Relapse Rate Research Articles

Acceptance and Commitment Therapy (Act) in Psychotic Patient

Introductions: Psychosis is a condition of severe mental disorder characterised by the presence of disability in assessing reality. Schizophrenia is the most common psychotic disorder. It is also associated with long-term disability. ACT is one of the newest psychological interventions for psychotic patients. This paper aims to describe ACT as the newest psychotherapy intervention and its advantages for psychotic patients. Review: The management of psychosis is a combination of the use of antipsychotics, psychotherapy, and psychosocial therapy. ACT is one of the newest psychological interventions for psychotic patients that aims to increase the patient’s psychological flexibility through six core processes of therapy: acceptance, cognitive defusion, being present, self as context, value, and committed action. ACT does not target symptom reduction. Therapists help patients recognise and reduce unnecessary struggles with psychological content so that patients can develop an accepting attitude and be able to move towards the values they hold. Conclusions: The use of third-wave behavioural therapy based on mindfulness and acceptance showed good results in patients with psychotic disorders. ACT aims to help individuals accept things that are beyond their control and commit to actions that can improve their lives. Research on the clinical adaptation of ACT for psychosis has shown good initial results in reducing distress due to psychotic symptoms, better regulation of emotions, and reducing relapsing rates.

Iraqi experts consensus on the management of relapsing remitting multiple sclerosis in adults

Objective In Iraq, a lack of evidence-based management protocols for diagnosing, treating, and managing multiple sclerosis (MS) poses risks of suboptimal outcomes and clinical practice variability and potential harm to the patients. This study aimed to develop consensus recommendations regarding the diagnosis and management of MS in Iraq, specifically focusing on treatment-naïve patients, suboptimal responders, and women of childbearing age during preconception, pregnancy planning, and lactation. Methods A survey was conducted to collect feedback from a panel of ten key opinion leaders (KOLs), who evaluated and discussed the statements to determine agreement levels. The mini-Delphi method was employed to establish a consensus on the management recommendations, and a meeting was held to analyze the responses and ensure that the recommendations were based on current evidence and followed a consensus-driven approach. Results The Revised McDonald Criteria is recommended for MS diagnosis, which includes evidence of dissemination of disease characteristics in space and time. Disease activity and progression can be monitored using relapses, MRI activity, and short-term disability progression. Experts suggest initiating treatment at diagnosis using higher efficacy medications, such as cladribine, ocrelizumab, natalizumab, or rituximab, for patients with high disease activity after careful risk stratification. Injectable interferon preparations have a tolerable risk profile but have drawbacks, such as the route and frequency of administration. Overall, disease-modifying therapies (DMTs) have shown efficacy in reducing relapse rates and short-term disability. Conclusion This article presents expert panel recommendations for managing MS in Iraq, taking into account international guidelines, medication updates, and local resources. However, practical questions remain regarding the real-world use of disease-modifying therapies (DMTs). Personalizing treatment based on disease severity, prognosis, and individual risk factors while adhering to guidelines is crucial. A collaborative approach between healthcare providers and patients, considering individual preferences, is vital for achieving treatment goals.

Inhibition of SRC-3 as a potential therapeutic strategy for aggressive mantle cell lymphoma.

Mantle cell lymphoma (MCL) has a poor prognosis and high relapse rates despite current therapies, necessitating novel treatment regimens. Inhibition of SRC-3 show effectiveness in vivo and in vitro in other B cell lymphomas. Additionally, previous studies have shown that SRC-3 is highly expressed in the lymph nodes of B cell non-Hodgkin's lymphoma patients, suggesting SRC-3 may play a role in the progression of B cell lymphoma. This study aimed to investigate novel SRC-3 inhibitors, SI-10 and SI-12, in mantle cell lymphoma. The cytotoxic effects of SI-10 and SI-12 were evaluated in vitro and demonstrated dose-dependent cytotoxicity in a panel of MCL cell lines. The in vivo efficacy of SI-10 was confirmed in two ibrutinib-resistant models: an immunocompetent disseminated A20 mouse model of B-cell lymphoma and a human PDX model of MCL. Notably, SI-10 treatment also resulted in a significant extension of survival in vivo with low toxicity in both ibrutinib-resistant murine models. We have investigated SI-10 as a novel anti-lymphoma compound via the inhibition of SRC-3 activity. These findings indicate that targeting SRC-3 should be investigated in combination with current clinical therapeutics as a novel strategy to expand the therapeutic index and to improve lymphoma outcomes.

