Longitudinal CT Imaging to Explore the Predictive Power of 3D Radiomic Tumour Heterogeneity in Precise Imaging of Mantle Cell Lymphoma (MCL)

The study’s primary aim is to evaluate the predictive performance of CT-derived 3D radiomics for MCL risk stratification. The secondary objective is to search for radiomic features associated with sustained remission. Included were 70 patients: 31 MCL patients and 39 control subjects with normal axillary lymph nodes followed over five years. Radiomic analysis of all targets (n = 745) was performed and features selected using the Mann Whitney U test; the discriminative power of identifying “high-risk MCL” was evaluated by receiver operating characteristics (ROC). The four radiomic features, “Uniformity”, “Entropy”, “Skewness” and “Difference Entropy” showed predictive significance for relapse (p < 0.05)—in contrast to the routine size measurements, which showed no relevant difference. The best prognostication for relapse achieved the feature “Uniformity” (AUC-ROC-curve 0.87; optimal cut-off ≤0.0159 to predict relapse with 87% sensitivity, 65% specificity, 69% accuracy). Several radiomic features, including the parameter “Short Axis,” were associated with sustained remission. CT-derived 3D radiomics improves the predictive estimation of MCL patients; in combination with the ability to identify potential radiomic features that are characteristic for sustained remission, it may assist physicians in the clinical management of MCL.

Predicting relapse or recurrence of depression: systematic review of prognostic models

Background Relapse and recurrence of depression are common, contributing to the overall burden of depression globally. Accurate prediction of relapse or recurrence while patients are well would allow the identification of high-risk individuals and may effectively guide the allocation of interventions to prevent relapse and recurrence. Aims To review prognostic models developed to predict the risk of relapse, recurrence, sustained remission, or recovery in adults with remitted major depressive disorder. Method We searched the Cochrane Library (current issue); Ovid MEDLINE (1946 onwards); Ovid Embase (1980 onwards); Ovid PsycINFO (1806 onwards); and Web of Science (1900 onwards) up to May 2021. We included development and external validation studies of multivariable prognostic models. We assessed risk of bias of included studies using the Prediction model risk of bias assessment tool (PROBAST). Results We identified 12 eligible prognostic model studies (11 unique prognostic models): 8 model development-only studies, 3 model development and external validation studies and 1 external validation-only study. Multiple estimates of performance measures were not available and meta-analysis was therefore not necessary. Eleven out of the 12 included studies were assessed as being at high overall risk of bias and none examined clinical utility. Conclusions Due to high risk of bias of the included studies, poor predictive performance and limited external validation of the models identified, presently available clinical prediction models for relapse and recurrence of depression are not yet sufficiently developed for deploying in clinical settings. There is a need for improved prognosis research in this clinical area and future studies should conform to best practice methodological and reporting guidelines.

Clinical research challenges posed by difficult-to-treat depression

Approximately one-third of individuals in a major depressive episode will not achieve sustained remission despite multiple, well-delivered treatments. These patients experience prolonged suffering and disproportionately utilize mental and general health care resources. The recently proposed clinical heuristic of ‘difficult-to-treat depression’ (DTD) aims to broaden our understanding and focus attention on the identification, clinical management, treatment selection, and outcomes of such individuals. Clinical trial methodologies developed to detect short-term therapeutic effects in treatment-responsive populations may not be appropriate in DTD. This report reviews three essential challenges for clinical intervention research in DTD: (1) how to define and subtype this heterogeneous group of patients; (2) how, when, and by what methods to select, acquire, compile, and interpret clinically meaningful outcome metrics; and (3) how to choose among alternative clinical trial design options to promote causal inference and generalizability. The boundaries of DTD are uncertain, and an evidence-based taxonomy and reliable assessment tools are preconditions for clinical research and subtyping. Traditional outcome metrics in treatment-responsive depression may not apply to DTD, as they largely reflect the only short-term symptomatic change and do not incorporate durability of benefit, side effect burden, or sustained impact on quality of life or daily function. The trial methodology will also require modification as trials will likely be of longer duration to examine the sustained impact, raising complex issues regarding control group selection, blinding and its integrity, and concomitant treatments.

