Utility of cerebrospinal fluid liquid biopsy in distinguishing CNS lymphoma from cerebrospinal infectious/demyelinating diseases.

BACKGROUND: Distinguishing between central nervous system lymphoma (CNSL) and CNS infectious and/or demyelinating diseases, although clinically important, is sometimes difficult even using imaging strategies and conventional cerebrospinal fluid (CSF) analyses. To determine whether detection of genetic mutations enables differentiation between these diseases and the early detection of CNSL, we performed mutational analysis using CSF liquid biopsy technique. METHODS: In this study, we extracted cell-free DNA from the CSF (CSF-cfDNA) of CNSL (N = 10), CNS infectious disease (N = 10), and demyelinating disease (N = 10) patients, and performed quantitative mutational analysis by droplet-digital PCR. Conventional analyses were also performed using peripheral blood and CSF to confirm the characteristics of each disease. RESULTS: Blood hemoglobin and albumin levels were significantly lower in CNSL than CNS infectious and demyelinating diseases, CSF cell counts were significantly higher in infectious diseases than CNSL and demyelinating diseases, and CSF-cfDNA concentrations were significantly higher in infectious diseases than CNSL and demyelinating diseases. Mutation analysis using CSF-cfDNA detected MYD88L265P and CD79Y196 mutations in 60% of CNSLs each, with either mutation detected in 80% of cases. Mutual existence of both mutations was identified in 40% of cases. These mutations were not detected in either infectious or demyelinating diseases, and the sensitivity and specificity of detecting either MYD88/CD79B mutations in CNSL were 80% and 100%, respectively. In the four cases biopsied, the median time from collecting CSF with the detected mutations to definitive diagnosis by conventional methods was 22.5 days (range, 18-93 days). CONCLUSIONS: These results suggest that mutation analysis using CSF-cfDNA might be useful for differentiating CNSL from CNS infectious/demyelinating diseases and for early detection of CNSL, even in cases where brain biopsy is difficult to perform.

Impaired autonomic function in type 2 diabetic patients during upper gastrointestinal endoscopy.

BACKGROUND: Cardiac autonomic neuropathy, representing decreased parasympathetic nerve activity and predominance of sympathetic tone, is often encountered in diabetic patients, and leads to an increased risk of cardiovascular events including arrhythmia. To evaluate the potential cardiovascular risk of diabetics in performing esophagogastroduodenoscopy (EGD), we compared the autonomic function and cardiovascular parameters during EGD between diabetic and nondiabetic patients. METHODS: The autonomic nervous responses in 86 consecutive outpatients (42 type 2 diabetics and 44 nondiabetics) were determined by power spectral analysis (PSA) of heart-rate variations on an electrocardiogram. PSA data were based on two peaks in the low-frequency (LF) and high-frequency (HF) ranges. HF power and the ratio of LF power/HF power represented parasympathetic and sympathetic nerve activities, respectively. RESULTS: Diabetic patients showed significantly lower DeltaHF power and significantly higher DeltaLF power/HF power than nondiabetics, suggesting enhanced predominance of sympathetic activity and marked suppression of parasympathetic function. Significant correlations were found between these autonomic parameters and the diabetic duration. A slightly higher incidence of ventricular premature contractures was observed in diabetics during EGD. However, no significant difference was found in pulse or blood pressure increments during EGD between the two groups. CONCLUSIONS: This is the first study demonstrating an imbalance of autonomic function in diabetics during EGD, which may be linked to a slightly higher risk of arrhythmia.

Autonomic nervous function in upper gastrointestinal endoscopy: a prospective randomized comparison between transnasal and oral procedures.

BACKGROUND: Transnasal esophagogastroduodenoscopy (EGD) using an ultrathin endoscope is less stressful to the cardiovascular system with less elevation of systolic blood pressure (BP) than oral procedures. To elucidate the mechanism of such beneficial cardiovascular responses, we performed a prospective patient-centered randomized study in which BP and pulse rate (P), as well as autonomic nervous functions, were estimated during transnasal EGD compared with those in oral procedures using the same ultrathin endoscope. METHODS: The study involved 781 patients, among whom 55 and 56 cases were assigned to transnasal and oral EGD groups, respectively. The autonomic nervous responses were determined employing power spectral analysis (PSA) of heart-rate variations on electrocardiogram. PSA data were based on two peaks in low frequency (LF) and high-frequency (HF) ranges. HF power and the ratio of LF power/HF power represented parasympathetic and sympathetic nervous activities, respectively. RESULTS: Our study confirmed the lesser elevation of BP and P in patients undergoing transnasal EGD than in those undergoing oral procedures. PSA revealed a lower increase in LH power/HF power in transnasal EGD than in oral EGD. However, both endoscopic procedures equally suppressed HF power. Significant correlations were found between the parameters of cardiovascular response (P and BP) and autonomic functions (LF power/HF power ratio and HF power). CONCLUSIONS: This is the first study demonstrating less sympathetic stimulation in patients undergoing transnasal EGD, leading to lesser elevation of BP and P.