Survival outcomes in pediatric patients with metastatic Ewing sarcoma who achieve a rapid complete response of pulmonary metastases.

Our objectives were to compare overall survival (OS) and pulmonary relapse between patients with metastatic Ewing sarcoma (EWS) at diagnosis who achieve rapid complete response (RCR) and those with residual pulmonary nodules after induction chemotherapy (non-RCR). This retrospective cohort study included children under 20years with metastatic EWS treated from 2007 to 2020 at 19 institutions in the Pediatric Surgical Oncology Research Collaborative. Chi-square tests were conducted for differences among groups. Kaplan-Meier curves were generated for OS and pulmonary relapse. Among 148 patients with metastatic EWS at diagnosis, 61 (41.2%) achieved RCR. Five-year OS was 71.2% for patients who achieved RCR, and 50.2% for those without RCR (p=.04), and in multivariable regression among patients with isolated pulmonary metastases, RCR (hazards ratio [HR] 0.42; 95% confidence interval [CI]: 0.17-0.99) and whole lung irradiation (WLI) (HR 0.35; 95% CI: 0.16-0.77) were associated with improved survival. Pulmonary relapse occurred in 57 (37%) patients, including 18 (29%) in the RCR and 36 (41%) in the non-RCR groups (p=.14). Five-year pulmonary relapse rates did not significantly differ based on RCR (33.0%) versus non-RCR (47.0%, p=.13), or WLI (38.8%) versus no WLI (46.0%, p=.32). Patients with EWS who had isolated pulmonary metastases at diagnosis had improved OS if they achieved RCR and received WLI, despite having no significant differences in rates of pulmonary relapse.

Comparing the effectiveness of depot buprenorphine (buvidal injection) and buprenorphine/naloxone (suboxone) treatment following custody release - a retrospective cohort study

ABSTRACT Background Many opioid-dependent people in prison experience unplanned opioid withdrawal upon entry into custody and face high rates of relapse, opioid overdose, & even death following custody release. The aim of the study was to examine and compare the effectiveness of depot buprenorphine and buprenorphine-naloxone sublingual treatments following custody release. Methods A retrospective descriptive comparative design, involving a review of electronic medical records (eMR) of 62 adults aged ±18 years who had received either buprenorphine-naloxone sublingual or depot buprenorphine treatment. The sample was identified from the intake register from 2019 to 2020. R statistical software was used for data analysis. Results Former inmates treated with depot buprenorphine tended to stay in treatment longer (M ± SD: 122.8 ± 59.8 days) than those treated with buprenorphine-naloxone sublingual (M ± SD: 89.4 ± 66.6 days). Out of 28 former inmates on depot buprenorphine, six (21%) were re-incarcerated, compared to 13 out of 34 on buprenorphine-naloxone sublingual treatment (38%). Conclusions Clients who received depot buprenorphine treatment prior to custody release exhibited better community treatment retention and a lower number of re-incarcerations compared to those who received buprenorphine-naloxone sublingual treatment. This study contributes to the limited knowledge base regarding depot buprenorphine and will inform future research.

Impact of different anastomosis methods on post-recurrence after intestinal resection for Crohn's disease: A meta-analysis.

Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract, often requiring intestinal resection as a common treatment. However, recurrence after surgery is common. The anastomotic configuration after bowel resection appears to be associated with the recurrence of CD. Previous studies have suggested that the Kono-S anastomosis may help to reduce the recurrence rate. However, the results remain controversial. Therefore, evidence-based evidence is needed to prove the advantages of Kono-S anastomosis. To measure the influence of anastomosis techniques on the long-term relapse rate of CD by conducting a meta-analysis. PubMed, Scopus, and Cochrane Library were searched until October 8, 2023. Patients who underwent intestinal resection due to CD were included. The intervention measures included Kono-S anastomosis, whereas the control group received traditional anastomosis such as end-to-end, end-to-side, and side-to-side anastomosis. Only randomized clinical trials and observational studies were included. The primary outcome measures were hospital stay post-surgery, overall postoperative complication incidence, the proportion of Clavien-Dindo grade IIIa or higher, overall postoperative recurrence rate, and Rutgeerts score. From 2011 to 2023, six articles met the inclusion and exclusion criteria. The results indicated that Kono-S anastomosis can reduce the hospital stay post-surgery of patients with CD [MD = -0.26, 95%CI: -0.42 to -0.10, P = 0.002] than other traditional anastomosis methods. Compared to other traditional anastomosis methods, Kono-S anastomosis can significantly reduce the total recurrence rate [MD = 0.40, 95%CI: 0.17 to 0.98, P = 0.05] and postoperative Rutgeerts score [MD = -0.81, 95%CI: -0.96 to -0.66, P < 0.001] in patients with CD. However, there is no significant disparity in the overall occurrence of postoperative complications and the proportion of Clavien-Dindo ≥ IIIa. Kono-S anastomosis has the potential to expedite the recuperation of CD and diminish relapse hazards; however, additional larger trials are necessary to authenticate its effectiveness.

Association between duration of antidepressant treatment for major depressive disorder and relapse rate after discontinuation: A meta-analysis

The optimal duration of antidepressant treatment for patients with major depressive disorder to reduce the risk of relapse after discontinuation remains uncertain. Medline, Cochrane Central Register of Controlled Trials, and Embase were systematically searched for randomized controlled trials (RCTs) with a discontinuation design. A single-group summary meta-analysis was performed to calculate 6-month relapse rates after discontinuation. Meta-regression with restricted cubic splines was performed to model the non-linear relationship between treatment duration and relapse rate after discontinuation. Thirty-five RCTs were included. The relapse rate after discontinuation was approximately 34.81 % at 6 months and 45.12 % at 12 months. After controlling for covariates, the meta-analysis shows that the duration of treatment is associated with the risk of relapse after discontinuation in a non-linear curve, with a relatively higher risk of relapse observed for a duration of less than three months. There appears to be no further reduction in the risk of relapse when treatment is continued for over six months. Our results indicate the importance of at least three months of treatment to avoid the relatively high risk of relapse after discontinuation. The additional benefit of longer treatment remains to be proven.

New-onset or relapse of uveitis after rapid spreading of COVID-19 infection in China and risk factor analysis for relapse

BackgroundThe aim of this study was to report the clinical profile of new-onset and relapse of uveitis following rapid spreading of coronavirus disease 2019 (COVID-19) infection due to change of anti-COVID-19 policies in China and investigate potential risk factors for inflammation relapse.MethodsIn this retrospective case-control study, patients with new-onset or a history of uveitis between December 23, 2022, and February 28, 2023, were included to assess the influence of COVID-19 infection on uveitis. Detailed information on demographic data, clinical characteristics, treatment measures, treatment response, and ocular inflammatory status before and after COVID-19 infection was collected.ResultsThis study included 349 patients with a history of uveitis. The uveitis relapse rate was higher (28.8%, n = 288) in those with COVID-19 infection than in patients without COVID-19 infection (14.8%, n = 61) (P = 0.024). Among the relapse cases, 50.8% experienced a relapse of anterior uveitis, while 49.2% had a relapse of uveitis involving the posterior segment. Multivariable regression analysis indicated a positive correlation between disease duration and uveitis relapse, while the last relapse exceeding one year before COVID-19 infection and the use of methotrexate during COVID-19 infection were negatively correlated with relapse of uveitis. Thirteen patients who developed new-onset uveitis following COVID-19 infection were included; among them, three (23.1%) had anterior uveitis and 10 (76.9%) had uveitis affecting the posterior segment. Regarding cases involving the posterior segment, four patients (30.8%) were diagnosed with Vogt-Koyanagi-Harada disease.ConclusionsCOVID-19 infection increases the rate of uveitis relapse. Long disease duration is a risk factor, while time since the last relapse more than 1 year and methotrexate use are protective factors against uveitis relapse.

