Helicobacter kumamotonensis sp. nov., isolated from human clinical specimens.

A Gram-stain-negative, spiral bacterium (PAGU 1991T) was isolated from the blood of a patient with diffuse large B-cell lymphoma. Phylogenetic analysis based on 16S rRNA gene sequences showed that the isolate was very closely related to Helicobacter equorum LMG 23362T (99.1 % similarity), originally isolated from a faecal sample from a healthy horse. PAGU 1991T was also very closely related to PAGU 1750 in our strain library (=CCUG 41437) with 99.7 % similarity. Additional phylogenetic analyses based on the 23S rRNA gene sequence and GyrA amino acid sequence further supported the close relationship between the two human isolates (PAGU 1991T and PAGU 1750) and the horse strain. However, a phylogenetic analysis based on 16S rRNA showed that the two human isolates formed a lineage that was distinct from the horse strain (less than 99.2 % similarity). In silico whole-genome comparisons based on digital DNA-DNA hybridization, average nucleotide identity based on blast and orthologous average nucleotide identity using usearch between the two human isolates and the type strain of H. equorum showed values of less than 52.40, 93.47, and 93.50 %, respectively, whereas those between the two human isolates were 75.8, 97.2, and 97.2 %, respectively. These data clearly demonstrated that the two human isolates formed a single species, distinct from H. equorum. Morphologically, the human isolates could be distinguished by the type of flagella; the human isolates showed a bipolar sheathed flagellum, whereas that of H. equorum was monopolar. Biochemically, the human isolate was characterized by growth at 42 °C under microaerobic conditions and nitrate reduction unability. We conclude that the two human isolates, obtained from geographically and temporally distinct sources, were a novel species, for which we propose the name Helicobacter kumamotonensis sp. nov., with the type strain PAGU 1991T (=GTC 16810T=CCUG 75774T).

Add-on effectiveness of methotrexate or iguratimod in patients with rheumatoid arthritis exhibiting an inadequate response to Janus kinase inhibitors: The ANSWER cohort study.

OBJECTIVES: This multicenter, retrospective study evaluated the effectiveness of add-on methotrexate (MTX) or iguratimod (IGU) in patients with rheumatoid arthritis exhibiting an inadequate response to Janus kinase inhibitors (JAKis). METHODS: Forty-five patients were treated with new additional MTX (n = 22) or IGU (n = 23) and followed for 6 months. Patients' background is as follows: age, 59.2 years; disease activity score of 28 joints with C-reactive protein (DAS28-CRP), 3.4; clinical disease activity index, 15.7; biological disease-modifying antirheumatic drug (DMARD)-switched cases, 77.8%; first JAKi cases, 95.6%; and JAKi treatment: tofacitinib (n = 25), baricitinib (n = 17), upadacitinib (n = 2), and peficitinib (n = 1) for 9.6 months. RESULTS: Thirty-five patients continued the combination therapy for 6 months without a significant change in concomitant glucocorticoid or other conventional synthetic DMARDs. DAS28-CRP (MTX, 3.6 to 2.6, p < 0.05; IGU, 3.3 to 2.1, p < 0.001) and clinical disease activity index (MTX, 16.7 to 8.8, p < 0.05; IGU, 14.6 to 6.5, p < 0.01) improved significantly from baseline. Using the 2019 European League Against Rheumatism criteria, 45.4% (MTX) and 39.1% (IGU) achieved moderate or good response and 40.9% (MTX) and 39.1% (IGU) achieved American College of Rheumatology 20% improvement criteria. CONCLUSIONS: Adding MTX or IGU to inadequate responders of JAKi can be considered as a complementary treatment.

Differential efficacy of TNF inhibitors with or without the immunoglobulin fragment crystallizable (Fc) portion in rheumatoid arthritis: the ANSWER cohort study.

