Progressive multifocal leukoencephalopathy associated with systemic lupus erythematosus: longitudinal observation of lymphocytes, JC virus in cerebrospinal fluid, and brain magnetic resonance imaging.

Progressive multifocal leukoencephalopathy (PML) rarely occurs in patients with systemic lupus erythematosus (SLE). This report presents the case of a patient who developed PML due to SLE-associated multiple factors. A 60-year-old woman diagnosed with SLE undergoing multiple immunosuppressive therapies, including azathioprine, presented with cerebral cortical symptoms, lymphocytopenia, and vitamin B12 deficiency and was subsequently diagnosed with SLE-associated PML. We evaluated the cause and disease activity of PML, focusing on the longitudinal assessment of lymphocytopenia, JC virus (JCV) DNA copy number in the cerebrospinal fluid, and magnetic resonance imaging (MRI) findings. Discontinuing azathioprine and initiating alternative immunosuppressive treatments with intramuscular vitamin B12 injections affected lymphocytopenia and disease management. However, despite recovery from lymphopenia and JCV DNA copy number being low, the large hyperintense and punctate lesions observed on the fluid-attenuated inversion recovery (FLAIR) images exhibited varying behaviors, indicating that the balance between contributing factors for PML may have fluctuated after the initial treatment. Clinicians should be meticulous when assessing the underlying pathology of the multifactorial causes of PML due to SLE. The difference in the transition pattern of these lesions on FLAIR images may be one of the characteristics of MRI findings in PML associated with SLE, reflecting fluctuations in disease activity and the progression stage of PML.

Prognostic Value of Global Coronary Flow Reserve Before and After Elective Percutaneous Coronary Intervention in Patients with Chronic Coronary Syndrome.

BACKGROUND: Impaired global coronary flow reserve (G-CFR), evaluated through phase-contrast cine cardiovascular magnetic resonance (PC-CMR), has been linked to worse outcomes in patients with cardiovascular disease. This study aimed to investigate the prognostic value of G-CFR improvement, as evaluated using PC-CMR imaging pre- and post-percutaneous coronary intervention (PCI). METHODS: In this single-center study, 320 patients with chronic coronary syndrome (CCS) who underwent pre- and post-PCI PC-CMR measurements were followed-up to determine major adverse cardiac or cerebrovascular events (MACCE) predictors. MACCE was defined as a composite of cardiac death, nonfatal myocardial infarction, hospitalization due to heart failure, or ischemic stroke. The association between CMR parameters, including baseline data, G-CFR changes post-PCI and MACCE was investigated. RESULTS: G-CFR improvement was observed in 165 (51.6%) patients, while MACCE occurred in 26 (8.1%) during a median follow-up period of 2.5 years. G-CFR improvement was significantly associated with a lower pre-PCI G-CFR. The log-rank test revealed a significant association between patients without G-CFR improvement post-PCI and a poor prognosis. Patients with lower pre-PCI G-CFR and lack of G-CFR improvement exhibited the highest incidence of MACCE. The multivariable Cox proportional hazard model revealed that lack of G-CFR improvement was an independently significant MACCE predictor from pre-PCI G-CFR and SYNTAX score. CONCLUSIONS: Besides the association between pre- and post-PCI lower G-CFR and worse prognosis, the presence or absence of G-CFR improvement post-PCI may provide novel insights into the prognosis following elective PCI in patients with CCS.

Association of Coronary Computed Tomography-Defined Myocardial Bridge With Pre- and Post-Procedural Fractional Flow Reserve in Patients Undergoing Elective Percutaneous Coronary Intervention.

