Diminution of experimental autoimmune uveoretinitis (EAU) in mice depleted of NK cells

To evaluate the potential role of NK1.1 (CD161c) cells in autoimmune uveoretinitis, we treated experimental autoimmune uveoretinitis (EAU)-susceptible mice with anti-CD161c antibodies (PK136) to deplete natural killer (NK) cells. Injection of anti-CD161c antibodies deleted NK cells from the peripheral blood of EAU-susceptible mice. The T cell proliferative response against the ocular autoantigen K2 was not suppressed in mice treated with anti-CD161c antibody when compared with T cells from control mice. Although mice treated with anti-CD161c developed EAU, the clinical severity on days 17 and 19 after induction of EAU was significantly mild in anti-CD161c-treated mice compared with control mice. In addition, the histopathological severity of EAU was significantly milder in mice treated with anti-CD161c antibodies than controls 21 days after induction of EAU. Our results indicate that the severity of EAU is augmented by NK1.1(+) NK cells.     

Magnetic Resonance Imaging Assessment of Abductor Muscles Shortly After Curved Periacetabular Osteotomy

BackgroundCurved periacetabular osteotomy (CPO) is performed via an anterior approach without detachment of the hip abductor muscles. This study aimed to evaluate the abductor muscle status shortly after CPO on magnetic resonance imaging (MRI).MethodsWe prospectively evaluated 38 hips in 38 patients 1 week and 3 months after CPO between October 2017 and July 2019. The status of the abductor muscles was assessed on MRI using the following criteria: grade 0, normal; grade I, strain/edema; grade II, partial tear; and grade III, complete tear. We also evaluated associations between muscle status and patients’ characteristics.ResultsOne week after CPO, the gluteus maximus was classified as grade 0 in all patients. The gluteus medius was grade 0 in 84.2% of patients and grade I in 15.8%. The gluteus minimus was grade I in 55.3% of patients and grade II in 44.7%. Three months after CPO, both the gluteus maximus and gluteus medius were grade 0 in all patients, while the gluteus minimus was still grade I in 47.4%. There were no significant differences between patients with a grade 0 and grade I gluteus minimus at 3 months after CPO in patients’ characteristics (age and body mass index) or clinical scores (Harris Hip Score and Japanese Orthopedics Association score).ConclusionBoth the gluteus minimus and medius showed abnormal appearances on MRI 1 week after CPO, whereas only the gluteus minimus showed abnormalities 3 months after CPO. This abductor muscle status did not affect the postoperative Harris Hip Score or Japanese Orthopedics Association score.     

Change in Nutritional Status during Hospitalization and Prognosis in Patients with Heart Failure with Preserved Ejection Fraction

The impact of changes in nutritional status during hospitalization on prognosis in patients with heart failure with preserved ejection fraction (HFpEF) remains unknown. We examined the association between changes in the Geriatric Nutritional Risk Index (GNRI) and prognosis during hospitalization in patients with HFpEF stratified by nutritional status on admission. Nutritional status did and did not worsen in 348 and 349 of 697 patients with high GNRI on admission, and in 142 and 143 of 285 patients with low GNRI on admission, respectively. Kaplan–Meier analysis revealed no difference in risk of the composite endpoint, all-cause death, or heart failure admission between patients with high GNRI on admission whose nutritional status did and did not worsen. In contrast, patients with low GNRI on admission whose nutritional status did not worsen had a significantly lower risk of the composite endpoint and all-cause death than those who did. Multivariable analysis revealed that worsening nutritional status was independently associated with a higher risk of the composite endpoint and all-cause mortality in patients with low GNRI on admission. Changes in nutritional status during hospitalization were thus associated with prognosis in patients with malnutrition on admission, but not in patients without malnutrition among those with HFpEF.     

Effectiveness of Screening Using Fecal Occult Blood Testing and Colonoscopy on the Risk of Colorectal Cancer: The Japan Public Health Center-based Prospective Study

BackgroundFew cohort studies have used multiple surveys of screening attendance to simultaneously evaluate the effectiveness of fecal occult blood test (FOBT) and colonoscopy.MethodsWe analyzed data of 30,381 middle-aged Japanese adults from a population-based prospective cohort study. Information on FOBT and colonoscopy was obtained from three questionnaire surveys (every 5 years). We classified the subjects into three groups: the FOBT (15,649 subjects), screening colonoscopy (2,407 subjects), and unscreened (12,325 subjects) groups. We used the unscreened group as the reference group to compare the mortality and incidence of colorectal cancer (CRC).ResultsDuring the 14-year follow-up, 64, 12, and 104 CRC deaths were identified in the FOBT, screening colonoscopy, and unscreened groups, respectively. The risk of CRC death reduced with increasing the number of FOBTs (P for trend = 0.02) and was reduced by 44% in the subjects screened twice or thrice using FOBT (hazard ratio [HR] 0.56; 95% confidence interval [CI], 0.33–0.94). Significant decreases were seen for the incidence of CRC but not seen for the incidence of non-advanced CRC in the FOBT group. Concerning the screening colonoscopy, subjects screened at the start of follow-up showed a 69% reduced risk of CRC death (HR 0.31; 95% CI, 0.10–0.9996). Significant decreases were also seen for the incidence of CRC and non-advanced CRC in the subjects screened at the start of follow-up.ConclusionFOBT, depending on the number of FOBTs, and colonoscopy, depending on recency, reduced the risk of death due to CRC and the incidence of CRC.Key words: colorectal cancer, colorectal cancer screening, fecal occult blood test, colonoscopy, prospective cohort study     

