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Frontiers in Immunology 2023Recent studies supported coagulation involvement in multiple sclerosis, an inflammatory-demyelinating and degenerative disease of the central nervous system. The main... (Observational Study)
Observational Study
OBJECTIVES
Recent studies supported coagulation involvement in multiple sclerosis, an inflammatory-demyelinating and degenerative disease of the central nervous system. The main objectives of this observational study were to identify the most specific pro-coagulative/vascular factors for multiple sclerosis pathogenesis and to correlate them with brain hemodynamic abnormalities.
METHODS
We compared i) serum/plasma levels of complement(C)/coagulation/vascular factors, viral/microbiological assays, fat-soluble vitamins and lymphocyte count among people with multiple sclerosis sampled in a clinical remission (=30; 23F/7M, 40 ± 8.14 years) or a relapse (=30; 24F/6M, age 41 ± 10.74 years) and age/sex-matched controls (=30; 23F/7M, 40 ± 8.38 years); ii) brain hemodynamic metrics at dynamic susceptibility contrast-enhanced 3T-MRI during relapse and remission, and iii) laboratory data with MRI perfusion metrics and clinical features of people with multiple sclerosis. Two models by Partial Least Squares Discriminant Analysis were performed using two groups as input: (1) multiple sclerosis vs. controls, and (2) relapsing vs. remitting multiple sclerosis.
RESULTS
Compared to controls, multiple sclerosis patients had a higher Body-Mass-Index, Protein-C and activated-C9; and a lower activated-C4. Levels of Tissue-Factor, Tie-2 and P-Selectin/CD62P were lower in relapse compared to remission and HC, whereas Angiopoietin-I was higher in relapsing vs. remitting multiple sclerosis. A lower number of total lymphocytes was found in relapsing multiple sclerosis vs. remitting multiple sclerosis and controls. Cerebral-Blood-Volume was lower in normal-appearing white matter and left caudatum while Cerebral-Blood-Flow was inferior in bilateral putamen in relapsing versus remitting multiple sclerosis. The mean-transit-time of gadolinium-enhancing lesions negatively correlated with Tissue-Factor. The top-5 discriminating variables for model (1) were: EBV-EBNA-1 IgG, Body-Mass-Index, Protein-C, activated-C4 and Tissue-Factor whereas for model (2) were: Tissue-Factor, Angiopoietin-I, MCHC, Vitamin A and T-CD3.
CONCLUSION
Tissue-factor was one of the top-5 variables in the models discriminating either multiple sclerosis from controls or multiple sclerosis relapse from remission and correlated with mean-transit-time of gadolinium-enhancing lesions. Tissue-factor appears a promising pro-coagulative/vascular biomarker and a possible therapeutic target in relapsing-remitting multiple sclerosis.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, identifier NCT04380220.
Topics: Adult; Humans; Middle Aged; Gadolinium; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Recurrence; Thromboplastin
PubMed: 37583699
DOI: 10.3389/fimmu.2023.1226616 -
Frontiers in Immunology 2023Bullous pemphigoid (BP) is an autoimmune skin-blistering disease. Systemic corticosteroids remain the first line treatment for moderate-to-severe BP with the potential...
BACKGROUND
Bullous pemphigoid (BP) is an autoimmune skin-blistering disease. Systemic corticosteroids remain the first line treatment for moderate-to-severe BP with the potential for severe adverse events. Dupilumab has emerged as an alternative option for BP patients.
OBJECTIVE
We evaluated the efficiency and safety of dupilumab on BP treatment and explored a mode of drug action in depth.