Rheumatoid factor (RF) binds to the fragment crystallizable (Fc) portion of immunoglobulin. It could bind to the Fc portion of anti-TNF inhibitors (TNFi) and attenuate the clinical efficacy. We tried to determine whether the therapeutic efficacy of TNFi with Fc might be lower than that of TNFi without Fc in rheumatoid arthritis (RA) patients with high titres of RF. The Kansai Consortium for Well-being of Rheumatic Disease Patients (ANSWER) cohort is an observational multi-center registry of patients with RA in the Kansai district of Japan. RA patients treated with TNFi were included and divided into two groups based on the structural characteristics between TNFi with Fc (infliximab, adalimumab, golimumab, and etanercept) and TNFi without Fc (certolizumab pegol). Patients were classified into 4 groups according to RF titre quartiles. The sequential disease activity score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) was compared by Mann-Whitney U test between TNFi with and without Fc in each RF titre group. Multiple linear regression analysis was used to analyze the effect of TNFi without Fc for the change of DAS28-ESR adjusted after potential confounders. A total of 705 RA patients were classified into four groups (RF1; RF 0-15.0 IU/mL, RF2; 15.0-55.0, RF3; 55.0-166, RF4; 166-7555). In RF4, RA patients treated with TNFi without Fc had a significantly lower DAS28-ESR than those treated with TNFi with Fc [3.2 (2.3-4.2) vs. 2.7 (2.0-3.0)] after 12 months. This effect of TNFi without Fc for the change of DAS28-ESR after 12 months treatment retained in multivariate analysis in RF4. TNFi without Fc may be more efficacious than TNFi with Fc in RA patients with high RF titres.

Development of potent antipseudomonal ß-lactams by means of polycarboxylation of aminopenicillins.

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that presents a serious risk to immunosuppressed individuals and other extremely vulnerable patients such as those in intensive care units. The emergence of multidrug-resistant Pseudomonas strains has increased the need for new antipseudomonal agents. In this study, a series of amino group-modified aminopenicillin derivatives was synthesized that have different numbers of carboxyl groups and structurally resemble carboxypenicillin-ureidopenicillin hybrids, and their antipseudomonal activities were evaluated. Among the derivatives synthesized, diethylenetriaminepentaacetic acid (DTPA)-modified amoxicillin (DTPA-Amox) showed potent antipseudomonal activity, not only against the laboratory strain PAO1 but also against clinically isolated Pseudomonas strains that were resistant to piperacillin and carbenicillin. DTPA-Amox had no obvious cytotoxic effects on cultured mammalian cells. In addition, in an in vivo model of leukopenia, DTPA-Amox treatment produced a moderate but statistically significant improvement in the survival of mice with P. aeruginosa strain PAO1 infection. These data suggest that polycarboxylation by DTPA conjugation is an effective approach to enhance antipseudomonal activity of aminopenicillins.

Prostaglandin E2-Induced Immune Exhaustion and Enhancement of Antiviral Effects by Anti-PD-L1 Antibody Combined with COX-2 Inhibitor in Bovine Leukemia Virus Infection.

Bovine leukemia virus (BLV) infection is a chronic viral infection of cattle and endemic in many countries, including Japan. Our previous study demonstrated that PGE2, a product of cyclooxygenase (COX) 2, suppresses Th1 responses in cattle and contributes to the progression of Johne disease, a chronic bacterial infection in cattle. However, little information is available on the association of PGE2 with chronic viral infection. Thus, we analyzed the changes in plasma PGE2 concentration during BLV infection and its effects on proviral load, viral gene transcription, Th1 responses, and disease progression. Both COX2 expression by PBMCs and plasma PGE2 concentration were higher in the infected cattle compared with uninfected cattle, and plasma PGE2 concentration was positively correlated with the proviral load. BLV Ag exposure also directly enhanced PGE2 production by PBMCs. Transcription of BLV genes was activated via PGE2 receptors EP2 and EP4, further suggesting that PGE2 contributes to disease progression. In contrast, inhibition of PGE2 production using a COX-2 inhibitor activated BLV-specific Th1 responses in vitro, as evidenced by enhanced T cell proliferation and Th1 cytokine production, and reduced BLV proviral load in vivo. Combined treatment with the COX-2 inhibitor meloxicam and anti-programmed death-ligand 1 Ab significantly reduced the BLV proviral load, suggesting a potential as a novel control method against BLV infection. Further studies using a larger number of animals are required to support the efficacy of this treatment for clinical application.

