Reversible Modulation of the Electronic and Spatial Environment around Ni(0) Centers Bearing Multifunctional Carbene Ligands with Triarylaluminum.

Designing and modulating the electronic and spatial environments surrounding metal centers is a crucial issue in a wide range of chemistry fields that use organometallic compounds. Herein, we demonstrate a Lewis-acid-mediated reversible expansion, contraction, and transformation of the spatial environment surrounding nickel(0) centers that bear N-phosphine oxide-substituted N-heterocyclic carbenes (henceforth referred to as (S)PoxIms). Reaction between tetrahedral (syn-κ-C,O-(S)PoxIm)Ni(CO)2 and Al(C6F5)3 smoothly afforded heterobimetallic Ni/Al species such as trigonal-planar {κ-C-Ni(CO)2}(µ-anti-(S)PoxIm){κ-O-Al(C6F5)3} via a complexation-induced rotation of the N-phosphine oxide moieties, while the addition of 4-dimethylaminopyridine resulted in the quantitative regeneration of the former Ni complexes. The corresponding interconversion also occurred between (SPoxIm)Ni(η2:η2-diphenyldivinylsilane) and {κ-C-Ni(η2:η2-diene)}(µ-anti-SPoxIm){κ-O-Al(C6F5)3} via the coordination and dissociation of Al(C6F5)3. The shape and size of the space around the Ni(0) center was drastically changed through this Lewis-acid-mediated interconversion. Moreover, the multinuclear NMR, IR, and XAS analyses of the aforementioned carbonyl complexes clarified the details of the changes in the electronic states on the Ni centers; i.e., the electron delocalization was effectively enhanced among the Ni atom and CO ligands in the heterobimetallic Ni/Al species. The results presented in this work thus provide a strategy for reversibly modulating both the electronic and spatial environment of organometallic complexes, in addition to the well-accepted Lewis-base-mediated ligand-substitution methods.

Return of the forgotten hero: the role of Y chromosome-encoded Zfy in male reproduction.

The Y-linked zinc finger gene ZFY is conserved across eutherians and is known to be a critical fertility factor in some species. The initial studies of the mouse homologues, Zfy1 and Zfy2, were performed using mice with spontaneous Y chromosome mutations and Zfy transgenes. These studies revealed that Zfy is involved in multiple processes during spermatogenesis, including removal of germ cells with unpaired chromosomes and control of meiotic sex chromosome inactivation during meiosis I, facilitating the progress of meiosis II, promoting spermiogenesis, and improving assisted reproduction outcomes. Zfy was also identified as a key gene in Y chromosome evolution, protecting this chromosome from extinction by serving as the executioner responsible for meiosis surveillance. Studies with targeted Zfy knock-outs revealed that mice lacking both homologues have severe spermatogenic defects and are infertile. Based on protein structure and in vitro assays, Zfy is expected to drive spermatogenesis as a transcriptional regulator. The combined evidence documents that the presence of at least one Zfy homologue is required for male fertility and that Zfy2 plays a more prominent role. This knowledge reinforces the importance of these factors for mouse spermatogenesis and informs our understanding of the human ZFY variants, which are homologous to the mouse Zfy1 and Zfy2.

Genetically-biased fertilization in APOBEC1 complementation factor (A1cf) mutant mice.

Meiosis, recombination, and gametogenesis normally ensure that gametes combine randomly. But in exceptional cases, fertilization depends on the genetics of gametes from both females and males. A key question is whether their non-random union results from factors intrinsic to oocytes and sperm, or from their interactions with conditions in the reproductive tracts. To address this question, we used in vitro fertilization (IVF) with a mutant and wild-type allele of the A1cf (APOBEC1 complementation factor) gene in mice that are otherwise genetically identical. We observed strong distortion in favor of mutant heterozygotes showing that bias depends on the genetics of oocyte and sperm, and that any environmental input is modest. To search for the potential mechanism of the 'biased fertilization', we analyzed the existing transcriptome data and demonstrated that localization of A1cf transcripts and its candidate mRNA targets is restricted to the spermatids in which they originate, and that these transcripts are enriched for functions related to meiosis, fertilization, RNA stability, translation, and mitochondria. We propose that failure to sequester mRNA targets in A1cf mutant heterozygotes leads to functional differences among spermatids, thereby providing an opportunity for selection among haploid gametes. The study adds to the understanding of the gamete interaction at fertilization. Discovery that bias is evident with IVF provides a new venue for future explorations of preference among genetically distinct gametes at fertilization for A1cf and other genes that display significant departure of Mendelian inheritance.

