Tumor necrosis factor receptor-associated factor 3 (TRAF3) is an anti-inflammatory molecule that negatively regulates the non-canonical nuclear factor-κB pathway. Although TRAF3 haploinsufficiency (TRAF3 HI) can influence innate and adaptive immune cells, its effect on inflammatory bowel disease (IBD) development remains unclear. Here, we report the first case of severe early-onset IBD with a novel TRAF3 variant leading to HI, successfully treated with ustekinumab. A 6-year-old girl with a recurrent parotitis, otitis media, tonsilitis, and atopic dermatitis developed IBD involving the stomach, small intestine, and colon. At diagnosis, the immunoglobulin (Ig)G and IgA levels were relatively high, and lymphocyte subsets showed increased counts of plasmablasts, class-switch recombination B cells, and circulating T-follicular helper cells. Treatment with azathioprine and infliximab failed to maintain remission marked by several relapses accompanied by erythema nodosum and arthritis; however, ustekinumab, an anti-interleukin (IL)-12/23p40 antibody, led to long-term clinical remission, normalizing the Ig level and reducing abnormal lymphocyte counts. Whole-exome sequencing revealed a novel heterozygous mutation in TRAF3 [p.(Pro487Leufs*8)], resulting in TRAF3 under-expression. Our case may highlight the contribution of TRAF3 HI to the development of IBD and provide insights into IBD pathophysiology, suggesting the involvement of the IL-12/23-T-follicular helper cell pathway affected by genetic mutations.

We here report three cases of choroidal metastases with ocular pain and visual symptoms treated with palliative irradiation. Case 1: A 71-year-old woman was treated with chemotherapy for multiple metastases after surgery for right breast cancer. Sixteen years after surgery, a right choroidal metastasis with ocular pain and visual disturbance was detected. Palliative irradiation to this lesion achieved reduction in ocular pain and shrank the tumor. Case 2: A 54-year-old man presented with right ocular pain and abnormal vision and was diagnosed as having right lung cancer with multiple systemic metastases. Palliative irradiation to a right choroidal metastasis achieved reduction in ocular pain and shrank the tumor. Case 3: A 71-year-old woman developed left eye pain 17 months after surgery for lung cancer in the right upper lobe. She was diagnosed as having a left choroidal metastasis. After palliative irradiation, the tumor shrank and the left eye pain temporarily resolved. Palliative radiation therapy for choroidal metastasis with ocular pain and visual symptoms seems to be effective in improving symptoms.

Objective: To determine the characteristics associated with mortality in patients with culture-positive pulmonary tuberculosis (PTB) in Airin, Osaka City, Japan. Methods: The characteristics of patients with culture-positive PTB registered between 2015 and 2018 in Airin, Osaka City, Japan, were compared between those who died of all causes before or during treatment and those who completed treatment. Results: Of the 241 culture-positive PTB patients eligible for this study, 170 completed treatment, with negative sputum culture tests, and 62 died. The all-cause case fatality rate was 26.7% (62/232). Multivariate analysis showed that mortality was associated with age >70 years, having a positive sputum smear, a body mass index of <18.5 and serious comorbidities such as cancer and heart and renal disease. Detection of tuberculosis (TB) by screening or in an outpatient department (OPD) for other diseases was inversely associated with mortality. Discussion: Detection of PTB by chest X-ray screening and during regular visits to OPDs for other diseases was associated with non-fatal TB and might contribute to early case finding. Therefore, current active TB case finding and health education on regular visits to physicians for other diseases should be strengthened further for the urban poor population of Osaka City, Japan.

Since the airways are constantly exposed to various pathogens and foreign antigens, various kinds of cells in the airways—including structural cells and immune cells—interact to form a precise defense system against pathogens and antigens that involve both innate immunity and acquired immunity. Accumulating evidence suggests that innate lymphoid cells (ILCs) play critical roles in the maintenance of tissue homeostasis, defense against pathogens and the pathogenesis of inflammatory diseases, especially at body surface mucosal sites such as the airways. ILCs are activated mainly by cytokines, lipid mediators and neuropeptides that are produced by surrounding cells, and they produce large amounts of cytokines that result in inflammation. In addition, ILCs can change their phenotype in response to stimuli from surrounding cells, which enables them to respond promptly to microenvironmental changes. ILCs exhibit substantial heterogeneity, with different phenotypes and functions depending on the organ and type of inflammation, presumably because of differences in microenvironments. Thus, ILCs may be a sensitive detector of microenvironmental changes, and analysis of their phenotype and function at local sites may enable us to better understand the microenvironment in airway diseases. In this review, we aimed to identify molecules that either positively or negatively influence the function and/or plasticity of ILCs and the sources of the molecules in the airways in order to examine the pathophysiology of airway inflammatory diseases and facilitate the issues to be solved.
Adaptive Immunity ; Cellular Microenvironment ; Cytokines ; Homeostasis ; Immunity, Innate ; Inflammation ; Lymphocytes ; Neuropeptides ; Phenotype ; Plastics ; Population Characteristics ; Respiratory Tract Diseases