Novel, infection-free, advanced hemostatic material: physical properties and preclinical efficacy.

Introduction: Self-assembling peptides are synthetic, amphipathic peptides that may serve as new hemostatic agents. The first-generation hemostat TDM-621 has been used in clinical practice in a limited capacity. The second-generation hemostat TDM-623 was developed for faster gel formation and better tissue-sealing capability. We compared the physical properties and hemostatic effects of TDM-621 and TDM-623.Material and methods: First, we evaluated the physical properties of both materials in a bench test setting, including the external appearance of the gel, rheological properties in sol/gel forms, and local self-weight pressure. We then performed a randomized preclinical trial using swine. Bleeding wounds were created on the liver surface, and randomized application of 1 mL of either TDM-621 or TDM-623 was performed. The hemostatic effects were evaluated two and five minutes after application. Resected specimens were histologically evaluated.Results: In the bench test setting, TDM-623 showed higher gel height, higher sol viscosity, and higher local self-weight pressure than TDM-621. In the preclinical setting, TDM-623 showed significantly greater hemostatic effects at two and five minutes after application than TDM-621. Histological examination showed no inflammatory reaction in either group.Conclusions: TDM-623 has greater hemostatic capability than TDM-621 and is therefore promising as a new hemostatic agent.

All-trans retinoic acid suppresses bone morphogenetic protein 4 in mouse diabetic nephropathy through a unique retinoic acid response element.

Diabetic nephropathy (DN) causes mesangial matrix expansion, which results in glomerulosclerosis and renal failure. Collagen IV (COL4) is a major component of the mesangial matrix that is positively regulated by bone morphogenetic protein 4 (BMP4)/suppressor of mothers against decapentaplegic (Smad1) signaling. Because previous studies showed that retinoids treatment had a beneficial effect on kidney disease, we investigated the therapeutic potential of retinoids in DN, focusing especially on the regulatory mechanism of BMP4. Diabetes was induced with streptozotocin in 12-wk-old male Crl:CD1(ICR) mice, and, 1 mo later, we initiated intraperitoneal injection of all-trans retinoic acid (ATRA) three times weekly. Glomerular matrix expansion, which was associated with increased BMP4, phosphorylated Smad1, and COL4 expression, worsened in diabetic mice at 24 wk of age. ATRA administration alleviated DN and downregulated BMP4, phosopho-Smad1, and COL4. In cultured mouse mesangial cells, treatment with ATRA or a retinoic acid receptor-α (RARα) agonist significantly decreased BMP4 and COL4 expression. Genomic analysis suggested two putative retinoic acid response elements (RAREs) for the mouse Bmp4 gene. Chromatin immunoprecipitation analysis and reporter assays indicated a putative RARE of the Bmp4 gene, located 11,488-11,501 bp upstream of exon 1A and bound to RARα and retinoid X receptor (RXR), which suppressed BMP4 expression after ATRA addition. ATRA suppressed BMP4 via binding of a RARα/RXR heterodimer to a unique RARE, alleviating glomerular matrix expansion in diabetic mice. These findings provide a novel regulatory mechanism for treatment of DN.

[Successful treatment with rituximab in acute disseminated encephalomyelitis with whole spinal cord involvement following HLA haploidentical transplantation].

Chronic graft versus host disease (cGVHD) of the central nervous system is a rare condition that could occur after allogeneic hematopoietic stem cell transplantation (SCT) but has been poorly documented. Here, we report a patient diagnosed with recurrent acute disseminated encephalomyelitis (ADEM) with longitudinal extensive transverse myelitis (LETM) as cGVHD after HLA haploidentical peripheral blood SCT using posttransplantation cyclophosphamide for mixed-phenotype acute leukemia. We observed clinical and radiological improvement after the rituximab treatment of the condition that had been refractory to steroids. To the best of our knowledge, no report of cGVHD presented recurrent ADEM with LETM after allogeneic SCT and successfully treated with rituximab. Hence, ADEM should be included in the differential diagnosis of neurological symptoms in posttransplant patients with cGVHD.

