Association of body mass index with glomerular filtration rate in Japanese: a cross-sectional study in work-site population

It has been shown that aging and hypertension are important risk factors to promote renal damage. However, little data are available on the effect of obesity on the progression of renal damage, especially in young and middle-aged individuals. The aim of this study was to determine the association between body mass index (BMI) and renal function evaluated by estimated glomerular filtration rate (eGFR) in Japanese men. We studied the cross-sectional association of BMI with eGFR in 3872 Japanese men in a work-site population (18-64 y; mean age 42.1 ± 0.2 y). Estimated glomerular filtration rate was calculated by a novel equation for Japanese men. Estimated glomerular filtration rate was negatively correlated with age, systolic blood pressure (SBP), hemoglobin A1c (HbA1c), and BMI. We performed multiple regression analysis, controlling for factors, such as SBP, low-density lipoprotein-cholesterol, gamma-glutamyl transpeptidase, age, HbA1c, and uric acid. The association between age and eGFR was highly statistically significant. In addition, BMI was still significantly associated with eGFR independently of SBP. Moreover, mean eGFR, which was adjusted for age, SBP, HbA1c, serum uric acid, and gamma-glutamyl transpeptidase, decreased from 88.9 mL/min/1.73 m(2) in the first quartile of BMI to 87.5 mL/min/1.73 m(2) in the second, 86.9 mL/min/1.73 m(2) in the third, and 85.9 mL/min/1.73 m(2) in the fourth quartile (test for trend, P < .0001). These results show that a close relationship is present between obesity and decreased eGFR in Japanese men. Keeping appropriate body weight, in addition to appropriate blood pressure, in young and middle age may be important to prevent renal damage in older age.     

Lifestyle changes and their impact on glycemic control and weight control in patients with diabetes during the coronavirus disease 2019 pandemic in Japan

Aims/IntroductionThis study aimed to reveal lifestyle changes and their impact on glycemic control and weight control in patients with diabetes during the coronavirus disease 2019 (COVID‐19) pandemic in Japan.Materials and MethodsWe retrospectively analyzed 1,402 outpatients with diabetes at a clinic in Osaka, Japan, who responded to an interview sheet regarding lifestyle changes during the COVID‐19 pandemic between 28 March and 30 May 2020. The association of lifestyle changes with hemoglobin A1c (HbA1c) and weight changes from February to May 2020 was investigated using the linear regression model. We also investigated the association with clinically important change of HbA1c (by ≥0.3%) and bodyweight (by ≥3%), using the cumulative link model.ResultsLeisure time and other outside physical activities were decreased in one‐quarter of patients during the COVID‐19 pandemic, whereas the amount of meals and snacks was decreased and increased in approximately 10%, respectively. The change in leisure time physical activities was inversely associated with HbA1c and weight changes, whereas the quantitative change of meals with the decline in eating out and that of snacks were positively associated with HbA1c and weight changes (all P < 0.05). The quantitative change of meals without the decline in eating out was also positively associated with weight change (P = 0.012). The cumulative link model for clinically important HbA1c and weight change showed broadly similar associations, except for that between snacks and bodyweight (P = 0.15).ConclusionsA considerable number of outpatients with diabetes experienced lifestyle changes during the COVID‐19 pandemic. The lifestyle changes were associated with HbA1c and weight changes.     

Role of aldosterone in left ventricular hypertrophy in hypertension

BACKGROUND: Aldosterone induces cardiac fibrosis in experimental animal models, but only limited information is available on the association between aldosterone and left ventricular (LV) hypertrophy in human beings. The aim of the present study was to determine the role of aldosterone in LV geometry and to investigate other types of target organ damage in hypertensive patients. METHODS: A total of 25 patients with primary aldosteronism caused by Conn's adenoma, 29 patients with renovascular hypertension, and 29 patients with essential hypertension (EHT) were included in the present study. Echocardiographic examinations and 24-h ambulatory blood pressure (BP) monitoring were conducted in all subjects. RESULTS: The mean 24-h systolic and diastolic BP in primary aldosteronism and renovascular hypertension were found to be comparable to those in EHT. However, LV mass index adjusted by age, sex, mean 24-h systolic BP, mean 24-h pulse rate, body mass index, and duration of hypertension was significantly increased in the patients with primary aldosteronism and renovascular hypertension compared with values in patients with EHT (150.2 +/- 7.7, 142.3 +/- 7.2, and 115.2 +/- 7.2 g/m(2), respectively). Hypertensive organ damages, such as proteinuria and hypertensive retinopathy, were more pronounced in the patients with renovascular hypertension; however, LV hypertrophy was especially exaggerated in patients with primary aldosteronism. CONCLUSIONS: These results indicate that aldosterone may induce LV hypertrophy in human beings as well as in experimental animals, and that angiotensin II and aldosterone may differentially participate in causing hypertensive target organ damage.     