Predictors of Sustained Response With Tofacitinib Therapy in Patients With Ulcerative Colitis

Background Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis. We evaluate baseline characteristics as predictors of sustained response and remission in patients with ulcerative colitis receiving tofacitinib maintenance therapy. Methods Patients with clinical response following OCTAVE Induction 1 and 2 entered OCTAVE Sustain and were rerandomized to receive tofacitinib 5 or 10 mg twice daily or placebo. Baseline characteristics were stratified by week 52 efficacy endpoints (remission, sustained remission, clinical response, sustained clinical response). Associations between baseline characteristics and efficacy endpoints were evaluated using logistic regression analyses. Results Overall, 170 of 487 (34.9%) patients were in remission at week 52. In multivariable modeling, endoscopic subscore at baseline of OCTAVE Induction 1 and 2 (2 vs 3; odds ratio [OR], 1.60; 95% confidence interval [CI], 1.06-2.44]), partial Mayo score (&lt;2 vs ≥2; OR, 1.92; 95% CI, 1.27-2.90), and age (per 10-years; OR, 1.19; 95% CI, 1.02-1.39) at baseline of OCTAVE Sustain (following 8 weeks’ tofacitinib induction therapy) were associated with higher odds of remission at week 52. Oral corticosteroid use (OR, 0.63; 95% CI, 0.42-0.96) and C-reactive protein (per unit; OR, 0.94; 95% CI, 0.89-0.99) at baseline of OCTAVE Sustain were associated with reduced likelihood of remission at week 52. In general, opposite associations were observed for time to loss of response. Conclusion Patients with greater clinical improvement after 8 weeks of tofacitinib induction therapy are more likely to maintain response or remission with tofacitinib regardless of dose received during maintenance, highlighting the importance of a robust response to induction therapy.

Defining the Optimal Strategies for Achieving Drug-Free Remission in Rheumatoid Arthritis: A Narrative Review

Background: It is now accepted that the optimum treatment goal for rheumatoid arthritis (RA) is sustained remission, as this has been shown to be associated with the best patient outcomes. There is little guidance on how to manage patients once remission is achieved; however, it is recommended that patients can taper therapy, with a view to discontinuing and achieving drug-free remission if treatment goals are maintained. This narrative review aims to present the current literature on drug-free remission in rheumatoid arthritis, with a view to identifying which strategies are best for disease-modifying anti-rheumatic drug (DMARD) tapering and to highlight areas of unmet clinical need. Methods: We performed a narrative review of the literature, which included research articles, meta-analyses and review papers. The key search terms included were rheumatoid arthritis, remission, drug-free remission, b-DMARDS/biologics, cs-DMARDS and tapering. The databases that were searched included PubMed and Google Scholar. For each article, the reference section of the paper was reviewed to find additional relevant articles. Results: It has been demonstrated that DFR is possible in a proportion of RA patients achieving clinically defined remission (both on cs and b-DMARDS). Immunological, imaging and clinical associations with/predictors of DFR have all been identified, including the presence of autoantibodies, absence of Power Doppler (PD) signal on ultrasound (US), lower disease activity according to composite scores of disease activity and lower patient-reported outcome scores (PROs) at treatment cessation. Conclusions: DFR in RA may be an achievable goal in certain patients. This carries importance in reducing medication-induced side-effects and potential toxicity, the burden of taking treatment if not required and cost effectiveness, specifically for biologic therapy. Prospective studies of objective biomarkers will help facilitate the prediction of successful treatment discontinuation.

A new indicator to measure discordance between patient reported outcomes and traditional disease activity holds promise to advance care trajectories improve care in patients with early Rheumatoid Arthritis

