Real-world treatment outcomes of metastatic biliary tract cancer patients in Japan: the Tokushukai REAl-world data project 04 (TREAD 04).

OBJECTIVES: To investigate temporal trends in treatment patterns and prognostic factors for overall survival in patients with metastatic biliary tract cancer. METHODS: From the Tokushukai REAl-world Data project, we identified 945 patients with metastatic biliary tract cancer treated with gemcitabine, tegafur/gimeracil/oteracil, gemcitabine plus cisplatin, gemcitabine plus tegafur/gimeracil/oteracil or gemcitabine plus cisplatin and tegafur/gimeracil/oteracil between April 2010 and March 2022. Stratified/conventional Cox regression analyses were conducted to examine the association between overall survival and patient- and tumour-related factors, study period, hospital volume, hospital type and first-line chemotherapy regimen. Using inverse probability of treatment weighting with propensity scores, overall survival was also compared between monotherapy and combination therapy groups. RESULTS: We enrolled 366 patients (199 men; median age, 72 years). Over a median follow-up of 5.2 months, the median overall survival was 7.0 months (95% confidence interval 6.2-9.0), and the median time to treatment failure was 3.5 months (95% confidence interval 3.1-4.5). Median overall survival and time to treatment failure for gemcitabine/tegafur-gimeracil-oteracil/gemcitabine plus cisplatin/gemcitabine plus tegafur-gimeracil-oteracil/gemcitabine plus cisplatin and tegafur-gimeracil-oteracil regimen were 6.2/6.6/7.9/16.2/15.1 and 2.8/3.4/4.1/15.3/7.4 months, respectively. Primary disease site, previous surgery, previous endoscopic procedures and hospital type were identified as significant prognostic factors. Inverse probability of treatment weighting analysis demonstrated that combination therapy had a significantly better prognosis than monotherapy (hazard ratio 0.61, 95% confidence interval 0.43-0.88, P = 0.006). CONCLUSIONS: Our real-world data analysis showed that standard care for metastatic biliary tract cancer is widely used in hospitals throughout Japan and verified the survival benefits of combination therapy over monotherapy observed in prior clinical trials. CLINICAL TRIAL NUMBER: UMIN000050590 (http://www.umin.ac.jp/ctr/index.htm).

Recurrence of Large-Vessel Vasculitis Induced by Multiple Types of Granulocyte Colony-Stimulating Factor Preparation in Patient with Large-Cell Neuroendocrine Lung Carcinoma: A Case Report.

With the increased use of granulocyte colony-stimulating factor (G-CSF) preparations, there is concern about the increase in G-CSF-associated large-vessel vasculitis; however, there have been no previous reports of vasculitis caused by multiple types of G-CSF preparations. We experienced a case of drug-induced large-vessel vasculitis caused by two different G-CSF products, which was difficult to diagnose. When treating patients with a history of large-vessel vasculitis caused by pegfilgrastim, we need to pay attention to its recurrence when using other G-CSF preparations.

Validation of the LPA-SQUASH in post-liver-transplant patients.

AIM: This study aimed to validate the revised Short Questionnaire to Assess Health-Enhancing Physical Activity (SQUASH) to measure sedentary activity in post-liver-transplant patients. The proposed scale could be useful for transplantation nurses to assess and modify sedentary lifestyles and increase physical activity. METHODS: The SQUASH was modified to include items on sitting time and light-intensity physical activity (LPA-SQUASH). A pilot study was conducted with 20 liver transplant patients, and an expert panel validated the scale contents. Then, post-liver-transplant outpatients at a Japanese university hospital participated in the main study (September-October 2020), in which questionnaires were mailed twice to assess test-retest reliability, and accelerometers used to establish criterion validity. Intra-class correlation coefficients (ICC) were calculated for test-retest reliability. Spearman correlations and Bland-Altman plots were used to assess validity and measurement error. RESULTS: In total, 173 participants returned the questionnaires, and 106 and 71 completed the reliability and validation studies, respectively. The range of LPA-SQUASH correlation coefficients for test-retest was .49-.58. ICCs ranged from .72 to .80 for items other than leisure. Accelerometer data and the LPA-SQUASH total physical activity amount and light-intensity physical activity correlated moderately. CONCLUSION: We modified the SQUASH, which was developed to measure physical activity in healthy adults, to assess light-intensity physical activity in post-liver-transplant patients. The LPA-SQUASH showed acceptable validity and reliability. The questionnaire may be used by transplantation nurses to examine light-intensity physical activity content/duration, deliver patient education considering patients' sedentary lifestyle, and facilitate goal setting for physical activity interventions to prevent metabolic syndrome.

