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PurposePostoperative spinal cord injury is a devastating complication after aortic arch replacement. The purpose of this study was to determine the predictors of this complication.MethodsA group of 254 consecutive patients undergoing aortic arch replacement via median sternotomy, with (n = 78) or without (n = 176) extended replacement of the upper descending aorta, were included in a risk analysis. The frozen elephant trunk technique was used in 46 patients. The patients’ atherothrombotic lesions (extensive intimal thickening of > 4 mm) were identified from computed tomography images.ResultsComplete paraplegia (n = 7) and incomplete paraparesis (n = 4) occurred immediately after the operation (permanent spinal cord injury rate, 1.97%; transient spinal cord injury rate, 2.36%). A multivariable logistic regression analysis identified the use of the frozen elephant trunk technique (odds ratio 36.3), previous repair of thoracoabdominal aorta or descending aorta (odds ratio 29.4), proximal atherothrombotic aorta (odds ratio 9.6), chronic obstructive lung disease (odds ratio 7.1) and old age (odds ratio 1.1) as predictors of spinal cord injury (p < 0.0001, area under curve 0.93).ConclusionsSpinal cord injury occurs with a non-negligible incidence following aortic arch replacement. The full objective assessment of the morphology of the whole aorta and the recognition of the risk factors are mandatory.

PurposeThe clinical application of gemcitabine (GEM) is limited by its pharmacokinetic properties. The aim of this study was to characterize the stability in circulating plasma, tumor targeting, and payload release of liposome-encapsulated GEM, FF-10832.MethodsAntitumor activity was assessed in xenograft mouse models of human pancreatic cancer. The pharmacokinetics of GEM and its active metabolite dFdCTP were also evaluated.ResultsIn mice with Capan-1 tumors, the dose-normalized areas under the curve (AUCs) after FF-10832 administration in plasma and tumor were 672 and 1047 times higher, respectively, than after using unencapsulated GEM. The tumor-to-bone marrow AUC ratio of dFdCTP was approximately eight times higher after FF-10832 administration than after GEM administration. These results indicated that liposomal encapsulation produced long-term stability in circulating plasma and tumor-selective targeting of GEM. In mice with Capan-1, SUIT-2, and BxPC-3 tumors, FF-10832 had better antitumor activity and tolerability than GEM. Internalization of FF-10832 in tumor-associated macrophages (TAMs) was revealed by flow cytometry and confocal laser scanning microscopy, and GEM was efficiently released from isolated macrophages of mice treated with FF-10832. These results suggest that TAMs are one of the potential reservoirs of GEM in tumors.ConclusionThis study found that FF-10832 had favorable pharmacokinetic properties. The liposomal formulation was more effective and tolerable than unencapsulated GEM in mouse xenograft tumor models. Hence, FF-10832 is a promising candidate for the treatment of pancreatic cancer.

Introduction and Aims: This study examined whether zinc supplementation with zinc acetate hydrate improved renal anemia with hypozincemia in patients undergoing hemodialysis. Methods: The study participants included 21 patients undergoing hemodialysis who presented with a serum zinc level < 60 mg/dL and who were administered zinc acetate hydrate at 50 mg (reduced to 25 mg, as appropriate) for 6 months. Patients with a hemorrhagic lesion, acute-phase disease (pneumonia or cardiac failure), or hematologic disease and those whose treatment was switched from peritoneal dialysis to hemodialysis were excluded. The changes in the erythropoietin resistance index (ERI) before and after zinc acetate hydrate administration were examined. ERI was defined as the dose (IU) of erythropoiesis-stimulating agent (ESA)/week/body weight (kg)/hemoglobin content (g/dL). The differences between the two groups were analyzed using the Wilcoxon signed rank sum test, and p < 0.05 was considered statistically significant. Results: The study participants included 19 men and 2 women aged 41–95 years (mean ± standard deviation (SD): 67.1 ± 13.6). The changes in the values of parameters measured before and after zinc acetate hydrate administration were as follows: Blood Hb did not change significantly, from 10.0–13.6 g/dL (11.5 ± 1.0 g/dL) to 10.2–12.4 g/dL (11.4 ± 0.7 g/dL); serum zinc concentration significantly increased, from 33.0–59.0 mg/dL μg/dL (52.4 ± 7.6 mg/dL μg/dL) to 57.0–124.0 mg/dL μg/dL (84.1 ± 16.3 mg/dL μg/dL; p < 0.01); the ESA dose significantly decreased, from 0–12,000 IU/week (5630 ± 3351 IU/week) to 0–9000 IU/week (4428 ± 2779; p = 0.04); and ERI significantly decreased, from 0.0–18.2 (8.1 ± 5.1) to 0.0–16.0 (6.3 ± 4.3; p = 0.04). Conclusions: Zinc supplementation increased the serum zinc concentration and significantly reduced the ESA dose and ERI, suggesting that a correction of hypozincemia contributes to lessening renal anemia in these patients.

