Pathophysiology of unilateral asterixis due to thalamic lesion.

[Objective]:Unilateral asterixis has been reported in patients with thalamic lesion. This study aims at elucidating the pathophysiology of the thalamic asterixis. [Methods]:Two cases with unilateral asterixis caused by an infarction in the lateral thalamus were studied by analysing the asterixis-related cortical activities, transcranial magnetic stimulation (TMS) for motor cortex excitability and probabilistic diffusion tractography for the thalamo-cortical connectivity. [Results]:Averaging of electroencephalogram (EEG) time-locked to the asterixis revealed rhythmic oscillations of a beta band at the central area contralateral to the affected hand. TMS revealed a decrease in the motor evoked potential (MEP) amplitude and a prolongation of the silent period (SP). The anatomical mapping of connections between the thalamus and cortical areas using a diffusion-weighted image (DWI) showed that the lateral thalamus involved by the infarction was connected to the premotor cortex, the primary motor cortex (M1) and the primary somatosensory cortex (S1) of the corresponding hemisphere. [Conclusions]:The thalamic asterixis is mediated by the sensorimotor cortex, which is subjected to excessive inhibition as a result of the thalamic lesion involving the ventral lateral nucleus. [Significance]:This is the first demonstration of participation of the sensorimotor cortex in the generation of asterixis due to the lateral thalamic lesion

Retroperitoneal hemorrhage with COVID-19

Introduction: Early prophylactic administration of anticoagulants is recommended in patients with coronavirus disease 2019 (COVID-19). A case of retroperitoneal hemorrhage during inpatient treatment for COVID-19 is reported. Case Presentation : A 69-year-old man was diagnosed with COVID-19 6 days after symptom onset. After admission for difficulty of breathing, he was treated with steroid pulse therapy, remdesivir, and heparin sodium. On day 16 after admission, his hemoglobin and blood pressure dropped. Computed tomography showed a left retroperitoneal hematoma and multiple areas of extravasation in bilateral iliopsoas muscles. Anticoagulation therapy was stopped, and blood transfusion therapy was chosen by considering poor general condition caused by severe pneumonia. On day 19, the hemoglobin and blood pressure improved, and blood transfusion was stopped. However, he died on day 25 due to pneumonia. Conclusion : When retroperitoneal hemorrhage occurs as a complication of COVID-19, appropriate treatment decision, transcatheter arterial embolization or conservative treatment, should be chosen based on patient’s condition

Site‐specific methylation patterns of the GAL and GALR1/2 genes in head and neck cancer: Potential utility as biomarkers for prognosis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136246/1/mc22577.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136246/2/mc22577_am.pd

Analysis of Site-Specific Methylation of Tumor-Related Genes in Head and Neck Cancer: Potential Utility as Biomarkers for Prognosis

Clarifying the epigenetic regulation of tumor-related genes (TRGs) can provide insights into the mechanisms of tumorigenesis and the risk for disease recurrence in HPV-negative head and neck cancers, originating in the hypopharynx, larynx, and oral cavity. We analyzed the methylation status of the promoters of 30 TRGs in 178 HPV-negative head and neck cancer patients using a quantitative methylation-specific PCR. Promoter methylation was correlated with various clinical characteristics and patient survival. The mean number of methylated TRGs was 14.2 (range, 2–25). In the multivariate Cox proportional hazards analysis, the methylation of COL1A2 and VEGFR1 was associated with poor survival for hypopharyngeal cancer, with hazard ratios: 3.19; p = 0.009 and 3.07; p = 0.014, respectively. The methylation of p16 and COL1A2 were independent prognostic factors for poor survival in laryngeal cancer (hazard ratio: 4.55; p = 0.013 and 3.12; p = 0.035, respectively). In patients with oral cancer, the methylation of TAC1 and SSTR1 best correlated with poor survival (hazard ratio: 4.29; p = 0.005 and 5.38; p = 0.029, respectively). Our findings suggest that methylation status of TRGs could serve as important site-specific biomarkers for prediction of clinical outcomes in patients with HPV-negative head and neck cancer

Lenvatinib-induced Interstitial Pneumonia in a Patient with Hepatocellular Carcinoma

Lenvatinib is a multi-targeted tyrosine kinase inhibitor available for the treatment of unresectable hepatocellular carcinoma (HCC). We herein report an 84-year-old-man with interstitial pneumonia caused by lenvatinib. Four months after the start of lenvatinib administration for HCC, chest computed tomography revealed bilateral ground-glass opacity. However, he continued to take lenvatinib for four more months until he complained of dyspnea on exertion. This is a case of lenvatinib-induced interstitial pneumonia that progressed relatively slowly with a long asymptomatic period despite the appearance of pneumonia on image findings