High-dose Alemtuzumab-Cyclosporine versus Tacrolimus-Methotrexate-Sirolimus for Chronic Graft-versus-Host Disease Prevention

Chronic graft-versus-host disease (cGVHD) remains a significant problem for patients after allogeneic hematopoietic stem cell transplants (allo-HSCT). While in vivo lymphodepletion by antibodies for cGVHD prophylaxis has been explored in the myeloablative setting, its effects after reduced intensity conditioning (RIC) are not well described. Patients (n=83) with hematologic malignancies underwent targeted lymphodepletion chemotherapy followed by a RIC allo-HSCT using peripheral blood stem cells from unrelated donors. Patients were randomized to two GVHD prophylaxis arms: high-dose alemtuzumab/cyclosporine (AC, n=44) and tacrolimus/methotrexate/sirolimus (TMS, n=39) with the primary endpoint of cumulative incidence of severe cGVHD. The incidence of severe cGVHD was lower with AC vs TMS prophylaxis at 1- and 5-years (0% vs 10.3% and 4.5% vs 28.5%, overall p=0.0002), as well as any grade (p=0.003) and moderate-severe (p<0.0001) cGVHD. AC was associated with higher rates of grade III-IV infections (p=0.02) and relapse (52% vs 21%, p=0.003) with a shorter 5-year PFS (18% vs 41%, p=0.01) and no difference in 5-year GRFS, OS, or NRM. AC severely depleted naïve T-cells reconstitution, resulting in reduced TCR repertoire diversity, smaller populations of CD4 Treg and CD8 Tscm, but a higher ratio of Treg to naïve T-cells at 6 months. In summary, an alemtuzumab-based regimen successfully reduced the rate and severity of cGVHD after RIC allo-HSCT and resulted in a distinct immunomodulatory profile which may have reduced cGVHD incidence and severity. However, increased infections and relapse resulted in a lack of survival benefit after long-term follow-up. ClinicalTrials.gov identifier: NCT00520130.

The effectiveness of using cognitive behavioral therapy and internet-based cognitive behavioral therapy interventions on relapse prevention and severity of symptoms among patients diagnosed with major depressive disorder: a systematic review of randomized controlled trials

Purpose This study aims to evaluate and summarize the effectiveness of cognitive behavioral therapy (CBT) and internet-based CBT (ICBT) interventions on relapse prevention and severity of symptoms among individuals with major depressive disorder (MDD). CBT is one of the most used and suggested interventions to manage MDD, whereas ICBT is a novel effective proposed approach. Design/methodology/approach The review was conducted following the preferred reporting items for systematic review and meta-analysis protocol. A comprehensive and extensive search was performed to identify and evaluate the relevant studies about the effectiveness of CBT and ICBT on relapse prevention and severity of symptoms among patients with MDD. Findings A total of eight research studies met the inclusion criteria and were included in this systematic review. RCT studies were conducted to assess and evaluate the effectiveness of CBT and ICBT on relapse prevention and severity of symptoms among patients with MDD. It has been found that CBT is a well-supported and evidently based effective psychotherapy for managing depressive symptoms and reducing the relapse and readmission rate among patients diagnosed with MDD. The ICBT demonstrated greater improvements in depressive symptoms during major depressive episodes among patients with MDDS. The ICBT program had good acceptability and satisfaction among participants in different countries. Research limitations/implications Despite the significant findings from this systematic review, certain limitations should be acknowledged. First, it is important to note that all the studies included in this review were exclusively conducted in the English language, potentially limiting the generalizability of the findings to non-English speaking populations. Second, the number of research studies incorporated in this systematic review was relatively limited, which may have resulted in a narrower scope of analysis. Finally, a few studies within the selected research had small sample sizes, which could potentially impact the precision and reliability of the overall conclusions drawn from this review. The authors recommend that nurses working in psychiatric units should use CBT interventions with patients with MDD. Practical implications This paper, a review of the literature gives an overview of CBT and ICBT interventions to reduce the severity of depressive symptoms and prevent patients’ relapse and rehospitalization and shows that CBT interventions are effective on relapse prevention among patients with MDD. In addition, there is still no standardized protocol to apply the CBT intervention in the scope of reducing the severity of depressive symptoms and preventing depression relapse among patients with major depressive disorder. Further research is needed to confirm the findings of this review. Future research is also needed to find out the most effective form and contents of CBT and ICBT interventions for MDD. Social implications CBT is a psychological intervention that has been recommended by the literature for the treatment of major depressive disorder (MDD). It is a widely recognized and accepted approach that combines cognitive and behavioral techniques to assist individuals overcome their depressive symptoms and improve their overall mental well-being. This would speculate that effectiveness associated with several aspects and combinations of different approaches in CBT interventions and the impact of different delivery models are essential for clinical practice and appropriate selection of the interventional combinations. Originality/value This systematic review focuses on the various studies that explore the effectiveness of face-to-face CBT and ICBT in reducing depressive symptoms among patients with major depressive disorder. These studies were conducted in different countries such as Iran, Australia, Pennsylvania and the USA.