Long-term health-related quality of life of total hip arthroplasty patients and cost-effectiveness analysis in the Japanese universal health insurance system.

AIM: Total hip arthroplasty can effectively improve patients' motility with end-stage osteoarthritis. This study aimed to: (1) compare gradual changes in utility values with total hip arthroplasty and estimated values without; (2) evaluate total hip arthroplasty cost-effectiveness; and (3) evaluate cost-effectiveness by age, diagnosis, and comorbidity. METHODS: Patients who underwent total hip arthroplasty between January 2008 and December 2009 were included. Patients completed the EuroQol preoperatively and at 1, 3, 5 and 7 years postoperatively. To derive the quality-adjusted life years gained, a utility score was obtained from the EuroQol item scores and combined with 7 years, and estimates were obtained by discounting the postoperative 1-year utility value at an annual rate of 2%-4%. Mixed-effects regression models were used to compare the estimated and the measured utility values. RESULTS: Mean total cost was 1,921,849 yen, and quality-adjusted life years gain score was 1.746 with per cost as 1,100,715 yen. Compared with actual measurements, the estimated values from 1 to 7 years post-surgery differed significantly, and interaction was observed. Regarding age, the older the patient, the higher the cost per quality-adjusted life years. Patients with lower preoperative physical function had higher quality-adjusted life years gains, while the cost per quality-adjusted life years was lower. CONCLUSIONS: Total hip arthroplasty was cost-effective. Compared with actual measurements, the estimated utility values from 1 to 7 years post-surgery significantly differed. Even among older patients and those with impaired preoperative physical functions, its cost was lower than patients' willingness to pay in Japan.

Significance of localized expression of full-length growth differentiation factor-15 in cachexia of advanced non-small cell lung cancer.

PURPOSE: Growth differentiation factor-15 (GDF-15) is one of the key cachexia-inducing factors. Clinical trials on therapies targeting GDF-15 for cancer and cancer cachexia are underway. While the role of circulating GDF-15 in cachexia has been clarified, the effects of GDF-15 expression within cancer cells remain to be fully elucidated. Hence, the objective of this study was to investigate the expression of GDF-15 in advanced lung cancer tissues and to understand its role in cachexia. METHODS: We retrospectively examined the expression level of full-length GDF-15 in advanced non-small cell lung cancer tissues and analyzed the relationship between the staining intensity and clinical data in 53 samples. RESULTS: We found that 52.8% of the total samples were GDF-15 positive, and GDF-15 expression significantly correlated with improved C-reactive protein/albumin ratio (p = 0.008). It did not correlate with the existence of cancer cachexia and overall survival (p = 0.43). CONCLUSION: Our findings show that GDF-15 expression significantly correlated with improved C-reactive protein/albumin ratio, but not the existence of cancer cachexia in advanced NSCLC patients.

The landscape of cancer cachexia in advanced non-small cell lung cancer: a narrative review.