METHODS AND RESULTS
A multicenter retrospective cohort included 20 BP patients who received dupilumab with or without systemic corticosteroid in dupilumab group, and 20 matched BP patients who received corticosteroid alone in conventional group. Serum samples were collected from 20 patients (10 from dupilumab group and 10 from conventional group) at baseline and week 4. Compared to systemic corticosteroid alone, dupilumab with or without systemic corticosteroid was similarly efficacious in clinical remission at week4 (complete remission plus partial remission: 100%) and week24 (complete remission plus partial remission:100%), but allowing significant decreases in the cumulative doses of corticosteroids with reducing the incidence of adverse events. However, dupilumab did not decrease BP180 antibody despite an obvious clinical improvement. Comparative plasma proteomic analysis performed before and after treatment in 3 BP patients from dupilumab group revealed that drug use was associated with 30 differentially expressed proteins, including 26 down-regulated and 4 up-regulated proteins. The former consisted of immune related proteins involved in T/B cell interactions (inducible T-cell co-stimulator ligand, ICOSL) and in the activation of eosinophils (PRG2), mast cells (S100A12), and complement (CR2). TARC and ICOSL levels correlated with BP severity in patients who received either dupilumab or conventional treatment.
CONCLUSION
Dupilumab has similar efficacy in treating BP as conventional drugs, by inhibiting the activities of many types of immune cells and complement, and regulating the interactions between T and B cells.
Topics: Humans; Pemphigoid, Bullous; Retrospective Studies; Proteomics; Autoimmune Diseases; Adrenal Cortex Hormones
PubMed: 37575240
DOI: 10.3389/fimmu.2023.1194088 -
Immune Network Feb 2024The key role of T cells in cancer immunotherapy is well established and is highlighted by the remarkable capacity of Ab-mediated checkpoint blockade to overcome T-cell... (Review)
Review
The key role of T cells in cancer immunotherapy is well established and is highlighted by the remarkable capacity of Ab-mediated checkpoint blockade to overcome T-cell exhaustion and amplify anti-tumor responses. However, total or partial tumor remission following checkpoint blockade is still limited to only a few types of tumors. Hence, concerted attempts are being made to devise new methods for improving tumor immunity. Currently, much attention is being focused on therapy with IL-2. This cytokine is a powerful growth factor for T cells and optimises their effector functions. When used at therapeutic doses for cancer treatment, however, IL-2 is highly toxic. Nevertheless, recent work has shown that modifying the structure or presentation of IL-2 can reduce toxicity and lead to effective anti-tumor responses in synergy with checkpoint blockade. Here, we review the complex interaction of IL-2 with T cells: first during normal homeostasis, then during responses to pathogens, and finally in anti-tumor responses.
PubMed: 38455463
DOI: 10.4110/in.2024.24.e5 -
ACG Case Reports Journal Sep 2023Most gastric cancers are adenocarcinomas, but other malignancies can arise in the stomach. Patients with leukemia may develop myeloid sarcoma (MS) in the...
Most gastric cancers are adenocarcinomas, but other malignancies can arise in the stomach. Patients with leukemia may develop myeloid sarcoma (MS) in the gastrointestinal tract. Our patient was a 68-year-old woman who was initially diagnosed with acute myeloid leukemia and underwent a matched unrelated stem cell transplantation. She was in remission for 10 years before developing a rare case of gastric MS without acute myeloid leukemia. She had partial response to chemotherapy but ultimately died because of infection. Gastric MS has an incidence of less than 1%. Gastrointestinal involvement usually involves the small intestine and rarely the stomach.
PubMed: 37674880
DOI: 10.14309/crj.0000000000001137 -
PloS One 2023Infliximab (IFX) effectively treats patients with inflammatory bowel disease (IBD). IFX-biosimilar (IFX-BS) has the same amino acid sequence as that of the IFX... (Observational Study)
Observational Study
BACKGROUND
Infliximab (IFX) effectively treats patients with inflammatory bowel disease (IBD). IFX-biosimilar (IFX-BS) has the same amino acid sequence as that of the IFX originator, and its increasing use is expected to reduce national healthcare costs. Long-term efficacy and safety of IFX-BS in patients with Crohn's disease (CD) and ulcerative colitis (UC) have not been completely investigated.