Room-Temperature Reversible Chemisorption of Carbon Monoxide on Nickel(0) Complexes.

Chemisorption on organometallic-based adsorbents is crucial for the controlled separation and long-term storage of gaseous molecules. The formation of covalent bonds between the metal centers in the adsorbents and the targeted gases affects the desorption efficiency, especially when the oxidation state of the metal is low. Herein, we report a pressure-responsive nickel(0)-based system that is able to reversibly chemisorb carbon monoxide (CO) at room temperature. The use of N-heterocyclic carbene ligands with hemi-labile N-phosphine oxide substituents facilitates both the adsorption and desorption of CO on nickel(0) via ligand substitution. Ionic liquids were used as the reaction medium to enhance the desorption rate and establish a reusable system. These results showcase a way for the sustainable chemisorption of CO using a zero-valent transition-metal complex.

Two acquired mouse Y chromosome-linked genes, Prssly and Teyorf1, are dispensable for male fertility‡.

Prssly (Protease, serine-like, Chr Y) and Teyorf1 (Testis expressed, chromosome Y open reading frame 1) are two acquired single-copy genes located on the distal tip of the non-pairing short arm of the mouse Y chromosome adjacent to telomeric sequence. Both genes lack X chromosome-linked homologues and are expressed in testicular germ cells. We first performed analysis of Prssly and Teyorf1 genomic sequences and demonstrated that previously reported Prssly sequence is erroneous and the true Prssly sequence is longer and encodes a larger protein than previously estimated. We also confirmed that both genes encode pseudogenes that are not expressed in testes. Next, using CRISPR/Cas9 genome targeting, we generated Prssly and Teyorf1 knockout (KO) mice and characterized their phenotype. To create Prssly KO mice, we targeted the conserved exon 5 encoding a trypsin domain typical for serine proteases. The targeting was successful and resulted in a frame shift mutation that introduced a premature stop codon, with the Prssly KO males retaining only residual transcript expression in testes. The Teyorf1 targeting removed the entire open reading frame of the gene, which resulted in no transcript expression in KO males. Both Prssly KO and Teyorf1 KO males were fertile and had normal testis size and normal sperm number, motility, and morphology. Our findings show that Prssly and Teyorf1 transcripts with potential to encode proteins are dispensable for male fertility.

Loss of mouse Y chromosome gene Zfy1 and Zfy2 leads to spermatogenesis impairment, sperm defects, and infertility.

Using mice with Y chromosome deficiencies and supplementing Zfy transgenes, we, and others, have previously shown that the loss of Y chromosome Zfy1 and Zfy2 genes is associated with infertility and spermiogenic defects and that the addition of Zfy transgenes rescues these defects. In these past studies, the absence of Zfy was linked to the loss of other Y chromosome genes, which might have contributed to spermiogenic phenotypes. Here, we used CRISPR/Cas9 to specifically remove open reading frame of Zfy1, Zfy2, or both Zfy1 and Zfy2, and generated Zfy knockout (KO) and double knockout (DKO) mice. Zfy1 KO and Zfy2 KO mice were both fertile, but the latter had decreased litters size and sperm number, and sperm headshape abnormalities. Zfy DKO males were infertile and displayed severe spermatogenesis defects. Postmeiotic arrest largely prevented production of sperm and the few sperm that were produced all displayed gross headshape abnormalities and structural defects within head and tail. Infertility of Zfy DKO mice could be overcome by injection of spermatids or sperm directly to oocytes, and the resulting male offspring had the same spermiogenic phenotype as their fathers. The study is the first describing detailed phenotypic characterization of mice with the complete Zfy gene loss. It provides evidence supporting that the presence of at least one Zfy homolog is essential for male fertility and development of normal sperm functional in unassisted fertilization. The data also show that while the loss of Zfy1 is benign, the loss of Zfy2 is mildly detrimental for spermatogenesis.

