Relapse Rate Research Articles

Safety and efficacy of fecal microbiota transplantation for viral diseases: A systematic review of clinical trials.

Gut microbiota play important roles in several diseases like viral infections. In this systematic review, our objective was to assess the efficacy and safety of fecal microbiota transplantation (FMT) in treating various viral diseases. We conducted searches on databases including PubMed, Web of Science, Scopus, and Google Scholar until November 2023. Clinical trials reported outcomes related to safety of FMT or its efficacy in patients with viral diseases were included. We excluded other types of studies that enrolled healthy individuals or patients with other disorders and did not use FMT. The assessment of bias risk was conducted using the National Institutes of Health (NIH) study quality evaluation tool. Eight studies with total 196 participants were included. Viral diseases were human immunodeficiency virus (HIV), hepatitis B, COVID-19 and Clostridioides difficile coinfection, and cytomegalovirus colitis. In hepatitis B cases, HBeAg clearance was significant in those received FMT (p<0.01), while it was not significant in another one (p = 0.19). A clinical response was noted in 37.5% of patients with cytomegalovirus colitis, with an equal percentage achieving clinical remission post-FMT. There was a significant reduction in Clostridioides difficile relapse rate in FMT group than controls in coinfection of Clostridioides difficile and COVID-19 (2.17% vs. 42.5%, p<0.05). In patients with HIV, partial engraftment of the donor microbiome and increases in alpha diversity were observed after FMT. No severe adverse events were reported. Most studies had fair or good qualities. Our findings revealed FMT as a promising, safe treatment for some viral diseases. It improved viral clearance, clinical outcomes, and inflammation. However, the varying responses and small sample sizes call for more trials on FMT in viral diseases.

Clinical impact of large genomic explorations at diagnosis in 198 pediatric solid tumors: a monocentric study aiming practical feasibility of precision oncology

IntroductionFaced to the growing development of collecting systematic molecular analyses in relapsed pediatric cancers to transform their targeted matched therapies, this study aimed to assess the clinical and therapeutic indications of systematic diagnostic genomic explorations performed in pediatric solid cancers to determine which type of screening and if it afford at relapse time an accurate targeted strategy.MethodsA total of 280 patients less than 22 years, referred at the University Hospitals of Strasbourg for a newly diagnosed solid tumor from January 2015 to December 2021, were prospectively genomically investigated since diagnosis. Using 7 different molecular tests going from single-gene methods (IHC, FISH, RT-PCR, Sanger sequencing, droplet digital PCR) to largescale analyses (Next-Generation sequencing, RNAsequencing and FoundationOne®CDx), we explored retrospectively the molecular findings in those pediatric solid tumors (except hematolymphoid cancers) to improve diagnosis, prognosis assessment and relapse therapeutics.ResultsOne hundred and ninety-eight patients (71%) underwent molecular biology (MB) at diagnosis. Thirty-eight different histologies were grouped into cerebral tumors (30%), sarcomas (26%, bone and soft tissues), various blastomas (27%), and other entities (17%). Over a median 40-month follow-up, the overall survival rate of patients was 85% and the relapse rate 28%. Of the 326 analyses carried out, 245 abnormalities (single nucleotide variations: 50%, fusions: 25%, copy number alteration: 20%) concerning 70 oncogenes were highlighted. The overall clinical impact rate was 84%. Broad-spectrum analyses had a higher therapeutic impact (57%) than the targeted analyses (28%). 75% of broad-spectrum tests found an actionable variant conducting 23% of patients to receive rapidly a matched targeted therapy since first relapse.ConclusionOur experience highlighted the clinical utility of molecular profiling of solid tumors as soon as at diagnosis in children to expect improving access to innovative agents at relapse.

Enhancing glioma treatment with 3D scaffolds laden with upconversion nanoparticles and temozolomide in orthotopic mouse model.

