The third and fourth doses of the vaccine against coronavirus disease 2019 (COVID-19) were widely administered in Japan since December 2021. Currently, however, data are scarce regarding acute adverse events with the third and fourth doses. The present study reports the profiles of acute adverse events after the third and fourth COVID-19 vaccine doses, seen at the site of a mass vaccination center in Japan. Between December 2021 and July 2022, 267,515 individuals received the third, and 32,934 received the fourth COVID-19 vaccine dose at the mass vaccination center, of whom 442 recipients of the third (0.19%), and 22 recipients of the fourth (0.07%) dose reported acute adverse events and were examined by doctors on site. The most common diagnosis was vasovagal syncope/presyncope (incidence: 0.01-0.10%), followed by other miscellaneous complaints, acute allergic reactions (0.05-0.005%), and anaphylaxis (< 0.005%). Vasovagal syncope/presyncope occurred most frequently in recipients in those in their 20s, whereas acute allergic reactions were most frequent in those in their 40s. Both reactions were more frequent in women than men. The peak occurrence of vasovagal syncope/presyncope was earlier than 15 min after the injection, whereas that of acute allergic reaction was later than 15 min after the injection. The incidence of acute allergic reactions appeared to differ between various vaccine manufacturers, whereas that of vasovagal syncope/presyncope did not. These real-world data may benefit the safe and efficient implementation of mass vaccination campaigns for citizens who want to receive COVID-19 vaccines now and in the future.

Mast cells protect a host from invasion by infectious agents and environmental allergens through activation of innate and adaptive immune receptors, their excessive activation being tightly regulated by inhibitory receptors, such as leukocyte immunoglobulin-like receptor (LILR)B4 (gp49B in mice). However, the regulatory mechanism of LILRB4/gp49B expressed on mast cells remains to be clarified in relation to their recently identified ligand, fibronectin (FN), a direct activator of integrins and an indirect stimulator of high-affinity Fc receptor for IgE (FcεRI). Confocal microscopic analysis suggested that gp49B is spatially close to integrin β₁ on non-adhered bone marrow-derived mast cells (BMMCs). Their spatial relatedness increases further at robust focal adhesion sites on cells adhering to immobilized FN. However, the confocal fluorescence signal of the α subunit of FcεRI was found to be correlated to neither gp49B nor integrin β₁ on non-adherent and adherent BMMCs. Stimulation of FcεRI with an immobilized antigen caused FcεRIα signals to accumulate in an inside area surrounded by robust focal adhesion with a concomitant slight increase in the signal correlation of FcεRIα and integrin β₁, accompanied by a less significant increase of the FcεRIα and gp49 correlation. Thus, activating and inhibitory FN receptors integrin and gp49B, respectively, were co-localized via FN at robust focal adhesion sites on BMMCs, while FcεRI was not close to gp49B spatially.

Castleman disease (CD) is a lymphoproliferative disorder that manifests as hypergammaglobulinemia and severe inflammation with multiorgan involvement. However, renal involvement has been infrequently described in CD. We present a case of a 63-year-old Japanese male patient with multicentric CD (MCD) in whom kidney involvement, including impaired renal function and massive proteinuria, is present. He had a 2-year history of inflammatory arthritis and was referred to our clinic with newly developed proteinuria, renal dysfunction, and elevated levels of acute-phase proteins. Abdominal computed tomography scan revealed hepatosplenomegaly, including mesenteric and inguinal lymph node enlargements. The patient underwent inguinal lymph node resection. Excisional biopsy of the inguinal lymph node showed multiple lymphoid follicles and expansion of interfollicular areas by marked plasmacytosis consistent with mixed type CD. The patient was diagnosed with human herpes virus 8-negative MCD according to the international diagnostic criteria for CD. Diagnostic renal biopsy was not performed following the medical viewpoint. Tocilizumab (TCZ) treatment was highly effective in reducing proteinuria and stabilizing renal function, as well as improving other clinical symptoms. The patient responded to TCZ treatment, and the renal involvement was rapidly improved. Our preliminary immunohistochemical analysis indicated AA amyloid deposits in urinary epithelial cells suggesting a possible renal involvement of AA amyloidosis. TCZ could potentially be one of the therapeutic options in patients with MCD with renal involvement.