A pragmatic method for transforming clinical research data from the research electronic data capture "REDCap" to Clinical Data Interchange Standards Consortium (CDISC) Study Data Tabulation Model (SDTM): Development and evaluation of REDCap2SDTM.

The Clinical Data Interchange Standards Consortium (CDISC) Study Data Tabulation Model (SDTM) can be used for new drug application studies as well as secondarily for creating a clinical research data warehouse to leverage clinical research study data across studies conducted within the same disease area. However, currently not all clinical research uses Clinical Data Acquisition Standards Harmonization (CDASH) beginning in the set-up phase of the study. Once already initiated, clinical studies that have not utilized CDASH are difficult to map in the SDTM format. In addition, most electronic data capture (EDC) systems are not equipped to export data in SDTM format; therefore, in many cases, statistical software is used to generate SDTM datasets from accumulated clinical data. In order to facilitate efficient secondary use of accumulated clinical research data using SDTM, it is necessary to develop a new tool to enable mapping of information for SDTM, even during or after the clinical research. REDCap is an EDC system developed by Vanderbilt University and is used globally by over 2100 institutions across 108 countries. In this study, we developed a simulated clinical trial to evaluate a tool called REDCap2SDTM that maps information in the Field Annotation of REDCap to SDTM and executes data conversion, including when data must be pivoted to accommodate the SDTM format, dynamically, by parsing the mapping information using R. We confirmed that generating SDTM data and the define.xml file from REDCap using REDCap2SDTM was possible. Conventionally, generation of SDTM data and the define.xml file from EDC systems requires the creation of individual programs for each clinical study. However, our proposed method can be used to generate this data and file dynamically without programming because it only involves entering the mapping information into the Field Annotation, and additional data into specific files. Our proposed method is adaptable not only to new drug application studies but also to all types of research, including observational and public health studies. Our method is also adaptable to clinical data collected with CDASH at the beginning of a study in non-standard format. We believe that this tool will reduce the workload of new drug application studies and will support data sharing and reuse of clinical research data in academia.

Epidemiological and outcome data in Japanese patients with deep vein thrombosis with and without malignancy.

There are very few epidemiological studies on Japanese patients with deep vein thrombosis (DVT). In particular, mortality rate differences in Japanese DVT patients with and without malignancy have rarely been evaluated. To elucidate these differences, we enrolled 211 patients who had been diagnosed with de-novo acute DVT of the pelvis or lower extremities between January 2012 and December 2015. The clinical characteristics, treatment information, and follow-up data were retrospectively assessed. We compared these variables in patients with (n = 120) and without (n = 91) concomitant malignancies. The median age of patients was 67 years, 33.7% were male, and 82.9% patients were treated with oral anticoagulants including direct oral anticoagulants. The clinical characteristics and treatment provided were almost identical in the two groups with some exceptions. Three-year survival rates of the total population, patients with malignancy, and patients without malignancy were 80.6, 67.6, and 97.6%, respectively (log-rank p < 0.001). Multivariable Cox regression analysis demonstrated that malignancy was independently associated with high risk of 3-year all-cause mortality with an adjusted hazard ratio of 9.1 (95% confidence interval; 2.1-39.0, p = 0.003). Bootstrap validation demonstrated an acceptable index corrected slope of 0.766 without significant overfitting in a multivariable model. In conclusion, we analyzed epidemiological data on Japanese patients with DVT. Malignancy was independently associated with increased 3-year all-cause mortality.

Myosin XI-I is Mechanically and Enzymatically Unique Among Class-XI Myosins in Arabidopsis.

