Risk Of Relapse Research Articles

Ultrasound in GCA: Halo Sign Quantification and Visual Symptoms, Systemic Inflammation and Relapse Risk.

A sonographic scoring system, termed Halo count and Halo score, of temporal and axillary arteries (TAXA) in suspected giant cell arteritis (GCA) has been proposed for outcome prognostication. We conducted a retrospective review into the relationship of Halo count and Halo score and clinical-laboratory parameters amongst patients diagnosed with GCA via our rapid-access pathway to determine whether these measures should form part of our local routine clinical practice. This review of TAXA ultrasound (US) images in patients with diagnosed GCA did not identify any correlation between Halo count/score and ocular symptoms, jaw claudication, 6-month relapse risk or inflammatory markers. This suggests that further prospective evaluation of Halo count and -score is required before adopting these measures into routine US scanning of TAXA for suspected GCA.

Comparison of Drug-Free Remission after the End of Phase III Trials of Three Different Anti-IL-23 Inhibitors in Psoriasis.

Knowing the remission duration after biologics discontinuation in patients with psoriasis is important, especially when disease relapse is defined as the restart of systemic agents, because it also reflects the real-world clinical practice when topical treatment alone is not adequate for disease control, and a systemic treatment, including biologic, is needed. Biologics are currently indicated for patients with psoriasis who are candidates for systemic treatments. We included 42 patients who were followed up with regularly after the end of risankizumab, guselkumab and mirikizumab trials and investigated the drug-free remission (DFR). A Kaplan-Meier survival analysis and Cox regression model were employed to identify the possible risk factors for relapse. Overall, 38/42 (90.5%) patients experienced relapses after discontinuing trial biologics during the follow-up period of at least 96weeks and up to 227weeks. In all patients with relapse, the median DFR was 104days. Kaplan-Meier survival analysis revealed a significant 1-year drug-free survival (DFS) difference between risankizumab (Z) and guselkumab (T) + mirikizumab (M) (p = 0.0462). A difference in DFS curves was noted when patients were categorized by disease duration > or ≤ 2years (p = 0.1577) and maintenance of a psoriasis area and severity index score (PASI) of 90 at the end of trials (p = 0.1177). Univariate Cox regression model identified that age [hazard ratio (HR) = 1.030 (1.000-1.060), p = 0.0467] and disease duration [HR = 1.046(1.009-1.084), p = 0.0134] were significantly associated with relapse risk. A risk model was established on the basis of multivariable Cox regression results. Risk value = 0.021038 * Age + 0.515628 * Biologic_type (Z = 0,T/M = 1) + 0.025048 * Disease_Duration. The validated patients were divided into two groups by median risk value (1.5). The high-risk group (risk value > 1.5) had a non-significant higher relapse risk than the low-risk group (risk value < 1.5), with a hazard ratio of 1.62 [95% confidence interval (CI) = 0.82-3.23, p = 0.1809]. Types of biologics used, disease duration > or ≤ 2years, and PASI 90 improvement at the end of trial affect the 1-year DFS after biologics discontinuation. Further studies consisting of a larger patient number and longer follow-up period are needed to verify our findings. ClinicalTrials.gov identifiers NCT02694523, NCT03047395, NCT02207224, NCT02576431, NCT03482011, and NCT03556202.

Comparison of Thiotepa-based Conditioning Regimens for Older Adults with Primary Diffuse Large B-cell Lymphoma of the Central Nervous System Undergoing Autologous Hematopoietic Cell Transplantation