BACKGROUND: Myocardial bridge (MB) is a common coronary anomaly characterized by a tunneled course through the myocardium. Coronary computed tomography angiography (CCTA) can identify MB. The impact of MB detected by CCTA on coronary physiological parameters before and after percutaneous coronary intervention (PCI) is unknown. METHODS AND RESULTS: We investigated 141 consecutive patients who underwent pre-PCI CCTA and fractional flow reserve (FFR)-guided elective PCI for de novo single proximal lesions in the left anterior descending artery (LAD). We compared clinical demographics and physiological parameters between patients with and without CCTA-defined MB. MB was identified in 46 (32.6%) patients using pre-PCI CCTA. The prevalence of diabetes was higher among patients with MB. Median post-PCI FFR values were significantly lower among patients with than without MB (0.82 [interquartile range 0.79-0.85] vs. 0.85 [interquartile range 0.82-0.89]; P=0.003), whereas pre-PCI FFR values were similar between the 2 groups. Multivariable linear regression analysis revealed that the presence of MB and greater left ventricular mass volume in the LAD territory were independently associated with lower post-PCI FFR values. Multivariable logistic regression analysis also revealed that the presence of MB and lower pre-PCI FFR values were independent predictors of post-PCI FFR values ≤0.80. CONCLUSIONS: CCTA-defined MB independently predicted both lower post-PCI FFR as a continuous variable and ischemic FFR as a categorical variable in patients undergoing elective PCI for LAD.

Predictors of Optical Coherence Tomography-Defined Calcified Nodules in Patients With Acute Coronary Syndrome　- A Substudy From the TACTICS Registry.

BACKGROUND: Recent studies suggest that the presence of calcified nodules (CN) is associated with worse prognosis in patients with acute coronary syndrome (ACS). We investigated clinical predictors of optical coherence tomography (OCT)-defined CN in ACS patients in a prospective multicenter registry. METHODS AND RESULTS: We investigated 695 patients enrolled in the TACTICS registry who underwent OCT assessment of the culprit lesion during primary percutaneous coronary intervention. OCT-CN was defined as calcific nodules erupting into the lumen with disruption of the fibrous cap and an underlying calcified plate. Compared with patients without OCT-CN, patients with OCT-CN (n=28) were older (mean [±SD] age 75.0±11.3 vs. 65.7±12.7 years; P<0.001), had a higher prevalence of diabetes (50.0% vs. 29.4%; P=0.034), hemodialysis (21.4% vs. 1.6%; P<0.001), and Killip Class III/IV heart failure (21.4% vs. 5.7%; P=0.003), and a higher preprocedural SYNTAX score (median [interquartile range] score 15 [11-25] vs. 11 [7-19]; P=0.003). On multivariable analysis, age (odds ratio [OR] 1.072; P<0.001), hemodialysis (OR 16.571; P<0.001), and Killip Class III/IV (OR 4.466; P=0.004) were significantly associated with the presence of OCT-CN. In non-dialysis patients (n=678), age (OR 1.081; P<0.001), diabetes (OR 3.046; P=0.014), and Killip Class III/IV (OR 4.414; P=0.009) were significantly associated with the presence of OCT-CN. CONCLUSIONS: The TACTICS registry shows that OCT-CN is associated with lesion severity and poor clinical background, which may worsen prognosis.

Detection of episodic nocturnal hypercapnia in patients with neurodegenerative disorders.

PURPOSE: Episodic nocturnal hypercapnia (eNH) in transcutaneous carbon dioxide pressure (PtcCO2) corresponding to rapid eye movement sleep hypoventilation is a useful biomarker for detecting nocturnal hypoventilation. However, the relationship between eNH and neurodegenerative diseases with sleep-related breathing disorders (SRBDs) is unknown. The aim of this study was to evaluate the relationship between eNH and nocturnal hypoventilation in neurodegenerative diseases. METHODS: Patients with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), multiple system atrophy (MSA), Parkinson's disease, progressive supranuclear palsy, corticobasal syndrome, and idiopathic normal pressure hydrocephalus, were enrolled and received overnight PtcCO2 monitoring. The patients were divided into groups for eNH and sleep-associated hypoventilation (SH) prevalence analysis: A (ALS), B (MSA), and C (others). RESULTS: Among 110 patients, twenty-three (21%) and 10 (9%) of the patients met eNH and SH criteria, respectively. eNH and SH were significantly more frequent in groups A and B than in C. The prevalence of SH in the patients with eNH was 39% whereas most of patients with SH (90%) presented with eNH. Among patients with daytime carbon dioxide pressure in arterial blood ≤ 45 mmHg, eNH frequency was 13%, whereas none of the patients met SH criteria. The frequency of noninvasive positive pressure ventilation after PtcCO2 monitoring was significantly higher in those with than without eNH. CONCLUSIONS: eNH is common in patients with MSA and ALS who present with SRBD. eNH with overnight PtcCO2 monitoring is a useful biomarker to detect hypoventilation among neurodegenerative diseases with different SRBD mechanisms.