Arabidopsis possesses 13 genes encoding class-XI myosins. Among these, myosin XI-I is phylogenetically distant. To examine the molecular properties of Arabidopsis thaliana myosin XI-I (At myosin XI-I), we performed in vitro mechanical and enzymatic analyses using recombinant constructs of At myosin XI-I. Unlike other biochemically studied class-XI myosins, At myosin XI-I showed extremely low actin-activated ATPase activity (Vmax = 3.7 Pi s(-1) head(-1)). The actin-sliding velocity of At myosin XI-I was 0.25 µm s(-1), >10 times lower than those of other class-XI myosins. The ADP dissociation rate from acto-At myosin XI-I was 17 s(-1), accounting for the low actin-sliding velocity. In contrast, the apparent affinity for actin in the presence of ATP, estimated from Kapp (0.61 µM) of actin-activated ATPase, was extremely high. The equilibrium dissociation constant for actin was very low in both the presence and absence of ATP, indicating a high affinity for actin. To examine At myosin XI-I motility in vivo, green fluorescent protein-fused full-length At myosin XI-I was expressed in cultured Arabidopsis cells. At myosin XI-I localized not only on the nuclear envelope but also on small dots moving slowly (0.23 µm s(-1)) along actin filaments. Our results show that the properties of At myosin XI-I differ from those of other Arabidopsis class-XI myosins. The data suggest that At myosin XI-I does not function as a driving force for cytoplasmic streaming but regulates the organelle velocity, supports processive organelle movement or acts as a tension generator.

Serum Levels of Albumin-ß-Amyloid Complex in Patients with Depression.

OBJECTIVE: Epidemiologic studies have demonstrated that suffering from depression may be a risk for Alzheimer disease (AD). As a possible biologic mechanism underlying the transition from depression to AD, it has been speculated that pathologic changes in ß-amyloid (Aß) metabolism are involved. To further understand the peripheral kinetics of amyloid in patients with depression, we investigated serum levels of free Aß and albumin-bound Aß. METHODS: Seventy inpatients with DSM-IV major depressive disorder (MDD) and 81 healthy individuals (the comparison group) were recruited between June 2012 and February 2014. Serum Aß40 and Aß42 levels, Aß40/Aß42 ratio, and serum levels of albumin-Aß complexes (SLAACs) were compared between the comparison group and patients in two age groups comprising younger (<60 years) and elderly (≥60 years) people. RESULTS: SLAAC was decreased in older patients with MDD but not in younger patients. The serum-free Aß40/Aß42 ratio was higher in patients with depression, even in younger patients. CONCLUSION: Our findings suggest that free Aß and the albumin-bound Aß reflect a different serum amyloid kinetics in depression. We speculate that serum-free Aß reflects changes in amyloid metabolism in patients suffering from depression and albumin-bound Aß reflects AD pathology and may be a potential predictor of the prodromal stage of AD.

Molecular characterization and subcellular localization of Arabidopsis class VIII myosin, ATM1.

Land plants possess myosin classes VIII and XI. Although some information is available on the molecular properties of class XI myosins, class VIII myosins are not characterized. Here, we report the first analysis of the enzymatic properties of class VIII myosin. The motor domain of Arabidopsis class VIII myosin, ATM1 (ATM1-MD), and the motor domain plus one IQ motif (ATM1-1IQ) were expressed in a baculovirus system and characterized. ATM1-MD and ATM1-1IQ had low actin-activated Mg(2+)-ATPase activity (Vmax = 4 s(-1)), although their affinities for actin were high (Kactin = 4 µM). The actin-sliding velocities of ATM1-MD and ATM1-1IQ were 0.02 and 0.089 µm/s, respectively, from which the value for full-length ATM1 is calculated to be ∼0.2 µm/s. The results of actin co-sedimentation assay showed that the duty ratio of ATM1 was ∼90%. ADP dissociation from the actin·ATM1 complex (acto-ATM1) was extremely slow, which accounts for the low actin-sliding velocity, low actin-activated ATPase activity, and high duty ratio. The rate of ADP dissociation from acto-ATM1 was markedly biphasic with fast and slow phase rates (5.1 and 0.41 s(-1), respectively). Physiological concentrations of free Mg(2+) modulated actin-sliding velocity and actin-activated ATPase activity by changing the rate of ADP dissociation from acto-ATM1. GFP-fused full-length ATM1 expressed in Arabidopsis was localized to plasmodesmata, plastids, newly formed cell walls, and actin filaments at the cell cortex. Our results suggest that ATM1 functions as a tension sensor/generator at the cell cortex and other structures in Arabidopsis.

