Relation between nutrition therapy in the acute phase and outcomes of ventilated patients with COVID-19 infection: a multicenter prospective observational study.

BACKGROUND: Optimal nutrition therapy has not yet been established for the acute phase of severe coronavirus disease 2019 (COVID-19) infection. OBJECTIVES: We aimed to examine the effects of nutrition delivery in the acute phase on mortality and the long-term outcomes of post-intensive care syndrome (PICS). METHODS: A multicenter prospective study was conducted on adult patients with COVID-19 infection requiring mechanical ventilation during an intensive care unit (ICU) stay. Daily total energy (kcal/kg) and protein (g/kg) deliveries in the first week of the ICU stay were calculated. The questionnaire for PICS evaluation was mailed within a median of 6 mo after hospital discharge. The primary outcome was in-hospital mortality, and secondary outcomes were the PICS components of physical impairment, cognitive dysfunction, and mental illness. RESULTS: Among 414 eligible patients, 297 who received mechanical ventilation for 7 d or longer were examined. PICS was evaluated in 175 patients among them. High protein delivery on days 4-7 correlated with a low in-hospital mortality rate. In contrast, high protein delivery on days 1-3 correlated with physical impairment. A multivariate logistic regression analysis adjusted for age, sex, BMI, and severity revealed that average energy and protein deliveries on days 4-7 correlated with decreased in-hospital mortality (OR: 0.94; 95% CI: 0.89, 0.99; P = 0.013 and OR: 0.40; 95% CI: 0.17, 0.93; P = 0.031, respectively). Nutrition delivery did not correlate with PICS outcomes after adjustments. In the multivariate regression using a restricted cubic spline model, in-hospital mortality monotonically decreased with increases in average nutrition delivery on days 4-7. CONCLUSIONS: In patents with COVID-19 on mechanical ventilation for ≥7 d, nutrition delivery in the late period of the acute phase was monotonically associated with a decrease in in-hospital mortality. Adequate protein delivery is needed on days 4-7.This trial was registered at https://www.umin.ac.jp as UMIN000041276.

Development of Quality Indicators of Stroke Centers and Feasibility of Their Measurement Using a Nationwide Insurance Claims Database in Japan　­ J-ASPECT Study ­

BACKGROUND: We aimed to develop quality indicators (QIs) related to primary and comprehensive stroke care and examine the feasibility of their measurement using the existing Diagnosis Procedure Combination (DPC) database. METHODS AND RESULTS: We conducted a systematic review of domestic and international studies using the modified Delphi method. Feasibility of measuring the QI adherence rates was examined using a DPC-based nationwide stroke database (396,350 patients admitted during 2013-2015 to 558 hospitals participating in the J-ASPECT study). Associations between adherence rates of these QIs and hospital characteristics were analyzed using hierarchical logistic regression analysis. We developed 17 and 12 measures as QIs for primary and comprehensive stroke care, respectively. We found that measurement of the adherence rates of the developed QIs using the existing DPC database was feasible for the 6 QIs (primary stroke care: early and discharge antithrombotic drugs, mean 54.6% and 58.7%; discharge anticoagulation for atrial fibrillation, 64.4%; discharge antihypertensive agents, 51.7%; comprehensive stroke care: fasudil hydrochloride or ozagrel sodium for vasospasm prevention, 86.9%; death complications of diagnostic neuroangiography, 0.4%). We found wide inter-hospital variation in QI adherence rates based on hospital characteristics. CONCLUSIONS: We developed QIs for primary and comprehensive stroke care. The DPC database may allow efficient data collection at low cost and decreased burden to evaluate the developed QIs.

Immunonutrition suppresses acute inflammatory responses through modulation of resolvin E1 in patients undergoing major hepatobiliary resection.

