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.     

Absolute lymphocyte count and C-reactive protein-albumin ratio can predict prognosis and adverse events in patients with recurrent esophageal cancer treated with nivolumab therapy

Predicting the prognosis and adverse events (AEs) of nivolumab therapy for recurrent esophageal cancer is very important. The present study investigated whether a simple blood biochemical examination could be used to predict prognosis and AEs following nivolumab treatment for relapse of esophageal cancer. A total of 41 patients who received nivolumab treatment for recurrent esophageal cancer after esophagectomy were analyzed. The absolute lymphocyte count (ALC), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR) and C-reactive protein-albumin ratio (CAR) were assessed at the time of nivolumab induction as indices that can be calculated by blood biochemical examinations alone. Median values were 1,015 for ALC, 3.401 for NLR, 242.6 for PLR, 0.458 for MLR and 0.119 for CAR, and patients were divided into two groups according to values. A high ALC, low NLR, low PLR, low MLR and low CAR were associated with a better response to nivolumab. In addition, patients with the aforementioned indices, with the exception of low PLR, or better response were more likely to develop AEs in univariate analysis. In multivariate analysis, a high ALC [odds ratio (OR): 4.857, P=0.043] and low CAR (OR: 9.099, P=0.004) were identified as independent risk factors for AEs. Survival analysis revealed that overall survival and progression-free survival (PFS) rates after nivolumab treatment differed significantly between the high and low groups of ALC, NLR, PLR, MLR and CAR. The multivariate analysis identified a low ALC [hazard ratio (HR): 3.710, P=0.003] and high CAR (HR: 2.953, P=0.007) as independent poor prognostic factors of PFS. In conclusion, ALC and CAR have potential as biomarkers for outcomes of recurrent esophageal cancer following nivolumab treatment.     

Phospholamban p.Arg14del Cardiomyopathy: A Japanese Case Series

Phospholamban p.Arg14del is reported to cause hereditary cardiomyopathy with malignant ventricular tachycardia (VT) and advanced heart failure. However, the clinical courses of Japanese cardiomyopathy patients with phospholamban p.Arg14del remain uncharacterized. We identified five patients with this variant. All patients were diagnosed with dilated cardiomyopathy (DCM), developed end-stage heart failure and experienced VT requiring implantable cardioverter defibrillator discharge. Four patients survived after implantation of a left ventricular assist device (LVAD), while one patient who refused LVAD implantation died of heart failure. Based on the severe course of the disease, we propose genetic screening for phospholamban p.Arg14del in DCM patients.     

Safe Concurrent Use of Anti-tuberculosis Drugs and Pembrolizumab in a Patient with Non-small-cell Lung Cancer Who Was Infected with Mycobacterium tuberculosis

A 68-year-old Japanese man was diagnosed with lung adenocarcinoma stage IVB. We introduced a first-line chemotherapy of four cycles of carboplatin and pemetrexed and pembrolizumab, followed by pemetrexed and pembrolizumab maintenance therapy. Approximately four months after anticancer therapy, a small nodule appeared in the right peripheral S3 lesion. After five months, the nodule was confirmed as a Mycobacterium tuberculosis (TB) nodule. We initiated anti-TB therapy without stopping pembrolizumab, and the right S3 nodule shrank immediately. This report supports the concurrent use of anti-TB treatment with an immune checkpoint inhibitor when the TB infection area is limited.     

Long-term results of elective hepatectomy for the treatment of ruptured hepatocellular carcinoma

Background/Purpose According to the General rules for the clinical and pathological study of primary liver cancer, compiled by the Liver Cancer Study Group of Japan, ruptured hepatocellular carcinoma (HCC) is classified as stage 4, even if the tumor is small and solitary. We examined the long-term results of elective hepatectomy for the treatment of ruptured HCC. Methods A first hepatectomy was performed without operative death in 193 patients with HCC. Ten patients had ruptured HCC (ruptured group) and 183 patients had nonruptured HCC (nonruptured group). The extension of HCC was macroscopically classified as stage 1 in 23 patients, stage 2 in 71, stage 3 in 53, and stage 4 in 46. Results Cumulative survival rates in the ruptured group at 1, 5, and 10 years were 90.0%, 67.5%, and 20.3%, respectively. The cumulative survival rate was lower in patients with stage 4 disease in the nonruptured group than that in patients in the ruptured group (P < 0.05). Cumulative survival rates did not differ significantly between patients in the ruptured group and those with stage 2 or stage 3 disease. Conclusions Survival rates after elective hepatectomy in patients with ruptured HCC are good, even if the disease is classified as stage 4.     

Severe Post-COVID-19 Organizing Pneumonia during Cancer Immunochemotherapy

A 44-year-old man developed coronavirus disease 2019 (COVID-19) pneumonia during immunochemotherapy consisting of carboplatin, paclitaxel, and pembrolizumab for non-small cell lung cancer. Low-grade fever, followed by mild hypoxemia, and febrile neutropenia, were observed, and granulocyte colony-stimulating factor (G-CSF) was administered until the recovery of neutropenia, when he developed a high fever, severe hypoxemia, and hypotension accompanied by consolidation in the bilateral lungs. His conditions promptly improved after treatment including hydrocortisone and the primary and metastatic tumors remained regressed for 10 months without further treatment. Post-COVID-19 organizing pneumonia during cancer immunochemotherapy can be aggravated by immune-checkpoint inhibitors and G-CSF.     