In-hospital mortality associated with community-acquired pneumonia due to methicillin-resistant Staphylococcus aureus: a matched-pair cohort study.

BACKGROUND: It remains unclear whether methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is associated with higher mortality compared with non-MRSA pneumonia. This study's objective was to compare outcomes including in-hospital mortality and healthcare costs during hospitalisation between patients with MRSA pneumonia and those with non-MRSA pneumonia. METHODS: Using a national inpatient database in Japan, we conducted a 1:4 matched-pair cohort study of inpatients with community-acquired pneumonia from 1 April 2012 to 31 March 2014. In-hospital outcomes (mortality, length of stay and healthcare costs during hospitalisation) were compared between patients with and without MRSA infection. We performed multiple imputation using chained equations followed by multivariable regression analyses fitted with generalised estimating equations to account for clustering within matched pairs. All-cause in-hospital mortality and healthcare costs during hospitalisation were compared for pneumonia patients with and without MRSA infection. RESULTS: Of 450,317 inpatients with community-acquired pneumonia, 3102 patients with MRSA pneumonia were matched with 12,320 patients with non-MRSA pneumonia. The MRSA pneumonia patients had higher mortality, longer hospital stays and higher costs. Multivariable logistic regression analysis revealed that MRSA pneumonia was significantly associated with higher in-hospital mortality compared with non-MRSA pneumonia (adjusted odds ratio = 1.94; 95% confidence interval: 1.72-2.18; p < 0.001). Healthcare costs during hospitalisation were significantly higher for patients with MRSA pneumonia than for those with non-MRSA pneumonia (difference = USD 8502; 95% confidence interval: USD 7959-9045; p < 0.001). CONCLUSIONS: MRSA infection was associated with higher in-hospital mortality and higher healthcare costs during hospitalisation, suggesting that preventing MRSA pneumonia is essential.

Risk of drug-induced interstitial lung disease in hospitalised patients: a nested case-control study.

INTRODUCTION: Information on drug-induced interstitial lung disease (DILD) is limited due to its low incidence. This study investigated the frequencies of drug categories with potential risk in patients developing DILD during hospitalisation and analysed the risk of developing DILD associated with each of these drugs. METHODS: Using a Japanese national inpatient database, we identified patients without interstitial pneumonia on admission who developed DILD and required corticosteroid therapy during hospitalisation from July 2010 to March 2016. We conducted a nested case-control study; four controls from the entire non-DILD patient cohort were matched to each DILD case on age, sex, main diagnosis, admission year and hospital. We defined 42 classified categories of drugs with 216 generic names as drugs with potential risk of DILD, and we identified the use of these drugs during hospitalisation for each patient. We analysed the association between each drug category and DILD development using conditional logistic regression analyses. RESULTS: We retrospectively identified 2342 patients who developed DILD. After one-to-four case-control matching, 1541 case patients were matched with 5677 control patients. Six drug categories were significantly associated with the increased occurrence of DILD. These included epidermal growth factor receptor inhibitors (OR: 16.84, 95% CI 9.32 to 30.41) and class III antiarrhythmic drugs (OR: 7.01, 95% CI 3.86 to 12.73). Statins were associated with reduced risk of DILD (OR: 0.68, 95% CI 0.50 to 0.92). CONCLUSIONS: We demonstrated significant associations between various drug categories and DILD. Our findings provide useful information on drug categories with potential risk to help physicians prevent and treat DILD.