Multiple system atrophy variant with severe hippocampal pathology

The striatonigral and olivopontocerebellar systems are known to be vulnerable in multiple system atrophy (MSA), showing neuronal loss, astrogliosis, and alpha-synuclein-immunoreactive inclusions. MSA patients who displayed abundant neuronal cytoplasmic inclusions (NCIs) in the regions other than the striatonigral or olivopontocerebellar system have occasionally been diagnosed with variants of MSA. In this study, we report clinical and pathologic findings of MSA patients characterized by prominent pathologic involvement of the hippocampus. We assessed 146 consecutively autopsied MSA patients. Semi-quantitative analysis of anti-alpha-synuclein immunohistochemistry revealed that 12 of 146 patients (8.2%) had severe NCIs in two or more of the following areas: the hippocampal granule cells, cornu ammonis areas, parahippocampal gyrus, and amygdala. In contrast, the remaining 134 patients did not show severe NCIs in any of these regions. Patients with severe hippocampal involvement showed a higher representation of women (nine women/three men; Fisher's exact test, p = 0.0324), longer disease duration (13.1 ± 5.9 years; Mann–Whitney U-test, p = 0.000157), higher prevalence of cognitive impairment (four patients; Fisher's exact test, p = 0.0222), and lower brain weight (1070.3 ± 168.6 g; Mann–Whitney U-test, p = 0.00911) than other patients. The hippocampal granule cells and cornu ammonis area 1/subiculum almost always showed severe NCIs. The NCIs appeared to be ring-shaped or neurofibrillary tangle-like, fibrous configurations. Three of 12 patients also had dense, round-shaped NCIs that were morphologically similar to pick bodies. The patients with Pick body-like inclusions showed more severe atrophy of the medial temporal lobes and broader spreading of NCIs than those without. Immunohistochemistry for hyperphosphorylated tau and phosphorylated TDP-43 revealed minimal aggregations in the hippocampus of the hippocampal MSA patients. Our observations suggest a pathological variant of MSA that is characterized by severe involvement of hippocampal neurons. This phenotype may reinforce the importance of neuronal alpha-synucleinopathy in the pathogenesis of MSA.     

Relationship between plasma total homocysteine level and dietary caffeine and vitamin B6 intakes in pregnant women

A high total homocysteine (tHcy) level during pregnancy is a risk factor for adverse perinatal outcomes, such as fetal growth restriction and preeclampsia. Caffeine is assumed to increase tHcy levels by acting as a vitamin B₆ antagonist. The objective of this study was to examine a relationship between circulating tHcy levels and dietary caffeine and vitamin B₆ intakes in pregnant Japanese women. A total of 321 healthy women with singleton pregnancies were recruited in metropolitan Tokyo, from June to December 2008, resulting in the final number included in the study as 254. Dietary caffeine intakes did not correlate with plasma tHcy levels. When we analyzed the data according to caffeinated beverages, caffeinated tea consumption was positively associated with plasma tHcy levels only among the women with a high intake of vitamin B₆, after controlling for confounding factors (P = 0.029). No correlation between coffee consumption and plasma tHcy levels was found. Pregnant Japanese women might need to cut down the consumption of caffeinated tea as well as take sufficient vitamin B₆ in order to prevent the tHcy levels from increasing.     

Endoscopic submucosal dissection with a combination of small-caliber-tip transparent hood and flex knife is a safe and effective treatment for superficial esophageal neoplasias

Background  

Superficial esophageal neoplasias resected in piecemeal manner with endoscopic mucosal resection (EMR) sometimes recur locally, and additional treatments need to be developed. Efficacy and safety of endoscopic submucosal dissection (ESD) for esophageal neoplasias are not sufficiently demonstrated, so we conducted a retrospective study to evaluate the efficacy and safety of ESD for superficial esophageal neoplasias.     

Postoperative complications after induction chemoradiotherapy in patients with non-small-cell lung cancer

Objective: This study evaluates the risks of postoperative complications in 124 patients with non-small-cell lung cancer who received pre-operative induction chemoradiotherapy and surgery. Methods: All patients with non-small-cell lung cancer who underwent surgery after induction therapy between January 1990 and December 2003 were reviewed. We adopted univariate and multiple logistic regression models to identify predictors that increased the incidence of postoperative complications. Results: Of 124 patients, 59 received carboplatin and docetaxel, 53 received cisplatin and etoposide, and 12 received other platinum-based combinations. Pre-operative thoracic radiotherapy was performed concurrently with chemotherapy. The median dose to the primary tumor was 40 Gy, and 29 patients (23.4%) received radiotherapy of more than 45 Gy before surgery. There were 25 pneumonectomies (20.2%). The overall postoperative mortality was 9 of 124 patients (7.3%), and complications developed in 54 patients (43.5%). Multivariate analysis demonstrated that only thoracic radiotherapy of more than 45 Gy predicted postoperative complications (P = 0.021; odds ratio, 3.620; 95% confidence interval, 1.214–10.797). Conclusions: Thoracic radiotherapy of more than 45 Gy, in combination with chemotherapy, was a significant risk factor for postoperative complications.     