Background and Objective: Cancer cachexia presents with weight loss, anorexia, and fatigue and worsens the prognosis and quality of life of cancer patients. We aimed to summarize the current relevant discourse in the literature about cancer cachexia in the setting of non-small cell lung carcinoma and the possible current and future treatments. Methods: We conduct a narrative review of the literature on the landscape of cancer cachexia in the context of non-small cell lung cancer, multimodality therapy, markers, imaging, tumor biology, pathology, chemoprevention, and technical advances. Key Content and Findings: The need for appropriate intervention for cancer cachexia is increasing as the prognosis of patients with advanced non-small cell lung cancer is improving with advances in treatment. Tumor cells play a role in the pathogenesis of cachexia, where they release factors that elicit the production of inflammatory cytokines by the immune system resulting in decreased appetite, abnormal energy metabolism, and skeletal muscle degeneration. Comorbid chronic lung diseases are associated with pulmonary cachexia and sarcopenia and commonly occur in the context of lung cancer, further contributing to the increased incidence of cachexia in patients with lung cancer. Currently, a ghrelin-like agonist, anamorelin, is approved for the treatment of cancer cachexia and is used in clinical practice in Japan. The role that nutritional and exercise therapies can play as added treatments must be further explored. Conclusions: Cancer cachexia remains a poorly understood phenomenon, and awareness must be raised through educational activities for health care providers and patient family members. In addition, new therapeutics targeting cancer cachexia, such as GDF-15 antibodies, are in development, and further progress is expected.

Predictive value of p53 and AXL immunostaining for the efficacy of immune checkpoint inhibitor-based therapy after osimertinib treatment in patients with epidermal growth factor-mutant non-small cell lung cancer.

BACKGROUND: Current evidence indicates that immune checkpoint inhibitors (ICIs) have a limited efficacy in patients with lung cancer harboring epidermal growth factor receptor (EGFR) mutations. However, there is a lack of data on the efficacy of ICIs after osimertinib treatment, and the predictors of ICI efficacy are unclear. METHODS: We retrospectively assessed consecutive patients with EGFR-mutant NSCLC who received ICI-based therapy after osimertinib treatment at 10 institutions in Japan, between March 2016 and March 2021. Immunohistochemical staining was used to evaluate the expression of p53 and AXL. The deletions of exon 19 and the exon 21 L858R point mutation in EGFR were defined as common mutations; other mutations were defined as uncommon mutations. RESULTS: A total of 36 patients with advanced or recurrent EGFR-mutant NSCLC were analyzed. In multivariate analysis, p53 expression in tumors was an independent predictor of PFS after ICI-based therapy (p = 0.002). In patients with common EGFR mutations, high AXL expression was a predictor of shorter PFS and overall survival after ICI-based therapy (log-rank test; p = 0.04 and p = 0.02, respectively). CONCLUSION: The levels of p53 in pretreatment tumors may be a predictor of ICI-based therapy outcomes in patients with EGFR-mutant NSCLC after osimertinib treatment. High levels of AXL in tumors may also be a predictor of ICI-based therapy outcomes, specifically for patients with common EGFR mutations. Further prospective large-scale investigations on the predictors of ICI efficacy following osimertinib treatment are warranted.

Comparison of the prognosis of symptomatic cerebral infarction and pulmonary embolism in patients with advanced non-small cell lung cancer.

BACKGROUND: Lung cancer patients face a high risk of thromboembolism (TE), which is considered to be a poor prognostic factor. However, the impact of symptomatic cerebral infarction (CI) and pulmonary embolism (PE) on the prognosis of advanced non-small cell lung cancer (NSCLC) patients is not fully understood. METHODS: We retrospectively identified 46 patients with advanced NSCLC who developed symptomatic CI or PE at five hospitals in Japan between January 2010 and December 2019. Prognosis and biomarker levels after incident CI and PE were investigated. RESULTS: Of the 46 patients, 36 developed symptomatic CI, and 10 developed symptomatic PE. The median follow-up duration after incident CI and PE was 18.2 months. Although the proportion of Common Terminology Criteria for Adverse Events grade 4 tended to be higher in patients with PE than in those with CI (30% vs. 11%, p = 0.16), the overall survival (OS) after incident TE tended to be worse in patients with CI than in those with PE (median 2.3 months vs. 9.1 months, log-rank test p = 0.17). Multivariate analysis showed that OS after CI was worse in patients with high D-dimer (DD) levels than in those with low DD levels at the time of incident CI (median 1.3 months vs. 8.3 months, log-rank p < 0.001). CONCLUSIONS: This retrospective study demonstrated that the prognosis of patients tended to be poorer after CI than after PE. The DD levels at the time of incident CI might be a promising predictor of clinical outcomes in advanced NSCLC patients who develop CI.