Early Arterial Embolization and Mortality in Mechanically Ventilated Patients With Hemoptysis: A Nationwide Retrospective Cohort Study.

OBJECTIVES: Hemoptysis, a symptom common across various respiratory diseases, can cause airway obstruction leading to a life-threatening condition. Arterial embolization has been used to control bleeding from the lower airways. However, limited studies have evaluated its effects on in-hospital mortality in patients with hemoptysis requiring mechanical ventilation. The objective of this study was to clarify whether early intervention by arterial embolization reduced mortality in mechanically ventilated patients with hemoptysis. DESIGN: Retrospective cohort study from July 2010 to March 2017. SETTING: More than 1,200 acute-care hospitals, comprising approximately 90% of all tertiary-care emergency hospitals in Japan. PATIENTS: The study cohort was patients with pulmonary diseases hospitalized for hemoptysis and mechanically ventilated within 2 days of admission. INTERVENTIONS: We compared patients who had undergone arterial embolization within 3 days of endotracheal intubation (early embolization group) with patients who did not (control group). MEASUREMENTS AND MAIN RESULTS: A total of 12,287 patients with hemoptysis requiring mechanical ventilation were analyzed. After 1:4 propensity score matching, there were 226 and 904 patients in the early embolization and control groups, respectively. The early embolization group was associated with lower 7-day and 30-day mortalities (7-d mortality: 1.3% vs 4.0%; odds ratio, 0.39; 95% CI, 0.16-0.97; p = 0.044 and 30-d mortality: 7.5% vs 16.8%; odds ratio, 0.45; 95% CI, 0.28-0.73; p = 0.001) and shorter duration of mechanical ventilation (median 6 d, interquartile range 4-13 d vs 8 d, interquartile range 4-19 d; p = 0.003) compared with the control group. CONCLUSIONS: Our results show that early intervention by arterial embolization may be effective in reducing 7-day and 30-day mortalities in patients with life-threatening hemoptysis requiring mechanical ventilation.

Pregnancy environment, and not preconception, leads to fetal growth restriction and congenital abnormalities associated with diabetes.

Maternal diabetes can lead to pregnancy complications and impaired fetal development. The goal of this study was to use a mouse model of reciprocal embryo transfer to distinguish between the preconception and gestational effects of diabetes. To induce diabetes female mice were injected with a single high dose of streptozotocin and 3 weeks thereafter used as oocyte donors for in vitro fertilization (IVF) and as recipients for embryo transfer. Following IVF embryos were cultured to the blastocyst stage in vitro or transferred to diabetic and non-diabetic recipients. Diabetic and non-diabetic females did not differ in regard to the number of oocytes obtained after ovarian stimulation, oocytes ability to become fertilized, and embryo development in vitro. However, diabetic females displayed impaired responsiveness to superovulation. Reciprocal embryo transfer resulted in similar incidence of live fetuses and abortions, and no changes in placental size. However, fetuses carried by diabetic recipients were smaller compared to those carried by non-diabetic recipients, regardless hyperglycemia status of oocyte donors. Congenital abnormalities were observed only among the fetuses carried by diabetic recipients. The findings support that the diabetic status during pregnancy, and not the preconception effect of diabetes on oogenesis, leads to fetal growth restriction and congenital deformities.

Self-management activities of older people with chronic obstructive pulmonary disease by types of healthcare services utilised: A cross-sectional questionnaire study.

