Cilostazol may improve cognition better than clopidogrel in non-surgical adult patients with ischemic moyamoya disease: subanalysis of a prospective cohort

ABSTRACT

Objective: Adult patients with ischemic moyamoya disease (MMD) who receive treatment with antiplatelet drugs reportedly show improvements in neuropsychological test scores after around 2 years. The purpose of the present study subanalyzing the same patient cohort used in a previous study was to determine which antiplatelet drug, clopidogrel or cilostazol, results in better improvement of cognitive function among non-surgical adult patients showing ischemic MMD without severe hemodynamic compromise.

Methods: Sixty-six patients without cerebral misery perfusion on ¹⁵O gas positron emission tomography were treated with pharmacotherapy alone. Patients ≥50 years old and <50 years old initially received clopidogrel and cilostazol, respectively. Any patient suffering side effects of the antiplatelet drug switched to the other antiplatelet drug. Neuropsychological tests were performed at study entry and at the end of the 2-year follow-up, and differences in each neuropsychological test score between the two time points (second test score – first test score) were calculated and defined as Δ scores.

Results: Among the five neuropsychological tests, Δ scores for two tests were significantly greater in patients treated with cilostazol (n = 36) than in those treated with clopidogrel (n = 30), and Δ scores of the remaining three tests did not differ between patient groups. Based on Δ scores, 15 patients (23%) were defined as showing interval cognitive improvement. On multivariate analysis, cilostazol administration (95% confidence interval, 1.19–193.98; P = 0.0361) represented an independent predictor of interval cognitive improvement.

Conclusions: Cilostazol may improve cognition better than clopidogrel in non-surgical adult patients with ischemic MMD.     

Esophageal Cancer Surgery in Dialyzed Patients: A Single Institution Case Series

We sought to evaluate the feasibility of esophageal carcinoma (EC) surgery in cases requiring dialysis. Among 250 consecutive patients undergoing surgical resection for EC, three on maintenance dialysis were identified. We retrospectively analyzed their clinical characteristics. The three dialyzed patients were all males, 39–77 years old at EC surgery. The operations were thoracoscopic esophagectomy with nodal clearance (Case 1), cervical esophageal resection without thoracic procedures (Case 2), and thoracoscopic esophagectomy without reconstruction, emergently conducted for tumor bleeding (Case 3). Reoperation had been required for postoperative abdominal hematoma in Case 1. Postoperative tracheostomy had been performed due to severe pneumonia in Case 2. EC surgery for dialyzed patients, despite appearing to be feasible, might be associated with a high risk of life-threatening morbidities. To minimize surgical risk, therapeutic decision-making for such cases should be based on the balance between radicality and safety.     

Effects of Histamine 2-receptor Antagonists and Proton Pump Inhibitors on the Pharmacokinetics of Gefitinib in Patients With Non–small-cell Lung Cancer

Introduction

In this study, we investigated the degree of drug interactions between gefitinib and gastric acid suppressants (ie, histamine 2-receptor antagonists [H2RAs] or proton pump inhibitors [PPIs]) with a clinical standard dose in Japanese patients with non–small-cell lung cancer.

Immune checkpoint inhibitor-induced refractory polyarthritis rapidly improved by sarilumab and monitoring with joint ultrasonography: A case report

Rationale:Immune checkpoint inhibitors (ICIs) have shown efficacy for the treatment of various kinds of malignant tumors. However, ICIs can cause immune-related adverse events, such as arthritis. Nevertheless, the treatment of ICI-induced arthritis has not been established yet. Here we report a case of ICI-induced polyarthritis successfully treated using sarilumab and monitored using joint ultrasonography.Patient concerns:A 61-year-old man presented with polyarthritis. He had been treated with nivolumab for recurrent renal cell carcinoma 11 months before. He developed ICI-induced nephritis (proteinuria and elevated serum creatinine) 3 months before, which resolved after discontinuing nivolumab for 1 month. Two months after resuming nivolumab, he developed polyarthralgia and joint swelling, which were suspected to be associated with nivolumab administration, and hence we discontinued nivolumab again. Laboratory tests revealed elevated C-reactive protein level and erythrocyte sedimentation rate, but were negative for rheumatoid factor and anti-cyclic citrullinated peptide antibody. Joint ultrasonography revealed active synovitis in several joints, but a joint X-ray revealed no bone erosion.Diagnoses:We diagnosed polyarthritis as ICI-induced arthritis because the findings were not typical of rheumatoid arthritis (no bone erosion and seronegativity) and the patient had already developed other immune-related adverse events (ICI-induced nephritis).Interventions:After discontinuation of nivolumab, we started treatment with 15 mg daily prednisolone and 1000 mg daily sulfasalazine, although it was ineffective. Hence, we initiated 200 mg biweekly sarilumab.Outcomes:Following sarilumab administration, polyarthritis improved rapidly, and joint ultrasonography confirmed the rapid improvement of synovitis. Hence, we tapered off the glucocorticoid treatment. No recurrence of renal cell carcinoma was noted for 2 years after the initiation of sarilumab despite no anti-tumor therapy.Lessons:Sarilumab may serve as a good treatment option for treating refractory ICI-induced polyarthritis. Joint ultrasonography may contribute to the evaluation of ICI-induced polyarthritis and monitoring the effects of treatments.     