BackgroundIn this study, we compare outcomes of older patients with primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) undergoing autologous hematopoietic cell transplantation (autoHCT) with either thiotepa/carmustine (BCNU/Thio) or thiotepa/busulfan/cyclophosphamide (TBC) conditioning. MethodsWe used a post-publication dataset made available by the Center for International Blood and Marrow Research (CIBMTR) including patients who were ≥65 years in age with PCNSL and underwent autoHCT as consolidation with TBC or BCNU/Thio conditioning. ResultsOut of 147 patients; n=84 received BCNU/Thio and n=63 received TBC. The 1-year NRM in the BCNU/Thio group was 10% versus 22% in the TBC group (p=0.05) and the 2-year relapse rate was 5% versus 5%, respectively (p=1.00). The 2-year PFS in the BCNU/Thio group was 85% versus 71% in the TBC group (p=0.05) and 2-year OS was 86% vs 74% (p=0.08). In a multivariable regression model, BCNU/Thio was associated with a lower risk for NRM [Hazard Ratio (HR), 0.33, p=0.009], improved PFS (HR, 0.41, p=0.008) and OS (HR, 0.37, p=0.007), but there was no association with relapse risk. ConclusionWe found that in older adults with PCNSL undergoing consolidation with autoHCT, BCNU/Thio conditioning is associated with lower NRM and improved OS compared to TBC.

Immune-related adverse events in a nationwide cohort of real-world melanoma patients treated with adjuvant anti-PD1 – Seasonal variation and association with outcome

IntroductionImmune checkpoint inhibitors (ICIs) carry the risk of immune-related adverse events (irAEs), a significant concern as therapy has transitioned to the adjuvant setting. Balancing therapeutic benefits against potential risks is crucial, necessitating real-world data from an unselected patient population in addition to clinical trial data to ensure optimal clinical decision-making. MethodsThis nationwide real-world study assessed irAEs in patients receiving adjuvant anti-PD1 therapy, primarily nivolumab, for resected stage III-IV melanoma between 2018-2022. Data were retrieved from two national databases: the IMMUNOTOX database and the Danish Metastatic Melanoma Database (DAMMED). IrAEs were sub-grouped according to organ systems graded using CTCAE ver. 5.0 ranging from mild toxicities (grade 1-2) to severe (grade 3-4) and fatal (grade 5). ResultsAmong 792 included patients, (55% male, median age 62 years (range 16-88)), 697 patients (88%) experienced an irAE. Severe irAEs occurred in 116 patients (15%) and five (0.6%) died due to toxicity. A landmark analysis showed that patients who experienced at least one irAE before the 1st evaluation at 90 days had an increased progression free survival (PFS) (p=0.032) and overall survival (OS) (p=0.0071). Additionally, a seasonal pattern was noted with higher incidence of irAEs during summer. ConclusionThe prevalence of irAEs in real-world patients is comparable to the observed risk in clinical trials. Patients experiencing irAEs demonstrate a lower risk of melanoma relapse. Further, gender, age and seasonal variation may impact the incidence of irAEs.

Immunosuppressive agents or intravenous immunoglobulin in addition to glucocorticoids in the treatment of Susac syndrome: a French national cohort study

Susac syndrome is a rare disease affecting mainly young women and is characterised by an occlusive microvessel disease limited to the brain, retina, and inner ear. No randomised controlled trial has been published or declared as ongoing to investigate treatments for Susac syndrome. We aimed to compare the effect of glucocorticoids given alone or in combination with immunosuppressive agents or intravenous immunoglobulin for the prevention of relapse in patients with Susac syndrome. The Phenotypic and Etiological Characterization of Susac Syndrome-National Clinical Research Hospital Program study is a prospective national cohort study that started enrolling on Nov 29, 2011, and included all consecutive patients aged 18 years or older with Susac syndrome who were referred to the French reference centre (Department of Internal Medicine, Bichat-Claude Bernard Hospital, Paris). Susac syndrome was defined by either the triad of encephalopathy with typical brain MRI abnormalities, cochleo-vestibular damage, and multiple occlusions of retinal central artery branches, or at least two of the three criteria without any alternative diagnosis. Collected data included fundoscopy, retinal angiography, audiometry, cerebrospinal fluid, brain MRI, and treatment received at diagnosis; months 1, 3, 6, and 12 after diagnosis; and then annually for 5 years or in the case of a relapse. The primary outcome was defined as the first relapse occurring within a 36-month follow-up period from the first day of treatment, characterised by new clinical symptoms or signs, and new abnormalities observed on retinal angiography, audiometry, or brain MRI, necessitating treatment intensification. There was no involvement of people with lived experience at any stage. The study is registered at ClinicalTrials.gov, NCT01481662. Between Nov 29, 2011, and Dec 2, 2022, 64 patients were included in the study, with a mean age at diagnosis of 35 years (SD 11); 41 (64%) were women and 23 (36%) were men. At diagnosis, 60 patients received glucocorticoids; 40 (63%) of 64 patients received glucocorticoids alone as a first-line therapy while 20 (31%) received glucocorticoids in combination with immunosuppressive agents or intravenous immunoglobulin. Overall, 46 (72%) of 64 patients had a first relapse with a median relapse-free survival time of 3·96 months (95% CI 2·24-16·07). Comparison of relapse-free survival showed no significant difference between the two treatment strategies (hazard ratio [HR] 1·11 [95% CI 0·56-2·17], p=0·76), compared with glucocorticoids alone as the reference group. In patients who first relapsed while treated with glucocorticoids alone, there was no significant difference in second relapse-free survival between those who did or did not receive immunosuppressive agents or intravenous immunoglobulin as a second-line therapy (HR 2·66 [95% CI 0·63-11·18], p=0·18). The combination of glucocorticoids with immunosuppressive agents or intravenous immunoglobulin did not appear to reduce the risk of Susac syndrome relapse compared with glucocorticoids alone. Our findings did not support the systematic use of immunosuppressive agents in Susac syndrome. French Ministry of Health.