METHODS
We conducted a retrospective, multicenter observational study of patients with IBD who received IFX-BS treatment at three hospitals between October 2016 and April 2022. Clinical data were collected from electronic medical records and evaluated for achieving clinical remission (CR) using Crohn's disease activity index (CDAI) and partial Mayo (pMayo) score, persistency of long-term IFX-BS administration, and clinical response rate in the bio-naïve and bio-failure groups.
RESULTS
A total of 117 patients with IBD (90 CD and 27 UC) were included. The study findings indicated that both bio-naïve and bio-failure groups of patients with UC showed similar effectiveness of IFX-BS. The treatment persistence rate in patients with CD was significantly higher in the bio-naïve (P = 0.042) and switch (P = 0.010) groups than in the bio-failure group. In the former two groups, the treatment persistence rate was high at two years after administration (more than 80%). In patients with UC, the findings indicated higher treatment persistence rate in the switch group than in the bio-naïve group. Univariable and multivariable analyses for treatment persistence rate showed that the albumin level at the initial IFX-BS administration and groups (bio-naïve, bio-failure and switch) were effective factors for patients with CD. Adverse events were reported in 18 patients (15.4%).
CONCLUSION
The present study demonstrates the long-term effectiveness and safety of IFX-BS. In addition to the favorable remission induction in the bio-naïve and bio-failure groups, we demonstrated remission maintenance and treatment persistence rates beyond two years. Albumin level and groups were associated with better treatment persistence in patients with CD.
Topics: Humans; Infliximab; Crohn Disease; Biosimilar Pharmaceuticals; Retrospective Studies; Colitis, Ulcerative; Inflammatory Bowel Diseases; Phoeniceae; Albumins
PubMed: 37699041
DOI: 10.1371/journal.pone.0288393 -
Medicina Sep 2023Self-limited Focal Epilepsies of Childhood (SELFEs) are the most prevalent electroclinical syndromes in pediatric age, whose typical evolution, with age-dependent onset... (Review)
Review
Self-limited Focal Epilepsies of Childhood (SELFEs) are the most prevalent electroclinical syndromes in pediatric age, whose typical evolution, with age-dependent onset and remission, has allowed the ILAE Nosology and Definitions Working Group (2022) to define them as "Selflimited Focal Epilepsies of Childhood", thus establishing alert and exclusion criteria to standardize their diagnosis. These syndromes include: Self-limited Epilepsy with Centrotemporal Spikes (previously Rolandic Epilepsy), Self-limited Epilepsy with Autonomic Seizures (previously Panayiotopoulos Syndrome), Childhood Occipital Visual Epilepsy, (previously Gastaut Syndrome), and Photosensitive Occipital Lobe Epilepsy. Using the term "benign" to refer to them is no longer recommended, as this would ignore the comorbidities some individuals suffer. Also, the term "idiopathic" is now only used to refer to the syndromes classified as Idiopathic Generalized Epilepsies.
Topics: Humans; Child; Epilepsies, Partial; Seizures; Epilepsy, Generalized; Lennox Gastaut Syndrome
PubMed: 37714124
DOI: No ID Found -
International Journal of Surgery... Sep 2023This study aimed to investigate the prospects of using chemotherapy in combination with atezolizumab in the neoadjuvant or conversion treatment of small cell lung cancer...
BACKGROUND
This study aimed to investigate the prospects of using chemotherapy in combination with atezolizumab in the neoadjuvant or conversion treatment of small cell lung cancer (SCLC).
METHODS
Prior to surgery, untreated patients with limited-stage SCLC received three cycles of neoadjuvant or conversion atezolizumab combined with chemotherapy of etoposide and platinum. The primary endpoint of the trial was pathological complete response (pCR) in the per-protocol (PP) cohort. In addition, safety was assessed based on treatment-related adverse events (AEs) and postoperative complications.