Objective: To identify individual characteristics related to the development of pulmonary tuberculosis (PTB) among residents in the Airin area (Airin), Osaka City, Japan. Methods: We conducted a retrospective case-control study of individual characteristics potentially related to the development of PTB by comparing PTB patients and residents without tuberculosis (TB) in Airin. The following binominal data of characteristics were compared: age (<65 or >65); body mass index (BMI) (<18.5 or >18.5); diabetes mellitus (diagnosed or not diagnosed); smoking (currently smoking any amount or not smoking); and alcohol use (currently drinking any amount or not drinking). Results: We compared the individual characteristics of 192 PTB patients notified from January 2015 to December 2018 and 190 residents of supportive houses who attended a health education programme from April 2016 to March 2018. Univariable analysis showed that the following characteristics were significantly related with PTB: BMI <18.5 (odds ratio [OR]: 6.54, 95% confidence interval [CI]: 3.58–11.97, P < 0.001) and current alcohol use (OR: 1.88; 95% CI: 1.24–2.85, P = 0.003). Multivariable analysis showed similar results: BMI <18.5 (adjusted odds ratio [aOR]: 6.90, 95% CI: 3.72–12.79, P < 0.001) and current alcohol use (aOR: 2.15, 95% CI: 1.36–3.42, P = 0.001). Discussion Undernutrition and alcohol use are individual characteristics associated with PTB among residents in Airin, Osaka City. To strengthen the TB control programme further, it is suggested to develop new programmes for primary prevention.

Objectives: “Adverse Drug Reaction Relief System” (hereinafter called the Relief System) has been established to provide prompt relief to patients experiencing health damage caused by adverse drug reactions. Since 2018, the Relief System has required community pharmacies that acquire additional points as local support system to actively report adverse drug reactions. Here, we investigated the recognition and utilization of the relief system among community pharmacists.Method: A questionnaire survey was conducted among community pharmacists between August 1 and September 30, 2019.Results: The survey achieved a response rate of 58.1%. The recognition rates of the relief system and Pharmaceuticals and Medical Devices Agency (PMDA) as its application destination were 98.9 and 74.5%, respectively. Of the community pharmacists, 2.6% had experience in utilizing the relief system; and 8.8% did not want to recommend the utilization of the relief system for patients mainly because of the “low recognition of the system” and “the complicated and troublesome preparation of the necessary documents such as medical certificates.” The community pharmacists who acquire additional points as local support system, compared with those who do not, achieved significantly higher rates in two items, including that for preparation of the documented procedures pertaining to adverse drug reactions.Conclusion: Despite the high recognition of the relief system among community pharmacists, the percentage of pharmacists with experience in actually utilizing the relief system and applying to the PMDA was low. One reason that the use of the relief system was not widespread was the low recognition particularly of the destination and procedures of reports on adverse drug reactions. In the future, educational campaigns to improve pharmacists’ comprehension of the relief system will be needed. Moreover, pharmacists must play a central role in enhancing the recognition of the public relief system and promoting medical safety.

BACKGROUND: Adjuvants used in inactivated vaccines often upregulate type 2 immunity, which is dominant in allergic diseases. We hypothesised that cumulative adjuvant exposure in infancy may influence the development of allergies later in life by changing the balance of type 1/type 2 immunity. We examined the relationship between immunisation with different vaccine types and later allergic disease development. METHODS: We obtained information regarding vaccinations and allergic diseases through questionnaires that were used in The Japan Environment and Children's Study (JECS), which is a nationwide, multicentre, prospective birth cohort study that included 103,099 pregnant women and their children. We examined potential associations between the initial vaccination before 6 months of age and symptoms related to allergies at 12 months of age. RESULTS: Our statistical analyses included 56,277 children. Physician-diagnosed asthma was associated with receiving three (aOR 1.395, 95% CI 1.028-1.893) or four to five different inactivated vaccines (aOR 1.544, 95% CI 1.149-2.075), compared with children who received only one inactivated vaccine. Similar results were found for two questionnaire-based symptoms, i.e. wheeze (aOR 1.238, 95% CI 1.094-1.401; three vaccines vs. a single vaccine) and eczema (aOR 1.144, 95% CI 1.007-1.299; four or five vaccines vs. a single vaccine). CONCLUSIONS: Our results, which should be cautiously interpreted, suggest that the prevalence of asthma, wheeze and eczema among children at 12 months of age might be related to the amount of inactivated vaccine exposure before 6 months of age. Future work should assess if this association is due to cumulative adjuvant exposure. Despite this possible association, we strongly support the global vaccination strategy and recommend that immunisations continue. TRIAL REGISTRATION UMIN000030786 .
Asthma ; epidemiology ; etiology ; Cohort Studies ; Dermatitis, Atopic ; epidemiology ; etiology ; Female ; Food Hypersensitivity ; epidemiology ; etiology ; Humans ; Hypersensitivity ; epidemiology ; etiology ; Infant ; Infant, Newborn ; Japan ; Male ; Vaccines, Inactivated ; adverse effects ; Viral Vaccines ; adverse effects