Prognostic factors in post-prostatectomy salvage radiotherapy setting with and without hormonotherapy: An individual patient data analysis of randomized trials from ICECaP database

BackgroundEarly salvage radiotherapy (SRT) is the standard of care for biochemical recurrence post-prostatectomy but outcomes are heterogeneous. ObjectiveTo develop a risk scoring system based on relevant standard-of-care clinico-pathological prognostic factors for patients treated with SRT with and without hormonal therapy (HT). Design, setting, and participantsThe Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) database included three randomized trials (Individual patients’ data from 1647 subjects) assessing SRT (GETUG-AFU-16; NRG/RTOG-9601, and a subset of EORTC-22911). Outcome measurements and statistical analysisOutcomes were clinical progression (CP). metastasis free-survival (MFS) and overall survival (OS). Clinico-pathological factors, including pathological Gleason Score (GS), PSA at SRT start, margin status, persistent PSA post-RP and time from RP to SRT were evaluated by multivariable models stratified by type of treatment. Results and limitationsOn multivariable analysis PSA ≥ 0.5 ng/mL at SRT start, GS ≥ 8 and negative margin status were the three strongest prognostic factors. Three prognostic groups defined by number of these risk features (high risk: 2 or 3; intermediate risk: 1 and low risk: 0) were strongly associated with OS, MFS and CP outcomes with SRT alone or with HT. This prognostic group definition was also relevant for patients with persistent PSA post RP and for patients treated < 1 year from RP to SRT and with and without HT. ConclusionA risk score for patients receiving SRT with or without HT, using three standard-of-care clinico-pathological risk factors provides refined prognostic information for individual patient counselling. Patient summaryBy using a composite score of pathology grading (Gleason Score), PSA at start of salvage radiation and margin status data, physicians can provide patients with more refined information on the risk of a second relapse after receiving radiation to the prostate bed after a prostatectomy for a rising or persistent PSA, both with and without hormonal therapy.

A randomized study of 6 versus 3 years of adjuvant imatinib in patients with localized GIST at high risk of relapse