Targeted drug delivery for primary brain tumors, particularly gliomas, is currently a promising approach to reduce patient relapse rates. The use of substitutable scaffolds, which enable the sustained release of clinically relevant doses of anticancer medications, offers the potential to decrease the toxic burden on the patient's organism while also enhancing their quality of life and overall survival. Upconversion nanoparticles (UCNPs) are being actively explored as promising agents for detection and monitoring of tumor growth, and as therapeutic agents that can provide isolated therapeutic effects and enhance standard chemotherapy. Our study is focused on the feasibility of constructing scaffolds using methacrylated hyaluronic acid with additional impregnation of UCNPs and the chemotherapeutic drug temozolomide (TMZ) for glioma treatment. The designed scaffolds have been demonstrated their efficacy as a drug and UCNPs delivery system for gliomas. Using the aggressive orthotopic glioma model in vivo, it was found that the scaffolds possess the capacity to ameliorate neurological disorders in mice. Moreover, upon intracranial co-implantation of the scaffolds and glioma cells, the constructs disintegrate into distinct segments, augmenting the release of UCNPs into the surrounding tissue and concurrently reducing postoperative damage to brain tissue. The use of TMZ in the scaffold composition contributed to restraining glioma development and the reduction of tumor invasiveness. Our findings unveil promising prospects for the application of photopolymerizable biocompatible scaffolds in the realm of neuro-oncology.

Radiation-Induced Breast Angiosarcoma-A Single-Institution Experience.

Introduction: Radiation-induced breast angiosarcoma (RIBAS) is a rare adverse event associated with postoperative breast irradiation. The data from the literature indicate that RIBAS occurs in less than 0.3% of patients treated with adjuvant radiotherapy for breast cancer. Given the rarity, diverse clinical presentation, poor prognosis, and lack of consensus on the management, this study aimed to present experiences of our specialized cancer center with RIBAS, in terms of the incidence, presentation, management, and outcomes. Methods: We reviewed the medical records of 10,834 breast cancer patients treated at the Institute for Oncology and Radiology of Serbia between January 2013 and June 2024 to detect patients that had breast-conserving surgery, followed by postoperative irradiation, and developed angiosarcoma in the irradiated area at least 3 years after radiotherapy, without distant metastases. The incidence, latency period, management, and treatment outcomes were analyzed. Results: A total of nine female patients with RIBAS were identified and included in this study. The median age at RIBAS diagnosis was 64 years (range: 36-68), with a median latency of 64 months (95% CI > 57) from irradiation to diagnosis. The mean tumor size was 55 mm (SD 32.78). Patients were followed for a median of 30 months (range: 7-40) after initial RIBAS surgery. Local recurrence occurred in seven patients (77.8%), with five undergoing re-do surgery with curative intent. Three patients developed distant metastases during follow-up. The median overall survival (OS) was 31 months (95% CI > 30), with a 3-year survival rate of 15.2% (95% CI 2.5-91.6%). The median local recurrence-free interval was 10 months (95% CI > 3). Median OS after RIBAS local recurrence and after breast cancer treatment was 17 months (95% CI > 15) and 108 months (95% CI > 88), respectively. Conclusions: RIBAS is a rare but increasingly prevalent adverse event associated with BC irradiation, marked by an aggressive disease course and high relapse rates. Awareness, prompt diagnosis, and a radical surgical approach with wide clear margins are critical for improving patients' outcomes.

Recent evidence on rates and factors influencing smoking behaviours after release from smoke-free prisons: a scoping review.

Smoke-free prison policies have been introduced in some countries, in part to address very high levels of tobacco use in people in prison. However, relapse rates post-release remain high. This papers aims to improve understanding of post-release smoking and/or vaping behaviour is necessary to inform support for a priority population. The authors searched health, social science and criminal justice databases for studies about smoking/vaping behaviours among people released from smoke-free prisons. Studies were included if they reported primary data and were published between January 2017 and March 2024 in English; the population was adults/young people (16 yr+) imprisoned or formerly imprisoned, in prisons with comprehensive smoke-free policies; and at least one of the following was reported: pre-release intention to smoke, vape or remain abstinent post-release; smoking/vaping behaviour post-release and factors influencing smoking/vaping behaviour; attempts to quit again following post-release smoking/vaping relapse. Nine studies met our criteria. The evidence base is small and mainly from the USA or Australia. Evidence continues to suggest that most people resume smoking after leaving a smoke-free prison. No new interventions have been successful in reducing relapse rates. No studies report on vaping post-release, although two studies report on perceived factors affecting smoking relapse post-release from prisons allowing vaping. Given very high rates of relapse, there remains a significant need to better understand what approaches are feasible and acceptable for reducing return to smoking post-release. This review updates the limited evidence on smoking behaviours after leaving a smoke-free prison.