Comprehensive Tool to Assess Oral Feeding Support for Functional Recovery in Post-acute Rehabilitation

Objective

To determine the influence of the Kuchi-kara Taberu (KT) index on rehabilitation outcomes during hospitalized convalescent rehabilitation.

cAbl tyrosine kinase mediates reactive oxygen species- and caveolin-dependent AT1 receptor signaling in vascular smooth muscle: role in vascular hypertrophy

Important output signals of the angiotensin subtype 1 receptor (AT1R) in vascular smooth muscle cells (VSMCs) are mediated by angiotensin II (Ang II)-stimulated transactivation of the epidermal growth factor receptor (EGF-R), which is critical for vascular hypertrophy. Ang II-induced EGF-R transactivation is mediated through cSrc, a proximal target of reactive oxygen species (ROS) derived from NAD(P)H oxidase (NOX) and is dependent on AT(1)R trafficking through caveolin1 (Cav1)-enriched lipid rafts. Underlying molecular mechanisms are incompletely understood. The nonreceptor tyrosine kinase, proto-oncogene cAbl is a substrate of Src and is a major mediator for ROS-dependent tyrosine phosphorylation of Cav1. We thus hypothesized that cAbl is important for ROS-, cSrc-, and Cav1-dependent growth-related AT1R signal transduction. Here we show that Ang II induces tyrosine phosphorylation of cAbl in rat VSMCs and mouse aorta, and that Ang II promotes association of cAbl with AT(1)R, both of which are Src-dependent. Pretreatment of rat VSMCs with the NOX inhibitor diphenylene iodonium or the antioxidants N-acetylcysteine or ebselen significantly inhibited Ang II-induced cAbl phosphorylation. Cell fractionation shows that both EGF-Rs and cAbl are found basally in Cav1-enriched membrane fractions. Knockdown of cAbl protein using small interference RNA inhibits Ang II-stimulated: (1) trafficking of AT1R into, and EGF-R out of, Cav1-enriched lipid rafts; (2) EGF-R transactivation; (3) appearance of the transactivated EGF-R and phospho-Cav1 at focal adhesions; and (4) vascular hypertrophy. These studies provide a novel role of cAbl in the spatial and temporal organization of growth-related AT1R signaling in VSMCs and suggest that cAbl may be generally important in signaling of G-protein coupled receptors.     

Efficacy of thromboelastography in the management of anticoagulation for veno-venous extracorporeal membrane oxygenation in a coronavirus disease 2019 patient: A case report

Rationale:In coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome refractory to optimal conventional management, we should consider the indication for veno-venous extracorporeal membrane oxygenation (V-V ECMO). Growing evidence indicates that COVID-19 frequently causes coagulopathy, presenting as hypercoagulation and incidental thrombosis. For these reasons, a multifactorial approach with several anticoagulant markers should be considered in the management of anticoagulation using heparin in COVID-19 patients on V-V ECMO.Patient concerns:A 48-year-old man was infected with COVID-19 with a worsening condition manifesting as acute respiratory distress syndrome.Diagnoses:He was refractory to conventional therapy, thus we decided to introduce V-V ECMO. We used heparin as an anticoagulant therapy for V-V ECMO and adjusted the doses of heparin by careful monitoring of the activated clotting time (ACT) and activated partial thromboplastin time (APTT) to avoid both hemorrhagic and thrombotic complications. We controlled the doses of heparin in the therapeutic ranges of ACT and APTT, but clinical hemorrhaging and profound elevation of coagulant marker became apparent.Interventions:Using thromboelastography (TEG; Haemonetics) in addition to ACT and APTT, we were able to clearly detect not only sufficient coagulability of COVID19 on V-V ECMO (citrated rapid thromboelastography-R 0.5 min, angle 75.5°, MA 64.0 mm, citrated functional fibrinogen-MA 20.7 mm) but also an excessive effect of heparin (citrated kaolin -R 42.7 min, citrated kaolin with heparinase 11.7 min).Outcomes:Given the TEG findings indicating an excessive heparin effect, the early withdrawal of ECMO was considered. After an evaluation of the patient''s respiratory capacity, withdrawal from V-V ECMO was achieved and then anticoagulation was stopped. The hemorrhagic complications and elevated thrombotic marker levels dramatically decreased.Lessons:TEG monitoring might be a useful option for managing anticoagulation in COVID-19 patients on V-V ECMO frequently showing a hypercoagulative state and requiring massive doses of heparin, to reduce both hemorrhagic and thrombotic complications.     

A Rare Case of Delayed Perigastric Abscess after Curative Resection of Early Gastric Cancer by Uncomplicated Endoscopic Submucosal Dissection: Successful Treatment with Endoscopic Ultrasound-guided Drainage

A 72-year-old man had undergone uncomplicated endoscopic submucosal dissection (ESD) with en bloc resection of a localized 20-mm IIc lesion in the anterior wall of the gastric angle. Twenty-eight days later, he was re-admitted with epigastric pain of one-week duration. Contrast-enhanced computed tomography (CT) revealed a 60-mm mass bordered by viscera; repeat endoscopy confirmed a smooth elevated submucosal tumor at the greater curvature on the oral side of the post-ESD ulcer. We diagnosed him with a perigastric abscess as a complication of ESD and performed endoscopic ultrasound-guided drainage. Subsequently, the symptoms and blood inflammatory parameters improved, and follow-up CT showed the disappearance of the abscess.