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Abstract Despite the growing epidemic worldwide, diabetes is an incurable disease. We have been focusing on why diabetes manifests refractoriness to any therapy. We recently found that abnormal bone marrow-derived cells (BMDCs), namely, Vcam-1+ST-HSCs, was a key mechanism for diabetic complications. We then hypothesize that those aberrant BMDCs sustainedly impair pancreatic β cells. Here we show that eliminating abnormal BMDCs using bone marrow transplantation results in controlling serum glucose in diabetic mice, in which normoglycemia is sustained even after cessation of insulin therapy. Alternatively, abnormal BMDCs exhibiting epigenetic alterations are treated with an HDAC inhibitor, givinostat, in diabetic mice. As a result, those mice are normoglycemic along with restored insulin secretion even following the cessation of both insulin and givinostat. Diabetic cell fusion between abnormal BMDCs and resident cells is significantly blocked by the combination therapy in the pancreatic islets and thymus while surgical ablation of the thymus completely eliminates therapeutic protection in diabetic mice. In conclusion, diabetes is an epigenetic stem cell disorder with thymic disturbances. The combination may be applied to patients aiming at complete remission from diabetes in clinical medicine.

Katagi et al. show that abnormal bone marrow-derived cells originated from hematopoietic stem cells (CD106-positive short-term HSCs) aberrantly fuse with neurons to develop diabetic neuropathy. This study suggests that the pathological abnormality is memorized in the bone marrow and that it cannot be erased by conventional therapy.

Aim Out‐of‐hospital cardiac arrests (OHCA) are a significant public health problem; to improve patients’ prognoses, various interventions, such as providing physician‐staffed ambulances, have been implemented. We aimed to examine whether physician‐staffed ambulances were associated with patients’ prognoses after OHCA with respect to first‐monitored rhythms. Methods This retrospective observational study was undertaken between 1 September 2011 and 31 December 2015, using data based on Utstein‐style guidelines. We extracted data on age, sex, first‐monitored rhythm (shockable or non‐shockable), presence of a witness, bystander cardiopulmonary resuscitation, time from call to arrival at the scene, out‐of‐hospital adrenaline administration, out‐of‐hospital intubation, return of spontaneous circulation before arrival at the hospital, and survival and neurological outcomes 30 days after OHCA, according to cerebral performance categories. We undertook logistic regression analyses to assess the association between physician‐staffed ambulances and patients’ prognoses. Results A total of 882 OHCA patients were eligible for this study. Physician‐staffed ambulances attended to 164 OHCA patients. Multivariable analysis found that in non‐shockable rhythm patients, physician‐staffed ambulances significantly improved good neurological outcome (odds ratio, 3.65; 95% confidence interval [CI], 1.28–10.50; P = 0.02), return of spontaneous circulation before arrival at the hospital (odds ratio, 2.68; 95% CI, 1.62–4.42; P

Aim We aimed to investigate the association between aortic calcification and 90‐day mortality in sepsis patients admitted to the intensive care unit. Methods We evaluated adult patients (≥18 years) diagnosed with sepsis based on the Sepsis‐3 criteria and admitted to our intensive care unit between April 2011 and March 2015. They were classified according to the degree of abdominal aortic calcification (severe and non‐severe), grouped per age (75 years), and matched. Survival curves were generated, and between‐group differences were evaluated. Results Overall, 164 patients were included. The Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were not significantly different between the severity groups, whereas there were significant differences in age (P