Detection of unrecognized myocardial infarction by preprocedural transthoracic echocardiography in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: Previous studies showed that unrecognized myocardial infarction (UMI) identified on cardiac magnetic resonance (CMR) was related to worse prognosis. We aimed to investigate the efficacy of preprocedural transthoracic echocardiography (TTE) to detect the presence of UMI in patients undergoing percutaneous coronary intervention (PCI). METHODS: A total of 138 patients with chronic coronary syndrome (CCS) and preserved left ventricular ejection fraction (LVEF) without history of myocardial infarction or revascularization were retrospectively studied. UMI was evaluated with pre-PCI late gadolinium enhancement (LGE)-CMR. TTE and two-dimensional speckle-tracking echocardiography (2D-STE) were performed before PCI. All patients were divided into two groups according to the presence or absence of UMI, and clinical and echocardiographic findings were compared between these two groups. RESULTS: UMI was detected in 43 patients (31.2%). Multivariable logistic regression analysis revealed that higher SYNTAX score, the presence of wall motion abnormalities (WMAs) and lower global longitudinal strain (GLS) were independent predictors of the presence of UMI. Furthermore, GLS provided incremental efficacy for the detection of UMI over abnormal Q waves, SYNTAX score and WMAs. CONCLUSIONS: Preprocedural TTE in combination with 2D-STE could help identify patients with UMI regardless of the presence or absence of ECG findings and WMAs.

Gastrointestinal cancer occurs as extramuscular manifestation in FSHD1 patients.

Facioscapulohumeral dystrophy type1 (FSHD1) patients with a shortened D4Z4 repeat containing the DUX4 gene have a broad spectrum of clinical manifestations. In addition, high expression of DUX4 protein with an aberrant C terminus is frequently identified in B cell acute lymphoblastic leukemia. We investigated clinical manifestations in 31 FSHD1 patients and 30 non-affected individuals. Gastrointestinal cancers (gastric and colorectal cancers) increased after the age of 40 years and were more frequently observed in FSHD1 patients (n = 10) than in non-affected individuals (n = 2, p = 0.0217), though the incidence of cancers occurring in non-gastrointestinal tissues of FSHD1 patients was the same as that of non-affected individuals (p > 0.999). These comorbidities of FSHD1 patients were not associated with D4Z4 repeat number. Our results suggest that gastrointestinal cancers are among the extramuscular manifestations of adult FSHD1 patients, and do not depend on D4Z4 repeat number.

Prognostic Implications of Fractional Flow Reserve and Coronary Flow Reserve After Drug-Eluting Stent Implantation.