Inotuzumab Ozogamicin and Low-Intensity Chemotherapy in Older Patients With Newly Diagnosed CD22+ Philadelphia Chromosome-Negative B-Cell Precursor Acute Lymphoblastic Leukemia.

The use of inotuzumab ozogamicin (InO), a conjugated anti-CD22 monoclonal antibody, is becoming a promising frontline treatment for older patients with ALL. EWALL-INO is an open-label prospective multicenter phase II trial (ClinicalTrials.gov identifier: NCT03249870). Patients age 55 years and older with newly diagnosed CD22+ Philadelphia chromosome-negative (Ph-) B-cell precursor (BCP) ALL were eligible. After a prephase, a first induction consisting of vincristine, dexamethasone, and three injections of InO (0.8 mg/m2 day 1, 0.5 mg/m2 day 8/day 15) was followed by a second induction combining cyclophosphamide, dexamethasone, and two injections of InO (0.5 mg/m2 day 1/day 8). Responders received up to six cycles of chemotherapy consolidation and 18-month chemotherapy maintenance. Allotransplant was allowed after three consolidations. The primary end point was 1-year overall survival (OS). Between December 2017 and March 2022, 131 patients (median age 68 years) were included. Three patients died during induction 1 (n = 130), two from multiple organ failure and one from hemorrhage, and none during induction 2 (n = 120). After induction 2, 90% of the patients achieved complete remission (CR) or CR with incomplete platelet recovery (CRp) and 80% had measurable residual disease (MRD2) <10-4. Among responders (n = 119), 47 relapsed and 14 died in CR/CRp. One-year OS, relapse-free survival (RFS), and cumulative incidence of relapse (CIR) rates were 73.2%, 66%, and 25%, respectively. High-risk cytogenetics and lower CD22 expression (<70%) were associated with worse OS, while both high-risk cytogenetics and MRD2 ≥10-4 were associated with lower RFS and higher CIR. The 10 allotransplanted patients had very favorable outcomes (90% 2-year OS/RFS and no relapse). Only one nonfatal sinusoidal obstructive syndrome was documented during the study. Our results support InO's use in first-line regimens for older patients with CD22+ Ph- BCP-ALL.

Seasonal Variations in Multiple Sclerosis Relapses in Oman: A Single Tertiary Centre Experience

(1) Background and Aims: The seasonal factors influencing multiple sclerosis (MS) relapses remain elusive. This study aims to investigate the seasonal variation of MS relapses in Oman and compare it globally. (2) Subject and Methods: This retrospective study was conducted on N = 183 Omani MS patients treated at Sultan Qaboos University Hospital, a tertiary hospital in Muscat, Oman, over sixteen-year period (2007–2022). Demographic and clinical data of all MS patients were juxtaposed with the monthly weather data during this period, using descriptive and inferential statistical techniques. (3) Results: Among the N = 183 MS patients studied, 508 relapses were recorded during the study period. The average number of relapses per patient was 2.8 (range: 1–15). There were significant seasonal variations in MS relapse rate, with the highest prevalence in the winter months of January and February. However, no correlation was found between MS relapses and other climatic parameters (humidity, temperature, and rainfall). (4) Conclusion: The seasonal patterns of MS relapses in Oman differ from other parts of the world, which the local clinicians should take into account while diagnosing and making management decisions. The potential impact of climate change on the anomalous changes in the seasonality of MS relapses warrants further investigation.

Anticoagulant Treatment May Decrease the Relapse Rate of Pulmonary Arterial Involvement in Behçet's Disease.