Aim The complement system is important for defending against pathogens, however, excessive complement activation is associated with a poor prognosis and organ dysfunction in sepsis. Complement factor H (CFH) acts to prevent excessive complement activation and damage to the self through the regulation of the complement alternative pathway. We investigated the association between plasma CFH levels on admission to the intensive care unit (ICU) and 90‐day mortality, severity scores, and organ dysfunction in patients with sepsis. Methods We assessed the relationship between the plasma CFH on admission to the ICU and 90‐day mortality, severity scores such as the Acute Physiology and Chronic Health Evaluation II score, Sequential Organ Failure Assessment score, and Simplified Acute Physiology Score 2, and organ dysfunction. Results This analysis included 62 patients. The plasma CFH levels were significantly lower in 90‐day non‐survivors than in survivors (70.0 μg/mL [interquartile range, 51.2–97.6] versus 104.8 μg/mL [interquartile range, 66.8–124.2]; P = 0.006) . The plasma CFH levels were associated with 90‐day mortality (odds ratio 0.977; 95% confidence interval, 0.957–0.994; P = 0.01). The plasma CFH levels were negatively correlated with severity scores. The Sequential Organ Failure Assessment scores for the coagulation and neurological components were negatively correlated with the CFH concentration. Conclusion Lower plasma levels of CFH were associated with increased severity and mortality in patients with sepsis on admission to the ICU and were correlated with central nervous system dysfunction and coagulopathy.

Abstract Introduction Dexmedetomidine is a sedative used during spinal anaesthesia. However, it frequently induces bradycardia. Although intravenous atropine is often used for treating bradycardia during regional anaesthesia, the response to atropine might be attenuated by concomitantly administering sedatives. Methods We examined the effects of atropine used for treating bradycardia during spinal anaesthesia among patients receiving dexmedetomidine (D group), propofol (P group), or neither (nonDnonP group) for sedation, retrospectively. Results A total of 108 patients were included. Heart rate was significantly slower at all time points in the D group (n = 69) than in the nonDnonP group (n = 14) (p

Background: Severe sepsis is commonly associated with mortality among critically ill patients and is known to cause coagulopathy. While antithrombin is an anticoagulant used in this setting, serum albumin levels are known to influence serum antithrombin levels. Therefore, this study aimed to evaluate the outcomes of antithrombin supplementation in patients with sepsis-associated coagulopathy, as well as the relationship between serum albumin levels and the effects of antithrombin supplementation. Methods: This retrospective study evaluated patients who were >18 years of age and had been admitted to either of two intensive care units for sepsis-associated coagulopathy. The groups that did and did not receive antithrombin supplementation were compared for outcomes up to 1 year after admission. Subgroup analyses were performed for patients with serum albumin levels of

Unexpected reintubation may occur, even if the risk factors are considered and a spontaneous breathing trial is successful. Reintubation is thought to be caused by various factors. Several studies have investigated the risk factors of reintubation, but most did not classify reintubation by cause. We retrospectively classified patients undergoing reintubation at intensive care unit by cause (respiratory insufficiency vs. nonrespiratory insufficiency) to examine the cause-specific risk factors of reintubation. A total of 262 patients were included; reintubation within 48 hours after extubation was performed in 12 patients (reintubation rate, 4.5%). After classification by cause of reintubation, the pressure of arterial oxygen to fractional inspired oxygen concentration (P/F) ratio exhibited a significant association with reintubation only in the respiratory insufficiency group (odds ratio (OR) 0.989, 95% confidence interval (CI) 0.980 to 0.999, p=0.036, and OR 0.989, 95% CI 0.979 to 0.999, p=0.026, in the univariate and multivariate analyses, respectively). In the propensity score analysis, a P/F ratio ≤ 200 may be a risk factor for reintubation in the respiratory insufficiency group (OR 7.811, 95% CI 1.345 to 45.367, p=0.022). In the nonrespiratory insufficiency group, intubation duration was significantly related to reintubation (OR 1.165, 95% CI 1.012 to 1.342, p=0.033, and OR 1.163, 95% CI 1.004 to 1.348, p=0.044, in the univariate and multivariate analyses, respectively). In conclusion, a low P/F ratio at extubation may be a risk factor for reintubation due to respiratory insufficiency. In the nonrespiratory insufficiency group, intubation duration may be significantly related to reintubation. The risk factors for reintubation may differ by the cause of reintubation. Further large-scale randomized controlled trials are required.