BACKGROUND: Fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) provides prognostic information, but limited data are available regarding prognostication using post-PCI coronary flow reserve (CFR). In this study we aimed to assess the prognostic value of post-procedural FFR and CFR for target vessel failure (TVF) after PCI.Methods and Results: This lesion-based post-hoc pooled analysis of previously published registry data involved 466 patients with chronic coronary syndrome with single-vessel disease who underwent pre- and post-PCI FFR and CFR measurements, and were followed-up to determine the predictors of TVF. The prognostic value of post-PCI CFR and FFR was compared with that of FFR or CFR alone. Post-PCI FFR/CFR discordant results were observed in 42.5%, and 10.3% of patients had documented TVF. Receiver-operating characteristic curve analysis revealed that the optimal cutoff values of post-PCI FFR and CFR to predict the occurrence of TVF were 0.85 and 2.26, respectively. Significant differences in TVF were detected according to post-PCI FFR (≤0.85 vs. >0.85, P=0.007) and post-PCI CFR (<2.26 vs. ≥2.26, P<0.001). Post-PCI FFR ≤0.85 and post-PCI CFR <2.26 were independent prognostic predictors. CONCLUSIONS: After PCI completion, discordant results between FFR and CFR were not uncommon. Post-PCI CFR categorization showed incremental prognostic value for predicting TVF independent of post-PCI FFR risk stratification.

Paradoxical effects of levetiracetam in people with epilepsy with rhythmic epileptiform discharges.

OBJECTIVE: To elucidate the incidence and risk factors for paradoxical effects (i.e., increased seizure frequency, increased seizure severity, or onset of new seizure types) of levetiracetam (LEV) in people with epilepsy (PWE) and identify the usefulness of electroencephalography (EEG) in predicting these effects. METHODS: We examined data for consecutive PWE treated with LEV. All PWE underwent EEG and magnetic resonance imaging (MRI) before LEV administration. We also evaluated the incidence of paradoxical LEV effects and conducted multivariate logistic regression analyses to identify the associated factors. RESULTS: In total, 210 (66.2%) of 317 PWEs treated in our department had a history of LEV use. The incidence of paradoxical LEV effects was 5.2% (n = 11) and was significantly associated with a high LEV dose (p = 0.029), high seizure frequency (p = 0.005), temporal lobe epilepsy (p = 0.004), focal awareness seizure (p = 0.004), focal impaired awareness seizure (p = 0.007), spike (p = 0.015), rhythmic epileptiform discharges (REDs; p = 0.003), and MRI-identified focal cortical dysplasia (FCD; p < 0.0001). Multivariate analyses revealed that REDs (odds ratio [OR] = 5.35, p = 0.048, 95% confidence interval [CI]: 1.01-28.21) were independently associated with paradoxical LEV effects. CONCLUSIONS: Paradoxical LEV effects occurred in PWE, particularly in those with drug-resistant focal epilepsy. Furthermore, the occurrence of REDs in EEG was an independent factor associated with the paradoxical effects of LEV in PWE.

Comparative Outcomes of Anterior and Posterior Plating for Distal-Third Humerus Shaft Fractures.

PURPOSE: When treating distal-third humerus shaft fractures (HSFs) surgically, the optimal approach for plating is controversial. We conducted a retrospective multicenter study to investigate and compare the clinical outcomes of anterior and posterior plating in distal-third HSFs and the incidence of complications including iatrogenic radial nerve palsy. METHODS: We identified 116 patients from our multicenter trauma database who were diagnosed as having distal-third HSFs and who underwent surgical treatment, including intramedullary nailing between 2011 and 2020. We analyzed 50 cases treated in one of two ways: open reduction internal fixation with anterior plating (group A: 20 cases) and open reduction internal fixation with posterior plating (group P: 30 cases). RESULTS: The findings were similar in terms of operation time, estimated bleeding, and clinical and radiographic outcomes between the groups. Postoperative radial nerve palsy occurred only in group P (4 cases) and never in group A. CONCLUSIONS: The results of this study suggest that the anterior approach is a safe and effective method for treating distal-third HSFs with satisfactory outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Effect of percutaneous coronary intervention on global hemodynamics and the prevalence of residual microvascular dysfunction.

