BACKGROUND: Different prophylactic protocols are available for preventing graft-versus-host disease (GVHD) after matched sibling donor (MSD) allogeneic hematopoietic cell transplantation (allo-HCT). This study aimed to compare the effectiveness of post-transplantation cyclophosphamide plus cyclosporine A (PT-CY/CSA) versus methotrexate plus CSA (MTX/CSA) as GVHD prophylaxis protocols in adult acute myeloid leukemia (AML) patients who received peripheral blood stem cells (PBSC) from fully matched donors.
METHODS: The 1-year outcomes of 89 patients treated with PT-CY/CSA and 90 patients treated with MTX/CSA who had MSD allo-HCT for AML using unmanipulated mobilized PBSC were examined and compared.
RESULTS: The cumulative incidence of acute GVHD at 100 days was considerably lower in the PT-CY/CSA group (4% vs 19.3%, p = 0.002), however there were no statistically significant difference in the cumulative incidence of chronic GVHD at 1-year (19.6% vs 37.4%, p = 0.053). Significant delays in neutrophil and platelet engraftments were reported in the PT-CY/CSA group (17 vs 12 days) and (13 vs 12 days), respectively (p < 0.001). The cumulative incidences of relapse (19.1% vs 13.7%, p = 0.470), overall survival (79.1% vs 77.3%, p = 0.986), non-relapse mortality (16.5% vs 16.8%, p = 0.837), and the GVHD and relapse-free survival (GRFS) (53.7% vs 46.6%, p = 0.478) did not differ statistically at 1-year.
CONCLUSIONS: PT-CY/CSA demonstrated a significant decrease in the rate of acute GVHD. However, it was associated with engraftment delay.

An isolate of a Gram-positive, strictly aerobic, motile, rod-shaped, endospore forming bacterium was originally isolated from soil when screening and bioprospecting for plant beneficial microorganisms. Phylogenetic analysis of the 16S rRNA gene sequences indicated that this strain was closely related to Lysinibacillus fusiformis NRRL NRS-350T (99.7%) and Lysinibacillus sphaericus NRRL B-23268T (99.2%). In phenotypic characterization, the novel strain was found to grow between 10 and 45 °C and tolerate up to 8% (w/v) NaCl. Furthermore, the strain grew in media with pH 5 to 10 (optimal growth at pH 7.0). The predominant cellular fatty acids were observed to be iso-C15: 0 (52.3%), anteiso-C15: 0 (14.8%), C16:1ω7C alcohol (11.2%), and C16: 0 (9.5%). The cell-wall peptidoglycan contained lysine-aspartic acid, the same as congeners. A draft genome was assembled and the DNA G+C content was determined to be 37.1% (mol content). A phylogenomic analysis on the core genome of the new strain and 5 closest type strains of Lysinibacillus revealed this strain formed a distinct monophyletic clade with the nearest neighbor being Lysinibacillus fusiformis. DNA-DNA relatedness studies using in silico DNA-DNA hybridizations (DDH) showed this species was below the species threshold of 70%. Based upon the consensus of phylogenetic and phenotypic analyses, we conclude that this strain represents a novel species within the genus Lysinibacillus, for which the name Lysinibacillus pinottii sp. nov. is proposed, with type strain PB211T (= NRRL B-65672T, = CCUG 77181T).

Methotrexate (MTX) is the primarily used disease-modifying antirheumatic drug (DMARD) for the treatment of Rheumatoid Arthritis (RA). MTX is a safe agent, even when used for years - provided that treatment is regularly monitored and prescribers follow some simple rules, such as prescribing tablets of a single strength only. Proper patient education contributes greatly to safe treatment. The knowledge of important pharmacologic facts, possible interactions, and clinical warning signs also helps to prevent or recognize intoxications early. Therefore, this review addresses key aspects regarding the safety of MTX. In this respect, it includes adverse events, possible interactions with frequently used drugs and details on the rare but life-threatening intoxication, e.g., due to erroneous daily intake.