RESULTS
Overall, 13 of 17 patients (including 14 males and 3 females) underwent surgery. In the PP cohort, pCR and major pathological response were observed in 8 (8/13, 61.5%) and 12 (12/13, 92.3%) patients, respectively. According to the intention-to-treat (ITT) analysis, the pCR and major pathological response in the ITT cohort were 47.1% (8/17) and 70.6% (12/17), respectively. In addition, an overall response rate of 100% was recorded in the PP cohort. Moreover, 15 (15/17, 88.2%) patients and 1 (1/17, 5.9%) in the ITT cohort attained partial remission (PR), and complete remission, respectively, with an overall response rate of 94.1%. The median overall survival of the patients of pCR and the median event-free survival of the patients on surgery had not achieved. However, the median overall survival of the patients of non-pCR was 18.2 months and the median event-free survival of the nonsurgical patients was 9.5 months. During the neoadjuvant treatment, the incidence of grade 3 or higher AEs was 58.8% (10/17). Additionally, three patients (17.6%) developed immune-related adverse event (grades 1-2).
CONCLUSION
In patients with SCLC, neoadjuvant or conversion atezolizumab combined with chemotherapy significantly improved pCR with manageable AEs. Therefore, this regimen may be considered a safe and effective treatment for SCLC.
Topics: Female; Male; Humans; Neoadjuvant Therapy; Cohort Studies; Small Cell Lung Carcinoma; Lung Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37428211
DOI: 10.1097/JS9.0000000000000501 -
BMC Rheumatology Oct 2023To determine the safety and efficacy of biological agents used in the treatment of systemic lupus erythematosus (SLE) in adults.
BACKGROUND
To determine the safety and efficacy of biological agents used in the treatment of systemic lupus erythematosus (SLE) in adults.
METHODS
Systematic review and meta-analysis following PRISMA guidelines.
DATA SOURCES
MEDLINE (through Pubmed), EMBASE, Cochrane library, Clinicaltrials.gov, Australianclinicaltrials.gov.au, ANZCTR.org.au and WHO International Clinical Trials Registry Platform for studies published from 20 May 2021 and 15 years prior. A grey literature search was performed and completed on 31 May 2021.
STUDY CRITERIA
Phase II, III or quasi randomised controlled trials, studies with only cerebral or cutaneous lupus were excluded.
DATA EXTRACTION
Two authors independently screened studies for eligibility, extracted, reviewed data for accuracy, and used the Cochrane tool to assess risk of bias.
RESULTS
Forty-four studies were identified, consisting of 15 groups of drugs and 25 different biological agents, totalling 16,889 patients. The main outcomes assessed included Systemic Lupus Erythematosus Responder Index (SRI), BILAG-Based Composite Lupus Assessment (BICLA) and combined combined/partial renal remission (CRR/PRR). Four groups of biologics were found to improve outcomes. Anti-interferons: Anifrolumab increased BICLA response and SRI 5 to 8, decreased prednisone dosages, with increased herpes zoster infections, but fewer serious adverse events. Sifalimumab improved SRI but also increased herpes zoster infections. Anti BAFF/BLyS and/or APRIL: Belimumab consistently improved SRI 4, decreased prednisone dosages, increased combined CRR/PRR, and had no adverse safety outcomes. Tabalumab increased SRI 5 at 52 weeks with no steroid sparing effect but was associated with increased infusion related adverse events. Telitacicept improved SRI 4 at 52 weeks, with no increased adverse events, though data was rather sparse. Anti CD-20 monoclonal antibody, Obinutuzumab increased combined CRR/PRR at 1 and 2 years. Anti IL12/23 monoclonal antibody, Ustekinumab, increased SRI 4 to 6, but not BICLA at 24 weeks, with no concerning safety outcomes.
CONCLUSION
Multiple biologic agents are shown in high quality studies to have a significant therapeutic impact on outcomes in SLE.
PubMed: 37807057
DOI: 10.1186/s41927-023-00358-3 -
Experimental and Therapeutic Medicine Oct 2023The present study aimed to study the efficacy and adverse effects of anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) cell therapy in relapsed...