The administration of adjuvant imatinib during 3 years is indicated after resection of primary localized GIST at high risk of recurrence, but many patients relapse afterwards. IMADGIST (NCT02260505) was a multicenter, open-label, randomized phase III study evaluating the maintenance of imatinib for 3 more years (6-year arm) compared with interruption (3-year arm) from the day of randomization, conducted in the French Sarcoma Group. The primary endpoint was intent-to-treat disease-free survival. Secondary endpoints included overall survival, time to imatinib resistance, response after imatinib reintroduction at relapse, and safety. From 24 December 2014 to 4 April 2023, 136 patients aged ≥18 years, Eastern Cooperative Oncology Group performance status ≤2, with a localized gastrointestinal stromal tumor with an R0 or R1 surgery, and a risk of tumor recurrence ≥35% according to National Comprehensive Cancer Network (NCCN) risk classification were randomized in 14 centers. Sixty-five patients were randomized to the 3-year arm versus 71 to the 6-year arm. There were 68 males and females. Primary sites were gastric and small bowel in 60 (44%) and 64 (47%) patients, respectively. Respectively, 52 (38%) and 71 (52%) patients had a risk of relapse of 35%-70% and >70%. With a median follow-up of 55 months (interquartile range 46-59 months) after randomization, disease-free survival was significantly superior in the 6-year arm [hazard ratio: 0.40 (0.20-0.69), P= 0.0008]. Time to imatinib resistance, survival, adverse events, and quality of life were not different in the two arms. Three additional years of adjuvant imatinib reduces the risk of relapse in patients who have received 3 years of adjuvant imatinib with an acceptable tolerance.

BRAF-V600E mutations in plasma and peripheral blood mononuclear cells correlate with prognosis of pediatric Langerhans cell histiocytosis treated with first-line therapy.

The clinical relevance of BRAF-V600E alleles in peripheral blood mononuclear cells (PBMCs) and the prognostic impact of the mutants in cell-free (cf) and PBMC DNAs of Langerhans cell histiocytosis (LCH) have not been fully clarified in pediatric LCH. We retrospectively determined the levels of BRAF-V600E mutation in paired plasma and PBMC samples at the time of diagnosis of LCH. Subsequently, we performed a separate or combined analysis of the clinical and prognostic impact of the mutants. We assessed BRAF-V600E mutation in peripheral blood from 94 patients of childhood LCH. Our data showed that cfBRAF-V600E was related to young age, multiple-system (MS) disease, involvements of organs with high risk, increased risk of relapse, and worse progression-free survival (PFS) of patients. We also observed that the presence of BRAF-V600E in PBMCs at baseline was significantly associated with MS LCH with risk organ involvement, younger age, and disease progression or relapse. The coexisting of plasma(+)/PBMC(+) identified 36.2% of the patients with the worst outcome, and the hazard ratio was more significant than either of the two alone or neither, indicating that combined analysis of the mutation in plasma and PBMCs was more accurate to predict relapse than evaluation of either one. Concurrent assessment of BRAF-V600E mutation in plasma and PBMCs significantly impacted the prognosis of children with LCH. Further prospective studies with larger cohorts need to validate the results of this study.

‘Yoga is a way of life’: A qualitative study of the experiences of using yoga as a treatment for substance use: An interpretive phenomenological analysis

AbstractIntroductionYoga is a form of complementary medicine for substance use disorder (SUD). Randomised controlled trials involving yoga for the treatment of SUD have found that yoga practice reduces the risk of relapse and improves mood and well‐being for people undergoing treatment for SUD; however, the lived experience of yoga practice involving the benefits of reducing SUD is unknown. The aim of this study was to examine the in‐depth experience of yoga to inform the treatment of SUD.MethodsFive semi‐structured interviews explored experiences of yoga among people with a prior history of substance use. Four out of the five participants reported prior use of alcohol, and one reported the use of ‘GBL’ and methamphetamine. Data were analysed using interpretative phenomenological analysis.ResultsThe analysis resulted in three final superordinate themes: (1) growing awareness of the body, mind and emotions; (2) yoga opens a positive way of life; and (3) blending the worlds of yoga and 12‐step recovery. Yoga was reported to enhance awareness of muscle tension, reduce physical stress, increase positive emotions and build tolerance to negative emotions. The integration of the eight‐limb philosophy of yoga, notably withdrawing of the senses, helped combat internal cues and triggers (negative thoughts and emotions) for relapse. Yoga was reported to be compatible with an abstinence‐based lifestyle found in 12‐step mutual aid programmes and helped extend social networks to support long‐term abstinence.ConclusionsThe experience of integrating the eight‐limb philosophy to support abstinence and the asana practice helped participants to reduce cue reactivity. Yoga appeared to enhance interoceptive awareness, which is useful for reducing physical stress related to triggers for relapse, making yogic practice a valuable tool to integrate within mainstream group and individual relapse prevention programmes. Therefore, programmes and health policymakers may want to consider treatments that integrate yogic practices to enhance and support long‐term abstinence for SUD.

