symptoms were relieved within a few months, whereas polyp regression often required more than 6 months. Maintenance of endoscopic remission with or without steroids for 3 years significantly lowered the development of CCS-related cancer, compared with relapsers or nonresponders, underscoring the importance of sustained endoscopic remission for cancer prevention.ConclusionsThe prognosis of CCS has greatly improved through the use of improved medical treatment. Although CCS continues to be relentlessly progressive, carrying a high cancer risk, a sufficient dose and duration of corticosteroid therapy accompanied by nutritional support and periodic endoscopic surveillance appears to improve its natural history

The Diabetes Remission Clinical Trial (DiRECT): protocol for a cluster randomised trial

Background: Despite improving evidence-based practice following clinical guidelines to optimise drug therapy, Type 2 diabetes (T2DM) still exerts a devastating toll from vascular complications and premature death. Biochemical remission of T2DM has been demonstrated with weight loss around 15kg following bariatric surgery and in several small studies of non-surgical energy-restriction treatments. The non-surgical Counterweight-Plus programme, running in Primary Care where obesity and T2DM are routinely managed, produces >15 kg weight loss in 33 % of all enrolled patients. The Diabetes UK-funded Counterpoint study suggested that this should be sufficient to reverse T2DM by removing ectopic fat in liver and pancreas, restoring first-phase insulin secretion. The Diabetes Remission Clinical Trial (DiRECT) was designed to determine whether a structured, intensive, weight management programme, delivered in a routine Primary Care setting, is a viable treatment for achieving durable normoglycaemia. Other aims are to understand the mechanistic basis of remission and to identify psychological predictors of response. Methods/Design: Cluster-randomised design with GP practice as the unit of randomisation: 280 participants from around 30 practices in Scotland and England will be allocated either to continue usual guideline-based care or to add the Counterweight-Plus weight management programme, which includes primary care nurse or dietitian delivery of 12-20weeks low calorie diet replacement, food reintroduction, and long-term weight loss maintenance. Main inclusion criteria: men and women aged 20-65years, all ethnicities, T2DM 0-6years duration, BMI 27-45 kg/m2. Tyneside participants will undergo Magnetic Resonance (MR) studies of pancreatic and hepatic fat, and metabolic studies to determine mechanisms underlying T2DM remission. Co-primary endpoints: weight reduction ≥ 15 kg and HbA1c <48 mmol/mol at one year. Further follow-up at 2 years. Discussion: This study will establish whether a structured weight management programme, delivered in Primary Care by practice nurses or dietitians, is a viable treatment to achieve T2DM remission. Results, available from 2018 onwards, will inform future service strategy

Efficacy of adalimumab as second-line therapy in a pediatric cohort of crohn’s disease patients who failed infliximab therapy: The Italian society of pediatric gastroenterology, hepatology, and nutrition experience

Background: Adalimumab (Ada) treatment is an available option for pediatric Crohn’s disease (CD) and the published experience as rescue therapy is limited. Objectives: We investigated Ada efficacy in a retrospective, pediatric CD cohort who had failed previous infliximab treatment, with a minimum follow-up of 6 months. Methods: In this multicenter study, data on demographics, clinical activity, growth, laboratory values (CRP) and adverse events were collected from CD patients during follow-up. Clinical remission (CR) and response were defined with Pediatric CD Activity Index (PCDAI) score ≤10 and a decrease in PCDAI score of ≥12.5 from baseline, respectively. Results: A total of 44 patients were consecutively recruited (mean age 14.8 years): 34 of 44 (77%) had active disease (mean PCDAI score 24.5) at the time of Ada administration, with a mean disease duration of 3.4 (range 0.3–11.2) years. At 6, 12, and 18 months, out of the total of the enrolled population, CR rates were 55%, 78%, and 52%, respectively, with a significant decrease in PCDAI scores (P<0.01) and mean CRP values (mean CRP 5.7 and 2.4 mL/dL, respectively; P<0.01) at the end of follow-up. Steroid-free remission rates, considered as the total number of patients in CR who were not using steroids at the end of this study, were 93%, 95%, and 96% in 44 patients at 6, 12, and 18 months, respectively. No significant differences in growth parameters were detected. In univariate analysis of variables related to Ada efficacy, we found that only a disease duration >2 years was negatively correlated with final PCDAI score (P<0.01). Two serious adverse events were recorded: 1 meningitis and 1 medulloblastoma. Conclusion: Our data confirm Ada efficacy in pediatric patients as second-line biological therapy after infliximab failure. Longer-term prospective data are warranted to define general effectiveness and safety in pediatric CD patients