Pseudobulbar palsy and bulbar palsy cause dysphagia in patients with amyotrophic lateral sclerosis (ALS). Dysphagia in patients with ALS not only increases the risk of aspiration and pneumonia but also leads to malnutrition and weight loss, which are poor prognostic factors. Gastrostomy is the preferred route of feeding and nutritional support in patients with dysphagia. However, there are no established standards to determine the ideal timing of gastrostomy for patients with ALS. Therefore, we used the videofluoroscopic dysphagia scale (VDS), which objectively quantifies swallowing function, in videofluoroscopic swallowing study (VFSS) to investigate whether this scale at diagnosis can be a useful predictor for the timing of gastrostomy. We retrospectively evaluated 22 patients with ALS who were diagnosed at our hospital. We assessed the VDS scores in all patients within 3 months of diagnosis. A decline in the ALS functional rating scale revised (ALSFRS-R) scores was used as an indicator of disease progression. As a result, we found that the VDS score of the pharyngeal phase and the total VDS score were significantly correlated with the ΔALSFRS-R scores. These scores were also associated with the existing indicators for the timing of gastrostomy, i.e., decreased body weight and percent-predicted forced vital capacity. We demonstrated the noninferiority of the VDS scores relative to the existing indicators. In addition, the VDS score of the pharyngeal phase was significantly correlated with the time from diagnosis to gastrostomy. The VDS score could estimate the timing of gastrostomy in patients with ALS with dysphagia at diagnosis.

We recently reported the decrease in the number of gastrointestinal (GI) cancer diagnoses in 2020 due to disturbance of the healthcare system by the coronavirus disease 2019 (COVID-19) pandemic, using a hospital-based cancer registration system in Akita prefecture, Japan. In this study, we extended the research by showing the latest data (2021) on the number of cancers and examinations. Information on the occurrence and stage of esophageal, gastric, and colorectal cancers was collected from the same database. The number of GI examinations (cancer screening procedures and endoscopic examinations) was also investigated. Following the immediate decrease in the numbers of both GI examinations and GI cancer diagnoses in 2020, a rebound increase in the numbers of GI cancer diagnoses—especially colorectal cancers—was observed in 2021, resulting from an increased number of GI examinations i.e., the total number of colorectal cancers in 2021 increased by 9.0% and 6.8% in comparison to 2020 and pre-pandemic era, respectively. However, the rebound increase in 2021 was largely due to an increase in early-stage cancers, and there was no apparent trend toward the increased predominance of more advanced cancers. It therefore seems that we managed to escape from the worst-case scenario of disturbance of the healthcare system due to pandemic (i.e., an increase in the number of more advanced cancers due to delayed diagnoses). We need to continue to watch the trends in Akita prefecture, which has the highest rate of mortality from the 3 major GI cancers in Japan.

Adequate physical activity during pregnancy is crucial for maternal and fetal health. Although physical activity during pregnancy is restricted, social support and trust may have a favorable influence on physical activity. This study aimed to examine the association between cognitive social capital during pregnancy and prenatal physical activity among Japanese individuals. We also investigated whether social capital has an extended influence during pregnancy on physical activity 1.5 years after delivery. The cognitive social capital of 3,055 pregnant women in their second trimester was measured using nine questions on a self-administered questionnaire. Each cognitive social capital was classified into two or four groups based on their scores. Physical activity during pregnancy was measured using a validated questionnaire in the second trimester and at 1.5 years after delivery. Participants were classified as having adequate physical activity (≥ 150 min/week) or inadequate physical activity (< 150 min/week) based on the physical activity guidelines during pregnancy. After adjusting for confounders, emotional support was positively associated with the prevalence of adequate prenatal physical activity (P for trend = 0.002). Moreover, there was a positive association between emotional support during pregnancy and the prevalence of adequate physical activity 1.5 years after delivery. Among Japanese women, emotional support during pregnancy was associated with a higher prevalence of adequate prenatal physical activity during pregnancy and at 1.5 years after delivery.