BACKGROUND: Although several studies have reported the effects of immunonutrition on clinical outcomes, detailed mechanisms of immunonutrition after an operation are still unclear. It was recently reported that resolvin E1, a novel lipid mediator generated from eicosapentaenoic acid (EPA), activates factors that reduce inflammation. This randomized clinical trial was designed to investigate not only the effect of immunonutrition on postoperative complications but also the participation of resolvin E1 on anti-inflammatory effects of immunonutrition in patients undergoing major hepatobiliary resection. METHODS: Forty patients who underwent major hepatobiliary resection were divided into 2 groups. Twenty patients received oral supplementation enriched with EPA, arginine, and nucleotides before the operation (group IN). Twenty patients (control group) received no artificial nutrition before the operation (group C). RESULTS: The rate of infectious complications and severity of complications in group IN was significantly lower than in group C (P < .05). Immediately after the operation, plasma resolvin E1 levels were significantly higher in group IN than in group C (P < .05), and plasma interleukin-6 levels were significantly lower in group IN than in group C (P < .05). Preoperative serum EPA levels correlated with plasma resolvin E1 levels immediately after the operation. Plasma resolvin E1 levels correlated with plasma interleukin-6 levels immediately after the operation. CONCLUSION: Preoperative immunonutrition reduced inflammatory responses and protected against the aggravation of postoperative complications in patients undergoing major hepatobiliary resection. Resolvin E1 may play a key role in the resolution of acute inflammation when immunonutrition is supplemented with EPA. (ClinicalTrials.gov Identifier: NCT01256047.).

Identification of 3-methylbutanoyl glycosides in green Coffea arabica beans as causative determinants for the quality of coffee flavors.

The quality of coffee green beans is generally evaluated by the sensory cupping test, rather than by chemical compound-based criteria. In this study, we examined the relationship between metabolites and cupping scores for 36 varieties of beans, using a nontargeted LC-MS-based metabolic profiling technique. The cupping score was precisely predicted with the metabolic information measured using LC-MS. Two markers that strongly correlated with high cupping scores were determined to be isomers of 3-methylbutanoyl disaccharides (3MDs; 0.01-0.035 g/kg of beans) by spectroscopic analyses after purification, and one of them was a novel structure. Further, both the 3MDs were determined to be precursors of 3-methylbutanoic acid that enhance the quality of coffee. The applicability of 3MDs as universal quality indicators was validated with another sample set. It was concluded that 3MDs are the causative metabolites determining beverage quality and can be utilized for green bean selection and as key compounds for improving the beverage quality.

Preoperative immunonutrition decreases postoperative complications by modulating prostaglandin E2 production and T-cell differentiation in patients undergoing pancreatoduodenectomy.

BACKGROUND: An immune-enhancing diet has been used to alter eicosanoid synthesis, cytokine production, and immune function in an attempt to limit the undesired immune reactions after injury from surgery. This prospective randomized study was designed to investigate the effect of preoperative immunonutrition on operative complications, and the participation of prostaglandin E2 (PGE2) on T-cell differentiation in patients undergoing a severely stressful surgery. METHODS: The enrolled patients who were scheduled to undergo pancreatoduodenectomy were randomized into two groups. Patients in the immunonutrition group (n = 25) received oral supplementation containing arginine, ω-3 fatty acids, and RNA for 5 days before the procedure in addition to a 50% reduction in the amount of regular food. Patients in the control group (n = 25) received no artificial nutrition and were allowed to consume regular food before surgery. All patients received early postoperative enteral infusion of a standard formula intended to provide 25 kcal/kg/day. The primary endpoint was the rate of infectious complications; the secondary endpoint was immune responses. This study is registered with ClinicalTrials.gov (NCT01256034). RESULTS: Infectious complication rate and severity of complications (Clavien-Dindo classification) were lesser in the immunonutrition group than in the control group. mRNA expression levels of T-bet were greater in the immunonutrition group than in the control group (P < .05). Serum eicosapentaenoic acid and eicosapentaenoic acid/arachidonic acid ratios were greater in the immunonutrition group than in the control group (P < .05). The levels of plasma PGE2 were lesser in the immunonutrition group than in the control group (P < .05). CONCLUSION: Preoperative immunonutrition modulates PGE2 production and T-cell differentiation and may protect against the aggravation of operative complications in patients undergoing pancreatoduodenectomy.

Effects of perioperative immunonutrition on cell-mediated immunity, T helper type 1 (Th1)/Th2 differentiation, and Th17 response after pancreaticoduodenectomy.

