Influence of the COVID-19 Pandemic on Overall Physician Visits and Telemedicine Use Among Patients With Type 1 or Type 2 Diabetes in Japan

BackgroundRegular visits with healthcare professionals are important for preventing serious complications in patients with diabetes. The purpose of this retrospective cohort study was to clarify whether there was any suppression of physician visits among patients with diabetes during the spread of the novel coronavirus 2019 (COVID-19) in Japan and to assess whether telemedicine contributed to continued visits.MethodsWe used the JMDC Claims database, which contains the monthly claims reported from July 2018 to May 2020 and included 4,595 (type 1) and 123,686 (type 2) patients with diabetes. Using a difference-in-differences analysis, we estimated the changes in the monthly numbers of physician visits or telemedicine per 100 patients in April and May 2020 compared with the same months in 2019.ResultsFor patients with type 1 diabetes, the estimates for total overall physician visits were −2.53 (95% confidence interval [CI], −4.63 to 0.44) in April and −8.80 (95% CI, −10.85 to −6.74) in May; those for telemedicine visits were 0.71 (95% CI, 0.47–0.96) in April and 0.54 (95% CI, 0.32–0.76) in May. For patients with type 2 diabetes, the estimates for overall physician visits were −2.50 (95% CI, −2.95 to −2.04) in April and −3.74 (95% CI, −4.16 to −3.32) in May; those for telemedicine visits were 1.13 (95% CI, 1.07–1.20) in April and 0.73 (95% CI, 0.68–0.78) in May.ConclusionThe COVID-19 pandemic was associated with suppression of physician visits and a slight increase in the utilization of telemedicine among patients with diabetes during April and May 2020.Key words: COVID-19, telemedicine, outpatient, diabetes     

Detection and analysis of IgG antibodies in sera of patient with atopic dermatitis (AD) to individual wheat polypeptides by immunoblotting techniques

To detect IgG antibodies in sera of patients with atopic dermatitis (AD) to individual wheat polypeptides, wheat flour proteins were extracted with tris-citrate buffered saline containing urea and 2-mercaptoethanol (UTC solvent), and fractionated as polypeptides of molecular weights between 12 and 100 KDa. By means of the immunoblotting techniques, specific IgG antibodies to fractionated proteins could be detected in sera from healthy individuals and AD patients. Twenty AD patients' sera with high titers of wheat specific RAST (scores of more than 3) reacted not only to five major wheat components (33-38, 40-45, 55-60, 80, 90-98 KDa), which stained intensively with Coomassie brilliant blue G-250, but also to polypeptides of 14, 16, 22, 29, 70 KDa. Twelve control sera reacted to a limited number of the five major wheat components, and levels of specific IgG antibodies increased with age. The sera of AD patients in the present study contained increased level of IgG antibodies to the five major components, and additionally to several minor components, 70 KDa, 29 KDa and much smaller proteins.     

Effects of 1‐O‐hexyl‐2,3,5‐trimethylhydroquinone on carbon tetrachloride‐induced hepatic cirrhosis in rats

Aim: The present study was undertaken to evaluate the effects of 1‐O‐hexyl‐2,3,5‐trimethylhydroquinone (HTHQ), a synthesized vitamin E derivative, on carbon tetrachloride (CCl₄)‐induced cirrhosis. Methods: Rats were treated with hypodermic injections of CCl₄ twice a week to induce the hepatic cirrhosis, and given drinking water containing HTHQ or solvent. Primary cultures of rat hepatocytes were performed to evaluate the effects of HTHQ on the expression of inducible nitric oxide synthase (iNOS). Results: Masson's staining of rat livers showed fibrosis around pseudo‐lobules in the CCl₄ group, the lesions being reduced in the CCl₄ HTHQ group. Increases in liver tissue hydroxyproline and α₁(I) collagen, α‐smooth muscle actin and iNOS induced by CCl₄, were also markedly diminished by HTHQ. Furthermore, both HTHQ and vitamin E attenuated interleukin‐1β‐induced iNOS protein expression in cultured hepatocytes, the potency of HTHQ being 10‐times higher than that of vitamin E. Conclusion: HTHQ may inhibit development of hepatic cirrhosis in rats, more potently than vitamin E, by inhibiting the iNOS expression in hepatocytes. Because vitamin E has a radical scavenging action, roles of NO and peroxynitrite will be discussed in the effects of HTHQ on the fibrosis.     

High sensitivity assay using serum sample for IL28B genotyping to predict treatment response in chronic hepatitis C patients

Aim: Recent human genome‐wide association studies (GWAS) revealed a strong association between IL28B gene variation and the pegylated interferon‐α with ribavirin (PEG‐IFN‐α/RBV) treatment response in chronic hepatitis C patients. Two single nucleotide polymorphisms (SNP), rs8103142 and rs11881222 located in the IL28B gene, were found in significant association with the viral clearance. The present study employed these SNPs to develop a new accessible screening method allowing identification of potential non‐responders before starting the therapy. Methods: Primer sets were designed to amplify rs8103142 and rs11881222 fragments from genomic DNA extracted from serum samples. This method was validated using microarray typing (GWAS) and applied for genotyping of 68 hepatitis C virus‐infected patients with PEG‐IFN‐α/RBV treatment at baseline. Results: In comparison with GWAS, the screening method showed 100% and 95.6% accuracy in typing of rs8103142 and rs11881222, respectively, indicating incomplete specificity but 100% of sensitivity in both. Genotyping by both SNP showed that 53 (77.9%), 14 (20.6%) and one (1.5%) of the patients were of major homozygous, heterozygous and minor homozygous type, respectively. The majority (85%) of homozygous patients exhibited response to therapy in contrast to heterozygous patients (29%). Among all genotyped only one case was found with the minor homozygous genotype which had late virological response to therapy before relapsing. Conclusion: This study described a highly sensitive assay that can be useful in determining SNP genotypes as well as in predicting the response to IFN‐based treatment.     