Pulmonary arterial involvement (PAI) is one of the most common causes of mortality in Behçet's disease (BD). In this study, we aimed to evaluate the clinical features, course, and recurrence risk factors of BD-associated PAI. BD patients who were followed up in Marmara University BD outpatient clinic between 1990 and 2023 were included. All data were acquired from the medical records of the patients. PAIs were classified according to the type of the vascular involvement as thrombosis or aneurysm. Factors affecting the risk of relapses were determined using multivariate Cox regression analysis. Among 1350 BD patients, 110 (8.1%) had PAI. The mean age (SD) of patients with PAI was 42.4 (11.6) years, and the male/female ratio was 2.2 (76/34). Thirty-two (29.1%) of 110 patients were asymptomatic. Asymptomatic patients with PAI were significantly younger (p = 0.031) than the symptomatic group. Also, a greater prevalence of females (p = 0.001) and higher recurrence rates (p = 0.019) were observed in the symptomatic group. Pulmonary arterial thrombosis was seen in 104 (94.5%) and aneurysms in 9 patients (6.6%). At least one PAI relapse was observed in 31 patients (28.2%). In multivariate analysis, the Cox regression model was significant (p = 0.013), and not starting anticoagulants independently increased the PAI relapse risk (hazards ratio, 4.36; 95% confidence interval, 1.14-24.1; p = 0.042). Pulmonary arterial thrombosis is the main presentation type of PAI in BD, whereas aneurysmatic formation is rare. Despite immunosuppressive treatment, relapses occur during follow-up in one third of patients with PAI. When anticoagulant therapy is added to immunosuppressive therapy, the relapse rate in BD patients with PAI is significantly reduced.

Routine CSF parameters as predictors of disease course in multiple sclerosis: an MSBase cohort study

BackgroundIt remains unclear whether routine cerebrospinal fluid (CSF) parameters can serve as predictors of multiple sclerosis (MS) disease course.MethodsThis large-scale cohort study included persons with MS with CSF data documented...

Long-Term Outcomes of Rituximab-Treated Adult Patients with Podocytopathies

Background: Long-term outcomes of rituximab-treated adult patients with podocytopathies (either minimal change disease or focal segmental glomerulosclerosis) are largely unknown. Methods: A retrospective study at 30 nephrology departments from 15 countries worldwide included rituximab-treated adults with primary podocytopathies and a minimum clinical follow-up of 36 months. The primary outcome was relapse-free survival at 36 months. Results: 183 adult patients (n=64 with focal segmental glomerulosclerosis and n=119 with minimal change disease) with difficult-to-treat nephrotic syndrome (68% steroid-dependent/frequently relapsing, 22% steroid-resistant, 85% previously treated with two or more lines of immunosuppressive therapy) were treated with rituximab as part of a remission induction regimen. Complete or partial remission at 6 months after rituximab treatment was achieved in 82%. Eighty-three of 151 (55%) initial responders achieved long-term relapse-free survival over three years. Maintenance therapy with rituximab was associated with a better relapse-free survival (HR 2.05, 95% CI: 1.07-3.91), irrespective of the dosing regimen. At 36 months, 61% of initial responders receiving maintenance therapy with rituximab achieved long-term relapse-free survival and withdrawal of all concomitant immunosuppressive medication compared to 36% of patients without maintenance treatment (OR 2.69, 95% CI: 1.27-5.73). Relapses per year were reduced from an annual relapse rate of 1.0 (95% CI: 1.0-1.7) before to 0.17 (95% CI: 0.00-0.24) relapses/year after rituximab initiation. Over the 36 months of follow-up, a stable course of estimated glomerular filtration rate (eGFR) was observed in those who initially responded with either complete or partial remission, whereas non-responders experienced a reduction in eGFR reaching -11 (95% CI: -18 to -8) mL/min/1.73m2 . Conclusions: Rituximab facilitated achievement of initial and long-term response in a majority of adult patients with difficult-to-treat podocytopathies. Maintenance treatment with rituximab further associated with long-term relapse-free survival over three years. Non-response to initial rituximab treatment was associated with poor kidney prognosis.