The escalating effects of climate change, particularly global warming, are posing an increasing burden on human health. Older adults are particularly susceptible to the impact of extreme heat. Adequate water intake is essential to prevent dehydration in hot environments. Therefore, it is important to understand water turnover (WT) and intake. WT of older adults in hot environments remains unknown. This study aimed at investigating the seasonal effects on WT, total energy expenditure (TEE), and physical activity using doubly labeled water (DLW) and a triaxial accelerometer. A total of 26 older Japanese adult males and females aged ≥ 65 years participated in the study. WT and TEE were measured using DLW in May and August 2012. The mean values of maximum, mean, and minimum temperatures and mean humidity of the measurement days were 24 °C, 19 °C, 14 °C, and 57% in May (spring) and 35 °C, 29 °C, 25 °C, and 66% in August (summer) 2012, respectively. The mean (standard deviation, SD) age of the participants was 73.7 (5.4) years. Total body water increased significantly from 31.1 (4.6) to 31.9 (5.2) kg (+ 0.8 kg, P  = 0.009) from May to August. TEE decreased significantly from 2271 (280) to 2123 (470) kcal/day (- 149 kcal/d, P  = 0.036), while WT increased significantly from 2.939 (0.625) to 3.579 (0.943) L/day (+ 0.640 L/d, P  < 0.001). WT increased by 640 mL/day during summer compared to that during spring, when the average temperature was 19 °C. Our findings indicate that WT increases during hot weather in older adults, reflecting seasonal adaptation.

Sepsis-induced disseminated intravascular coagulation (DIC) is a serious condition because it is closely linked to the development of multiple organ dysfunctions. We compared molecular fibrinolysis markers for 117 patients with sepsis-induced DIC and 1627 patients with nonseptic DIC. Levels of fibrinogen and fibrin degradation products and D-dimer were significantly lower in sepsis-induced DIC cases than in nonseptic DIC cases. In septic DIC cases, plasma plasminogen activator inhibitor 1 (PAI-1) levels were significantly higher than in nonseptic DIC cases. D-dimer levels were negatively correlated with plasma PAI-1 levels in septic DIC cases. Multiple Organ Dysfunction Scores were significantly higher in septic DIC patients with PAI-1 levels >90 ng/mL than in the group with PAI-1 levels <30 ng/mL. The Kaplan-Meier survival functions until 28 days after DIC diagnosis were significantly lower in the group with PAI-1 levels >90 ng/mL than in the other groups. In a multivariate analysis, plasma PAI-1 levels at DIC diagnosis were an independent risk factor for mortality in sepsis-induced DIC (hazard ratio, 1.012; P = .008). These data suggest that plasma PAI-1 plays an important role in sustaining DIC in septic DIC cases and contributes to multiple organ failure and decreased survival in such patients.

Background and aimsConversion to laparotomy is among the serious intraoperative complications and carries an increased risk of postoperative complications. In this cohort study, we investigated whether or not the Endoscopic Surgical Skill Qualification System (ESSQS) affects the conversion rate among patients undergoing laparoscopic surgery for rectal cancer.MethodsWe performed a retrospective secondary analysis of data collected from patients undergoing laparoscopic surgery for cStage II and III rectal cancer from 2014 to 2016 across 56 institutions affiliated with the Japan Society of Laparoscopic Colorectal Surgery. Data from the original EnSSURE study were analyzed to investigate risk factors for conversion to laparotomy by performing univariate and multivariate analyses based on the reason for conversion.ResultsData were collected for 3,168 cases, including 65 (2.1%) involving conversion to laparotomy. Indicated conversion accounted for 27 cases (0.9%), while technical conversion accounted for 35 cases (1.1%). The multivariate analysis identified the following independent risk factors for indicated conversion to laparotomy: tumor diameter [mm] (odds ratio [OR] 1.01, 95% confidence interval [CI] 1.01–1.05, p = 0.0002), combined resection of adjacent organs [+/−] (OR 7.92, 95% CI 3.14–19.97, p < 0.0001), and surgical participation of an ESSQS-certified physician [−/+] (OR 4.46, 95% CI 2.01–9.90, p = 0.0002). The multivariate analysis identified the following risk factors for technical conversion to laparotomy: registered case number of institution (OR 0.99, 95% CI 0.99–1.00, p = 0.0029), institution type [non-university/university hospital] (OR 3.52, 95% CI 1.54–8.04, p = 0.0028), combined resection of adjacent organs [+/−] (OR 5.96, 95% CI 2.15–16.53, p = 0.0006), and surgical participation of an ESSQS-certified physician [−/+] (OR 6.26, 95% CI 3.01–13.05, p < 0.0001).ConclusionsParticipation of ESSQS-certified physicians may reduce the risk of both indicated and technical conversion. Referral to specialized institutions, such as high-volume centers and university hospitals, especially for patients exhibiting relevant background risk factors, may reduce the risk of conversion to laparotomy and lead to better outcomes for patients.Trial RegistrationThis study was registered with the Japanese Clinical Trials Registry as UMIN000040645.