The incidence of Brucella canis (B. canis) in humans is unknown in Northern Cyprus. In this study, we investigated the prevalence of B. canis and Brucella abortus (B. abortus) infection in human sera and evaluated the results obtained by agglutination-based techniques using standardized antigens made from B. canis comparatively. All of the subjects were negative in terms of Rose-Bengal plate test. Undiluted serum samples were initially screened by rapid slide agglutination test (RSAT), and those which were found positive were retested in the dilution of 1/25-1/200. Confirmation of the positive results was performed by using 2-mercaptoethanol standard agglutination test (SAT). The test antigen was prepared from the less mucoid M (−) variant of B. canis, and 1/1,048 titered dog antiserum was used as positive control. In 225 serum samples, 3.6% (8/225) was positive by B. canis M (−) RSAT, 4.4 % (10/225) was positive by B. canis M (−) indirect enzyme-linked immunosorbent assay (iELISA). 5.3% (12/225) was positive by B. abortus S99 RSAT and 9.8% (22/225) was positive by B. abortus S99 iELISA. Nine samples were positive by both B. abortus S99 RSAT and B. abortus S99 iELISA. Seven samples were positive by both B. canis M (−) RSAT and B. canis M (−) iELISA. One patient was positive by all methods. It is important to evaluate patient samples with RSAT and iELISA. Until the notification system gives better results to the Ministry of Health, in order to reach the real data for Northern Cyprus, multicenter prevalence determination studies should be done for future.

Gestational diabetes mellitus (GDM) is a state of pre-diabetic impaired glucose tolerance initially occurring during pregnancy. Although abnormalities in glucose metabolism normally resolve rapidly after delivery, women with GDM have a higher lifetime risk of developing diabetes mellitus than those without GDM; thus, postpartum healthcare is essential. Of all GDM patients, 5%-10% test positive for diabetes-related autoantibodies, which increase the risk of developing type 1 diabetes mellitus (T1DM). Autoantibody measurement in GDM screening remains debatable; however, it may be useful for the postnatal follow-up of GDM patients at high risk of developing T1DM. We treated a 29-year-old woman who was GDM positive for anti-glutamic acid decarboxylase antibody (GADA) requiring high-dose insulin therapy during pregnancy. As the patient tested positive for GADA, she received judicious postpartum management, allowing for early diagnosis of T1DM and resumption of treatment. Her insulin secretory capacity was preserved at 1 year after parturition, suggesting either slowly progressive insulin-dependent T1DM or latent autoimmune diabetes in adults. This was a rare case of slowly progressive insulin-dependent T1DM or latent autoimmune diabetes in adults in the early postpartum period, but the fact that GADA was positive during pregnancy enabled early treatment without overlooking it. Measuring diabetes-related autoantibodies in patients considered to be at a high risk for T1DM, such as those who are of slim build, young, or suffering from autoimmune thyroid disorders, may be important for appropriate individualized follow-up.

In Japan, a new medical specialist system started in 2018 and has established the “Comprehensive Medical Specialist” program. The Japan Medical Agency allows specially-appointed supervisors, such as specialists in particular branches of internal medicine, to transfer to the “general practitioner” program. These specialists are often considered as reserve general practitioners. In April 2016, we conducted a survey of 2,666 randomly selected specialists in 11 societies related to the Japanese Society of Internal Medicine. Of the 404 who responded (15.2% response rate), 142 (35.1%) were “certification-oriented.” Logistic regression analysis with the outcome of desire for certification as a general practitioner (yes = 1) showed odds of 2.293 (95% confidence interval: 1.379-3.811) for “cannot take the necessary time to prepare” and 12.417 (95% confidence interval: 2.856-53.986) for “should be eligible to take the exam without leaving my current job.” Creating an environment that allows specialists in internal medicine across various specialties to prepare for certification as a general practitioner, while continuing to work in their current positions, would help to increase the number of high-quality general practitioners to supply the need in Japan.