Intravenous Versus Subcutaneous Infliximab in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

Subcutaneous (SC) infliximab may provide multiple benefits over intravenous (IV) formulations. However, studies for efficacy and safety in inflammatory bowel disease (IBD) have been constrained by small sizes that limit the interpretation of outcomes, especially for subgroups potentially at high-risk of disease relapse. We conducted a systematic review and random-effects meta-analysis up to January 2023 to evaluate the change in clinical remission after transitioning from IV to SC infliximab in patients with IBD in clinical remission. The primary outcome was measured using the relative risk for meta-analysis. 15 studies of patients established ≥3 months on IV infliximab were identified, consisting of 1371 patients and 840 patient-years of follow-up. There was no loss of clinical remission in the IBD cohort overall, Crohn's disease (CD), and perianal CD p=0.55 & p=0.11 at 9-12 months, and p=0.50 at 6 months respectively). Neither prior IV dose (≤10mg/kg 6-weekly) (p=0.48) nor IBD disease subtype was associated with an increased clinical relapse rate at 6 months (p=0.48 and p=0.45 (UC vs CD), respectively). Changing patients established on IV infliximab to an SC formulation is associated with a high ongoing clinical remission and low adverse event rate. Furthermore, there are no signals for adverse outcomes among different IBD disease subtypes, nor in those on escalated IV infliximab dosing schedules up to 10mg/kg 6-weekly. This data should provide patients and clinicians alike with confidence in SC infliximab use in IBD.

Clonally unrelated primary large B‐cell lymphomas separated by over a decade involving the central nervous system and testicle: Possible predisposition to lymphomas of immune‐privileged sites?

AbstractPrimary large B‐cell lymphomas of immune‐privileged sites (IP‐LBCLs) comprise LBCLs arising within “immune sanctuaries,” including the central nervous system (CNS), vitreoretina, and testes. Although patients present with localized disease, the prognosis remains poor with high relapse rates, either at the originating site or within another immune‐privileged site. Generally, in the presence of an antecedent IP‐LBCL, subsequent LBCLs are expected to be clonally related. However, we present a primary CNS LBCL and later primary testicular LBCL in a middle‐aged man, diagnosed over a decade apart, which proved to be clonally unrelated by targeted ultra‐deep next‐generation sequencing of the IgH locus.

Clinical correlation between disease progression and central vein sign in pediatric onset multiple sclerosis: A binational study

BackgroundThe central vein sign (CVS) has been proposed as a novel MRI biomarker to improve diagnosis of pediatric-onset MS (POMS). However, the role of CVS in POMS progression has yet to be discovered. ObjectivesTo investigate the appearance of CVS and its correlation with POMS disease progression. MethodsOne hundred fifty-six POMS from two MS centers in Israel and Czech Republic MS centers were followed for five years. Patient assessment was performed by the Expanded Disability Status Scale (EDSS) and Annual Relapse Rate (ARR). Patients in whom at least 40 % of brain MRI lesions had CVS (“rule of 40”) were determined as CVS-positive. ResultsThe total group of POMS consisted of 96 CVS-negative (61.5 %), aged 14.6 ± 1.9 years, EDSS 2.0, 75 % Interquartile Range (IQR) 1.0–3.0, disease duration (DD) 6.28 ± 0.38 years, and 60 CVS-positive (38.5 %), aged 15.1 ± 0.3 years, EDSS 2.0, IQR 1.5–3.0, DD 5.62 ± 0.13 years, were analyzed. After a three and five-year follow-up, the CVS-positive patients had higher EDSS scores than those who were CVS-negative, 2.0, IQR 1.0–2.5, vs 1.0, IQR 1.0–2.0, (p = 0.009) and 2.0, IQR 1.0–3.25 vs 1.0, IQR 1.0–2.0, (p = 0.0003), respectively. Patients with CVS-positive POMS were characterized by a significantly higher ARR (0.78 ± 0.08 vs 0.57 ± 0.04, p = 0.002). These results were confirmed in subgroups of Disease Modifying Treatments (DMT) untreated and treated patients. ConclusionCVS-positive POMS is characterized by higher disability progression than CVS-negative, indicating the importance of CVS in disease pathogenesis.