Changes in Physical Activity Due to Fear of COVID-19 and Its Impact on Depression Among Post-Liver Transplant Patients in Japan: A Longitudinal Survey Study.

BACKGROUND Regular physical activity (PA) is important for maintaining mental and physical health after liver transplantation (LT); however, the fluctuations in routine PA during COVID-19 and its putative impacts are currently unknown. This study examined the changes in PA during the COVID-19 pandemic and explored its association with fear and depression during the pandemic. MATERIAL AND METHODS This longitudinal study included 83 LT patients whose PA was measured using the short form of the International Physical Activity Questionnaire before and during COVID-19. Fear of COVID-19 was estimated based on previous studies, and depression was assessed using the Patient Health Questionnaire-9. Participants were also asked about important sources of information on COVID-19. PA was classified as inactive or active depending on the changes in PA, and logistic regression analyses with PA as a dependent variable were conducted to explore the associations among PA, depression, and fear of COVID-19. RESULTS Moderate and high PA exhibited decreasing trends before and during the COVID-19 pandemic, especially in males. Fear of being infected with SARS-CoV-2, the virus that causes COVID-19, while shopping was significantly higher in females and was significantly independent of inactivity during the COVID-19 pandemic. Only 1 patient reported that their transplant center was their main source of information about COVID-19. Only 4.9% of the LT participants were depressed. CONCLUSIONS Our study results indicate the need to support the provision of accurate information about COVID-19 by health care professionals in transplant centers, especially for patients with low PA, to prevent PA decline in LT patients.

Carbon clusters on substrate surface for graphene growth- theoretical and experimental approach.

Growth morphology of carbon clusters deposited on different substrates were investigated by theoretical and experimental approach. For theoretical approach, molecular dynamics was employed to evaluate an adsorptive stability of different size of carbon clusters placed on different substrates. The adsorptive stability was estimated by the difference of total energy of supercell designed as carbon cluster placed on a certain crystal plane of substrate. Among the simulations of this study, carbon cluster flatly settled down on the surface of SrTiO[Formula: see text](001). The result was experimentally verified with layer by layer growth of graphene by pulsed laser deposition in carbon dioxide atmosphere. The absorptive stability can be useful reference for screening substrate for any target material other than graphene.

[Future Prospects of Cancer Cachexia].

Cancer cachexia(CC)is defined as a multifactorial syndrome that causes anorexia and an ongoing loss of skeletal muscle mass(with or without loss of fat mass). In 2011, the definition of CC was established and in 2021, the novel anti-CC drug, anamorelin was launched in Japan. A new era of CC treatment has begun. However, although anamorelin alone has been shown to increase appetite and lean body mass, it has not been shown to restore skeletal muscle function. Therefore, combined intervention therapy that combines nutrition and exercise interventions is required. Those non-pharmacologic therapy are not yet established, but clinical trials are currently underway in Japan or European countries. Further work on CC is underway to elucidate the mechanisms, establish biomarkers, develop new pharmacotherapies targeting the markers, establish new diagnostic and pathological assessment methods, and establish predictors of the efficacy of anamorelin.

Prognostic Nutritional Index and Lung Immune Prognostic Index as Prognostic Predictors for Combination Therapies of Immune Checkpoint Inhibitors and Cytotoxic Anticancer Chemotherapy for Patients with Advanced Non-Small Cell Lung Cancer.

