Ensuring continuous TB treatment across Asian borders.

BACKGROUND: Mid-treatment cross-border migration of patients with TB increases the risk of treatment interruption. OBJECTIVE: To establish a cross-border referral process for patients with TB in Japan, and enhance their access to health facilities and treatment outcomes. DESIGN: This prospective cohort study describes and assesses the process of foreign-born patients with TB who returned to their home countries during treatment, focusing on their access to healthcare facilities and treatment outcomes. RESULTS: We enrolled 135 foreign-born patients with TB, and confirmed that 112 (83.0%) were referred to and accessed healthcare facilities after returning to their home countries. Of 102 patients due to complete treatment as of July 2023, 87 (85.3%) completed their treatment. We did not identify significant differences in the treatment success rate among patient characteristics, except between the patients with confirmed access to a healthcare facility and those without (P < 0.001). We confirmed that 49/87 (56.3%) patients had completed treatment with official data. CONCLUSION: The access and treatment success rates of the cross-bordered patients with TB from Japan were >80%; however, we should further improve this proportion by confirming the treatment outcomes with official data.

CONTEXTE: La migration transfrontalière en milieu de traitement des patients atteints de TB augmente le risque d'interruption du traitement. OBJECTIF: Etablir un processus d'orientation transfrontalière pour les patients atteints de TB au Japon et à améliorer leur accès aux établissements de santé et les résultats de leur traitement. CONCEPTION: Cette étude de cohorte prospective décrit et évalue le processus des patients atteints de TB et nés à l'étranger qui sont retournés dans leur pays d'origine pendant le traitement, en se concentrant sur leur accès aux établissements de santé et sur les résultats du traitement. RÉSULTATS: Nous avons recruté 135 patients atteints de TB et nés à l'étranger et confirmé que 112 (83,0%) ont été orientés vers des établissements de santé et y ont accédé après leur retour dans leur pays d'origine. Des 102 patients qui devaient terminer leur traitement en juillet 2023, 87 (85,3%) l'ont terminé. Nous n'avons pas identifié de différences significatives dans le taux de réussite du traitement en fonction des caractéristiques des patients, sauf entre les patients ayant un accès confirmé à un établissement de santé et ceux qui n'en ont pas (P < 0,001). Nous avons confirmé que 49 (56,3%) des 87 patients avaient terminé leur traitement à l'aide des données officielles. CONCLUSION: Les taux d'accès et de réussite du traitement des patients transfrontaliers atteints de TB en provenance du Japon étaient >85% ; cependant, nous devrions encore améliorer cette proportion en confirmant les résultats du traitement à l'aide de données officielles.

Cutaneous ischemia-reperfusion injury is exacerbated by IL-36 receptor antagonist deficiency.

BACKGROUND: Loss-of-function homozygous or compound heterozygous mutations in IL36RN, which encodes interleukin-36 receptor antagonist (IL-36Ra), has been implicated in the pathogenesis of skin disorders. However, the pathogenic role of IL-36Ra in cutaneous ischemia-reperfusion (I/R) injury remains unclear. OBJECTIVES: We investigated the role of IL36Ra in cutaneous I/R injury. METHODS: We examined I/R injury in Il36rn-/- mice. The area of wounds, numbers of infiltrated cells, apoptotic cells and neutrophil extracellular trap (NET) formation were assessed. The expression levels of various genes were analysed using real-time RT-PCR. The expression of high mobility group box 1 (HMGB1), an endogenous toll-like receptor (TLR) 4 ligand, was confirmed using immunohistology, and serum HMGB1 levels were measured by ELISA. Cytokine production by stimulated cultured J774A.1 and HaCaT cells was examined. RESULTS: IL-36Ra deficiency resulted in significantly delayed wound healing and increased neutrophil and macrophage infiltration into the wound tissues. Il36rn-/- mice had increased mRNA expression levels of CXCL1, CXCL2, CCL4, TNF-α, TGF-ß, IL-1ß, IL-6 and IL-36γ relative to wild-type mice. Apoptosis was identified in keratinocytes by TUNEL assay. HMGB1 expression in the I/R site was decreased in both keratinocytes and adnexal cells, while serum HMGB1 levels were significantly elevated after reperfusion. The mRNA levels of various cytokines, including IL-1ß, were elevated in J774A.1 cells through TLR4 signalling by HMGB1 stimulation. In addition, HaCaT cells stimulated with IL-1ß showed significantly increased CXCL1, TNF-α, IL-6, IL-36ß and IL-36γ mRNA expression. Furthermore, NET formation was increased by IL-36Ra deficiency. Finally, either the blockade of TLR4 signalling by TAK-242 or inhibition of NET formation by Cl-amidine normalized exacerbated I/R injury in Il36rn-/- mice. CONCLUSIONS: This study indicated that IL-36Ra deficiency exacerbates cutaneous I/R injury due to excessive inflammatory cell recruitment, NET formation, and excessive cytokine and chemokine production via the TLR4 pathway by HMGB1 released from epidermal apoptotic cells.

Roles of aberrant hemichannel activities due to mutant connexin26 in the pathogenesis of KID syndrome.