Effectiveness of Antifungal Treatment for Onychomycosis

Onychomycosis is a prevalent fungal infection of the nails, which causes thickening, discoloration, and detachment of the nail bed. The condition is mainly caused by various fungal species, including dermatophytes, yeasts and molds. Treatment of onychomycosis is complex, with antifungal drugs playing a key role. This research aimed to evaluate the effectiveness of various antifungal treatments, both topical and systemic, in managing onychomycosis. This research used a descriptive qualitative approach, using secondary data through documentation analysis. Data were triangulated to increase reliability and validity. The findings showed that the effectiveness of antifungal treatment varied depending on the type of drug, duration of treatment, and patient compliance. Systemic antifungals, such as terbinafine and itraconazole, showed higher cure rates compared to topical treatments such as ciclopirox and amorolfine. However, all treatments had high relapse rates, underscoring the need for continuous monitoring and customized therapy. The implications of this research demonstrate the importance of personalized treatment plans and the development of strategies to prevent relapse, which remains a significant challenge in the management of onychomycosis.

A Case Report of Congenital Wilms’ Tumor and a Comprehensive Literature Review highlighting the spectrum between Wilms’ Tumor and Nephroblastomata’s

Abstract Introduction/Objective Wilms’ Tumour (WT) represents the most frequently encountered malignant renal neoplasm within pediatric pathology. To delineate the histopathological features of WT with perilobar nephrogenic rests (PLNR) and intralobar nephrogenic rests (ILNR) from nephroblastomatosis, we report a case with literature review to evaluate the clinical implications of WT with or without nephrogenic rests (NR), and nephroblastomatosis. Methods/Case Report Our patient is a 2-week-old neonate with VACTERL, germline mosaic triple X, and stage 1 WT with PLNR and substantial ILNR. The management approach involved radical nephrectomy exclusively. Obtaining a unifying clinical syndrome as well as deciding between WT or nephroblastomatosis was challenging in this case. The molecular testing with VACTERL panel was indeterminate and WT panel revealed DIS3L2 mutation that is indeterminate but likely pathogenic. She has been stable for 12 months and placed on 4-monthly left kidney ultrasound surveillance. Results (if a Case Study enter NA) Our literature review showed that the most common histologic subtype in WT patients without NR (n=59) and with NR (n=33) were classic triphasic (28.8%) and stromal-predominant (39.3%), respectively. WT patients with or without NR, underwent radical nephrectomy followed by adjuvant chemotherapy. Loss of heterozygosity (LOH) in TRIM28 was 4-fold higher in cases with NR. Mortality and relapse rates (12.5%) were higher in non-NR cohort. Conversely, nephroblastomatosis patients (n=14) underwent neoadjuvant chemotherapy, ipsilateral radical nephrectomy, and contralateral nephron-sparing surgery. Nephroblastomatosis patients had higher mortality (22.2%) and relapse rate (30%), with no identifiable mutations on molecular testing. Conclusion WT patients with NR have an earlier diagnosis and lower mortality and relapse rates compared to those without NR. The higher frequency of LOH in TRIM28 in WT patients with NR warrants future exploration to assess its implication in progression free survival. Nephroblastomatosis exhibits higher mortality and relapse rates, emphasizing the importance of reporting nephroblastomatosis in co-existing WT cases.

DEVELOPING CEREBROSPINAL flUID METABOLOMIC BIOMARKERS FOR MINIMAL RESIDUAL DISEASE AND RELAPSE IN EPENDYMOMA AND MEDULLOBLASTOMA