ABSTRACTObjectiveTo unravel disease impact in early RA patients by separately quantifying patient reported (PRF), clinical (CF) and laboratory (LF) factors. We put forward a new indicator, the discordance score (DS), for early identification and prediction of unmet patient outcomes in terms of future achievement of sustained remission and RA-related quality of life (QoL).MethodsWe obtained factor scores via factor analysis in the CareRA trial, then calculated the DS between PRF and the mean of the other scores. We computed the improvement from baseline to week 104 (%) and area-under-the-curve (AUC) across time-points per factor score and compared these between patients achieving or not achieving sustained (week 16 to 104) remission (DAS28CRP<2.6) with ANOVA. Logistic and linear regressions respectively were used to predict SR based on previous factor and discordance scores, and QoL at year 1 and 2 based on DS at week 16.ResultsPRF, CF and LF scores improved rapidly within 8 weeks. In patients achieving SR; PRF improved 57%, CF 90% and LF 27%, compared to 32% PRF (p=0.13), 77% CF (p<0.001) and 9% LF (p=0.36) score improvement in patients not achieving SR. Patients achieving SR had an AUC of 15.7, 3.4 and 4.8 for PRF, CF and LF respectively, compared to 33.2, 10.1, and 7.2 in participants not achieving SR (p<0.001 for all). Early factor and discordance scores were associated with later stage factor scores as well as QoL and PRF scores predicted SR (p<0.005 for PRF and DS).ConclusionsAll factor scores improved rapidly, especially in patients achieving SR. Patient-reported burden improved less extensively. Discordance scores could help in predicting the need for additional non-pharmacological interventions to achieve SR and decrease disease impact.KEY MESSAGESWhat is already known about this subject?Early and intensive RA drug-treatment using disease activity as a target allows rapid disease control and prevents joint destruction.Including pain, fatigue and physical function when assessing patients with early RA broadens the evaluation of disease impact.What does this study add?Leveraging patient reported outcomes (pain, fatigue and physical function) and traditional disease activity measures, we introduce a new indicator (named discordance score) for unraveling disease impact and treatment efficacy.We show how the discordance score stands for current unmet patient reported outcomes and could be used to predict future sustained disease contol and quality of life (1 and 2 years after baseline).We demonstrate this effect both in patients with and without sustained remissionHow might this impact on clinical practice or future developments?The earlier detection of unmet needs despite good disease control could allow to perform timely interdisciplinary interventions other than medication adaptations and could promote psychosocial wellbeing for patients.

A young girl with severe polyarteritis nodosa successfully treated with tocilizumab: a case report

Background Childhood Polyarteritis nodosa (PAN) is a systemic vasculitis with necrotizing inflammation of medium- and small-sized arteries. Disease evolution may be severe and refractory to standard treatment including prednisone, azathioprine and cyclophosphamide. Case presentation We present the case of a young girl with severe PAN resulting in progressive ischemia and necrosis of fingers and toes. Biological work-up revealed increased acute phase reactants and interleukin-6 levels. She was only partially controlled despite high-dose corticosteroids and cyclophosphamide infusions, and eventually achieved rapid improvement and sustained remission on tocilizumab. Further, we review the current evidence of the interleukin-6-inhibitor tocilizumab for the treatment of PAN. Conclusion Tocilizumab may be an efficient therapeutic option in a subset of treatment-refractory children with PAN.

Case Report: Unexpected Remission From Extreme and Enduring Bulimia Nervosa With Repeated Ketamine Assisted Psychotherapy

Background: Bulimia nervosa is a disabling psychiatric disorder that considerably impairs physical health, disrupts psychosocial functioning, and reduces overall quality of life. Despite available treatment, less than half of sufferers achieve recovery and approximately a third become chronically ill. Extreme and enduring cases are particularly resistant to first-line treatment, namely antidepressants and cognitive behavioral therapy, and have the highest rate of premature mortality. Here, we demonstrate that in such cases, repeated sessions of ketamine assisted psychotherapy (KAP) is an effective treatment alternative for improving symptoms.Case Presentation: A 21-year-old woman presented with extreme and enduring bulimia nervosa. She reported recurrent binge-eating and purging by self-induced vomiting 40 episodes per day, which proved refractory to both pharmacological and behavioral treatment at the outpatient, residential, and inpatient level. Provided this, her physician recommended repeated KAP as an exploratory and off-label intervention for her eating disorder. The patient underwent three courses of KAP over 3 months, with each course consisting of six sessions scheduled twice weekly. She showed dramatic reductions in binge-eating and purging following the first course of treatment that continued with the second and third. Complete cessation of behavioral symptoms was achieved 3 months post-treatment. Her remission has sustained for over 1 year to date.Conclusions: To our knowledge, this is the first report of repeated KAP used to treat bulimia nervosa that led to complete and sustained remission, a rare outcome for severe and enduring cases, let alone extreme ones. Additionally, it highlights the degree to which KAP can be tailored at the individual level based on symptom severity and treatment response. While its mechanism of action is unclear, repeated KAP is a promising intervention for bulimia nervosa that warrants future research and clinical practice consideration.