Factors Associated with Cancer-Related Pain Requiring High-Dose Opioid Use in Palliative Cancer Patients

Background:There are no universal tools to predict the necessity of high-dose opioid use for cancer-related pain. Early recognition and interventions for intractable cancer pain could minimize the distress of palliative patients.Objective:We sought to identify the clinical factors associated with high-dose opioid use in advanced cancer patients to recognize palliative patients who would develop intractable cancer pain, as early as possible.Setting/Subjects:Among 385 in-hospital cancer patients from April 1, 2014 to July 31, 2019, who were referred to the palliative care team for cancer-related pain, clinical factors significantly correlated to high-dose opioid use were retrospectively analyzed.Measurements:We conducted a multiple logistic regression analysis to identify variables significantly related to high-dose opioid use (>120 mg/day oral morphine equivalent dose).Results:Independent factors of high-dose opioid use included younger age (odds ratio [OR] 0.965, 95% confidence interval [CI] 0.944-0.986, p = 0.001), respiratory cancers (OR 1.882, 95% CI 1.069-3.312, p < 0.001), and opioid switch (OR 2.869, 95% CI 1.497-5.497, p = 0.001). The percentage of correct classifications of the regression equation was 86.9%.Conclusions:Younger age, respiratory cancers, and opioid switch were related to high-dose opioid use. Our findings may help palliative caregivers to deal with intractable cancer pain in palliative patients, and thus relieve their distress

Adherence with Long-Term Asthma Management in Patients Who Experienced Hospitalized Asthma Exacerbation

Background: In Japan, the number of asthma deaths has been gradually decreasing. However, in the management of asthma, there are still some problems originating from patient-related factors and iatrogenic factors, both of which should be further analyzed. Methods: We investigated clinical and background characteristics of 164 patients with asthma who were admitted to our hospital with acute exacerbations, by reviewing their clinical records. Results: Fifty-two patients had received long-term management (LTM) based on the guidelines (the LTM group), while 112 had not (the non-LTM group). In patients whose asthma severity had been intermittent (step 1), the proportion of severe and near fatal exacerbations was significantly higher in the non-LTM group than in the LTM group. However, even in the LTM-group, 23% of mild persistent (step 2) and 38% of moderately and severely persistent (step 3 & 4) patients had severe or near fatal exacerbations. In these patients, the peak expiratory flow rate significantly improved after discharge, and poor adherence was also significantly higher in the non-LTM group than in the LTM group. A multivariate analysis revealed that the factors associated with poor adherence were: 1) no history of previous admission due to asthma exacerbation; 2) the patient was male; and 3) the patient was young (<60 years). Conclusions: In the LTM group, re-evaluation of the actual severity of asthma and prompt treatment corresponding to the severity of disease should still be encouraged. In the non-LTM group, establishing countermeasures against factors causing poor adherence would be the next step in ensuring strong adherence with LTM

TH1 cell-inducing Escherichia coli strain identified from the small intestinal mucosa of patients with Crohn’s disease

International audienceDysbiotic microbiota contributes to the pathogenesis of Crohn's disease (CD) by regulating the immune system. Although pro-inflammatory microbes are probably enriched in the small intestinal (SI) mucosa, most studies have focused on fecal microbiota. This study aimed to examine jejunal and ileal mucosal specimens from patients with CD via double-balloon enteroscopy. Comparative microbiome analysis revealed that the microbiota composition of CD SI mucosa differs from that of non-CD controls, with an increased population of several families, including Enterobacteriaceae, Ruminococcaceae, and Bacteroidaceae. Upon anaerobic culturing of the CD SI mucosa, 80 bacterial strains were isolated, from which 9 strains representing 9 distinct species (Escherichia coli, Ruminococcus gnavus, Klebsiella pneumoniae, Erysipelatoclostridium ramosum, Bacteroides dorei, B. fragilis, B. uniformis, Parabacteroides distasonis, andStreptococcus pasteurianus) were selected on the basis of their significant association with CD. The colonization of germ-free (GF) mice with the 9 strains enhanced the accumulation of T(H)1 cells and, to a lesser extent, T(H)17 cells in the intestine, among which anE. colistrain displayed high potential to induce T(H)1 cells and intestinal inflammation in a strain-specific manner. The present results indicate that the CD SI mucosa harbors unique pro-inflammatory microbiota, including T(H)1 cell-inducingE. coli, which could be a potential therapeutic target