Abstract AIMS Relapse rates of 30% and 50% in medulloblastoma and ependymoma lead to poor outcomes for paediatric brain tumours. Occurring usually within two years, relapses imply minimal residual disease (MRD) is present below the imaging detection threshold. Patient outcomes might be improved by diagnosing MRD using a sensitive, minimally invasive cerebrospinal fluid (CSF) liquid biopsy, as CSF is proximal to tumour. Metabolites arising from aberrant cancer metabolism may be biomarkers in CSF. METHOD With only 25µl CSF, extracted with 75µl methanol, liquid chromatography coupled with tandem high-resolution mass spectrometry (LC-MS/MS) could differentiate these paediatric brain tumours (n=47; day 14 post-surgery) from controls (n=49). RESULTS Fourteen metabolites were increased in abundance in tumours and four decreased compared to controls. These included amino acids and derivatives (n=8), metabolites in one carbon metabolism (n=1), carnitine cycle (n=2), aerobic glycolysis (n=2), purine catabolism (n=2), ascorbate degradation (n=1) and creatinine synthesis (n=2). From those, betaine/creatinine ratio gave an area under the curve (AUC) of 0.96 (excellent) in receiver operating curve analysis. Using a cut-off ratio of 0.1775 for discriminating brain tumours from controls, had sensitivity and specificity of 92% and 89%. Specifically identifying tumours, a ratio of betaine/threonate with cut-off 2.1514 discriminated ependymomas from controls (sensitivity/specificity 92%/91%). A ratio of malic acid/hypoxanthine with cut-off 0.04429 discriminated medulloblastomas from controls (sensitivity/specificity 100%/98%). Medulloblastomas (n=14) were largely similar to ependymomas (n=33); nevertheless, three metabolites met the criteria of corrected p&amp;lt;0.05. A ratio of glutarate semialdehyde/malic acid with cut-off 0.04243 discriminated ependymomas from medulloblastomas (sensitivity/specificity 79%/82%) in a good model (AUC 0.85). CONCLUSION This is the first report of CSF metabolites in ependymoma. Ratios between metabolites levels could be useful as biomarkers to detect brain tumours and distinguish brain tumour type specifically and sensitively. Further work to develop a liquid biopsy test for the detection of MRD is ongoing.

Can sheep help to improve positive emotions, mindfulness, and self-efficacy expectancy? A pilot study of animal-assisted intervention as an enhanced CBT-based therapy for substance use disorders.

Substance use disorders (SUDs) are common, and there is evidence of clinically significant benefit of cognitive behavioral therapy (CBT). The efficacy of CBT in SUDs has been confirmed, although relapse rates of 40%-60% have been reported. An enhancement of CBT-based therapy through an animal-assisted intervention (AAI) with sheep to normalize the occurrence of negative emotions and improve positive emotions as well as mindfulness and self-efficacy expectancy was investigated. A single-session AAI with sheep in a group setting was investigated against treatment as usual over time. N = 36 psychiatric inpatients with SUDs were examined by questionnaires before and 1 week after the intervention and additionally immediately after the intervention. Positive emotions improved significantly in the AAI group 1 week after the intervention with a medium effect size, but not in the control group. Similarly, mindfulness and self-efficacy expectancy improved over time in the AAI group. When exploratory results were evaluated immediately after the intervention while still on the farm, the effects in favor of AAI were even larger. AAI can thus be considered effective in improving positive emotions, mindfulness, and self-efficacy expectancy. The impressive effect sizes immediately after the intervention encourage us to consider what can be done to maintain these even greater effect sizes over time. https://drks.de/search/de/trial/DRKS00027539, identifier DRKS 00027539.

Early results of treatment in accordance with the NB-HR-2018 protocol in patients with high-risk neuroblastoma in the Republic of Belarus

The development of new criteria for high-risk neuroblastoma treatment optimization and the introduction of new approaches to its management are a pressing problem in modern pediatric oncology. In this study, we aimed to develop and implement new high-risk and ultra-high-risk criteria, introduce tandem autologous hematopoietic stem cell transplantation (HSCT) as consolidation therapy for high-risk neuroblastoma patients as well as to assess patient tolerability of this treatment. The study was approved by the Independent Ethics Committee and the Scientific Council of the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology. In 2018, a new protocol called NB-HR-2018 was developed and implemented at the Center for Pediatric Oncology, Hematology, and Immunology (Belarus) that included new criteria defining high-risk groups. Twenty-three patients were treated according to the new protocol, with 20 of them receiving autologous HSCT. The comparison group included 56 high-risk patients who had undergone treatment in accordance with the NB 2004 protocol. Tandem autoHSCT significantly reduces the rates of underlying disease relapse/progression (p = 0.047) and demonstrates better event-free survival rates (56 ± 12% vs 36 ± 6%; р = 0.445). The use of the new high-risk criteria and the new treatment method (tandem autologous HSCT) is concluded to be a reasonable approach since it significantly reduces disease relapse rates and is well tolerated by the patients.

Selective Inhibition of Deamidated Triosephosphate Isomerase by Disulfiram, Curcumin, and Sodium Dichloroacetate: Synergistic Therapeutic Strategies for T-Cell Acute Lymphoblastic Leukemia in Jurkat Cells.