OBJECTIVES: We aimed to examine the changes in hyperemic coronary sinus flow (CSF) and global coronary flow reserve (g-CFR) after percutaneous coronary intervention (PCI) and investigate the predictors to improve these metrics and the prevalence of residual coronary microvascular dysfunction (CMD). METHODS: This prospective, single-center study included 118 patients with stable coronary artery disease undergoing PCI for a single proximal lesion. Phase-contrast cine-cardiac magnetic resonance (PC-CMR) was used to assess hyperemic CSF (HCSF) and g-CFR, before and after PCI. Residual CMD was defined as concordantly impaired post-PCI HCSF (<2.3 ml/min/g) and g-CFR (<2.0). RESULTS: HCSF significantly increased, although 38 (32.2%) patients showed a decrease. There was no significant change in g-CFR despite fractional flow reserve (FFR) improvement in all target territories. Concordantly increased HCSF and g-CFR were effectively discriminated by adding PC-CMR-derived information to pre-PCI FFR. Residual CMD was observed in 30 (25.4%) patients and was associated with pre-PCI renal dysfunction and lower pre-PCI rest and hyperemic CSF, but not with pre-PCI regional physiological indices. CONCLUSIONS: FFR-guided PCI was associated with increased HCSF, but not with increased g-CFR. After uncomplicated PCI, one-quarter of patients showed residual CMD. Our approach may help identify patients who may benefit from increased coronary perfusion or show residual CMD.

Genomic characterization of a rare Carica papaya X chromosome mutant reveals a candidate monodehydroascorbate reductase 4 gene involved in all-hermaphrodite phenomenon.

Sex form is one of the most important characteristics in papaya cultivation in which hermaphrodite is the preferable form. Self-pollination of H*-TSS No.7, an inbred line derived from a rare X chromosome mutant SR*, produced all-hermaphrodite progeny. The recessive lethal allele controlling the all-hermaphrodite phenomenon was proposed to be the recessive Germination suppressor (gs) locus. This study employed next-generation sequencing technology and genome comparison to identify the candidate Gs gene. One specific gene, monodehydroascorbate reductase 4 (MDAR4) harboring a unique polymorphic 3 bp deletion in H*-TSS No.7 was identified. The function of MDAR4 is known to be involved in the hydrogen peroxide (H2O2) scavenging pathway and is associated with seed germination. Furthermore, MDAR4 showed higher expression in the imbibed seeds than that in the dry seeds indicating its potential role in the seed germination. Perhaps this is the very first report providing the evidences that MDAR4 is the candidate of Gs locus in H*-TSS No.7. In addition, Gs allele-specific markers were developed which would be facilitated for breeding all-hermaphrodite lines.

Characteristic findings of microvascular dysfunction on coronary computed tomography angiography in patients with intermediate coronary stenosis.

OBJECTIVES: We aimed to assess the prevalence of coexistence of coronary microvascular dysfunction (CMD) in patients with intermediate epicardial stenosis and to explore coronary computed tomography angiography (CCTA)-derived lesion-, vessel-, and cardiac fat-related characteristic findings associated with CMD. METHODS: A retrospective cross-sectional single-center study included a total of 177 patients with intermediate stenosis in the left anterior descending artery (LAD) who underwent CCTA and invasive physiological measurements. The 320-slice CCTA analysis included qualitative and quantitative assessments of plaque, vessel, epicardial fat volume (ECFV) and epicardial fat attenuation (ECFA), and pericoronary fat attenuation (FAI). CMD was defined by the index of microcirculatory resistance (IMR) ≥ 25. RESULTS: In the entire cohort, median fractional flow reserve (FFR) and median IMR values were 0.77 (0.69-0.84) and 19.0 (13.7-27.7), respectively. The prevalence of CMD was 32.8 % (58/177) in the total cohort. The coexistence of CMD and functionally significant stenosis was 34.3 % (37/108), whereas CMD in nonsignificant intermediate stenosis was 30.4 % (21/69). CMD was significantly associated with greater lumen volume (p = 0.031), greater fibrofatty and necrotic component (FFNC) volume (p = 0.030), and greater ECFV (p = 0.030), but not with FAI (p = 0.832) and ECFA (p = 0.445). On multivariable logistic regression analysis, vessel volume, vessel lumen volume, lesion remodeling index, ECFV, and lesion FFNC volume were independent predictors of CMD. CONCLUSIONS: The prevalence of CMD was about one-third in patients with intermediate stenosis in LAD regardless of the presence or absence of functional stenosis significance. The integrated CCTA assessment may help in the identification of CMD. KEY POINTS: • The coexistence of coronary microvascular dysfunction (CMD) and functionally significant stenosis was 34.3 %, whereas CMD in nonsignificant intermediate stenosis was 30.4 %. • Coronary computed tomography angiography (CCTA)-derived CMD characteristics were vessel volume, vessel lumen volume, remodeling index, epicardial fat volume, and fibrofatty necrotic core volume. • Integrated CCTA assessment may help identify the coexistence of CMD and epicardial stenosis.