This study presents a rare case of an Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) co-existing with medication-related osteonecrosis of the jaw (MRONJ) in the mandible of a 54-year-old Japanese man who complained of painful swelling of the left mandibular gingiva over the past three months. The patient had a history of methotrexate (MTX) and bisphosphonates (BPs) use. Intraoral examination revealed a 35 mm large ulcerative lesion with marginal gingival swelling and bone exposure on the left side of the mandible. A biopsy was performed, confirming the diagnosis of EBVMCU with MRONJ. Due to the enlargement of the bone exposure, marginal resection of the mandible was performed under general anesthesia as a treatment for residual MRONJ. At the two-year follow-up, no evidence of recurrence was observed.

The treatment landscape for psoriatic arthritis (PsA) has evolved significantly with the introduction of biologic therapies, such as adalimumab, which effectively inhibits tumor necrosis factor-alpha (TNF-α) activity. However, despite their efficacy in controlling inflammation, biologic therapies are associated with heightened risks of infectious complications and malignancies. We present a case of a 66-year-old female with PsA treated with adalimumab who presented with recurrent systemic bacterial infections. Despite attempts to adjust dosing intervals to minimize infection risks, the patient experienced severe complications, including urosepsis, endocarditis, and liver abscesses. The dilemma arises in balancing PsA control with anti-TNFα therapy while minimizing infection risks. Current evidence supporting prophylactic antibiotics in such cases is limited, and determining the next steps for treatment involves challenging decisions such as withholding TNF inhibitors or switching to alternative immunomodulators. This case underscores the need for further research into prophylactic treatment and monitoring protocols to manage recurrent infections during anti-TNF-α therapy effectively.

The neuronal and renal deteriorations observed in patients exposed to methotrexate (MTX) therapy highlight the need for medical interventions to counteract these complications. Boswellic acid (BA) and apigenin (APG) are natural phytochemicals with prominent neuronal and renal protective impacts in various ailments. However, their impacts on MTX-provoked renal and hippocampal toxicity have not been reported. Thus, the present work is tailored to clarify the ability of BA and APG to counteract MTX-provoked hippocampal and renal toxicity. BA (250 mg/kg) or APG (20 mg/kg) were administered orally in rats once a day for 10 days, while MTX (20 mg/kg, i.p.) was administered once on the sixth day of the study. At the histopathological level, BA and APG attenuated MTX-provoked renal and hippocampal aberrations. They also inhibited astrocyte activation, as proven by the inhibition of glial fibrillary acidic protein (GFAP). These impacts were partially mediated via the activation of autophagy flux, as proven by the increased expression of beclin1, LC3-II, and the curbing of p62 protein, alongside the regulation of the p-AMPK/mTOR nexus. In addition, BA and APG displayed anti-inflammatory features as verified by the damping of NOD-2 and p-NF-κB p65 to reduce TNF-α, IL-6, and NLRP3/IL-1β cue. These promising effects were accompanied with a notable reduction in one of the gap junction proteins, connexin-43 (Conx-43). These positive impacts endorse BA and APG as adjuvant modulators to control MTX-driven hippocampal and nephrotoxicity.