Timing is essential: Humoral and cellular responses to SARS-CoV-2 vaccination in a cohort of patients with auto-immune diseases treated with rituximab

Rituximab (RTX), an anti CD20 monoclonal antibody, is now a gold standard treatment for several auto-immune and chronic inflammatory diseases. Receiving RTX exposes patients to more severe infections as vaccinations become virtually inefficient in terms of B cell responses. During the COVID-19 crisis, RTX–exposed patients exhibited more severe forms of the disease, and in some cases, the introduction of RTX was delayed or avoided to protect patients as much as possible against SARS-CoV-2 infections. We retrospectively collected cellular and humoral responses from thirteen patients with dermatological and rheumatological autoimmune diseases who had been vaccinated after receiving RTX. Memory T cells subsets from patients that exposed to RTX showed few differences when compared to a cohort of healthy donors. The IFNᵧ ELISpot assay using SARS-CoV-Prot_S1 showed that eight patients exhibited a positive response that was neither correlated to the time between RTX infusion and the sampling nor to the time between RTX and the vaccination. Conversely, analysis of the SARS-CoV-2 serology showed a clearly lower binding antibody units per mL in case of recent RTX infusion. The safe threshold forconsistently positive serology was to vaccinate at least 300 days after RTX infusion (p = 0.02). Our data illustrate the difficulty in obtaining a satisfactory response to vaccination after RTX treatment within almost a year after the latest infusion, and emphasize the need to better evaluate the risk of relapses in auto-immune diseases before administering RTX in order to maintain RTX only in patients whose medical situation requires it.

Is there a correlation between increasing hospital falls and Covid-19 infection? Retrospective study on the entire hospital population.

Risk Management Unit at Mauriziano hospital analyzed in the present observational study possible correlation with Covid Pandemic and falls risk factors, through comparison of patients falls occurred during year 2021 in Covid and no-Covid wards. The primary outcome of the study is the evaluation of relationship between falls and Covid infection. The secondary outcome is identification of falls risk factors. No direct correlation between falls and Covid-19 infection was found. Among falls risk factors, the most interesting emerged is the fall itself that enhances the risk of relapse. Increasing in patients falls since 2020 could be affected indirectly by strong hospital organization modifications during Covid pandemic.

Brain age is not a significant predictor of relapse risk in late-life depression

Late-life depression (LLD) has been associated cross-sectionally with lower brain structural volumes and accelerated brain aging compared to healthy controls (HC). There are few longitudinal studies on the neurobiological predictors of recurrence in LLD. We tested a machine learning (ML) brain age model and its prospective association with LLD recurrence risk. We recruited individuals with LLD (n=102) and HC (n=43) into a multi-site 2-yr longitudinal study. Individuals with LLD were enrolled within 4 months of remission. Remitted LLD participants underwent baseline neuroimaging and longitudinal clinical follow-up. Over 2 years, 43 LLD participants relapsed (REL) and 59 stayed in remission (REM). We used a previously developed ML brain age algorithm to compute brain age at baseline and we evaluated brain age group differences (HC vs. LLD and HC vs. REM vs. REL). We conducted a Cox proportional hazards model to evaluate whether baseline brain age predicted time to relapse. We found that brain age did not significantly differ between HC and LLD as well as HC, REM, and REL groups. Brain age did not significantly predict time to relapse. In contrast to our hypothesis, we found that brain age did not differ between non-depressed controls and individuals with remitted LLD, and brain age was not associated with subsequent recurrence. This is in contrast to existing literature which has identified baseline brain age differences in late life but in line with work that shows no differences between those who do and do not relapse on gross structural measures.