Treatment of oral leukoplakia with a low-dose of beta-carotene and vitamin C supplements: a randomized controlled trial.

Management of oral leukoplakia-a potentially malignant disorder-is currently not evidence-based. Of the few randomized trials that have been reported, most have negative data. Therefore, a multi-centre, randomized, double-blind controlled trial (RCT) was undertaken to evaluate the use of low-dose beta-carotene combined with vitamin C supplements for the treatment and to prevent malignant transformation of oral leukoplakia. 46 Japanese participants with oral leukoplakia were allocated randomly either to an experimental arm (10 mg day(-1) of beta-carotene and 500 mg day(-1) of vitamin C) or placebo arm (50 mg day(-1) of vitamin C). Current or ex-smokers within 3 months of cessation were excluded. The supplements were continued over a period of 1 year. The primary endpoint was clinical remission at 1-year and the likelihood of malignant transformation during a 5-year follow-up period as a secondary endpoint. The overall clinical response rate in the experimental arm was 17.4% (4/23) and 4.3% (1/23) in the placebo arm (p = 0.346). During the median 60-month follow-up period, two subjects in the experimental arm and three in the control arm developed oral cancer. Under the intention-to-treat principle, relative risk by supplementing with beta-carotene and vitamin C was 0.77 (95%CI: 0.28-1.89) (p = 0.580) by the Cox proportional hazards model. No unfavorable side-effects were noted. Beta-carotene (10 mg day(-1) ) and vitamin C were neither effective for clinical remission, nor for protection against the development of cancer. Data from this RCT does not support the hypothesis that chemoprevention with this treatment is effective for oral leukoplakia.

[Relation between psychological development and respiratory management in patients with congenital central hypoventilation syndrome in Japan].

OBJECTIVE: To evaluate the psychological development of patients with congenital central hypoventilation syndrome (CCHS). METHODS: We performed a questionnaire-based survey of 17 patients with CCHS aged over 7 years and assessed their clinical course, respiratory management, and psychological development. RESULTS: CCHS was present at birth in 15 patients, of which eight presented with respiratory failure with a low Apgar score. Twelve patients required mechanical ventilation with intubation, and five received mask ventilation. All patients with intubation underwent tracheostomy between 1 and 12 months of age (median 5.5 months), and most of them had associated conditions such as Hirschsprung disease. Four of 12 patients with intubation were eventually switched to mask ventilation and one to diaphragm pacing and mask ventilation. The patients undergoing mask ventilation had relatively milder disease severity and had fewer complications than did the patients with intubation. The psychological development of patients who received tracheostomy ranged from normal to severe retardation. Retardation was more likely to be severe in patients who received tracheostomy in late infancy. All patients who received mask ventilation experienced borderline to moderate psychological retardation. This effect could be attributed to poor compliance with mask fitting. CONCLUSION: Our findings suggest that the psychological development of CCHS patients was influenced by hypoxia; tracheostomy and strict respiratory management since the neonatal period were needed for neurological protection.

The increase in prescriptions of bisphosphonates and the incidence proportion of osteonecrosis of the jaw after risk communication activities in Japan: a hospital-based cohort study.