Combination therapy with immune checkpoint inhibitors and cytotoxic chemotherapies (chemoimmunotherapy) is associated with significantly better survival outcomes than cytotoxic chemotherapies alone in patients with advanced non-small cell lung cancer (NSCLC). However, there are no prognostic markers for chemoimmunotherapy. The prognostic nutritional index (PNI) and lung immune prognostic index (LIPI) are prognostic biomarkers for immune checkpoint inhibitor (ICI) monotherapy or cytotoxic chemotherapies. Thus, we aimed to examine whether these factors could also be prognostic markers for chemoimmunotherapy. We retrospectively examined 237 patients with advanced NSCLC treated with chemoimmunotherapy. In the total group, the median overall survival (OS) was not reached, and the median progression-free survival (PFS) was 8.6 months. Multivariate analysis of OS and PFS revealed significant differences based on PNI and LIPI. Programmed cell death ligand 1 (PD-L1) was also significantly associated with OS and PFS. PNI and a PD-L1 tumor proportion score (TPS) of <50% and poor LIPI (regardless of PD-L1 TPS) were associated with poor prognosis. PNI and LIPI predicted survival outcomes in patients with advanced NSCLC treated with chemoimmunotherapy, especially in patients with PD-L1 TPS <50%. For patients in this poor category, chemoimmunotherapy may result in a worse prognosis than expected.

The effect of real-time monitoring of physical activity intensity in diabetic patients.

AIM: To evaluate the effects of an intensity display type accelerometer on diabetic patients' physical activity. METHODS: This was a two-arm, non-randomized controlled study. Both groups received information about the recommendation of 150 min/week moderate-to-vigorous physical activity (MVPA). The intervention group used an intensity display type accelerometer to monitor their physical activity intensity for 10 days at baseline and 3 months later. We compared intervention and control groups after 3 and 6 months. Primary outcomes were MVPA and number of steps over 7 days. Secondary outcomes were glycosylated hemoglobin (HbA1c), body mass index, and self-management. RESULTS: Of 62 participants, 30 and 32 were included in the intervention and control groups, respectively. Mean age in each group was 59.7 ± 10.8 and 58.8 ± 10.2 years, and mean HbA1c was 6.9 ± 0.9% and 6.9 ± 0.8%, respectively. There were no significant differences between the intervention and control groups at either time point, and no outcomes showed significant changes. In a subgroup analysis by physical activity intensity, MVPA of active individuals in the control group significantly decreased at 6 months from baseline. MVPA and number of steps among inactive individuals in the intervention group significantly increased at 6 months from baseline. Self-management of the intervention group showed a trend toward improvement, but HbA1c and body mass index showed no significant change. CONCLUSIONS: Monitoring physical activity intensity led to increased MVPA of inactive patients and maintained MVPA of active patients with diabetes mellitus. This straightforward intervention could be applied in clinical practice.

Impact of maintenance therapy following induction immunochemotherapy for untreated advanced non-small cell lung cancer patients.

PURPOSE: The primary objective of this study was to identify the potential predictors to assess the impact of maintenance therapy after induction immunochemotherapy in the real-world setting of patients with advanced non-small cell lung cancer (NSCLC). METHODS: We retrospectively identified 152 patients with advanced NSCLC who received immunochemotherapy at 8 hospitals in Japan between January 2019 and December 2019. Patients who received at least four cycles of induction immunochemotherapy and one cycle of maintenance therapy with immune checkpoint inhibitors were included. We investigated the biomarkers for progression-free survival (PFS) for maintenance therapy after induction immunochemotherapy. RESULTS: Out of the 92 patients with advanced NSCLC included in the study, 42 received maintenance therapy with cytotoxic agents, whereas 50 received maintenance therapy without cytotoxic agents. Among those who received maintenance therapy without cytotoxic agents, responders to prior immunochemotherapy had significantly longer PFS than non-responders (p = 0.004), except those with maintenance therapy with cytotoxic agents. In non-responders to prior immunochemotherapy, patients with maintenance therapy with cytotoxic agents had significantly longer PFS than those with maintenance therapy without cytotoxic agents (log-rank p = 0.007), whereas, among responders to prior immunochemotherapy, there was no significant difference in PFS for different maintenance regimens (log-rank p = 0.31). CONCLUSIONS: This retrospective study showed that response to prior immunochemotherapy was associated with clinical outcomes among patients with advanced NSCLC who received maintenance therapy.