Hepatic and Extrahepatic Characteristics of Autoimmune Hepatitis: A 23-year Hospital-Based Cohort Study.

The characteristics of autoimmune hepatitis (AIH) in Asia mostly remain elusive. A cohort study of liver biopsy-proven AIH patients was conducted in a tertiary care cancer of Taiwan. From 1999 to 2022, of 13,766 patients who underwent liver biopsy, 150 patients with AIH were enrolled. The female-to-male ratio was 2.26. At baseline, the mean age was 51.09 years, mean alanine aminotransferase level was 494.11 U/L, and 17 (11.3%) had cirrhosis. All except one patient had AIH type 1. The females were older and had higher baseline cirrhosis rates than did the males. The 23-year cumulative incidences of cirrhosis, hepatocellular carcinoma (HCC), mortality/liver transplantation, autoimmune diseases and extrahepatic cancer were 64.2%, 13.3%, 23.4%, 30.7% and 21.2%, respectively. The 1-year, 2-year, 3-year, 5-year, 10-year and 20-year postimmunosuppressive therapy relapse rates were 60%, 78.2%, 81.8%, 89.1%, 94.5% and 100%, respectively. Baseline associations were as follows: alkaline phosphatase (Alk-p) levels with postimmunosuppressive therapy flare [hazard ratio (HR): 1.003; 95% CI HR: 1.000-1.005]; age with HCC (1.072; 1.010-1.138) and all-cause cancer (1.041;1.005-1.079); cirrhosis with mortality/liver transplantation (11.933;1.984-71.787); and antinuclear antibody (ANA) titers with mortality/liver transplantation (1.001;1.000-1.003), cirrhosis (1.001;1.000-1.002), and autoimmune diseases (1.001; 1.000-1.002). In an Asian country endemic for viral hepatitis, the female-to-male and baseline cirrhosis rates of AIH patients were lower than expected, while over 60% of the patients eventually developed cirrhosis. The high posttherapy relapse rate warrants cautious monitoring, particularly for patients with high baseline Alk-p levels. Baseline age, cirrhosis status and ANA titers are crucial for outcomes.

Trends in Non-Tuberculous Mycobacterial Lung Disease and Treatment Outcomes in a Low-Tuberculosis Prevalence Setting: A Retrospective Analysis.

Information on the management of non-tuberculous mycobacterial (NTM) lung infection and disease is scarce. The aim of this study was to investigate the trends in NTM lung infections, and the factors associated with the initiation of treatment and treatment outcomes. A retrospective analysis was carried out on patient medical records from Haukeland University Hospital, Bergen, Norway, from 2000 to 2021. Among 154 patients with NTM lung infection, the majority (70%) were older than 65 years, and 49% had an underlying pulmonary comorbidity. The most frequently observed mycobacterial species was M. avium complex (MAC), followed by M. malmoense and M. abscessus. In total, 72 (47%) patients received antibiotic treatment. Patients with high symptom scores, aged below 65, and with MAC infection had more than three times the odds of receiving antibiotic treatment. A favourable response and culture conversion was observed in 53 of 72 (74%) patients. However, 17 (32%) of them had a relapse. Out of 82 patients who did not receive treatment, 45 (55%) had spontaneous culture conversion, and 8 (18%) of them had a relapse. No factor was identified to be significantly associated with a favourable treatment response. A favourable response to treatment was seen in 74% of patients with a high relapse rate.