PURPOSE: The purpose of this study was to investigate the impact of risk communication about bisphosphonate (BP)-related osteonecrosis of the jaw (ONJ) on the number of reported cases to the Drug Adverse Reactions Reporting System and on the incidence proportion of ONJ in a hospital-based cohort study in Japan. METHOD: We conducted a survey of the safety information on BP-related ONJ available from regulatory authorities, pharmaceutical manufacturers and academic associations. We also performed a trend analysis of a dataset from the Drug Adverse Reactions Reporting System and a sub-analysis, using previously constructed data from a retrospective cohort study. RESULTS: Risk communication from pharmaceutical manufacturers and academic associations began within 1 year after revisions were made to the package inserts, in October 2006. Twenty times more cases of ONJ have been reported to regulatory authority since 2007, compared with the period before 2007. In our cohort, the incidence proportion of ONJ during and after 2009 was four times greater than before 2009. During this period, BPs were frequently prescribed, whereas there was no increase in the use of alternative agents, such as selective estrogen receptor modulators. CONCLUSION: ONJ was increasingly diagnosed after risk communication efforts, but the impact of the communications was not clear. Safety notifications were diligently disseminated after the package insert was revised. However, there was no surveillance for ONJ before the revision.

A single-center analysis of the survival benefits of adjuvant gemcitabine chemotherapy for biliary tract cancer.

BACKGROUND: Surgical resection is the only curative treatment of biliary tract cancer (BTC). However, the prognosis of BTC remains unsatisfactory. The aim of this study is to evaluate the benefits of adjuvant gemcitabine chemotherapy for BTC. METHODS: We performed a historical cohort study that involved 198 patients who underwent R0 surgical resection. Patients who underwent major hepatectomy were administered biweekly intravenous gemcitabine at a dose of 800 mg/m(2). Otherwise, patients were administered intravenous gemcitabine at a dose of 1,000 mg/m(2) in 3 weekly infusions, which were followed by a 1-week pause. The primary outcome was overall survival. The hazard ratio (HR) of adjuvant chemotherapy was estimated by propensity score-stratified Cox regression that was adjusted for confounders. RESULTS: Forty patients received adjuvant chemotherapy. The HR of adjuvant chemotherapy was 0.47 [95 % confidence interval (CI) 0.28-0.95; P = 0.03]. Subgroup analysis showed that the survival benefits were possibly modified by lymph node positivity (HR 0.19; 95 % CI 0.07-0.58; interaction, P = 0.22), stage III (HR 0.11; 95 % CI 0.02-0.50; interaction, P < 0.01), intrahepatic cholangiocarcinoma (ICC) (HR 0.09; 95 % CI 0.01-0.67; interaction, P = 0.05), and poorly differentiated tumor (HR 0.16; 95 % CI 0.03-0.85; interaction, P = 0.13). CONCLUSIONS: Adjuvant gemcitabine chemotherapy for BTC may be effective, particularly for patients with stage III and ICC.

Cerebral infarction in the left hemisphere compared with the right hemisphere increases the risk of aspiration pneumonia.

BACKGROUND: Aspiration pneumonia (AP) following cerebral infarction (CI) has been considered as one of its most serious complications. Nevertheless, there are no reports on the association between the type or location of CI and the incidence of AP. In addition, the association between dysphagia, which leads to aspiration, and the type or location of CI has never been investigated. Therefore we hypothesized that the laterality of CI affects the development of both dysphagia and AP. METHODS: We performed a retrospective cohort study to examine the association between the laterality of CI and the incidence of dysphagia and AP in 133 patients. RESULTS: AP was found in 6.0% of the group with left CI and in 0.8% of the group with right CI. A univariate logistic regression analysis revealed that left CI was a significant predictor of AP (hazard ratio, 8.81; 95% confidence interval, 1.07-72.59; p = 0.043). Left CI was a significant predictor of AP even after adjusting for age, sex, CI type, or presence of diabetes mellitus. In addition, although the frequency of dysphagia as the direct cause of AP did not differ according to laterality, the frequency of AP that ensued from dysphagia in the left CI group was greater than that observed in the right CI group. CONCLUSIONS: The group with left CI from the motor cortex to the internal capsule complicated by dysphagia exhibited a high risk of AP.