Development of MDS in Pediatric Patients with GATA2 Deficiency: Increased Histone Trimethylation and Deregulated Apoptosis as Potential Drivers of Transformation.

GATA2 deficiency is a heterogeneous, multisystem disorder associated with a high risk of developing myelodysplastic syndrome (MDS) and the progression to acute myeloid leukemia. The mechanisms underlying malignant transformation in GATA2 deficiency remain poorly understood, necessitating predictive markers to assess an individual's risk of progression and guide therapeutic decisions. In this study, we performed a systematic analysis of bone marrow biopsies from 57 pediatric MDS patients. Focusing on hematopoiesis and the hematopoietic niche, including its microenvironment, we used multiplex immunofluorescence combined with multispectral imaging, gene expression profiling, and multiplex RNA in situ hybridization. Patients with a GATA2 deficiency exhibited a dysregulated GATA2 transcriptional network. Disease progression (GATA2-EB, n = 6) was associated with increased GATA2 mRNA levels, restored expression of the GATA2 target EZH2, and increased H3K27me3. GATA2-EB was further characterized by the high expression of the anti-apoptotic protein BCL2, a feature absent in children with a GATA2 deficiency and refractory cytopenia of childhood (GATA2-RCC, n = 24) or other pediatric MDS subgroups (RCC, n = 17; MDS-EB, n = 10). The multispectral imaging analysis of additional BCL2 family members revealed significantly elevated Mediators of Apoptosis Combinatorial (MAC) scores in GATA2-EB patients. Taken together, our findings highlight the potential drivers of disease progression in GATA2 deficiency, particularly increased histone trimethylation and dysregulated apoptosis. Furthermore, upregulated BCL2 and EZH2 and increased MAC scores provide a strong rationale for the use of venetoclax and azacitidine in therapeutic regimens for GATA2-EB.

Characteristics of Changes in Intrathecal Baclofen Dosage over Time due to Causative Disease.

Intrathecal baclofen (ITB) therapy effectively treats spasticity caused by brain or spinal cord lesions. However, only a few studies compare the course of treatment for different diseases. We investigated the change in daily dose of baclofen per year and its associated adverse events in patients presenting with the three most common etiologies at our institute: hereditary spastic paraplegia, cerebral palsy, and spinal cord injury. The ITB pumps were implanted from July 2007 to August 2019, with a mean follow-up period of 70 months. In patients with hereditary spastic paraplegia, baclofen dosage was reduced after eight years following ITB introduction, and the treatment was terminated in one patient owing to disease progression. In patients with cerebral palsy, the dosage increased gradually, and became constant in the 11th year. Patients with spinal cord injury gradually increased their baclofen dosage throughout the entire observation period. Severity and adverse event rates were higher in patients with cerebral palsy than in others. The degree and progression of spasticity varied depending on the causative disease. Understanding the characteristics and natural history of each disease is important when continuing ITB treatment.

Burr hole locations are associated with recurrence in single burr hole drainage surgery for chronic subdural hematoma.

Background: Various factors have been reported as risk factors for chronic subdural hematomas (CSDH) recurrence. However, few studies have quantitatively evaluated the impact of CSDH locations and burr hole positions on recurrence. This study aimed to reveal the relation between CSDH recurrence and the locations of CSDH and burr holes. Methods: Initial single burr hole surgeries for CSDH with a drainage tube between April 2005 and October 2021 at Otemae Hospital were enrolled. Patients' medical records, CSDH volume, and CSDH computed tomography values (CTV) were evaluated. The locations of CSDH and burr holes were assessed using Montreal Neurological Institute coordinates. Results: A total of 223 patients were enrolled, including 34 patients with bilateral CSDH, resulting in 257 surgeries investigated. The rate of CSDH recurrence requiring reoperation (RrR) was 13.5%. The RrR rate was significantly higher in patients aged ≥76 years, those with bilateral CSDH, and those with postoperative hemiplegia. In RrR, the preoperative CSDH volume was significantly larger, and CTV was significantly smaller. The locations of CSDH had no influence on recurrence. However, in RrR, the locations of burr holes were found to be more lateral and more ventral. Multivariate Cox proportional hazards regression analysis showed that bilateral CSDH, more ventral burr hole positions, and postoperative hemiplegia were risk factors for recurrence. Conclusions: The locations of burr holes are associated with CSDH recurrence. In RrR, CSDH profiles tend to show a larger volume and reduced CTV. Hemiplegia after burr hole surgery serves as a warning sign for RrR.

Tight adhesions after spinal cord stimulation observed during dorsal root entry zone lesioning for pain after spinal root avulsion: illustrative cases.

BACKGROUND: Patients often experience strong shooting pains after spinal root avulsion. The efficacy of spinal cord stimulation (SCS) for this type of pain is inconsistent; however, dorsal root entry zone (DREZ) lesioning (DREZ-lesion) has often proven to be an effective treatment modality. The authors report two cases in which DREZ-lesion was performed to treat pain after spinal root avulsion after implantation of SCS, but the operations were challenging due to strong adhesions. OBSERVATIONS: The authors present two cases of patients with pain after spinal root avulsion in whom SCS implantation was only temporarily effective. Patients complained of persistent and paroxysmal shooting pains in the upper extremities. SCS removal and DREZ-lesion were performed, but adhesions in the epidural and subdural space contacting the leads were strong, making it difficult to expose the DREZ. LESSONS: Although adhesions around the spinal cord can be caused by trauma, the authors believe that in these cases, the adhesions could have been caused by the SCS leads. There are few previous reports confirming the efficacy of SCS in treating pain after spinal root avulsion; therefore, caution is required when considering SCS implantation.

Adrenal tropism of SARS-CoV-2 and adrenal findings in a post-mortem case series of patients with severe fatal COVID-19.

Progressive respiratory failure and hyperinflammatory response is the primary cause of death in the coronavirus disease 2019 (COVID-19) pandemic. Despite mounting evidence of disruption of the hypothalamus-pituitary-adrenal axis in COVID-19, relatively little is known about the tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to adrenal glands and associated changes. Here we demonstrate adrenal viral tropism and replication in COVID-19 patients. Adrenal glands showed inflammation accompanied by inflammatory cell death. Histopathologic analysis revealed widespread microthrombosis and severe adrenal injury. In addition, activation of the glycerophospholipid metabolism and reduction of cortisone intensities were characteristic for COVID-19 specimens. In conclusion, our autopsy series suggests that SARS-CoV-2 facilitates the induction of adrenalitis. Given the central role of adrenal glands in immunoregulation and taking into account the significant adrenal injury observed, monitoring of developing adrenal insufficiency might be essential in acute SARS-CoV-2 infection and during recovery.

Burst Spinal Cord Stimulation for the Treatment of Cervical Dystonia with Intractable Pain: A Pilot Study.

Pain is the most common and disabling non-motor symptom in patients with cervical dystonia. Here, we report four patients with painful cervical dystonia in whom burst spinal cord stimulation (SCS) in the cervical region produced sustained and significant improvements in both dystonic pain and motor symptoms. Further studies need to be performed to investigate the clinical efficacy of burst SCS for patients with cervical dystonia.

Extracellular electron transfer of a highly adhesive and metabolically versatile bacterium.

Bacterial adhesion to a solid plays a predominant role in mediating the extracellular electron transfer for genus Acinetobactor, a metabolically versatile bacterium that can couple toluene degradation and electricity generation.