BACKGROUND: The mechanisms of immunonutrition on reducing infectious complications are still poorly understood. This prospective randomized study was designed to determine whether immunonutrition influences the following factors: cell-mediated immunity, differentiation of T helper type 1 (Th1) and Th2 cells, interleukin (IL)-17-producing CD4(+) helper T (Th17) cell response, and infectious complication rate after pancreaticoduodenectomy. METHODS: Thirty patients who underwent pancreaticoduodenectomy were divided into 3 groups. Ten patients in the perioperative group received immune-enhancing diets enriched with arginine, omega-3 fatty acids, and RNA for 5 days before operative resection, which was prolonged after operative resection by enteral infusion. Ten patients in the postoperative group received early postoperative enteral infusion of the same enriched formula with no artificial nutrition before operative resection. Ten patients in the control group received total parenteral nutrition postoperatively. The primary endpoint was immune responses; the secondary endpoint was the rate of infectious complications. RESULTS: Concanavalin A (Con A)- or phytohemagglutinin (PHA)-stimulated lymphocyte proliferation and natural killer cell activity were significantly higher in the perioperative group than in the other groups. Messenger RNA (mRNA) expression levels of T-bet, interferon-gamma (IFN-gamma), related orphan receptor gammat (RORgammat), and interleukin-17F (IL-17F) were significantly higher in the perioperative group than in the other groups. In the perioperative group, the rate of infectious complications was significantly reduced compared with that in the other groups. CONCLUSION: Perioperative immunonutrition reduced stress-induced immunosuppression after a major stressful operative resection. The modulation of Th1/Th2 differentiation and Th17 response may play important roles in this immunologic effect.

Effects of changeover from voglibose to acarbose on postprandial triglycerides in type 2 diabetes mellitus patients.

INTRODUCTION: In this study, we examined the effects of the alpha-glucosidase inhibitors acarbose and voglibose on postprandial plasma glucose and serum triglyceride levels in patients with type 2 diabetes mellitus. METHODS: Twenty-one Japanese patients with type 2 diabetes were enrolled in this study. Subjects had been treated with voglibose for at least 3 months. They underwent a 400 kcal balanced food meal tolerance test before and 8 weeks after the changeover from voglibose to acarbose. Subjects were divided into two groups: the first group (low-dose group; n=11) was changed over from 0.6 mg/day voglibose to 150 mg/day acarbose, and the other (high-dose group; n=10) from 0.9 mg/day voglibose to 300 mg/day acarbose. RESULTS: The increment rate of postprandial plasma glucose ([plasma glucose 2 hours after test meal - fasting glucose]/fasting glucose) decreased from 34.7%+/-23.9% to 25.0%+/-24.6% (P=0.13) in the low-dose group, and decreased significantly from 56.1%+/-53.1% to 31.5%+/-36.0% (P=0.03) in the high-dose group after changeover. However, there were no significant changes in blood glycated hemoglobin (HbA(1c)) levels before and after changeover in either group. The increment rate of postprandial serum triglyceride (TG) ([serum TG 2 hours after test meal - fasting TG]/fasting TG) decreased significantly only in the high-dose group (52.4%+/-60.0% to 24.3%+/-16.6%) (P=0.05). No significant changes in serum high-density lipoprotein cholesterol levels were observed in either group, whereas serum low-density lipoprotein cholesterol levels decreased significantly from 3.20+/-0.25 to 2.65+/-0.18 mmol/L (P=0.04), only in the high-dose group. CONCLUSIONS: In patients with type 2 diabetes our findings suggest that acarbose 300 mg/day is superior to voglibose 0.9 mg/day in improving postprandial hyperglycemia and hypertriglyceridemia.

Effect of hyperbaric oxygen therapy on patients with adhesive intestinal obstruction associated with abdominal surgery who have failed to respond to more than 7 days of conservative treatment.

BACKGROUND/AIMS: To investigate the effects of hyperbaric oxygen (HBO) therapy on patients with adhesive intestinal obstruction who have failed to respond to more than 7 days of conservative treatment. METHODOLOGY: Six hundred eighty-five patients, who were admitted a total of 879 times for adhesive intestinal obstruction, were divided into groups according to the treatment and interval between the first day of the therapy and clinical symptoms of obstruction; tube decompression therapy within 7 days after appearance of clinical symptoms (Group I: n = 321), clinical symptoms that have persisted for less than 7 days before the start of HBO therapy (Group II: n = 498), and for more than 7 days (Group III: n = 60). RESULTS: The overall resolution and mortality rates in the cases of adhesive intestinal obstruction were 79.8% and 2.2% in Group I, 85.9% and 1.4% in Group II, and 81.7% and 1.6% in Group III, respectively. Group II had significantly better resolution rates than Group I (odds ratio 1.6, p < 0.02). CONCLUSIONS: HBO therapy may be useful in management of adhesive intestinal obstruction associated with abdominal surgery, even in patients who fail to respond to other conservative treatments. HBO therapy may be a preferred option for treatment of patients for whom surgery should be avoided.