Flecainide ameliorates arrhythmogenicity through NCX flux in Andersen-Tawil syndrome-iPS cell-derived cardiomyocytes

Andersen-Tawil syndrome (ATS) is a rare inherited channelopathy. The cardiac phenotype in ATS is typified by a prominent U wave and ventricular arrhythmia. An effective treatment for this disease remains to be established. We reprogrammed somatic cells from three ATS patients to generate induced pluripotent stem cells (iPSCs). Multi-electrode arrays (MEAs) were used to record extracellular electrograms of iPSC-derived cardiomyocytes, revealing strong arrhythmic events in the ATS-iPSC-derived cardiomyocytes. Ca2+ imaging of cells loaded with the Ca2+ indicator Fluo-4 enabled us to examine intracellular Ca2+ handling properties, and we found a significantly higher incidence of irregular Ca2+ release in the ATS-iPSC-derived cardiomyocytes than in control-iPSC-derived cardiomyocytes. Drug testing using ATS-iPSC-derived cardiomyocytes further revealed that antiarrhythmic agent, flecainide, but not the sodium channel blocker, pilsicainide, significantly suppressed these irregular Ca2+ release and arrhythmic events, suggesting that flecainide's effect in these cardiac cells was not via sodium channels blocking. A reverse-mode Na+/Ca2+exchanger (NCX) inhibitor, KB-R7943, was also found to suppress the irregular Ca2+ release, and whole-cell voltage clamping of isolated guinea-pig cardiac ventricular myocytes confirmed that flecainide could directly affect the NCX current (INCX). ATS-iPSC-derived cardiomyocytes recapitulate abnormal electrophysiological phenotypes and flecainide suppresses the arrhythmic events through the modulation of INCX

Factors Associated with Cancer-Related Pain Requiring High-Dose Opioid Use in Palliative Cancer Patients

Background:There are no universal tools to predict the necessity of high-dose opioid use for cancer-related pain. Early recognition and interventions for intractable cancer pain could minimize the distress of palliative patients.Objective:We sought to identify the clinical factors associated with high-dose opioid use in advanced cancer patients to recognize palliative patients who would develop intractable cancer pain, as early as possible.Setting/Subjects:Among 385 in-hospital cancer patients from April 1, 2014 to July 31, 2019, who were referred to the palliative care team for cancer-related pain, clinical factors significantly correlated to high-dose opioid use were retrospectively analyzed.Measurements:We conducted a multiple logistic regression analysis to identify variables significantly related to high-dose opioid use (>120 mg/day oral morphine equivalent dose).Results:Independent factors of high-dose opioid use included younger age (odds ratio [OR] 0.965, 95% confidence interval [CI] 0.944-0.986, p = 0.001), respiratory cancers (OR 1.882, 95% CI 1.069-3.312, p < 0.001), and opioid switch (OR 2.869, 95% CI 1.497-5.497, p = 0.001). The percentage of correct classifications of the regression equation was 86.9%.Conclusions:Younger age, respiratory cancers, and opioid switch were related to high-dose opioid use. Our findings may help palliative caregivers to deal with intractable cancer pain in palliative patients, and thus relieve their distress

Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota

Manipulation of the gut microbiota holds great promise for the treatment of inflammatory and allergic diseases1, 2. Although numerous probiotic microorganisms have been identified3, there remains a compelling need to discover organisms that elicit more robust therapeutic responses, are compatible with the host, and can affect a specific arm of the host immune system in a well-controlled, physiological manner. Here we use a rational approach to isolate CD4+FOXP3+ regulatory T (Treg)-cell-inducing bacterial strains from the human indigenous microbiota. Starting with a healthy human faecal sample, a sequence of selection steps was applied to obtain mice colonized with human microbiota enriched in Treg-cell-inducing species. From these mice, we isolated and selected 17 strains of bacteria on the basis of their high potency in enhancing Treg cell abundance and inducing important anti-inflammatory molecules—including interleukin-10 (IL-) and inducible T-cell co-stimulator (ICOS)—in Treg cells upon inoculation into germ-free mice. Genome sequencing revealed that the 17 strains fall within clusters IV, XIVa and XVIII of Clostridia, which lack prominent toxins and virulence factors. The 17 strains act as a community to provide bacterial antigens and a TGF-β-rich environment to help expansion and differentiation of Treg cells. Oral administration of the combination of 17 strains to adult mice attenuated disease in models of colitis and allergic diarrhoea. Use of the isolated strains may allow for tailored therapeutic manipulation of human immune disorders