A Retrospective Observational Study of Adverse Reactions Associated With Intravenous Immunoglobulin Infusion.

Background: Although intravenous immunoglobulin (IVIG) therapy is generally safe and well tolerated, adverse reactions (ARs) do occur. The majority of these ARs are mild and transient. Risk factors for ARs associate with IVIG infusions are not well established. This study investigated possible risk factors influencing the occurrence of IVIG-associated ARs. Study Design and Methods: This was a retrospective observational analysis of data accumulated over 5 years, including patient demographics, clinical condition, IVIG dosing regimens, number of IVIG infusions, and any ARs. Results: ARs were associated with IVIG in 4.9% of patients and 2.5% of infusions. By univariate analyses, ARs correlated with female sex, adult age, high dose IVIG, and autoimmune disease. Multivariate logistic regression identified three statistically significant of risk factors: on a per-patient basis, being female (p=0.0018), having neuromuscular disease (p=0.0002), and receiving higher doses of IVIG per patient body weight (p<0.001), on a per-infusion basis, being female (p < 0.001), being adolescents to middle age (p < 0.001), and having neuromuscular disease (p < 0.001). Conclusion: Neuromuscular disease emerged as one of the significant factors for ARs to IVIG.

[The Treatment of Cancer Cachexia].

Cancer cachexia is defined as a multifactorial syndrome that causes anorexia and an ongoing loss of skeletal muscle mass (with or without loss of fat mass). When patients got cachexia, the effectiveness and tolerance for anti-cancer therapy is reduced, leading to their poor prognosis. Although known as such disease, there had been no effective cure for cancer cachexia. Ghrelin is a peptide hormone that promotes appetite and improve cachexia. However, there is a limitation as a drug because its half-life is short and must be intravenous injected. Anamorelin is a first novel drug, an orally active, non- peptidic ghrelin mimetic and growth hormone secretagogue approved in Japan in January 2021. Like ghrelin, anamorelin also increases the appetite and lean body mass of patients with cancer cachexia. On the other hand, in clinical trials, there was no statistical significance for increasing the 6-minute walk test distance and recovering non-dominant hand grip strength. As for the functional recovery, a new program has been developed for non-pharmacotherapy with nutritional and exercise interventions. These 2 kinds of interventions will become effective anti-cachexia therapy. Research is also underway to produce anti-cachexia drugs other than anamorelin. Somes are already in their clinical trials. Anti-cachexia therapy will be a new option for treating advanced cancer.

Development and evaluation of the sedentary behavior and light-intensity physical activity questionnaire.

[Purpose] To describe our newly developed Sedentary Behavior and Light-Intensity Physical Activity Questionnaire and examine its reliability and validity. [Participants and Methods] We identified and selected self-reported items through a literature review and interviews with 11 inactive individuals. Thirty-one individuals with lower limb prostheses and an expert panel assessed the content validity of the integrated items and identified 17 items. Patients who had undergone lower limb surgeries were regarded as inactive individuals, and 112 patients completed the questionnaire twice for test-retest reliability and wore an accelerometer for criterion validity. The ethics committee of Kyushu University approved this study (2019-126 and 2019-273). [Results] Item analysis was revised to the Sedentary Behavior and Light-Intensity Physical Activity Questionnaire-10 (six light-intensity physical activity and four sedentary behavior items) because of the floor effect. The test-retest correlation coefficient showed high reliability. Moderate to weak correlation coefficient was observed between the questionnaire and accelerometer (light-intensity physical activity: 0.43 and sedentary behavior: 0.20), and the Bland-Altman plots indicated no bias. [Conclusion] The Sedentary Behavior and Light-Intensity Physical Activity Questionnaire-10 had acceptable validity and reliability among inactive individuals and it could be used for studying light-intensity physical activity.