Switching from natalizumab to an anti-CD20 monoclonal antibody in relapsing remitting multiple sclerosis: A systematic review

BackgroundUse of natalizumab (NTZ) is precluded in many Multiple Sclerosis (MS) patients by the risk of progressive multifocal leukoencephalopathy (PML). Regardless, some patients may commence natalizumab for short term disease control in spite of being seropositive, and others may seroconvert whilst on treatment. In these circumstances, discontinuation of NTZ should not occur until a clear exit strategy is established to prevent post-NTZ disease reactivation, which often exceeds the severity of disease activity prior to NTZ treatment. The objective of this systematic review was to summarise the available evidence for CD20-monoclonal antibodies (CD20mAb) as a suitable NTZ exit strategy, and to identify whether a superior switch protocol can be established. MethodsIn accordance with PRISMA guidelines, a total of 2393 references were extracted from a search of three online databases (PubMed, Scopus, MEDLINE). Following the application of inclusion/exclusion criteria, a total of 5 studies representing 331 patients were included. ResultsThe overall incidence of clinical relapse during washout periods ranging from 4.4–10.7 weeks was 0 %. The incidence of clinical relapse during two-year follow-up ranged from 1.8 % to 10 % for switches to all types of CD20 monoclonal antibody. The weighted mean for clinical relapse at 12 months was 8.8 %. Three studies reported an annualised relapse rate (ARR) ranging from 0.02–0.12 with a weighted mean ARR of 0.07. The overall incidence of PML during washout was 0 % and the overall incidence of PML within 6 months follow-up was 0.6 %. ConclusionsThis systematic review provides the first attempt at identifying a superior switch protocol in patients at risk of PML transitioning from NTZ to a CD20mAb. Our results indicate that CD20mAb's are a suitable transitional option for patients who discontinue NTZ, with our cohort demonstrating very low rates of carryover PML and low rates of clinical relapse. The most appropriate washout period is unclear due to confounding factors but is likely between 4 and 12 weeks.

Superior protection in a relapsing Plasmodium cynomolgi rhesus macaque model by a chemoprophylaxis with sporozoite immunization regimen with atovaquone-proguanil followed by primaquine

BackgroundTo gain a deeper understanding of protective immunity against relapsing malaria, this study examined sporozoite-specific T cell responses induced by a chemoprophylaxis with sporozoite (CPS) immunization in a relapsing Plasmodium cynomolgi rhesus macaque model.MethodsThe animals received three CPS immunizations with P. cynomolgi sporozoites, administered by mosquito bite, while under two anti-malarial drug regimens. Group 1 (n = 6) received artesunate/chloroquine (AS/CQ) followed by a radical cure with CQ plus primaquine (PQ). Group 2 (n = 6) received atovaquone-proguanil (AP) followed by PQ. After the final immunization, the animals were challenged with intravenous injection of 104P. cynomolgi sporozoites, the dose that induced reliable infection and relapse rate. These animals, along with control animals (n = 6), were monitored for primary infection and subsequent relapses. Immunogenicity blood draws were done after each of the three CPS session, before and after the challenge, with liver, spleen and bone marrow sampling and analysis done after the challenge.ResultsGroup 2 animals demonstrated superior protection, with two achieving protection and two experiencing partial protection, while only one animal in group 1 had partial protection. These animals displayed high sporozoite-specific IFN-γ T cell responses in the liver, spleen, and bone marrow after the challenge with one protected animal having the highest frequency of IFN-γ+ CD8+, IFN-γ+ CD4+, and IFN-γ+ γδ T cells in the liver. Partially protected animals also demonstrated a relatively high frequency of IFN-γ+ CD8+, IFN-γ+ CD4+, and IFN-γ+ γδ T cells in the liver. It is important to highlight that the second animal in group 2, which experienced protection, exhibited deficient sporozoite-specific T cell responses in the liver while displaying average to high T cell responses in the spleen and bone marrow.ConclusionsThis research supports the notion that local liver T cell immunity plays a crucial role in defending against liver-stage infection. Nevertheless, there is an instance where protection occurs independently of T cell responses in the liver, suggesting the involvement of the liver's innate immunity. The relapsing P. cynomolgi rhesus macaque model holds promise for informing the development of vaccines against relapsing P. vivax.

Post-Transplant Cyclophosphamide versus Anti-Thymocyte Globulin in Patients with Hematological Malignancies Treated with Allogeneic Hematopoietic Stem Cell Transplantation from Haploidentical and Matched Unrelated Donors: A Real-Life Experience.