cnm-Positive Streptococcus mutans and diffusion-weighted imaging hyperintensities in acute intracerebral hemorrhage.

BACKGROUND: Strains of Streptococcus mutans expressing the cell surface collagen-binding protein, Cnm, encoded by cnm (cnm-positive S. mutans), are associated with hypertensive intracerebral hemorrhage (ICH) and the occurrence of cerebral microbleeds (CMBs). Small diffusion-weighted imaging (DWI) hyperintensities in patients with acute ICH are also associated with CMBs. However, the association between cnm-positive S. mutans and DWI hyperintensities is unclear. Hence, this study aimed to investigate the association between cnm-positive S. mutans and DWI hyperintensities in patients with acute ICH. METHODS: Patients with acute ICH were prospectively registered at three hospitals. Dental plaque specimens were collected within 4 days after admission, and cnm-positive S. mutans was detected using the polymerase chain reaction. Magnetic resonance imaging at 14 ± 5 days after admission was used to evaluate DWI hyperintensities and CMBs. RESULTS: A total of 197 patients were enrolled in this study. cnm-positive S. mutans was detected in 30 patients (15.2%), and DWI hyperintensities were observed in 56 patients (28.4%). Patients with cnm-positive S. mutans had a higher frequency of DWI hyperintensities (50.0% vs 24.6%; p = 0.008) and a higher number of CMBs (5.5 vs 1.5; p < 0.001) than those without cnm-positive S. mutans. Multivariable logistic analysis revealed that the presence of cnm-positive S. mutans was independently associated with DWI hyperintensities (OR 2.38; 95% CI 1.01-5.61; p = 0.047) after adjusting for several confounding factors. CONCLUSION: This study found an association between the presence of cnm-positive S. mutans and DWI hyperintensities in patients with acute ICH.

Clinical Significance of Increased Computed Tomography Attenuation of Periaortic Adipose Tissue in Patients With Abdominal Aortic Aneurysms.

BACKGROUND: Recent imaging studies reported an association between vascular inflammation and progression of abdominal aortic aneurysm (AAA). This study investigated the clinical significance of periaortic adipose tissue inflammation derived from multidetector computed tomography angiography (MDCTA).Methods and Results:Patients with asymptomatic AAA (n=77) who underwent an index and >6 months follow-up MDCTA examinations were retrospectively investigated. MDCTA analysis included AAA diameter and the periaortic adipose tissue attenuation index (PAAI). The PAAI was defined as the mean CT attenuation value within a predefined range from -190 to -30 Hounsfield units of adipose tissue surrounding the AAA. The growth rate of the AAA was calculated as the change in diameter. AAA progression (AP) was defined as an AAA growth rate ≥5 mm/year. Univariate and multivariate logistic regression analysis were performed to determine the predictors of AP. AP was observed in 19 patients (24.7%), the median baseline AAA diameter was 38.9 mm (interquartile range [IQR] 32.7-42.9 mm), and the median growth rate was 3.1 mm/year (IQR 1.5-4.9 mm/year). Baseline AAA diameter (odds ratio [OR] 1.16; 95% confidence interval [CI] 1.05-1.28; P=0.001) and PAAI (OR 1.12; 95% CI 1.05-1.20; P=0.004) were independent predictors of AP. CONCLUSIONS: PAAI was an independent and significant predictor of AP, supporting the notion that local adipose tissue inflammation may contribute to aortic remodeling.