The present study aimed to study the efficacy and adverse effects of anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) cell therapy in relapsed or refractory multiple myeloma. Patients were divided into three dose groups based on cell therapy concentration. After CAR-T cell therapy for 10 patients with recurrent or refractory multiple myeloma, the patients were monitored and evaluated regularly to observe the efficacy and adverse reactions of CAR-T cell therapy. At a median follow-up of 337 (253-504) days, one patient succumbed 24 days due to rapidly progressing disease. The overall response rate of nine patients was 88.9%, including 77.8% (7/9) with minimal residual disease negative complete remission (CR) and 11.1% (1/9) with partial remission. A total of three patients were maintained in remission state for more than a year and eight were maintained for more than six months. Among the three patients with extramedullary invasion, two extramedullary lesions disappeared and one was stable. The highest copy number of CAR-T cells in seven patients with CR was >1x10 copies/µl gDNA, and the best therapeutic effect can be achieved within 30 (7-30) days after the copy number of CAR-T cells reached 1x10 copies/µl genomic DNA. The median onset time in the nine patients was 43 (22-169) days, and the median progression-free survival was 337 (253-504). Among the 10 patients, nine (90%) had cytokine release syndrome, all of which were below grade II. There were nine (90%) patients with hematological adverse reactions, six (60%) patients with severe anemia, five (50%) patients with grade III and above leukopenia, five (50%) patients with granulocytopenia, four (40%) patients with grade III and above thrombocytopenia, and three (30%) patients with grade III and above pancytopenia. It was concluded that anti-BCMA CAR-T cell therapy is a promising treatment method for relapsed or refractory multiple myeloma and extramedullary invasion, with stable efficacy and controllable adverse effects.
PubMed: 37664681
DOI: 10.3892/etm.2023.12170 -
Journal of Crohn's & Colitis Mar 2024Although ulcerative proctitis [UP] can dramatically impair quality of life, treatment efficacy has been poorly investigated in UP as it was historically excluded from...
BACKGROUND
Although ulcerative proctitis [UP] can dramatically impair quality of life, treatment efficacy has been poorly investigated in UP as it was historically excluded from phase 2/3 randomised controlled trials in ulcerative colitis. Our aim was to assess the effectiveness and safety of tofacitinib for the treatment of UP.
METHODS
We conducted a retrospective, multicentre study in 17 GETAID centres, including consecutive patients with UP treated with tofacitinib. The primary endpoint was steroid-free remission between Week 8 and Week 14, defined as a partial Mayo score of 2 [and no individual subscore above 1]. Secondary outcomes included clinical response and steroid-free remission after induction and at 1 year.
RESULTS
All the 35 enrolled patients previously received anti-tumour necrosis factor [TNF] therapy and 88.6% were exposed to at least two lines of biologics. At baseline, the median partial Mayo score was 7 (intequartile range [IQR] [5.5-7]). After induction [W8-W14], 42.9% and 60.0% of patients achieved steroid-free remission and clinical response, respectively. At 1 year, the steroid-free clinical remission and clinical response rates were 39.4% and 45.5%, respectively, and 51.2% [17/33] were still receiving tofacitinib treatment. Survival without tofacitinib withdrawal was estimated at 50.4% (95% confidence interval [CI] [35.5-71.6]) at 1 year. Only a lower partial Mayo at baseline was independently associated with remission at induction (0dds ratio [OR] = 0.56 for an increase of 1, (95% CI [0.33-0.95], p = 0.03). Five [14.3%] adverse events were reported, with one leading to treatment withdrawal [septic shock secondary to cholecystitis].
CONCLUSION
Tofacitinib may offer a therapeutic option for patients with refractory UP.
Topics: Humans; Tumor Necrosis Factor Inhibitors; Retrospective Studies; Quality of Life; Proctitis; Piperidines; Pyrimidines
PubMed: 37796025
DOI: 10.1093/ecco-jcc/jjad169