Detection of circulating intercellular adhesion molecule-1 antigen in malignant diseases.

A new monoclonal antibody (MoAb) HA58 (IgG1) was prepared, which recognizes the binding site on the intercellular adhesion molecule-1 (ICAM-1) antigen to the lymphocyte function-associated antigen-1 (LFA-1). The double-determinant immunoassay (DDIA) was established with use of MoAb HA58 and another anti-ICAM-1, MoAb CL207, to detect the soluble, shedding ICAM-1 antigen. Human recombinant interferon-gamma (IFN-gamma) induced not only the expression of cell surface ICAM-1, but also the shedding ICAM-1 antigen in an IFN-gamma concentration-dependent and incubation-time-dependent manner. DDIA was applied to detect the shedding ICAM-1 antigen in the sera of patients with malignant or benign diseases. The incidence of positivity for ICAM-1 antigen in malignant diseases was higher than that in benign diseases or in healthy controls. Furthermore, the sera of cancer patients with liver metastasis showed higher levels of the shedding ICAM-1 antigen. These findings suggest that serum ICAM-1 antigen may be a useful marker to monitor tumor burden in cancer patients.     

Pathogenic role of polyclonal and polymeric IgA in a murine model of mesangial proliferative glomerulonephritis with IgA deposition.

Molecular size and charge distribution of IgA of sera and glomerular eluates were investigated in ddY mice, spontaneously developing mesangial proliferative glomerulonephritis (GN) with IgA deposition after 40 weeks of age. Serum IgA levels were increased in aged ddY mice more than 40 weeks old with a significant increase (P less than 0.01) at the age of 60 weeks, comparing with those of BALB/c mice. The isoelectric focusing (IEF) spectrotype of pooled serum IgA in 60-week-old mice ranged from 4.2 to 5.5, being similar to those in younger ddY (16 weeks old) and control BALB/c mice (12 weeks old) without enhanced expression of specific IgA peaks. However, IgA in the glomerular eluate from the 60-week-old mice showed limited anionic spectrotypes from pH 4.2 to 4.8. HPLC of IgA in pooled sera and glomerular eluates of 16-, 40- and 60-week-old ddY mice, revealed markedly increased ratios of the dimeric IgA (dIgA) and polymeric IgA (pIgA) in the total IgA with age. In the contrast to serum profiles, monomeric IgA (mIgA) was always detected as the smallest peak of the IgA fractions in glomerular eluates. Furthermore, aged mice with severe GN showed a higher percentage of dIgA and pIgA in total IgA (80%) in the sera than that of the mice with mild GN (64%). HPLC analysis under acid condition of glomerular IgA from 40-week-old ddY mice showed a similar pattern of dIgA and pIgA peaks in neutral buffer without the appearance of mIgA. These findings suggest that there is a selective mechanism for glomerular accumulation of more acid IgA among the polyclonally expanded IgA in old ddY mice, and that the polymeric form of IgA plays a pathogenic role in the development of mesangial proliferative GN in these mice.     

Hepatic adrenal rest tumor: Diagnostic pitfall and proposed algorithms to prevent misdiagnosis as lipid‐rich hepatocellular carcinoma

We present a case of adrenal rest tumor of the liver in which differential diagnosis from lipid rich‐hepatocellular carcinoma (HCC) was challenging. The patient was a 50‐year‐old woman in whom a 3‐cm tumorous mass was discovered in segment 7 of the liver during computed tomography evaluation of a uterine leiomyoma. The preoperative diagnosis was HCC, and subsegmental liver resection was performed. The tumor appeared as a well‐demarcated golden yellow nodule consisting of clear or partially eosinophilic cells arranged in a trabecular pattern. The initial impression of this lesion was that of clear cell type or lipid‐rich type HCC because it stained positive for Hep Par1, but negative for arginase‐1 and positive for CD56 which is one of the neuroendocrine markers. The lesion also stained positive for SF‐1 and 3β‐HSD, both of which are markers of adrenocortical tissue. The final diagnosis was hepatic adrenal rest tumor. Hepatic adrenal rest tumor should be considered in the differential diagnosis of segment 7 tumor. A diagnostic algorithm that includes immunohistochemical staining for CD56 and arginase‐1 is to rule out the possibility of lipid‐rich HCC.     

Clusters of proliferating endothelial cells and smooth muscle cells in rabbit carotid arteries

Schwarz and Benditt found clustering of replicating cells in aortic endothelium in 1976 and discussed how homeostasis of the arterial wall is maintained through this nonrandom distribution of replicating cells. However, it is still unclear how cells of vascular walls turnover. In order to address this issue, we evaluated distribution of the cells in mitotic cycle, labeled by Ki67‐immunostaining, in serial histological sections of twelve carotid arteries of six adult male Japanese rabbits. As a result, a total of 1713 Ki67‐positive endothelial cells (ECs) and 1247 Ki67‐positive smooth muscle cells (SMCs) were identified. The Ki67‐positivity rate in ECs and SMCs were about 0.048% and 0.0027%, respectively. Many of the Ki67‐positive cells clustered in two (EC, 37%; SMC, 33%), three to four (EC, 8%; SMC, 28%), and five to eight cells (EC, 5%; SMC, 10%). Clusters having more than eight cells were not found. Thus, it can be speculated that the cell division of proliferating ECs and SMCs occur four times at most. These novel findings offer great insights for better understanding of the mechanism that underlies cell number regulation of the blood vessel.