Impact of pericoronary adipose tissue inflammation on left ventricular hypertrophy and regional physiological indices in stable coronary artery disease patients with preserved systolic function.

Systemic low-grade inflammation has been shown to be associated with left ventricular hypertrophy (LVH). However, the relationship between pericoronary adipose tissue attenuation (PCATA) and both LVH and regional physiological indices remains unknown. This study aimed to evaluate the association of PCATA with LVH and regional physiological indices in stable coronary artery disease (CAD) patients with preserved systolic function. A total of 114 CAD patients who underwent coronary CT angiography (CTA) and invasive physiological tests showing ischemia due to a single de novo lesion were included in the study. On proximal 40-mm segments of all three major coronary vessels on CTA, PCATA was assessed by the crude analysis of the mean CT attenuation value [- 190 to - 30 Hounsfield units [HU)] and the culprit vessel PCATA was used for the analysis. Regional physiological indices were invasively obtained by pressure-temperature sensor-tipped wire. The patients were divided into three groups by culprit vessel PCATA tertiles, and clinical, CTA-derived, and physiological indices were compared. Univariable and multivariable analyses were further performed to determine the predictors of LVH. Angiographic stenosis severity, culprit lesion locations, culprit vessel fractional flow reserve, coronary flow reserve, index of microcirculatory resistance, total and target vessel coronary calcium score, and biomarkers including high-sensitivity C-reactive protein were not different among the groups. The left ventricular (LV) mass, LV mass index (LVMI), and LV mass at risk were all significantly different in the three groups with the greatest values in the highest tertile group (all, P < 0.05). On multivariable analysis, male gender, NT-proBNP, and PCATA were independent predictors of LVMI. Culprit vessel PCATA was significantly associated with LVMI, but not with regional physiology in CAD patients with functionally significant lesions and preserved systolic function. Our results may offer insight into the pathophysiological mechanisms linking pericoronary inflammation and LVH to worse prognosis.

Utility of Magnetic Resonance Spectroscopy for the Progression of Neurological Symptoms in Lenticulostriate Artery Territory Infarction.

OBJECTIVES: The present study aimed to examine the effectiveness of proton magnetic resonance spectroscopy (1HMRS) in determining the progression of neurological symptoms resulting in acute ischemic stroke in patients with lenticulostriate artery (LSA) infarction. MATERIALS AND METHODS: 1HMRS was performed within 72 h after neurological symptom onset. Voxel of interest was placed in tissue that included the pyramidal tract and identified diffusion weighted echo planar spin-echo sequence (DWI) coronal images. Infarct volume in DWI was calculated using the ABC/2 method. 1HMRS data (tNAA, tCr, Glx, tCho, and Ins) were analyzed using LCModel. Progressive neurological symptoms were defined as an increase of 1 or more in the NIHSS score. Patients who underwent 1HMRS after progressive neurological symptoms were excluded. RESULTS: In total, 77 patients were enrolled. Of these, 19 patients had progressive neurological symptoms. The patients with progressive neurological symptoms were significantly more likely to be female and had higher tCho/tCr values, higher rates of axial slices ≥ 3 slices on DWI, higher infarct volume on DWI, higher maximum diameter of infarction of axial slice on DWI, and higher SBP on admission compared to those without. Multivariable logistic analysis revealed that higher tCho/tCr values were independently associated with progressive neurological symptoms after adjusting for age, sex, and initial DWI infarct volume (tCho/tCr per 0.01 increase, OR 1.26, 95% CI 1.03-1.52, P = 0.022). CONCLUSIONS: Increased tCho/tCr score were associated with progressive neurological symptoms in patients with LSA ischemic stroke. Quantitative evaluation of 1HMRS parameters may be useful for predicting the progression of neurological symptoms.