Although pharmacy students receive professional education regarding dementia, it is the current state that many pharmacy students cannot learn the countermeasures to treat people with dementia. We conducted the “Otani dementia supporter education lecture” which improved a lecture by Caravan Mate targeting pharmacy students, and subjected the students to a questionnaire survey after the lecture. One hundred and forty-nine students participated and there were most percentages of third grades by 40.9%. After attending the lecture, most of the students opined that one can help a patient with dementia by understanding the patients’ feeling. It was the answer obtained by the lecture for the students to ensure that a pharmacist responds to consultations and requests from their family with a dementia patient. The first information that the students additionally wanted to know about dementia pertained to a method for the early detection of dementia. The results of text mining on the correspondence for patient with dementia showed that categories of “dementia patient,” “correspondence,” “understanding the patients’ feeling,” and “tact,” independently had strong mutual relations. Moreover, the results of text mining on the feedbacks obtained for the lecture showed that categories such as “dementia patient,” “When close person and one were,” “A chance was obtained,” and “correspondence” independently had significant mutual relations. Students who participate in this lecture understand that it is necessary to contact with dementia patients appropriately and feel that there is a need to become a presence that can support dementia patients as a pharmacist in the future. Therefore, this lecture was effective in motivation to correspondence to a person with dementia.

Background  The number of foreign tourists visiting Japan has increased to about 30 million people per year. 1.5% of them were injured or became sick during their travelin Japan and had to undergo medical treatment. Among the foreign tourists, 27% were not covered by travel health insurance.Case  A 40-year-old man from Southeast Asia who was visiting his relative in Japan experienced sudden hemiparesis and was diagnosed with cerebral infarction. During the initial treatment, it was found that the patient did not have health insurance and the relatives could not afford to pay the treatment costs. No other source of financial support was available to him During our consultations with the patient and his relatives about the medical treatment including medical expenses, he continued to be treated as an outpatient and it was aimed at an early return to his home country.Discussion  Foreigners, who are not covered under travel health insurance, could fall ill or sustain an injury during their stay in Japan. Appropriate medical care should be provided regardless of their ability to pay. However, a situation that could lead them to incur huge medical expenses from availing medical care should be avoided. For medical consultations of non-insured foreigners, it is better to consult the available systems and pay attention about feasible medical expenses. There is a need for a long-term vision of medical care to make a smooth transition from medical treatment in Japan to treatment in their home country.Conclusion  Although medical institutions can offer only a limited response, it is necessary to accumulate case examples from across the nation and prepare specific countermeasures and counselors.

Postsurgical persistent pain, once entrenched, may be resistant to western medical treatments. A 39-year-old man who underwent thoracic repair with blood vessel prosthesis for dissecting aneurysm was presented to our pain clinic due to postoperative persistent pain. He complained his pain mainly around the sternum on which skin became keloid scar and presented tactile allodynia. Initially, we treated the patient with pregabalin, duloxetine and tramadol/acetaminophen fixed-dose combination tablets, leading to no pain relief. Then, we started the treatments with Kampo medicine as well as Yamamoto New Scalp Acupuncture and Unblocking acupuncture. We initially treated him with keishibukuryogan (TJ-23 ; Tsumura ®, Japan) and saikokeishito (TJ-10 ;Tsumura ®, Japan) based on the signs of blood stasis, hypochondrial resistance and pain, but no relief of pain was obtained. Thus, we administered ogikeishigomotsuto in addition to the above Kampo formulas. His pain was gradually decreased with increasing doses of ogi from 3 to 10 g/day and aconite tuber from 1.5 to 6 g/day due to cold sensation, and finally disappeared at 20 months since the start of Kampo treatments. The duration of effectiveness for relieving his pain with acupuncture was gradually increased in proportion to his pain relief. Our experiences suggest that ogikeishigomotsuto with aconite tuber as well as acupuncture may be optimal treatments for the patients with cold sensation suffering from postsurgical persistent pain.