Psychosocial functioning and its influencing factors in patients with depression post-remission: Implications for assessment and interventions

Background: Enhancing psychosocial functioning is crucial for reducing relapse in depression, but methods for monitoring and recovery are unclear. MethodA 1-year follow-up study assessed psychosocial functioning in 182 patients with remitted depression at baseline (T0) as well as at 1, 2, 6, 9, and 12 months post-remission (T1–T5). Using generalized estimating equations (GEE) and multiple linear regression (MLR), we analyzed the impact of changes in psychosocial functioning on relapse/recurrence risk, and assessed the influence of various factors. ResultsAn increase in psychosocial functioning significantly lowered relapse/recurrence odds by 54.2 %, averaging a risk reduction of 3.1 %. GEE analyses indicated subjective depressive symptoms (β = −0.315) most significantly impacted psychosocial functioning, followed by social support (β = 0.236), positive coping (β = 0.225), and negative automatic thoughts (β = −0.183). Negative coping and expressed emotion exhibited non-significant effects. MLR revealed that the impact of negative automatic thoughts was most significant at initial remission, but the relative importance of residual subjective depressive symptoms, positive coping, and social support on psychosocial functioning remained stable over time. LimitationsPredetermined follow-up assessments may not fully capture psychosocial functioning at relapse/recurrence, and the inclusion of factors might not be sufficiently comprehensive. ConclusionsRecovery of psychosocial functioning significantly reduces relapse risk in post-remission patients with depression more than residual subjective depressive symptoms. The degree of influence of factors on psychosocial functioning can change with the length of remission time.

Antimetabolite dose intensity and adverse outcomes in children with acute lymphoblastic leukemia: a COG-AALL03N1 report

AbstractThe association between antimetabolite dose intensity (DI) and adverse events among children receiving maintenance therapy for acute lymphoblastic leukemia (ALL) remains unclear, especially in the context of antimetabolite adherence. Using Children’s Oncology Group AALL03N1 data, we examined the association between high DI during the first 4 study months and (i) treatment-related toxicities during the subsequent 2 study months; and (ii) relapse risk. Patients were classified into a high DI phenotype (either 6-mercaptopurine [6-MP] or methotrexate [MTX] DI ≥110% during the first 4 study months, or 6-MPDI or MTXDI 100%-110% at study enrollment and ≥25% increase over the 4 study months) and normal DI phenotype (all others). Only patients with wild-type TPMT and NUDT15 were included. 6-MP adherence data were available for 63.7% of study participants and used to stratify as adherent (median adherence ≥85%) and nonadherent (median adherence <85%) participants. Multivariable analyses were adjusted for sociodemographic and clinical prognosticators. Of the 644 patients, 29.3% were exposed to high DI. High DI was associated with a 2.1-fold greater odds of hematologic toxicity (95% confidence interval [CI] = 1.4-3.1; reference: normal DI) in the entire cohort and 2.9-fold higher among adherers (95% CI = 1.6-5.1); odds were comparable among nonadherers (2.1-fold; 95% CI = 0.4-10.1). Although high DI was not associated with relapse in the entire cohort (adjusted hazard ratio [aHR] = 1.4; 95% CI = 0.8-2.4), it was associated with a greater hazard of relapse among adherent participants (aHR = 2.4; 95% CI = 1.0-5.5) but not among nonadherent participants (aHR = 0.9; 95% CI = 0.2-3.8). Dose escalation above protocol doses during maintenance therapy for ALL should be done cautiously after assessing adherence to prescribed therapy.

Scarce perinatal social support for women with OUD: Opportunities for doula services