Background: Post-transplant cyclophosphamide (PTCY) is widely used as graft versus host disease (GvHD) prophylaxis in allogeneic hematopoietic stem cell transplant (HSCT) recipients, with reported clinical benefits in patients who underwent transplant from a matched unrelated donor (MUD). However, real-life data on clinical efficacy and safety of PTCY in haploidentical and MUD transplantations are still poor. Methods: In our real-life retrospective observational study, we included a total of 40 consecutive adult patients who underwent haploidentical or MUD HSCT for various hematological malignancies and who received PTCY (n = 24) or ATG (n = 16) as GvHD prophylaxis at Hematology Units from hospitals of Salerno and Avellino, Italy, and clinical outcomes were compared. Results: We showed protective effects of PTCY against disease relapse with the relapse rate after transplantation of 16% versus 50% in the ATG arm (p = 0.02). All-cause mortality was lower (36% vs. 75%; p = 0.02) and the 2-year overall survival was slightly superior in patients administered PTCY (61% vs. 42%; p = 0.26). Conclusions: We support the use of PTCY, even in a real-life setting; however, the optimization of this protocol should be further investigated to better balance relapse prevention and GvHD prophylaxis.

Long‐term efficacy and safety of tailored immunosuppressive therapy in immune‐mediated biopsy‐proven myocarditis: A propensity‐weighted study

AbstractAimsStandardized immunosuppressive therapy (IS) had been previously investigated in biopsy‐proven (BP) lymphocytic myocarditis with heart failure (HF). This study evaluated efficacy and safety of tailored IS in BP immune‐mediated myocarditis, irrespective of histology and clinical presentation.Methods and resultsConsecutive BP myocarditis patients treated with long‐term tailored IS on top of optimal medical therapy (OMT), were compared with OMT non‐IS controls using propensity‐score weighting. The primary outcome was a composite of death or heart transplant, the secondary outcome was a composite of biventricular function, New York Heart Association (NYHA) class variation, and relapse. IS was managed by a multidisciplinary Cardioimmunology Team, involved a safety checklist and active patients' education. Ninety‐one IS patients were compared with 267 non‐IS patients. IS patients more frequently had systemic immune‐mediated diseases (35% vs. 9.7%), lower baseline echocardiographic left ventricular ejection fraction (35% vs. 43%), lower right ventricular fractional area change (34% vs. 41%) and higher frequency of active lymphocytic, eosinophilic and giant cell myocarditis (71% vs. 58%, 12% vs. 1.1%, and 6.6% vs. 1.5%, respectively). At 5‐year follow up, no difference was observed in the primary outcome (survival rate 93% in IS vs. 87% in non‐IS), but IS patients had a higher relapse rate. Thus, IS patients, with a lower biventricular function and a higher risk profile at baseline, presented similar biventricular function and NYHA class to non‐IS patients at follow‐up. Minor adverse drug reactions occurred in 13% of patients, all resolved with therapy switch.ConclusionsProlonged tailored IS is effective and safe in BP immune‐mediated myocarditis irrespective of histology and clinical presentation.

Transforming the Niche: The Emerging Role of Extracellular Vesicles in Acute Myeloid Leukaemia Progression.

Acute myeloid leukaemia (AML) management remains a significant challenge in oncology due to its low survival rates and high post-treatment relapse rates, mainly attributed to treatment-resistant leukaemic stem cells (LSCs) residing in bone marrow (BM) niches. This review offers an in-depth analysis of AML progression, highlighting the pivotal role of extracellular vesicles (EVs) in the dynamic remodelling of BM niche intercellular communication. We explore recent advancements elucidating the mechanisms through which EVs facilitate complex crosstalk, effectively promoting AML hallmarks and drug resistance. Adopting a temporal view, we chart the evolving landscape of EV-mediated interactions within the AML niche, underscoring the transformative potential of these insights for therapeutic intervention. Furthermore, the review discusses the emerging understanding of endothelial cell subsets' impact across BM niches in shaping AML disease progression, adding another layer of complexity to the disease progression and treatment resistance. We highlight the potential of cutting-edge methodologies, such as organ-on-chip (OoC) and single-EV analysis technologies, to provide unprecedented insights into AML-niche interactions in a human setting. Leveraging accumulated insights into AML EV signalling to reconfigure BM niches and pioneer novel approaches to decipher the EV signalling networks that fuel AML within the human context could revolutionise the development of niche-targeted therapy for leukaemia eradication.