Vascular Endothelial Growth Factor C Promotes Lymph Node Metastasis in a Rectal Cancer Orthotopic Model

Purpose Vascular endothelial growth factor C (VEGF-C), a novel member of the vascular endothelial growth factor family, is a relatively specific lymphangiogenic growth factor. It has been suggested that increased expression of VEGF-C in primary tumors is correlated with lymph node metastasis. We conducted this study to determine whether VEGF-C directly affects lymphangiogenesis and lymph node metastasis in colorectal cancer.Methods For an accurate analysis and clear visualization of metastases, the rectal cancer cell line, DLD1, was engineered to stably express green fluorescent protein (GFP) (DLD1/GFP). We implanted DLD1/GFP cells overexpressing VEGF-C orthotopically into the rectal walls of nude mice.Results Lymph node metastasis was confirmed in all (100%) of the mice bearing DLD1/GFP-VEGF-C tumors, but in only 25% of the mice bearing control tumors. There were more lymph node metastases per mouse in the mice bearing DLD1/GFP-VEGF-C tumors than in the mice bearing control tumors. There were no differences in cell growth and motility in vitro or in the resulting tumor volume from the implanted cells between the two groups. Immunohistochemical staining revealed that VEGF-C induced the growth of lymphatic vessels, which were enlarged in the tumor periphery and contained tumor cell emboli.Conclusion These results suggest that VEGF-C-induced lymphangiogenesis mediates tumor spread and the formation of lymph node metastasis.     

Overshoot phenomenon of oxygen uptake during recovery from maximal exercise in patients with previous myocardial infarction

The overshoot in oxygen uptake ([(V)\dot] \dot{\rm{V}} O₂ overshoot) during recovery from maximal exercise is thought to reflect an overshoot in cardiac output. We investigated whether this phenomenon is related to cardiopulmonary function during exercise in cardiac patients. A total of 201 consecutive patients with previous myocardial infarction underwent cardiopulmonary exercise testing (CPX). An apparent [(V)\dot] \dot{\rm{V}} O₂ overshoot during the recovery from CPX (6.5 ± 8.1% increase relative to the peak [(V)\dot] \dot{\rm{V}} O₂) was observed in ten patients. A comparison of patients with the [(V)\dot] \dot{\rm{V}} O₂ overshoot to those without the [(V)\dot] \dot{\rm{V}} O₂ overshoot revealed that the former had a significantly lower left ventricular ejection fraction (40.1 ± 19.1 vs. 55. 2 ± 14.9%, respectively, p = 0.002) and larger left ventricular diastolic and systolic dimensions. Patients with the [(V)\dot] \dot{\rm{V}} O₂ overshoot also had a significantly lower peak [(V)\dot] \dot{\rm{V}} O₂ (13.1 ± 6.1 vs. 18.1 ± 4.5 ml/min/kg, p < 0.001), lower Δ[(V)\dot] \dot{\rm{V}} O₂/ΔWR (work rate) (6.6 ± 3.8 vs. 9.5 ± 1.7 mL/min/W, p < 0.0001), and a higher [(V)\dot] \dot{\rm{V}} E (minute ventilation)/[(V)\dot] \dot{\rm{V}} CO₂ (carbon dioxide output) slope (45.0 ± 18.6 vs. 32.6 ± 6.6, p < 0.0001) than those without the overshoot. A [(V)\dot] \dot{\rm{V}} O₂ overshoot during recovery from maximal exercise was found in 5% of patients with previous myocardial infarction. This condition, which suggests a transient mismatch between cardiac contractility and afterload reduction, was found to be related to impaired cardiopulmonary function during exercise.     

Pharmacokinetics of ivermectin applied topically by whole‐body bathing method in healthy volunteers

As a novel administration method of ivermectin (IVM) for scabies treatment, we proposed a “whole‐body bathing method (WBBM)”. In this method, the patients would bathe themselves in a bathing fluid containing IVM at an effective concentration. Previously, we demonstrated that WBBM could deliver IVM to the skin but not to the plasma in rats. In the present study, to assess the clinical validity of the method an arm bathing examination (first trial) and a whole‐body bathing examination (second trial) were conducted in healthy volunteers. In both the first and second trials, after bathing in fluid containing IVM, the exposure in the stratum corneum was higher compared with that after taking IVM p.o. as reported previously. IVM was not detected in plasma at any sampling point after the whole‐body bathing in the second trial. Furthermore no serious adverse events were found. These results in both trials suggest that WBBM can deliver IVM to the human stratum corneum without systemic exposure or serious adverse effects in healthy volunteers, and at concentrations that would be adequate for scabies treatment.