ProblemPersons with opioid use disorder (OUD) often lack social support, which is associated with improved recovery outcomes. BackgroundIn the last two decades, the rate of opioid use disorder (OUD) among pregnant people has quadrupled. QuestionThis study aimed to describe the prenatal and postpartum social support networks and needs of persons with OUD and assess perceived acceptability of community-based social supports such as doulas. MethodsThis mixed methods study utilized quantitative and qualitative data to understand social support structures and needs. Data was collected through surveys –demographics and social mapping; Adverse Childhood Experiences (ACE) tool; Connor Davidson Resilience 25-item (CDRS-25) scale– and a semi-structured interview. A total of 34 participants from a single urban opioid treatment program consented to participate. FindingsParticipants were on average 34.9 years old, White (64.7%), and unemployed (91.2%). Participants described small perinatal social support networks, which decreased in size from the prenatal to postpartum period. Only half (52.9%) reported adequate prenatal and postpartum social support. Doulas and peer recovery support specialists were perceived as valuable in perinatal health, social support, and recovery domains, with interest in doulas seen particularly amongst those with fewer reported supports. Discussion: The scarcity of prenatal and postpartum social support among persons with OUD is critical to address, given the increased risk of relapse during the postpartum period which has implications for the maternal child dyad. Conclusion: Due to multiple disparities in prenatal and postpartum social support (small networks, inadequate support), doulas represent a trusted community-based support to be integrated into healthcare teams to address maternal morbidity/mortality associated with opioid use.

Relationship between morphologic remission with or without hematologic recovery and outcome after allogeneic hematopoietic cell transplantation in adult acute myeloid leukemia.

Outcomes of adults with AML after allografting vary widely. While numerous covariates have been associated with relapse, non-relapse mortality (NRM), and/or shorter survival, the impact of incomplete blood count recovery before transplantation has remained unclear. To address this uncertainty, we examined all adults with AML or MDS/AML who received an allograft in first or second remission between 2006 and 2023 at a single institution. Of 1264 patients, 891 (70%) met criteria for CR, whereas 291 (23%), 24 (2%), and 58 (5%) were classified as CRh, CRi, and morphologic leukemia-free state (MLFS), respectively. CR, CRh, CRi, and MLFS patients differed significantly regarding demographics, disease biology, pre-transplant measurable residual disease, and types of transplants. After multivariable adjustment, outcomes for CRh and CRi patients were not significantly different from each other or from those of CR patients. In contrast, outcomes of MLFS patients were substantially worse than those of CR and CRh patients, with significantly higher risk of NRM and relapse, and significantly shorter relapse-free and overall survival. Similar results were obtained in several distinct subsets. Together, our analysis provides empiric evidence for the importance of distinguishing MLFS from CR and CRh patients for optimized risk assessment and, possibly, individualized treatment decision making.

Intraoperative Cavity Local Delivery System with NETs-Specific Drug Release for Post-Breast Cancer Surgery Recurrence Correction.

Postoperative breast cancer recurrence is tricky due to the limited therapeutic options. Transforming growth factors-β (TGF-β) is vital in promoting postoperative tumor recurrence. However, conventional blocking strategies fail to satisfy both bio-safety and sufficient relapse correction. Neutrophil extracellular traps (NETs) are essential for the spatiotemporal dynamics of TGF-β at tumor-resection sites, whose unique mechanism for local TGF-β amplification could remarkably increase the risk of relapse after surgery. Herein, the principle of NETs formation is ingeniously utilized to construct a surgical residual cavity hydrogel that mimics NETs formation. The hydrogel is prepared based on the electrostatic interaction between histidine (His) and sodium alginate (Alg). Then, arginine deiminase 4 (PAD4) protein is released during NETs formation. Simultaneously, the electrical property of His in hydrogel changes automatically, which further lead to promising localized release of anti-TGF-β. The hydrogel system can realize specific and selective drug release at targeted NETs site over a prolonged period while exhibiting excellent biocompatibility. Superior breast cancer recurrence inhibition is achieved by suppressing TGF-β and related indicators, impeding epithelial-mesenchymal transition (EMT) progression, and rectifying the locally exacerbated immunosuppressive environment within NETs. The novel NETs local microenvironment drug release functional hydrogel will provide inspiration for postoperative recurrence correction strategies.

The Potential of Molecular Remission: Tissue Neutrophil Elastase Is Better Than Histological Activity for Predicting Long-Term Relapse in Patients With Ulcerative Colitis in Endoscopic Remission.

