Histopathological changes in tear-secreting tissues and cornea in a mouse model of autoimmune disease

The tear film covers the cornea, and its abnormalities (including immunological) induce dry eye. Using autoimmune disease model mice, BXSB/MpJ-Yaa (BXSB-Yaa), histopathological changes in the eye and tear-secreting tissues were examined using histopathology, immunohistochemistry, and electron microscopy at 8, 20, and 28 weeks for early, middle, and late disease stages. Early and middle stage BXSB-Yaa showed increased serum autoantibody and spleen weight-to-body weight (S/B) ratio, respectively, and higher tear volume than controls, BXSB/MpJ (BXSB), at early stages, which decreased with ageing and negatively correlated with autoimmune disease indices. Smaller Meibomian gland acini, intraorbital lacrimal glands, and Harderian gland acinar cells were seen in late stage BXSB-Yaa than in BXSB; the latter two indices decreased with ageing and negatively correlated with the S/B ratio. Cell infiltration occurred in the middle stage BXSB-Yaa extraorbital lacrimal gland, and acinar cells were smaller than BXSB. The conjunctival goblet cells decreased from early to middle stages in both strains, but in BXSB-Yaa, they increased at late stages with a partial lack of microvilli on the cornea and were inversely altered with anterior epithelium thickness through ageing, suggesting that they compensated for anterior epithelium damage. In conclusion, the tear film was unstable due to an autoimmune disease condition in BXSB-Yaa. Impact statement Cornea, an outermost layer of mammalian eye, is protected by tear film and abnormalities of tear film causes dry eye. Dry eye injures the cornea which results lower vision in patients. Several factors cause dry eye, including altered systemic conditions, environment, and immunological abnormality of the patient in autoimmune disease like Sjogren's syndrome (SS). However, the detailed pathology of autoimmune abnormality-mediated dry eye is unclear. Here we demonstrated that systemic autoimmune abnormality in BXSB-Yaa mice was associated with histological changes in the exocrine glands and cornea of the eyes. We also showed that BXSB-Yaa mice developed mild or early stage dry eye-like disease and explain the existence of a compensatory mechanism associated with the dysfunction of these tissues. Thus, BXSB-Yaa could be a model for SS-like disease-associated dry eye and these data would contribute to the understanding of the pathogenesis of autoimmune-related dry eye disease

Adjuvant chemotherapy versus chemoradiotherapy for small cell lung cancer with lymph node metastasis: a retrospective observational study with use of a national database in Japan

Abstract Background The optimal postoperative treatment strategy for small cell lung cancer (SCLC) remains unclear, especially in patients with lymph node metastasis. We aimed to compare the outcomes of patients with SCLC and lymph node metastasis treated with postoperative adjuvant chemotherapy or chemoradiotherapy. Methods We retrospectively collected data on patients with postoperative SCLC diagnosed with N1 and N2 lymph node metastasis from the Diagnosis Procedure Combination database in Japan, between July 2010 and March 2015. We extracted data on patient age, sex, comorbidities, and TNM classification at lung surgery; operative procedures, chemotherapy drugs, and radiotherapy during hospitalization; and discharge status. Recurrence-free survival was compared between the chemotherapy and chemoradiotherapy groups using multivariable Cox regression analysis. Results Median recurrence-free survival was 1146 days (95% confidence interval [CI], 885–1407) in the chemotherapy group (n = 489) and 873 days (95% CI, 464–1282) in the chemoradiotherapy group (n = 75). There was no significant difference between these after adjusting for patient backgrounds (hazard ratio, 1.29; 95% CI, 0.91–1.84). Conclusions There was no significant difference in recurrence-free survival between patients with SCLC and N1-2 lymph node metastasis treated with postoperative adjuvant chemotherapy and chemoradiotherapy. Further randomized clinical trials are needed to address this issue

Author's personal copy Bacillus Calmette-Guérin vaccination using a microneedle patch

a b s t r a c t Tuberculosis (TB) caused by Mycobacterium tuberculosis continues to be a leading cause of mortality among bacterial diseases, and the bacillus Calmette-Guérin (BCG) is the only licensed vaccine for human use against this disease. TB prevention and control would benefit from an improved method of BCG vaccination that simplifies logistics and eliminates dangers posed by hypodermic needles without compromising immunogenicity. Here, we report the design and engineering of a BCG-coated microneedle vaccine patch for a simple and improved intradermal delivery of the vaccine. The microneedle vaccine patch induced a robust cell-mediated immune response in both the lungs and the spleen of guinea pigs. The response was comparable to the traditional hypodermic needle based intradermal BCG vaccination and was characterized by a strong antigen specific lymphocyte proliferation and IFN-␥ levels with high frequencies of CD4 + IFN-␥ + , CD4 + TNF-␣ + and CD4 + IFN-␥ + TNF-␣ + T cells. The BCG-coated microneedle vaccine patch was highly immunogenic in guinea pigs and supports further exploration of this new technology as a simpler, safer, and compliant vaccination that could facilitate increased coverage, especially in developing countries that lack adequate healthcare infrastructure

Effect of Hangeshashin-To (Japanese Herbal Medicine Tj-14) on Tolerability of Irinotecan: Propensity Score and Instrumental Variable Analyses

Irinotecan hydrochloride (CPT-11) is used to treat a wide spectrum of malignant tumors. Hangeshashin-to (Japanese herbal medicine TJ-14) is reportedly effective in preventing and controlling diarrhea associated with CPT-11. However, the effect of TJ-14 on tolerability of chemotherapy with CPT-11 has not been fully investigated. We used the Japanese Diagnosis Procedure Combination inpatient database to retrospectively identify patients who had received CPT-11 on their first admission with and without TJ-14. Patients who did receive TJ-14 (N = 7092) received CPT-11 more often and in larger doses than those who did not receive TJ-14 (N = 82,019). The incidence rate ratio of CPT-11 administration was 1.34 for frequency (95% confidence interval [CI], 1.31–1.38; p < 0.001), and 1.16 for total dose (95% CI, 1.14–1.19; p < 0.001) according to stabilized inverse probability treatment weighting using propensity scores. Instrumental variable analysis showed similar trends. In-hospital mortality was significantly lower in patients who received TJ-14 than in those who did not. Odds ratios of in-hospital death in patients receiving TJ-14 was 0.81 (95% CI, 0.71–0.93; p = 0.002) according to stabilized inverse probability treatment weighting using propensity scores and 0.42 (95% CI, 0.22–0.81; p = 0.009) according to instrumental variable analysis. Our findings indicate that TJ-14 improve the tolerability of CPT-11