Clinical Assessment of Central Blood Pressure

Central aortic blood pressure (CBP) is increasingly considered a better cardiovascular prognostic marker than conventional cuff brachial blood pressure. Because CBP cannot be directly measured noninvasively, it has to be estimated from peripheral pressure pulses. To assess estimated CBP appropriately, the accuracy and features of the estimation method should be considered. The aim of this review is to provide basic knowledge and information useful for interpreting and assessing estimated CBP from a methodological point of view. Precise peripheral pressure pulse recording has been enabled by the introduction of arterial applanation tonometry, for which the radial artery may be the optimal site. An automated tonometry device utilizing a sensor array is preferable in terms of reproducibility and objectivity. Calibration of a peripheral pressure waveform has unresolved problems for any estimation method, due to imperfect brachial sphygmomanometry. However, if central and peripheral pressure calibrations are equivalent, two major methods to estimate CBP-those based on generalized pressure transfer function or radial late systolic pressure-may be comparable in their accuracy of CBP parameter estimation.     

Perioperative Oral Administration of Cystine and Theanine Enhances Recovery After Distal Gastrectomy

Background: It has been reported that cystine and theanine, amino acids related to glutathione synthesis, have immunomodulatory effects, such as suppressing inflammation after strenuous exercise. In this study, we examined the effects of oral administration of cystine and theanine during the perioperative period as a pilot study. Methods: Forty‐three cases of distal gastrectomy for cancer conducted in our department were assigned to the cystine and theanine group (CT group) or to the placebo control group (P group), and a randomized, single‐blind, parallel‐group study was then performed. Cystine (700 mg) and theanine (280 mg) or a placebo was administered to participants for 10 continuous days (4 days before to 5 days after surgery). Changes in pre‐ and postoperative interleukin (IL)–6, C‐reactive protein (CRP), albumin, white blood cell (WBC) count, neutrophil count, total lymphocyte count, resting energy expenditure (REE), and body temperature were compared and examined. Results: Ten patients were excluded, leaving 33 patients in the study. The CT group had significantly lower IL‐6 values (postoperative day [POD] 4), CRP levels (POD 7), neutrophil counts (POD 4), and body temperatures (POD 5) than the P group (P < .05). In addition, REE in the P group peaked on day 1 (1.14 ± 0.16 [pre‐ and postoperative ratio]), whereas the CT group did not show any increase on POD 1 (0.99 ± 0.21, P < .05 vs P group). Conclusions: This study suggests that oral administration of cystine and theanine during the perioperative period may alleviate postgastrectomy inflammation and promote recovery after surgery.     

Reproducibility of ultrasound scan in the assessment of volume flow in the veins of the lower extremities

PURPOSE: The purpose of this study was the identification of the optimal settings of ultrasound scan flow measurement in the veins and the determination of whether the standardization of these settings can provide acceptable reproducibility of the venous flow measurements in individual segments of the lower extremity veins. METHODS: The venous cross-sectional area, the time average mean velocity, and the venous volume flow of 25 healthy volunteers were examined with duplex ultrasound scanning. Reproducibility was examined with different measurement settings. Doppler scan sample volume size, ultrasound scan beam incident angle, and time interval of measurement were varied across a spectrum for arrival at the setting for highest reproducibility of the flow volume measurements. Test-retest reproducibility of venous flow volume measurements then was investigated with optimized settings. RESULTS: The highest repeatability of volume flow measurements was achieved when the full lumen of the vein was insonated (coefficient of repeatability [CR] = 1.88 cm/s), the ultrasound scan beam incident angle was equal to 60 degrees (CR = 1.56 cm/s), and the measurement time was more than 40 seconds (CR = 1.64 cm/s). The mean values of volume flow were 360 mL/min in the common femoral vein, 147 mL/min in the superficial femoral vein, 86 mL/min in the profunda femoral vein, and 38 mL/min in the greater saphenous vein. Test-retest repeatability coefficients were 96.9 mL/min for the common femoral vein, 70.2 mL/min for the superficial femoral vein, 40.8 mL/min for the profunda femoral vein, and 16.8 mL/min for the greater saphenous vein. CONCLUSION: The reproducibility of ultrasound scan measurements of volume flow in veins is optimized with the use of sampling volumes that cover the entire venous lumen, with an incident angle of 60 degrees and measuring for 40-second intervals or longer. With these defined variables, volumetric measurements are sufficiently repeatable. the values of flow volume measured with duplex ultrasound scanning were comparable to those with thermodilution techniques that were reported previously.     

Coronary artery bypass graft for Bland-White-Garland syndrome in an old age; report of a case

We report a case of Bland-White-Garland syndrome with advanced age. The patient, a 67-year-old women, presented with a history of congestive heart failure. Coronary catheterization revealed an anomalous origin of the left coronary artery (LCA) from the trunk of the pulmonary artery and huge right coronary aneurysm. Myocardial single photon emission computed tomography (SPECT) showed previous myocardial infarction with reversible ischemia in left anterior descending (LAD) region. We performed LCA direct closure and coronary artery bypass graft. The patient recovered uneventfully without signs of ischemia. Although a bypass graft was patent, left ventricular function had not been improved immediately probably due to the coronary flow pattern changes.