BACKGROUND: Low-dose weekly methotrexate (MTX) is the mainstay of treatment in juvenile idiopathic arthritis. Unfortunately, a substantial part of patients has insufficient efficacy of MTX. A potential cause of this inadequate response is suboptimal drug adherence. The aim of this study was to assess MTX adherence in juvenile idiopathic arthritis patients by quantification of MTX concentrations in plasma. Secondly, the association between MTX concentrations and either self-reported adherence issues, or concomitant use of biologics was examined.
METHODS: This was a retrospective, observational study using plasma samples from juvenile idiopathic arthritis patients. An ultrasensitive liquid chromatography-tandem mass spectrometry method was developed for quantification of MTX and its metabolite 7-hydroxy-MTX in plasma. The determined MTX plasma concentrations in juvenile idiopathic arthritis patients were compared with corresponding adherence limits, categorising them as either adherent or possibly non-adherent to MTX therapy.
RESULTS: Plasma samples of 43 patients with juvenile idiopathic arthritis were analysed. Adherence to MTX in this population was 88% shortly after initiation of MTX therapy and decreased to 77% after one year of treatment. Teenagers were more at risk for non-adherence (p = 0.002). We could not find an association between MTX adherence with either self-reported adherence issues, nor with the use of concomitant biological treatment (p = 1.00 and p = 0.27, respectively; Fisher\'s Exact).
CONCLUSIONS: Quantification of MTX in plasma is a feasible and objective method to assess adherence in patients using low-dose weekly MTX. In clinical practice, the use of this method could be a helpful tool for physicians to refute or support suspicion of non-adherence to MTX therapy.

Adjuvant treatment for Glioblastoma Grade 4 with Temozolomide (TMZ) inevitably fails due to therapeutic resistance, necessitating new approaches. Apoptosis induction in GB cells is inefficient, due to an excess of anti-apoptotic XPO1/Bcl-2-family proteins. We assessed TMZ, Methotrexate (MTX), and Cytarabine (Ara-C) (apoptosis inducers) combined with XPO1/Bcl-2/Mcl-1-inhibitors (apoptosis rescue) in GB cell lines and primary GB stem-like cells (GSCs). Using CellTiter-Glo® and Caspase-3 activity assays, we generated dose-response curves and analyzed the gene and protein regulation of anti-apoptotic proteins via PCR and Western blots. Optimal drug combinations were examined for their impact on the cell cycle and apoptosis induction via FACS analysis, paralleled by the assessment of potential toxicity in healthy mouse brain slices. Ara-C and MTX proved to be 150- to 10,000-fold more potent in inducing apoptosis than TMZ. In response to inhibitors Eltanexor (XPO1; E), Venetoclax (Bcl-2; V), and A1210477 (Mcl-1; A), genes encoding for the corresponding proteins were upregulated in a compensatory manner. TMZ, MTX, and Ara-C combined with E, V, and A evidenced highly lethal effects when combined. As no significant cell death induction in mouse brain slices was observed, we conclude that this drug combination is effective in vitro and expected to have low side effects in vivo.

UNASSIGNED: Optimized treatments for relapsed isolated CNS lymphoma (RI-SCNSL) remains under investigation. Temozolomide combination-based therapy, which is often used in glioblastoma may be used as potential treatment in RI-SCNSL.
UNASSIGNED: One of the most common types of non-Hodgkin lymphoma (NHL) is diffuse large B-cell lymphoma (DLBCL). Despite advances in treatment, relapsed isolated CNS lymphoma (RI-SCNSL) from DLBCL remains an issue. The optimal approach in RI-SCNSL remains an area of active investigation as currently there is no high level of evidence for the treatments due to lack of randomized studies. In this case report, we present a DLBCL patient with CNS recurrence treated radiotherapy and intrathecal methotrexate (MTX) followed by intravenous high-dose MTX, rituximab, and temozolomide. To the best of our knowledge, this is the first case report describing RI-SCNSL treated with the regiments above which also include temozolomide which is used for glioblastoma.

UNASSIGNED: This paper highlights that diagnosis and treatment of one ectopic pregnancy does not rule out the happening of a second ectopic pregnancy in the same patient concurrently, especially if the patient has rising β-hCG and persistent symptoms.
UNASSIGNED: Bilateral tubal pregnancy (BTP) is the most uncommon form of tubal ectopic pregnancy. Complications can lead to maternal morbidity and mortality. We reported a case of left tubal pregnancy and the patient underwent laparoscopic salpingostomy. During the follow-up, the contralateral ectopic pregnancy was discovered and treated with MTX.