AIMS AND DESIGN: Various healthcare services in Japan provide self-management interventions for older people with chronic obstructive pulmonary disease (COPD). To examine the influence of healthcare service utilisation on self-management activities, we conducted a cross-sectional survey of older people with COPD who received care through outpatient clinics (OC), outpatient rehabilitation centres (OR) or home care (HC) services. METHODS: The survey consisted of 34 originally developed self-report questions about three types of self-management activities: (a) strategies to minimise dyspnoea, (b) appropriate activities to maintain physical and mental health status and (c) communication with healthcare professionals or family members. We compared self-management activities in each setting (OC, OR and HC) using logistic regression analyses, controlling for dyspnoea level and age, which we chose as representative variables of disease severity. RESULTS: Among the total sample (n = 81; mean age: 78.2 years old), participants in the HC group (n = 25) had the most severe level of COPD, followed by those in the OR (n = 31) and OC (n = 12) groups. Compared with participants from the OC group, more participants from the OR and HC groups reported self-management activities, such as "moving body corresponding to breathing" (OR: adjusted odds ratio [AOR], 6.71; HC: AOR, 6.98), "trying not to move quickly" (OR: AOR, 5.46), "avoiding suffocating movements" (HC: AOR, 7.37), "getting an influenza vaccination"(OR: AOR, 8.12; HC: AOR, 7.81), "stretching exercise" (OR: AOR, 6.42; HC: AOR, 16.76), "muscle training" (OR: AOR, 8.49; HC: AOR, 9.73) and "discussing lifestyle goals with healthcare professionals" (HC: AOR, 5.75) after controlling for dyspnoea level and age. CONCLUSIONS: Some self-management activities (such as breathing techniques and home exercise) were associated with the use of OR or HC services, an effect persisting after adjusting for degree of breathlessness and age. IMPLICATIONS FOR PRACTICE: Findings suggest that we should provide additional services such as OR and HC besides OC to older people with COPD who are unable to practice self-management activities. We need to consider strategies to provide effective self-management intervention in each healthcare service setting according to the unique characteristics of each setting.

Inhaled corticosteroid withdrawal may improve outcomes in elderly patients with COPD exacerbation: a nationwide database study.

BACKGROUND: Inhaled corticosteroids (ICSs) are used for advanced-stage chronic obstructive pulmonary disease (COPD). The application and safety of ICS withdrawal remain controversial.This study aimed to evaluate the association between ICS withdrawal and outcomes in elderly patients with COPD with or without comorbid bronchial asthma, who were hospitalised for exacerbation. PATIENTS AND METHODS: We conducted a retrospective cohort study using the Japanese Diagnosis Procedure Combination database from July 2010 to March 2016. We identified patients aged ≥65 years who were hospitalised for COPD exacerbation. Re-hospitalisation for COPD exacerbation or death, frequency of antimicrobial medicine prescriptions and frequency of oral corticosteroid prescriptions after discharge were compared between patients with withdrawal and continuation of ICSs using propensity score analyses, namely 1-2 propensity score matching and stabilised inverse probability of treatment weighting. RESULTS: Among 3735 eligible patients, 971 and 2764 patients had ICS withdrawal and continuation, respectively. The hazard ratios (95% confidence intervals) of re-hospitalisation for COPD exacerbation or death for ICS withdrawal compared to continuation were 0.65 (0.52-0.80) in the propensity score matching and 0.71 (0.56-0.90) in the inverse probability of treatment weighting. The frequency of antimicrobial prescriptions but not corticosteroid prescriptions within 1 year was significantly less in the ICS withdrawal group. Among patients with comorbid bronchial asthma, ICS withdrawal was significantly associated with reduced re-hospitalisation for COPD exacerbation or death only in the propensity score matching analysis. CONCLUSION: ICS withdrawal after COPD exacerbation was significantly associated with reduced incidences of re-hospitalisation or death among elderly patients, including those with comorbid bronchial asthma.

Preoperative intervention with long-acting bronchodilators for the reduction of postoperative pulmonary complications in untreated patients with obstructive lung disease.