Background Patients with mandibular prognathism exhibit not only its characteristic maxillofacial morphology but also discrepancies in stomatognathic function, and understanding this morphology and function is vital for establishing a plan for surgical orthodontic treatment or providing guidance for recovery after orthognathic surgery. However, few studies have yet addressed the objective evaluation of masticatory function before and after surgical orthodontic treatment. In particular, the masticatory behaviors that show how you chew in your daily meals, including the number of chews, chewing rate, and posture during chewing, has not yet been fully studied in patients with mandibular prognathism. The aim of this study was to compare the masticatory behaviors of patients with mandibular prognathism with that of patients with individualized normal occlusion, to clarify the characteristics of masticatory behaviors in mandibular prognathism and to search for a relationship with maxillofacial morphology. Methods Participants were 23 patients (12 men, 11 women; mean age 17.9 years) with mandibular prognathism (patient group) and 23 patients (12 men, 11 women; mean age 24.4 years) with normal occlusion that had been achieved by orthodontic treatment (control group). Masticatory behaviors were measured by a wearable device fitted to each participant’s right ear. Parameters such as number of chews, chewing rate, number of chews per bite, mealtime, and head and neck posture were recorded, while participants consumed a 100-g rice ball. Body mass index, occlusal contact area, and lateral cephalograms were also measured, and their associations with masticatory behaviors were investigated. Results In patient group, the number of chews was lower, mealtime was shorter, and the head and neck were tilted further forward. There was a significant positive correlation between overjet and anteroposterior head and neck posture and a significant negative correlation between overbite and anteroposterior head and neck posture. Conclusion Due to morpho/functional discrepancies in the stomatognathic system, patient group chewed fewer times and for a shorter time and leaned further forward while chewing. The characteristics of the masticatory behaviors of patients with mandibular prognathism identified in the present study may be helpful when devising plans for changing behavior before and after orthodontic treatment or orthognathic surgery.

ObjectivesCurrent guidelines restrict the use of inotropes for the treatment for heart failure (HF) unless the patients are hypotensive or hypoperfused because of safety concerns. This study sought to characterise the contemporary real-world use of inotropes and associated long-term outcomes according to systolic blood pressure (sBP) and perfusion status.DesignA multicentre prospective cohort study.SettingThis study was nested from the Kyoto Congestive Heart Failure registry, which included consecutive Japanese patients admitted for HF.ParticipantsWe categorised 3995 patients into two groups: sBP ≥90 mm Hg and warm profile group, and sBP <90 mm Hg or cold profile group. In each group, patients were stratified across the use of inotropes within 24 hours of hospital presentation.Primary and secondary outcomesThe primary outcome was all-cause death throughout follow-up. Secondary outcomes included cardiovascular death throughout follow-up, all-cause death during index hospitalisation and after discharge, and HF hospitalisation.ResultsA total of 793 patients (20%) presented with sBP <90 mm Hg or cold profile, whereas 3202 patients had sBP ≥90 mm Hg and warm profile; 276 patients (35%) in the sBP <90 mm Hg/cold group and 312 patients (10%) in the sBP ≥90 mm Hg/warm group received initial inotropic treatment. Adjusted excess risk of inotrope use relative to no inotrope for the primary outcome measure was significant in the sBP ≥90 mm Hg/warm group (adjusted HR), 1.36; 95% CI 1.09 to 1.72, p=0.006) but not in the sBP <90 mm Hg/cold group (adjusted HR, 1.28, 95% CI 0.96 to 1.69, p=0.09). Risk for postdischarge all-cause death and HF hospitalisation was not significantly different between the patients with inotropes and no inotropes in both groups.ConclusionInotrope use in the absence of hypotension and hypoperfusion is still common, but associated with a worse long-term prognosis.Trial registration numberUMIN000015238.