Genes Located on 18q23 Are Epigenetic Markers and Have Prognostic Significance for Patients with Head and Neck Cancer

Loss of heterozygosity (LOH) on chromosome 18q23 is associated with significantly decreased survival in head and neck cancer. In agreement with such tumor suppressive roles, the loss of function of genes located in this region can be achieved through LOH and promotor hypermethylation. In this study, the methylation status of promoters of 18q23 genes in 243 head and neck cancer patients was assessed by quantitative methylation-specific PCR. Promoter methylation was then compared to various clinical characteristics and patient survival. GALR1 and SALL3 promoter methylation correlated with reduced disease-free survival (log-rank test, p = 0.018 and p = 0.013, respectively). Furthermore, based on multivariate Cox proportional hazards analysis, these methylation events were associated with poor disease-free survival, with hazard ratios of 1.600 (95% confidence interval: CI, 1.027–2.493; p = 0.038) and 1.911 (95% CI, 1.155–3.162; p = 0.012), respectively. By comparison, GALR1 and SALL3 methylation were not prognostic for overall survival in The Cancer Genome Atlas (TCGA) cohort. Our findings suggest that the methylation status of 18q23 genes could serve as important biomarkers for the prediction of clinical outcomes in well-annotated head and neck squamous cell carcinoma cohorts. GALR1 and SALL3 methylation could thus help to facilitate risk stratification for individualized treatment

Aberrant Epigenetic Regulation in Head and Neck Cancer Due to Distinct EZH2 Overexpression and DNA Hypermethylation

Enhancer of Zeste homologue 2 (EZH2) overexpression is associated with tumor proliferation, metastasis, and poor prognosis. Targeting and inhibition of EZH2 is a potentially effective therapeutic strategy for head and neck squamous cell carcinoma (HNSCC). We analyzed EZH2 mRNA expression in a well-characterized dataset of 230 (110 original and 120 validation cohorts) human head and neck cancer samples. This study aimed to investigate the effects of inhibiting EZH2, either via RNA interference or via pharmacotherapy, on HNSCC growth. EZH2 upregulation was significantly correlated with recurrence (p < 0.001) and the methylation index of tumor suppressor genes (p < 0.05). DNMT3A was significantly upregulated upon EZH2 upregulation (p = 0.043). Univariate analysis revealed that EZH2 upregulation was associated with poor disease-free survival (log-rank test, p < 0.001). In multivariate analysis, EZH2 upregulation was evaluated as a significant independent prognostic factor of disease-free survival (hazard ratio: 2.085, 95% confidence interval: 1.390⁻3.127; p < 0.001). Cells treated with RNA interference and DZNep, an EZH2 inhibitor, showed the most dramatic changes in expression, accompanied with a reduction in the growth and survival of FaDu cells. These findings suggest that EZH2 upregulation is correlated with tumor aggressiveness and adverse patient outcomes in HNSCC. Evaluation of EZH2 expression might help predict the prognosis of HNSCC patients

G Protein-Coupled Receptor Genes, PTGDR1, PTGDR2, and PTGIR, Are Candidate Epigenetic Biomarkers and Predictors for Treated Patients with HPV-Associated Oropharyngeal Cancer

Differences in the biology of human papillomavirus (HPV)-associated oropharyngeal cancers (OPCs) and HPV-negative OPCs may have implications in patient management. Early detection is imperative to reduce HPV-associated OPC mortality. Circulating tumor DNA (ctDNA) can potentially serve as a biomarker for monitoring clinically relevant cancer-related genetic and epigenetic modifications. We analyzed the methylation status of 24 G protein-coupled receptor (GPCR) genes in verification (85 OPC primary samples) and validation (8 OPC ctDNA samples) studies using quantitative methylation-specific polymerase chain reaction (Q-MSP). The Q-MSP-based verification study with 85 OPC primary samples revealed the GPCR genes that were significantly associated with recurrence in high methylation groups (≥14 methylated genes) with OPC and HPV-associated OPC (p < 0.001). In the Kaplan–Meier estimate and multivariate Cox proportional hazard analyses, 13 GPCR genes were significantly related to increased recurrence in the methylation group. Furthermore, the validation study on ctDNA showed that three of these genes (Prostaglandin D2 receptor 1: PTGDR1, Prostaglandin D2 receptor 2: PTGDR2, and Prostaglandin I2 Receptor: PTGIR) had a prediction performance as emerging biomarkers. We characterized the relationship between the methylation status of GPCR genes and outcomes in HPV-associated OPC. Our results highlight the potential utility of ctDNA methylation-based detection for the clinical management of HPV-associated OPC