Prognostic factors in older patients with wild-type epidermal growth factor receptor advanced non-small cell lung cancer: a multicenter retrospective study.

BACKGROUND: Over 40% Japanese patients with lung cancer are above 75 years of age. A specific strategy to treat such older patients is necessary because most trials exclude older patients with poor physical health. Herein, we aimed to identify predictive factors associated with overall survival (OS) in older patients by evaluating patient backgrounds and laboratory data before the start of treatment. METHODS: This multicenter retrospective medical chart review study was conducted at three Japanese institutions and involved patients aged 75 years and above with epidermal growth factor receptor (EGFR) mutation-negative advanced non-small cell lung cancer (NSCLC). Of the patients, 75 had received best supportive care (BSC) and 49 mono-chemotherapy or platinum-doublet chemotherapy, including immune checkpoint inhibitors (ICIs). OS after diagnosis was analyzed using the Kaplan-Meier survival analysis. Cox proportional hazard models, which included age, Eastern Cooperative Oncology Group performance status (ECOG PS), staging, serum albumin levels, and receipt of chemotherapy were analyzed. RESULTS: Age at diagnosis was not shown to be related to OS in patients receiving BSC. In patients aged 81 years and above, the chemotherapy group tended to have longer survival than did the BSC group, but there was no statistically significant difference in the median OS between the two groups due to the very small number of subjects (n: 30 vs. 12, median: 52 vs. 30 weeks, hazard ratio: 0.512, 95% confidence interval: 0.232-1.130, P=0.088). The patients' performance status and albumin levels at lung cancer diagnosis had the highest impact on OS in the BSC group. CONCLUSIONS: Careful consideration should be given to the indications of chemotherapy for patients aged 81 years and above with wild-type EGFR advanced non-small lung cancer.

Prevalence of antimicrobial-resistant staphylococci in nares and affected sites of pet dogs with superficial pyoderma.

Currently, antimicrobial-resistant staphylococci, particularly methicillin-resistant Staphylococcus pseudintermedius (MRSP), are frequently isolated from canine superficial pyoderma in Japan. However, little is known regarding the nasal prevalence of MRSP in pet dogs. Here, we determined the prevalence of antimicrobial-resistant staphylococci in nares and affected sites of pet dogs with superficial pyoderma. Of the 125 nares and 108 affected sites of pet dogs with superficial pyoderma, 107 (13 species) and 110 (eight species) staphylococci strains, respectively, were isolated. The isolation rate of S. pseudintermedius from pyoderma sites (82/110 strains, 74.5%) was significantly higher than that from nares (57/107 strains, 53.3%) (P<0.01). Notably, the prevalence of MRSP (18/57 strains, 31.6%) in nares was equivalent to that in pyoderma sites (28/82 strains, 34.1%). Furthermore, the phenotypes and genotypes of antimicrobial resistance in MRSP strains from nares were similar to those from pyoderma sites. Our findings revealed that the prevalence of antimicrobial-resistant staphylococci in the nares of pet dogs with superficial pyoderma is the same level as that in affected sites. Therefore, considerable attention should be paid to the antimicrobial resistance of commensal staphylococci in companion animals.

TRAPγ-CDG shows asymmetric glycosylation and an effect on processing of proteins required in higher organisms.

Newly synthesised glycoproteins enter the rough endoplasmic reticulum through a translocation pore. The translocon associated protein (TRAP) complex is located close to the pore. In a patient with a homozygous start codon variant in TRAPγ (SSR3), absence of TRAPγ causes disruption of the TRAP complex, impairs protein translocation into the endoplasmic reticulum and affects transport, for example, into the brush-border membrane. Furthermore, we observed an unbalanced non-occupancy of N-glycosylation sites. The major clinical features are intrauterine growth retardation, facial dysmorphism, congenital diarrhoea, failure to thrive, pulmonary disease and severe psychomotor disability.