Germline missense mutations in GJB2 encoding connexin (Cx) 26 have been found in keratitis, ichthyosis and deafness (KID) syndrome. We explored the effects of three mouse Cx26 mutants (Cx26-G12R, -G45E and -D50N) corresponding to KID syndrome-causative human mutants on hemichannel activities leading to cell death and the expression of immune response-associated genes. We analyzed the 3D images of cells expressing wild-type (WT) or mutant Cx26 molecules to demonstrate clearly the intracellular localization of Cx26 mutants and hemichannel formation. High extracellular Ca2+ conditions lead to the closure of gap junction hemichannels in Cx26-G12R or Cx26-G45E expressing cells, resulting in prohibition of the Cx26 mutant-induced cell death. Fluorescent dye uptake assays revealed that cells with Cx26-D50N had aberrantly high hemichannel activities, which were abolished by a hemichannel blocker, carbenoxolone and 18α-Glycyrrhetinic acid. These results further support the idea that abnormal hemichannel activities play important roles in the pathogenesis of KID syndrome. Furthermore, we revealed that the expressions of IL15, CCL5, IL1A, IL23R and TLR5 are down-regulated in keratinocytes expressing Cx26-D50N, suggesting that immune deficiency in KID syndrome expressing Cx26-D50N might be associated not only with skin barrier defects, but also with the down-regulated expression of immune response-related genes.

Granulocyte and monocyte apheresis can control juvenile generalized pustular psoriasis with mutation of IL36RN.

Patients with deficiency of interleukin-36 receptor antagonist (DITRA), due to mutation of IL36RN, exhibit psoriatic phenotypes, typically generalized pustular psoriasis (GPP). We report a paediatric patient with DITRA, whose cutaneous lesions varied from psoriasis vulgaris in infancy to annular pustular psoriasis with acute exacerbation to GPP at 13 years of age. Conventional systemic treatments for GPP, which include oral retinoids, ciclosporin and methotrexate, are controversial in paediatric cases, because of their adverse effects and uncertain long-term consequences. Granulocyte monocyte apheresis, a process associated with few adverse events, promptly controlled the GPP of our paediatric patient, and has potential as a suitable alternative treatment for paediatric patients with DITRA.

The age, breed and sex pattern of diagnosis for veterinary care in insured cats in Japan.

OBJECTIVES: To estimate the annual prevalence of different diagnostic categories by age, breed and sex in insured cats in Japan for which veterinary care claims had been made, and to identify if there is a pattern in these host factors. MATERIALS AND METHODS: Data from 48,187 cats insured for veterinary care in Japan in the period from April 2012 to March 2013 comprising 26,003 males and 22,184 females were analysed to calculate the annual prevalence of 18 diagnostic categories of disease by age, breed and sex. RESULTS: The prevalence was highest for urinary system disorders (12·2% for males and 10·0% for females), followed by digestive disorders (11·6% for males and 10·7% for females) and dermatological diseases (8·7% for males and 9·0% for females). The male cats had a higher prevalence than female cats for most diagnostic categories. The prevalence of cardiovascular, urinary, endocrine and neoplastic disorders increased with age; infectious and parasitic diseases had high prevalence at young ages, and the prevalence of respiratory, musculoskeletal disorders and injuries had bimodal peaks. Dermatological disorders had a high prevalence at all ages. A large variation in prevalence was observed between breeds for otic, dermatological, dental and cardiovascular disorders. CLINICAL SIGNIFICANCE: The findings can be used to increase awareness of patterns of health disorders in different categories of cat.

Quantitative risk assessment of the introduction of rabies into Japan through the importation of dogs and cats worldwide.

Japan has been free from rabies since 1958. A strict import regimen has been adopted since 2004 consisting of identification of an animal with microchip, two-time rabies vaccination, neutralizing antibody titration test and a waiting period of 180 days. The present study aims to quantitatively assess the risk of rabies introduction into Japan through the international importation of dogs and cats and hence provide evidence-based recommendations to strengthen the current rabies prevention system. A stochastic scenario tree model was developed and simulations were run using @RISK. The probability of infection in a single dog or cat imported into Japan is estimated to be 2·16 × 10-9 [90% prediction interval (PI) 6·65 × 10-11-6·48 × 10-9]. The number of years until the introduction of a rabies case is estimated to be 49 444 (90% PI 19 170-94 641) years. The current import regimen is effective in maintaining the very low risk of rabies introduction into Japan and responding to future changes including increases in import level and rabies prevalence in the world. However, non-compliance or smuggling activities could substantially increase the risk of rabies introduction. Therefore, policy amendment which could promote compliance is highly recommended. Scenario analysis demonstrated that the waiting period could be reduced to 90 days and the requirement for vaccination could be reduced to a single vaccination, but serological testing should not be stopped.

Case report of multiple pustules of the bilateral lower limbs caused by a granulocyte colony-stimulating factor-producing solid pseudopapillary tumour of the pancreas.

Here we report a rare case of neutrophilic dermatoses related to a granulocyte colony-stimulating factor (G-CSF)-producing solid pseudopapillary tumour (SPT). The patient was a 39-year-old woman presenting with scattered pustules and crusts of the palms, heels and thighs and plaques of the bilateral lower legs. The skin biopsy revealed dense neutrophil infiltration in the epidermis to the dermis. A pancreatic head tumour was detected using computed tomography. A pathological examination of the resected specimen suggested an SPT. As the skin eruption promptly disappeared after SPT resection, we hypothesized that SPT secretes growth factors including epidermal growth factor (EGF) and G-CSF. The SPT cells stained positive for both EGF and G-CSF tumour cells. The serum levels of interleukin (IL)-6 and IL-10 and tumour necrosis factor-α were within normal limits before and after the SPT resection. In contrast, the serum IL-8, EGF and G-CSF levels decreased after the SPT resection. This is a rare case of neutrophilic dermatoses related to a G-CSF-producing SPT. The present case suggests that physicians should be aware that a G-CSF-producing tumour is a differential diagnosis to consider in patients with unusual aseptic pustulosis.