Correlation between Serum 25-Hydroxyvitamin D Level and Peripheral Arterial Stiffness in Chronic Kidney Disease Stage 3–5 Patients

Vitamin D deficiency and high brachial-ankle pulse wave velocity (baPWV) are each independently associated with higher incidence of mortality and cardiovascular (CV) disease or CV events, respectively. This study aimed to evaluate the relationship between serum 25-hydroxyvitamin D levels and baPWV in non-dialysis patients with stage 3–5 chronic kidney disease (CKD). We enrolled 180 CKD patients. A commercial enzyme-linked immunosorbent assay was used to measure 25-hydroxyvitamin D levels. BaPWV values were measured using an automatic pulse wave analyzer. Either left or right baPWV > 18.0 m/s was considered indicative of peripheral arterial stiffness (PAS). In this study, 73 (40.6%) patients were found to have PAS. Compared to those without PAS (control group), patients with PAS were older and had higher incidence of diabetes mellitus, higher systolic and diastolic blood pressure, higher levels of intact parathyroid hormone, and C-reactive protein, and lower levels of 25-hydroxyvitamin D. Multivariate logistic regression analysis found 25-hydroxyvitamin D levels (odds ratio [OR]: 0.895, 95% confidence interval [CI] 0.828–0.968, p = 0.005) and old age (OR: 1.140, 95% CI 1.088–1.194, p < 0.001) to be independently associated with PAS in patients with stage 3–5 CKD. Lower serum 25-hydroxyvitamin D levels and older age were associated with PAS in these patients.     

SARS CoV-2 (Delta Variant) Infection Kinetics and Immunopathogenesis in Domestic Cats

Continued emergence of SARS-CoV-2 variants highlights the critical need for adaptable and translational animal models for acute COVID-19. Limitations to current animal models for SARS CoV-2 (e.g., transgenic mice, non-human primates, ferrets) include subclinical to mild lower respiratory disease, divergence from clinical COVID-19 disease course, and/or the need for host genetic modifications to permit infection. We therefore established a feline model to study COVID-19 disease progression and utilized this model to evaluate infection kinetics and immunopathology of the rapidly circulating Delta variant (B.1.617.2) of SARS-CoV-2. In this study, specific-pathogen-free domestic cats (n = 24) were inoculated intranasally and/or intratracheally with SARS CoV-2 (B.1.617.2). Infected cats developed severe clinical respiratory disease and pulmonary lesions at 4- and 12-days post-infection (dpi), even at 1/10 the dose of previously studied wild-type SARS-CoV-2. Infectious virus was isolated from nasal secretions of delta-variant infected cats in high amounts at multiple timepoints, and viral antigen was co-localized in ACE2-expressing cells of the lungs (pneumocytes, vascular endothelium, peribronchial glandular epithelium) and strongly associated with severe pulmonary inflammation and vasculitis that were more pronounced than in wild-type SARS-CoV-2 infection. RNA sequencing of infected feline lung tissues identified upregulation of multiple gene pathways associated with cytokine receptor interactions, chemokine signaling, and viral protein–cytokine interactions during acute infection with SARS-CoV-2. Weighted correlation network analysis (WGCNA) of differentially expressed genes identified several distinct clusters of dysregulated hub genes that are significantly correlated with both clinical signs and lesions during acute infection. Collectively, the results of these studies help to delineate the role of domestic cats in disease transmission and response to variant emergence, establish a flexible translational model to develop strategies to prevent the spread of SARS-CoV-2, and identify potential targets for downstream therapeutic development.     

Initial Abdominal CT and Laboratory Findings Prior to Diagnosis of Crohn’s Disease in Children

PurposeTo identify initial abdominal computed tomography (CT) and laboratory findings prior to a diagnosis of Crohn’s disease (CD) in children.Materials and MethodsIn this retrospective study, patients (≤18 year-old) who were diagnosed with CD from 2004 to 2019 and had abdominal CT just prior to being diagnosed with CD were included in the CD group. Patients (≤18 years old) who were diagnosed with infectious enterocolitis from 2018 to 2019 and had undergone CT prior to being diagnosed with enterocolitis were included as a control group. We assessed the diagnostic performances of initial CT and laboratory findings for the diagnosis of CD using logistic regression and the area under the curve (AUC).ResultsIn total, 107 patients (50 CD patients, 57 control patients) were included, without an age difference between groups (median 13 years old vs. 11 years old, p=0.119). On univariate logistic regression analysis, multisegmental bowel involvement, mesenteric vessel engorgement, higher portal vein/aorta diameter ratio, longer liver longitudinal diameter, lower hemoglobin (≤12.5 g/dL), lower albumin (≤4 g/dL), and higher platelet (>320×10³/µL) levels were significant factors for CD. On multivariate analysis, multisegmental bowel involvement [odds ratio (OR) 111.6, 95% confidence interval (CI) 4.778–2605.925] and lower albumin levels (OR 0.9, 95% CI 0.891–0.993) were significant factors. When these two features were combined, the AUC value was 0.985 with a sensitivity of 96% and specificity of 100% for differentiating CD.ConclusionMultisegmental bowel involvement on CT and decreased albumin levels can help differentiate CD from infectious enterocolitis in children prior to a definite diagnosis of CD.     