Growing interest exists in deep remission, beyond clinical and endoscopic remission, to enhance long-term prognosis in patients with ulcerative colitis (UC). Our study aimed to evaluate the risk of relapse according to tissue expression levels of calprotectin and neutrophil elastase (NE) in patients with quiescent UC. Rectal biopsies were performed on 218 patients with UC in clinical and endoscopic remission. Histological activity was prospectively scored using the Robarts Histological Index. Tissue calprotectin and NE levels were evaluated using immunohistochemistry. Optimal tissue calprotectin and NE cutoffs for relapse were determined using log-rank analysis. Cox proportional hazard analyses evaluated relapse risk factors. Tissue calprotectin and NE levels were significantly higher in patients with histological activity than in those in histological remission (P < .001). The optimal cutoffs of tissue calprotectin and NE for relapse were 10.61 and 22.08permm2, respectively. The 3-year clinical relapse risk was significantly lower in the low-tissue NE group than in the high-tissue NE group (P = .009); however, it did not differ between the low- and high-tissue calprotectin group (P = .094). In multivariate analyses, a low level of tissue NE expression was independently associated with a lower risk of 3-year clinical relapse (adjusted hazard ratio = 0.453, 95% confidence interval = 0.225-0.911, P = .026), unlike histological index and tissue calprotectin. In patients with UC who have achieved clinical and endoscopic remission, tissue expression of NE is a better predictor of long-term relapse than histological activity.

Self-control as mediator and social support as moderator in stress-relapse dynamics of substance dependency

Substance Use Disorders (SUDs) present a significant challenge to global public health, with prolonged drug use not only impairing individual health but also hindering social development. Despite various interventions aimed at addressing drug abuse and dependence, a high relapse rate remains a prominent issue. In light of this, this study aims to explore the impact of perceived stress on the relapse of individuals with SUDs, as well as the mediating role of self-control and the moderating role of social support, in hopes of providing new perspectives for interventions to reduce the risk of relapse among individuals with SUDs. By utilizing a convenience sampling method, 420 male individuals with SUDs were recruited from detoxification centers in Guangxi, China. They completed questionnaires on perceived stress, self-control, social support, and tendencies towards relapse. A total of 401 valid datasets were obtained and analyzed using the SPSS Process plugin to conduct a moderated mediation model analysis. Results: (1) Perceived stress had a positive impact on the relapse of individuals with SUDs, (2) Self-control played a partial mediating role between perceived stress and the relapse, (3) The direct effect of perceived stress on the relapse and its first half of the indirect effect were moderated by social support. The research emphasize the critical importance of learning stress management strategies, enhancing self-control, and receiving comprehensive social support in the prevention and treatment of substance dependence. By strengthening self-control and social support as both internal and external resources, the likelihood of relapse among individuals with SUDs can be reduced, contributing to more effective and comprehensive drug rehabilitation strategies.

Association between low incidence of TP53 mutations and reduced early relapse rates in Uygur DLBCL.

Diffuse large B-cell lymphoma (DLBCL) demonstrates significant heterogeneity, investigations into the distinctions in clinical and molecular characteristics between Chinese Uygur and Han DLBCL patients remain unexplored. We retrospectively reviewed 279 DLBCL patients (105 Uygur and 174 Han patients), of which 155 patients underwent genetic profiling by NGS. Compared with Han patient, Uygur patients have better clinical prognostic indicators, including a higher proportion of patients with 0-1 extranodal involvement and I/II Ann Arbor staging. Consistently, Uygur patients were significantly associated with lower risk of relapse (P = 0.06), with a one-year relapse rate of 5% vs 17% and two-year relapse rate of 19% vs 36% compared to Han patients. At the molecular level, TP53 (21.3%) was among the top frequently altered gene in the cohort. Notably, the Uygur patients exhibited a significantly lower frequency of TP53 alterations and higher frequency of ASXL3 alterations. Logistic regression analysis showed that the lowered frequency of TP53 and enrichment of ASXL3 in the Uygur patients were independent of other factors. However, only patients with TP53 mutations had higher relapse rate than those with wild type TP53 (one-year, 20% vs 10%; two-year, 51% vs 21%). Our findings highlight the notable contribution of a low TP53 mutation frequency in Uygur patients as a pivotal factor associated with the favorable prognosis of this population.