Hyperbaric oxygen therapy as a prophylactic and treatment against ileus and recurrent intestinal obstruction soon after surgery to relieve adhesive intestinal obstruction.

BACKGROUND AND AIM: Nonoperative management of cases of adhesive intestinal obstruction would be ideal, especially for patients who have recently undergone surgery to relieve the same condition. We aimed to examine whether hyperbaric oxygen (HBO) therapy might have therapeutic potential for the treatment of postoperative paralytic ileus and recurrent adhesive intestinal obstruction soon after surgery, to relieve adhesive intestinal obstruction, because of its unique mechanisms in these contexts. METHODS: A total of 133 patients were enrolled in the present study. We examined non-per os periods, hospital stay, and clinical course according to the postoperative course of the 133 patients. RESULTS: After surgical intervention, 75 patients left the hospital without morbidity. Nineteen patients were successfully administered prophylactic HBO therapy to facilitate intestinal motility and to prevent paralytic ileus. The remaining 39 patients suffered from postoperative paralytic ileus or early recurrence of obstruction during the same hospitalization period. The patients who underwent prophylactic HBO therapy had significantly shorter non-per os periods and hospital stays after surgery than those who were not initially given HBO therapy (P < 0.05). Similarly, there were significant differences in duration of hospital stay after surgery between patients with HBO therapy as treatment and those who received other conservative therapies (P < 0.05). CONCLUSIONS: HBO therapy may have a prophylactic effect on postoperative paralytic ileus and may be of therapeutic benefit in the management of early recurrent adhesive intestinal obstruction following surgery to relieve adhesive intestinal obstruction.

Hyperbaric oxygen therapy for the treatment of postoperative paralytic ileus and adhesive intestinal obstruction associated with abdominal surgery: experience with 626 patients.

BACKGROUND/AIMS: The results of hyperbaric oxygen (HBO) therapy for treatment of postoperative paralytic ileus and adhesive intestinal obstruction associated with abdominal surgery are unknown. METHODOLOGY: A retrospective review of postoperative paralytic ileus and adhesive intestinal obstruction associated with abdominal surgery in 626 patients required 758 admissions who underwent HBO therapy was undertaken to examine the efficacy of HBO therapy. RESULTS: The overall resolution rates for patients receiving HBO therapy in cases of postoperative paralytic ileus and adhesive intestinal obstruction were 92% and 85%, respectively. Among patients who were more than 75 years old, the therapies resolved 35 (97%) of 36 cases of postoperative paralytic ileus and 42 (81%) of 52 cases of adhesive intestinal obstruction, which was comparable to the results for patients less than 75 years old. The mortality rate was 1.2% overall. Complications related to HBO therapy occurred in 3.8% of the admissions, and most of them were not serious. CONCLUSIONS: These results suggest that HBO therapy might deserve further assessment for use in management of postoperative paralytic ileus and adhesive intestinal obstruction as a new modality. HBO therapy is safe and non-invasive, and may be useful in the elderly patients, since mortality was relatively low in this series.

[Surgical resection for pancreatic cancer combined with preoperative carbon-ion beam irradiation].

Prognosis of pancreatic cancer is still remarkably poor, even if complete resection was performed by enlarged abscission. On the other hand, carbon-ion beam therapy is giving good results in some selected carcinoma such as small cell lung cancer, prostate cancer, uterus cancer, and soft tissue/bone tumor. In this report, we discuss four patients with pancreatic cancer treated by surgical pancreatectomy combined with preoperative carbon-ion beam irradiation. All patients were irradiated with 48 GyE carbon-iron beam by HIMAC (Heavy Ion Medical Accelerator in Chiba) to the pancreatic area including lymph nodes and nerve plexus. Severe cholangitis, as the postoperative complication, had occurred in one of the patients. However, there was no complication or disorder caused by carbon-iron radiation. All four patients are alive now, but two of them developed tumor recurrence, one with hepatic metastasis and the other with peritoneal dissemination. Surgical treatment for pancreatic cancer combined with preoperative carbon-ion irradiation is expected as a promising cure, but it is necessary to examine more cases in the future to evaluate the clinical outcome of this treatment.