BACKGROUND: Obstructive lung disease (OLD) is a risk factor for postoperative pulmonary complications (PPC) and is incidentally discovered during preoperative evaluation. The key treatments for OLD are inhaled long-acting bronchodilators (LAB). However, the advantage of preoperative bronchodilator treatment for patients with OLD remains unclear. The aim of this study is to elucidate the effect of preoperative LAB treatment in patients with untreated OLD on postoperative outcomes. METHODS: In this propensity-matched cohort study, we included patients who were referred to the pulmonologists for untreated OLD. The patients were either treated with LAB or left untreated. The primary outcome was the incidence of prolonged oxygen therapy (>3 days) in the postoperative period. We evaluated patients' characteristics with and without the use of LAB using propensity score (PS) matching weight. Subsequently, the outcomes in the two groups were compared. RESULTS: We analysed 614 patients; 132 patients were part of the LAB group and 482 were included in the control group. In the crude analysis, the incidence of prolonged oxygen therapy was higher in the LAB group than in the control group (odds ratio [OR] = 1.35; P = 0.04). However, after PS matching weight, no statistically significant differences in prolonged oxygen therapy (OR = 1.15), incidence of prolonged intensive care unit stay, endotracheal re-intubation postoperatively and in-hospital death between the groups were identified. CONCLUSION: There is a limited benefit of preoperative treatment with inhaled LAB for the reduction of PPC in patients with untreated OLD.

Reference value for expiratory time constant calculated from the maximal expiratory flow-volume curve.

BACKGROUND: The expiratory time constant (RCEXP), which is defined as the product of airway resistance and lung compliance, enable us to assess the mechanical properties of the respiratory system in mechanically ventilated patients. Although RCEXP could also be applied to spontaneously breathing patients, little is known about RCEXP calculated from the maximal expiratory flow-volume (MEFV) curve. The aim of our study was to determine the reference value for RCEXP, as well as to investigate the association between RCEXP and other respiratory function parameters, including the forced expiratory volume in 1 s (FEV1)/ forced vital capacity (FVC) ratio, maximal mid-expiratory flow rate (MMF), maximal expiratory flow at 50 and 25% of FVC (MEF50 and MEF25, respectively), ratio of MEF50 to MEF25 (MEF50/MEF25). METHODS: Spirometric parameters were extracted from the records of patients aged 15 years or older who underwent pulmonary function testing as a routine preoperative examination before non-cardiac surgery at the University of Tokyo Hospital. RCEXP was calculated in each patient from the slope of the descending limb of the MEFV curve using two points corresponding to MEF50 and MEF25. Airway obstruction was defined as an FEV1/FVC and FEV1 below the statistically lower limit of normal. RESULTS: We retrospectively analyzed 777 spirometry records, and 62 patients were deemed to have airway obstruction according to Japanese spirometric reference values. The cut-off value for RCEXP was 0.601 s with an area under the receiver operating characteristic curve of 0.934 (95% confidence interval = 0.898-0.970). RCEXP was strongly associated with FEV1/FVC, and was moderately associated with MMF and MEF50. However, RCEXP was less associated with MEF25 and MEF50/MEF25. CONCLUSIONS: Our findings suggest that an RCEXP of longer than approximately 0.6 s can be linked to the presence of airway obstruction. Application of the concept of RCEXP to spontaneously breathing subjects was feasible, using our simple calculation method.

Naftopidil reduced the proliferation of lung fibroblasts and bleomycin-induced lung fibrosis in mice.

Naftopidil, an α-1 adrenoceptor antagonist with few adverse effects, is prescribed for prostate hyperplasia. Naftopidil inhibits prostate fibroblast proliferation; however, its effects on lung fibroblasts and fibrosis remain largely unknown. Two normal and one idiopathic pulmonary fibrosis human lung fibroblast lines were cultured with various naftopidil concentrations with or without phenoxybenzamine, an irreversible α-1 adrenoceptor inhibitor. We examined the incorporation of 5-bromo-2'-deoxyuridine into DNA and lactic acid dehydrogenase release by enzyme-linked immunosorbent assay, cell cycle analysis by flow cytometry, scratch wound-healing assay, and mRNA expressions of type IV collagen and α-smooth muscle actin by polymerase chain reaction. Effects of naftopidil on bleomycin-induced lung fibrosis in mice were evaluated using histology, micro-computed tomography, and surfactant protein-D levels in serum. Naftopidil, dose-dependently but independently of phenoxybenzamine, inhibited 5-bromo-2'-deoxyuridine incorporation in lung fibroblasts. Naftopidil induced G1 cell cycle arrest, but lactic acid dehydrogenase release and migration ability of lung fibroblasts were unaffected. Naftopidil decreased mRNA expressions of type IV collagen and α-smooth muscle actin in one normal lung fibroblast line. Histological and micro-computed tomography examination revealed that naftopidil attenuated lung fibrosis and decreased serum surfactant protein-D levels in bleomycin-induced lung fibrosis in mice. In conclusion, naftopidil may have therapeutic effects on lung fibrosis.