T-cell acute lymphoblastic leukemia (T-ALL) is a challenging childhood cancer to treat, with limited therapeutic options and high relapse rates. This study explores deamidated triosephosphate isomerase (dTPI) as a novel therapeutic target. We hypothesized that selectively inhibiting dTPI could reduce T-ALL cell viability without affecting normal T lymphocytes. Computational modeling and recombinant enzyme assays revealed that disulfiram (DS) and curcumin (CU) selectively bind and inhibit dTPI activity without affecting the non-deamidated enzyme. At the cellular level, treatment with DS and CU significantly reduced Jurkat T-ALL cell viability and endogenous TPI enzymatic activity, with no effect on normal T lymphocytes, whereas the combination of sodium dichloroacetate (DCA) with DS or CU showed synergistic effects. Furthermore, we demonstrated that dTPI was present and accumulated only in Jurkat cells, confirming our hypothesis. Finally, flow cytometry confirmed apoptosis in Jurkat cells after treatment with DS and CU or their combination with DCA. These findings strongly suggest that targeting dTPI represents a promising and selective target for T-ALL therapy.

Exploring the impact of wearing-off phenomenon in ocrelizumab-treated multiple sclerosis patients: Insights from a comprehensive study

BackgroundOcrelizumab (OCR) effectively modifies the disease course in multiple sclerosis (MS) patients but may cause a preinfusion "wearing-off phenomenon" (WoP). This study explored the prevalence, timing, and severity of this phenomenon in MS patients using the OCR, as well as the associated symptoms and treatment satisfaction. MethodsWe conducted a prospective multicenter study across 11 MS centers involving MS patients aged 18-70 years who had received at least two OCR doses. The study employed a questionnaire addressing demographic, clinical, and radiological data; symptom progression; and treatment satisfaction. ResultsOf the 409 patients included in the study, 406 participated. A significant portion experienced varying degrees of WoP: 39.2% sometimes, 25.9% usually, and 14.3% always, with 55.9% noting symptom onset over four weeks prior to their next dose. Common symptoms included fatigue, walking difficulties, and pain. Subgroup analysis of 334 patients revealed that 78.1% of patients experienced these effects, which correlated with shorter disease durations, a longer delay between the two doses before the last dose, and a greater rate of relapse (P>0.05). ConclusionThe WoP of the OCR is prevalent and significant among MS patients and is influenced by the dosing interval, disease duration, and relapse rate. These insights underscore the need for personalized treatment schedules and more research into factors affecting MS management.

The correlation between rituximab dose reduction and acute relapses of neuromyelitis optica spectrum disorder, lessons from COVID-19 epidemic

BackgroundCOVID-19 was a viral infection that led to a global pandemic in March 2020. At the beginning of the pandemic, clinicians encountered the challenge of how immunosuppressive treatments would affect the course of COVID-19 infection in people with autoimmune diseases. Neuromyelitis optica spectrum disorder is an autoimmune astrocytopathy that is caused by an inflammation in the CNS. Major treatments to prevent acute relapses include immunosuppressive drugs. Rituximab is a well-established immunosuppressive agent in NMOSD maintenance therapy. Some reports suggested that treatment with Rituximab might increase the risk of COVID-19 infection and its mortality in NMOSD. On the other hand, dose reduction or extended interval treatment might lead to acute relapses of NMOSD and permanent disability. MethodsIn this study, we evaluated the correlation between the dose of rituximab and the relapse rate of NMOSD during an epidemic. This was an observational study on 171 patients among whom 55 cases were seropositive. Some patients received full dose rituximab routinely (1000 mg/dose, every 6 months), but others were treated with half dose (500 mg/dose) during the epidemic. Also, some doses were prescribed with a delay, based on the level of CD19 and CD20. ResultsThe Pearson correlation coefficient (r) showed a negative and significant relation (r: - 0.19, p: 0.022) between the amount of drug and the number of relapses in the seropositive group, so low dosage of the drug was related to more acute relapses. In seronegative cases, there was not any valuable relationship. (p: 0.367). ConclusionLower dose of rituximab, especially in seropositive NMOSD patients, can potentially lead to acute relapses. So, the more frequent evaluation of the CD19, CD20, and, CD27 levels, and the general clinical condition of the patients should be considered.