Short-Term Outcomes of the First in Vivo Gene Therapy for RPE65-Mediated Retinitis Pigmentosa

Here, we report early treatment outcomes of gene therapy for early onset retinitis pigmentosa (RP) (Leber congenital amaurosis) associated with biallelic RPE65 mutation in a 30-year-old female patient. Initially, her visual acuity (VA) was 20/200, and her visual field (VF) was severely constricted to the center in the left eye. Her electroretinography showed nearly extinct signals. Full-field stimulus threshold test (FST) revealed diminished dark-adapted light sensitivity. Voretigene neparvovec-rzyl (VN) is the first in vivo viral gene therapy agent to be approved. At 3 months after subretinal injection of VN in the left eye, VA, VF, and FST showed sustained improvement. She did not exhibit any signs of adverse effects from the treatment. Gene therapy for RP proved to be an effective and safe treatment in an advanced case of RPE65-associatied early onset RP.     

Apathy and impulsiveness in Parkinson disease: Two faces of the same coin?

Apathy and impulsiveness are 2 common non-motor symptoms in Parkinson disease that could occur in different periods or simultaneously. Apathy and impulsiveness could be interpreted as opposite extremes of a spectrum of motivated behavior dependent on dopaminergic dysfunction, in which, impulsivity, is a result of a hyperdopaminergic state, whereas apathy is viewed as a hypodopaminergic. The study aimed to investigate the presence of impulsiveness and other neuropsychiatric symptoms in Parkinson disease patients with apathy symptoms.Eighty-one patients with Parkinson disease were enrolled in this retrospective study. All subjects were evaluated by the Italian version of the Dimensional Apathy Scale and the Barratt Impulsiveness Scale-version 11, to assess, respectively, apathy and impulsiveness; they were divided into 2 groups (apathy and no apathy). All patients were administered also with questionnaires assessing depressive and anxious symptoms.Statistical analyses showed relevant results. In no-apathy group, education was a significant predictor on impulsiveness (attentional and motor) and apathy (executive and emotional); depression was a significant predictor on planning impulsivity and apathy.This study aimed to consider the importance of apathy and impulsivity in Parkinson disease. Although these are considered as opposite extremes of a spectrum of motivated behavior dependent on dopaminergic dysfunction, these can also occur separately. Moreover, several variables could represent important predictors of apathy and impulsiveness, such as depression. Future investigations should deepen the role of other demographics and psychological variables.     

Acute rheumatic fever in adult patients

Acute rheumatic fever (ARF) is considered as a disorder of children, and attacks in adults are usually a recurrence of disease acquired in the child’s life. Although the incidence of ARF in children has a decreasing trend in developed countries, resurgent and sporadic epidemics still occur in adults. The first attacks of ARF in adult patients without a childhood history can lead to a diagnostic dilemma.A medical record review in adults at least 18 years of age with an arthralgia complaint fulfilling 2015 revised Jones criteria was performed from January 1, 2000 to December 31, 2019.Eleven ARF patients were identified, including 8 with initial attacks (6 females aged 26–42 years, 33.9 ± 5.3) and 3 pre-existing valvular heart disease with recurrent attacks (2 females aged 38–52 years, 45.0 ± 7.0). In addition to febrile pharyngitis and migratory polyarthritis in initial attacks, pericarditis was encountered in 1, valvulitis in 2, prolong PR interval in 3 and skin involvement in 2 patients with erythema marginatum and IgA vasculitis. All responded to antibiotics and nonsteroidal anti-inflammatory drugs therapy with normalized clinical and laboratory abnormalities, no new-onset carditis, and no recurrent disease during a long-term follow-up (3.8–19.8 years, 12.7 ± 5.4).A sporadic occurrence of adult ARF is observed in southern Taiwan. This disease should be considered by physicians for the differential diagnosis of febrile pharyngitis with arthritis and/or carditis in adults, even in areas with a low incidence of ARF.     

Multisystem Inflammatory Syndrome after Breakthrough SARS-CoV-2 Infection in 2 Immunized Adolescents,United States

Eight weeks after having laboratory-confirmed SARS-CoV-2 breakthrough infections, 2 otherwise healthy, fully immunized adolescent patients in the United States who were experiencing related signs and symptoms were diagnosed with multisystem inflammatory syndrome in children. Our findings indicate that COVID-19 vaccination does not completely protect adolescents against multisystem inflammatory syndrome.     

Chronic Pulmonary Disease Caused by Tsukamurella toyonakaense

Unidentified Mycobacterium species are sometimes detected in respiratory specimens. We identified a novel Tsukamurella species (Tsukamurella sp. TY48, RIMD 2001001, CIP 111916^T), Tsukamurella toyonakaense, from a patient given a misdiagnosis of nontuberculous mycobacterial pulmonary disease caused by unidentified mycobacteria. Genomic identification of this Tsukamurella species helped clarify its clinical characteristics and epidemiology.     

University-Associated SARS-CoV-2 Omicron BA.2 Infections,Maricopa County,Arizona, USA, 2022

We investigated a university-affiliated cohort of SARS-CoV-2 Omicron BA.2 infections in Arizona, USA. Of 44 cases, 43 were among students; 26 persons were symptomatic, 8 sought medical care, but none were hospitalized. Most (55%) persons had completed a primary vaccine series; 8 received booster vaccines. BA.2 infection was mild in this young cohort.