Immunoelectron microscopic study of tubulin and microtubule-associated proteins after transient cerebral ischemia in gerbils

Summary Differential vulnerability of microtubule components to cerebral ischemia has been reported previously. We investigated the disintegration of microtubules using immunoelectron microscopy for -tubulin and microtubule-associated protein 1A and 2 (MAP1A and 2). Mongolian gerbils were subjected to bilateral carotid occlusion for 10 to 30 min and reperfusion for up to 72h following ischemia for 10 min. After ischemia for 10 min, some dendrites in the stratum moleculare of the subiculum-CA1 region lost immunoreaction products for -tubulin and MAPs. Loss of the reaction products spread to the medial CA1 region during progressive ischemia for 30 min. In some dendrites, electron-dense precipitates for MAPs were dispersed in the dendritic cytoplasm with little reaction product on microtubules and without alteration of the reaction for -tubulin. After recirculation, loss of electron-dense precipitates for -tubulin and MAPs, as well as disintegration of microtubules, propagated further to the medial CA1 region and to the proximal dendrites. The present study demonstrated prompt disintegration of microtubules with rapid disappearance of the reaction for MAPs which seemed to be caused by detachment of MAPs from the microtubule cores.     

Universal Screening for Familial Hypercholesterolemia in Children in Kagawa,Japan

Aim: Familial hypercholesterolemia (FH) is an underdiagnosed autosomal dominant genetic disorder characterized by high levels of plasma low-density lipoprotein cholesterol (LDL-C) from birth. This study aimed to assess the genetic identification of FH in children with high LDL-C levels who are identified in a universal pediatric FH screening in Kagawa, Japan. Method: In 2018 and 2019, 15,665 children aged 9 or 10 years underwent the universal lipid screening as part of the annual health checkups for the prevention of lifestyle-related diseases in the Kagawa prefecture. After excluding secondary hyper-LDL cholesterolemia at the local medical institutions, 67 children with LDL-C levels of ≥ 140 mg/dL underwent genetic testing to detect FH causative mutations at four designated hospitals. Results: The LDL-C levels of 140 and 180 mg/dL in 15,665 children corresponded to the 96.3 and 99.7 percentile values, respectively. Among 67 children who underwent genetic testing, 41 had FH causative mutations (36 in the LDL-receptor, 4 in proprotein convertase subtilisin/kexin type 9, and 1 in apolipoprotein B). The area under the curve of receiver operating characteristic curve predicting the presence of FH causative mutation by LDL-C level was 0.705, and FH causative mutations were found in all children with LDL-C levels of ≥ 250 mg/dL. Conclusion: FH causative mutations were confirmed in almost 60% of the referred children, who were identified through the combination of the lipid universal screening as a part of the health checkup system and the exclusion of secondary hyper-LDL cholesterolemia at the local medical institutions.     

Potentially Life-threatening Arrhythmia Triggered by an Excessive Consumption of Dried Sweet Potato “Hoshi-Imo”

We herein report two cases of potentially life-threatening arrhythmia due to hyperkalemia triggered by the excessive consumption of “Hoshi-Imo” (dried sweet potato). Both patients with chronic renal disease on renin-angiotensin-aldosterone system inhibitors presented at the emergency room with non-specific symptoms. Electrocardiograms revealed potentially life-threatening arrhythmia due to hyperkalemia in both cases: sinus arrest with a ventricular escape rhythm, tall and peaked T waves; and a widened QRS complex in a nearly sine-wave configuration without discernible P wave. Both patients fully recovered after intensive care for hyperkalemia. Physicians should recognize the excessive consumption of “Hoshi-Imo” may lead to the development of life-threatening arrhythmia, especially in patients with risk factors for hyperkalemia.