Rescue of Sly Expression Is Not Sufficient to Rescue Spermiogenic Phenotype of Mice with Deletions of Y Chromosome Long Arm.

Mice with deletions of the Y-specific (non-PAR) region of the mouse Y chromosome long arm (NPYq) have sperm defects and fertility problems that increase proportionally to deletion size. Mice with abrogated function of NPYq-encoded gene Sly (sh367 Sly-KD) display a phenotype similar to that of NPYq deletion mutants but less severe. The milder phenotype can be due to insufficient Sly knockdown, involvement of another NPYq gene, or both. To address this question and to further elucidate the role of Sly in the infertile phenotype of mice with NPYq deletions, we developed an anti-SLY antibody specifically recognizing SLY1 and SLY2 protein isoforms and used it to characterize SLY expression in NPYq- and Sly-deficient mice. We also carried out transgene rescue by adding Sly1/2 transgenes to mice with NPYq deletions. We demonstrated that SLY1/2 expression in mutant mice decreased proportionally to deletion size, with ~12% of SLY1/2 retained in shSLY sh367 testes. The addition of Sly1/2 transgenes to mice with NPYq deletions rescued SLY1/2 expression but did not ameliorate fertility and testicular/spermiogenic defects. Together, the data suggest that Sly deficiency is not the sole underlying cause of the infertile phenotype of mice with NPYq deletions and imply the involvement of another NPYq gene.

Reduction in exacerbation of COPD in patients of advanced age using the Japanese Kampo medicine Dai-kenchu-to: a retrospective cohort study.

PURPOSE: Patients with symptomatic COPD are recommended to use inhaled bronchodilators containing long-acting muscarinic receptor antagonists (LAMAs). However, bronchodilators may cause gastrointestinal adverse effects due to anticholinergic reactions, especially in advanced-age patients with COPD. Dai-kenchu-to (TU-100, Da Jian Zhong Tang in Chinese) is the most frequently prescribed Japanese herbal Kampo medicine and is often prescribed to control abdominal bloating and constipation. The purpose of this study was to evaluate the role of Dai-kenchu-to as a supportive therapy in advanced-age patients with COPD. PATIENTS AND METHODS: We used the Japanese Diagnosis Procedure Combination inpatient database and identified patients aged ≥75 years who were hospitalized for COPD exacerbation. We then compared the risk of re-hospitalization for COPD exacerbation or death between patients with and without Dai-kenchu-to using 1-to-4 propensity score matching. A Cox proportional hazards model was used to compare the two groups. We performed subgroup analyses for patients with and without LAMA therapy. RESULTS: Patients treated with Dai-kenchu-to had a significantly lower risk of re-hospitalization or death after discharge; the HR was 0.82 (95% CI, 0.67-0.99) in 1-to-4 propensity score matching. Subgroup analysis of LAMA users showed a significant difference in re-hospitalization or death, while subgroup analysis of LAMA non-users showed no significant difference. CONCLUSION: Our findings indicate that Dai-kenchu-to may have improved the tolerability of LAMA in advanced-age patients with COPD and, therefore, reduced the risk of re-hospitalization or death from COPD exacerbation. Dai-kenchu-to may be recommended as a useful supportive therapy for advanced-age patients with COPD.