Survival and prognostic factors for relapsed childhood acute lymphoblastic leukemia after treatment with the Chinese children's cancer group ALL-2015 protocol: a single center results.

This retrospective study was conducted to assess the survival rates and prognostic factors in children with relapsed acute lymphoblastic leukemia (ALL) who were treated according to the Chinese Children's Cancer Group ALL-2015 protocol at the Children's Hospital of Chongqing Medical University. The study cohort involving 852 evaluable children with ALL reported a total of 146 relapses during a median follow-up period of 53 months. The primary outcomes measured were the second complete remission (CR2) rates, and 5-year event-free survival (EFS) and overall survival (OS) for patients who received re-treatment post-relapse. Patient data were stratified by ALL subtype (B-ALL vs. T-ALL), age at relapse, site of relapse, and timing of relapse. Univariate and multivariate analyses were performed to identify factors significantly associated with EFS and OS. As of March 31, 2023, 146 relapses were observed, including 128 B-ALL and 18 T-ALL cases. The 8-year CIR was (19.8 ± 1.6)%, with no significant difference between B-ALL and T-ALL (P=0.271). Among the 105 patients who underwent re-treatment, 70 achieved CR2, resulting in a CR2 rate of 67.6%. The 5-year EFS and OS rates for re-treated patients were (45.0 ± 5.4)% and (56.9 ± 5.2)%, respectively. Significant differences in 5-year OS and EFS were found between B-ALL and T-ALL relapses (P < 0.001). The 5-year EFS and OS varied significantly with relapse timing and site of relapse. Factors significantly affecting EFS after relapse included the site of relapse, immunophenotyping, CR2 achievement, and hematopoietic stem cell transplantation (HSCT). Immunophenotyping, CR2 achievement, and HSCT were also identified as significant factors affecting OS after relapse. Despite treatment with the CCCG-ALL-2015 protocol, a significant relapse rate was observed, with 72% of children opting for re-treatment post-relapse. The study highlights the importance of considering specific prognostic factors to inform tailored treatment strategies for relapsed childhood ALL. The findings emphasize the need for further research into improving therapeutic approaches for this patient population. This retrospective study was conducted to assess the survival rates and prognostic factors in children with relapsed acute lymphoblastic leukemia (ALL) who were treated according to the Chinese Children's Cancer Group ALL-2015 protocol at the Children's Hospital of Chongqing Medical University.

Racial, Ethnic, and Socioeconomic Disparities in Pediatric Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder

BackgroundOnly 5% of aquaporin-4-positive neuromyelitis optica spectrum disorder (AQP4+ NMOSD) cases emerge during childhood. Poorer outcomes have been suggested in black/African American (AA) adults with NMOSD; however, conflicting and limited data exist for pediatric-onset NMOSD. This study evaluates racial, ethnic, and socioeconomic disparities in pediatric AQP4+ NMOSD outcomes. MethodsThirty-eight pediatric patients with AQP4+ NMOSD cared for at three pediatric tertiary care centers between 2009 and 2021 were identified. Patient addresses connected to socioeconomic measures available from the US Census. Demographic characteristics, pertinent clinical outcomes, and health care utilization in the two years following diagnosis were captured. ResultsCompared with non-Hispanic White children, Black/AA children had a significantly higher Expanded Disability Status Scale (EDSS) (2.46 vs 0.33, P = 0.003), 2.37 more hospital admissions (P = 0.002), and 28.40 additional inpatient days (P = 0.002) in the two years following their NMOSD diagnosis. Additionally, children with public insurance had higher relapse rates than those with private insurance (P = 0.046). At two years and at the most recent follow-up, a significantly higher EDSS was correlated with children living in census tracts with a lower median income, higher deprivation index, and higher proportion of population on assisted income, in poverty, and with vacant housing (all P < 0.05). ConclusionsWe identified racial, ethnic, and socioeconomic disparities in clinical outcomes and health care utilization in pediatric AQP4+ NMOSD. Further prospective and household-level data are needed to dissect the interplay of genetics, structural racism, and social determinants of health so that interventions to optimize care and outcomes for this population may be developed.