Pomalidomide-associated progressive multifocal leukoencephalopathy in multiple myeloma: cortical susceptibility-weighted imaging hypointense findings prior to clinical deterioration.

Although there are several case reports of progressive multifocal leukoencephalopathy (PML) in multiple myeloma (MM), there are few reports of cases associated with pomalidomide. Here, we report the case of a 69-year-old female who had received 41 cycles of pomalidomide and dexamethasone treatment for relapsed/refractory IgG-κ MM presented with right-hand weakness; she was diagnosed as pomalidomide-associated PML. Fluid-attenuated inversion recovery (FLAIR) on admission showed high signals in the bilateral front-parietal lobe white matter, with multiple punctate lesions in the vicinity of the main lesions. These punctate pattern findings on FLAIR were similar to that of natalizumab-associated PML. Susceptibility weighted imaging (SWI) showed hypointense rims within the cortex at unaffected sites, in the initial stages. Subsequently, the clinical manifestations deteriorated, and the FLAIR images showed new hyperintense white matter lesions at the sites where cortical SWI hypointense rims were detected on the initial MRI examination. Our patient's serial MRI findings suggest that cortical SWI hypointense rims appear prior to the visible demyelinating white matter lesions in patients with PML.

Blockade of costimulatory CD27/CD70 pathway promotes corneal allograft survival.

PURPOSE: To determine whether the CD27/CD70 pathway plays a significant role in corneal allograft rejection by investigating the effect of blocking the CD27/CD70 pathway by anti-CD70 antibody on corneal allograft survival. METHODS: Orthotopic penetrating keratoplasty was performed using C57BL/6 donor grafts and BALB/c recipients. Expression of CD27 and CD70 on rejected cornea was examined by immunohistochemistry. Corneal transplant recipients received intraperitoneal injection of anti-CD70 antibody (FR70) or control rat IgG. Alloreactivity was measured by mixed lymphoid reaction (MLR) in recipients administered control rat IgG and those administered anti-CD70 antibody. Corneal expression of IFN-γ and IL-12 was also examined in both groups. Graft opacity was assessed over an 8-week period and graft survival was evaluated using Kaplan-Meier survival curves. Proportion of CD4+CD44+ memory T cells in lymph nodes was measured by flow cytometry. RESULTS: CD4+CD27+ cells and CD11c+CD70+ cells were present in rejected cornea. Anti-CD70 antibody administration suppressed alloreactivity in corneal allograft recipients, and inhibited IFN-γ expression in recipient cornea (p < 0.05). Anti-CD70 antibody suppressed opacity score of recipient cornea and prolonged corneal allograft survival (p < 0.05). Proportion of CD4+CD44+ memory T cells in recipient lymph nodes was reduced by anti-CD70 antibody treatment. CONCLUSION: The CD27/CD70 pathway plays a significant role in corneal allograft rejection by initiating alloreactive Th1 cells and preserving memory T cells. Anti-CD70 antibody administration prolongs corneal allograft survival indicating the potential therapeutic effect of CD27/CD70 pathway blockade on corneal allograft rejection.

The Insular Cortex, Alzheimer Disease Pathology, and Their Effects on Blood Pressure Variability.

Recent findings indicate that the human cardiovascular system is regulated by a cortical network comprised of the insular cortex (Ic), anterior cingulate gyrus, and amygdala which is necessary for the regulation of the central autonomic network system. Alzheimer disease (AD) affects the Ic at a preclinical stage. The pathology of AD at the Ic is suggested to predispose the cardiovascular system to detrimental changes such as increased blood pressure variability (BPV). In this review article, we focus on the physiology of the Ic in the relationship between the central autonomic network and BPV. We provide a summary of the published evidence regarding the relationship between Ic damage and exaggerated BPV in the context of AD pathology.