Japanese Clinical Practice Guidelines for Rehabilitation in Critically Ill Patients 2023 (J-ReCIP 2023).

Providing standardized, high-quality rehabilitation for critically ill patients is a crucial issue. In 2017, the Japanese Society of Intensive Care Medicine (JSICM) promulgated the "Evidence-Based Expert Consensus for Early Rehabilitation in the Intensive Care Unit" to advocate for the early initiation of rehabilitations in Japanese intensive care settings. Building upon this seminal work, JSICM has recently conducted a rigorous systematic review utilizing the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. This endeavor resulted in the formulation of Clinical Practice Guidelines (CPGs), designed to elucidate best practices in early ICU rehabilitation. The primary objective of this guideline is to augment clinical understanding and thereby facilitate evidence-based decision-making, ultimately contributing to the enhancement of patient outcomes in critical care settings. No previous CPGs in the world has focused specifically on rehabilitation of critically ill patients, using the GRADE approach. Multidisciplinary collaboration is extremely important in rehabilitation. Thus, the CPGs were developed by 73 members of a Guideline Development Group consisting of a working group, a systematic review group, and an academic guideline promotion group, with the Committee for the Clinical Practice Guidelines of Early Mobilization and Rehabilitation in Intensive Care of the JSICM at its core. Many members contributed to the development of the guideline, including physicians and healthcare professionals with multiple and diverse specialties, as well as a person who had been patients in ICU. Based on discussions among the group members, eight important clinical areas of focus for this CPG were identified. Fourteen important clinical questions (CQs) were then developed for each area. The public was invited to comment twice, and the answers to the CQs were presented in the form of 10 GRADE recommendations and commentary on the four background questions. In addition, information for each CQ has been created as a visual clinical flow to ensure that the positioning of each CQ can be easily understood. We hope that the CPGs will be a useful tool in the rehabilitation of critically ill patients for multiple professions.

Plasmodium Infection-Cure Cycles Increase the Capacity of Phagocytosis in Conventional Dendritic Cells.

Malaria stands as one of the most pervasive human infectious diseases globally and represents a prominent cause of mortality. Immunity against clinical malaria disease is achieved through multiple infection and treatment cycles, culminating in a substantial reduction in parasite burden. To investigate this phenomenon, we established a murine model involving repeated infection-cure cycles, whereby mice were infected with the lethal rodent malarial parasite Plasmodium berghei ANKA and subsequently treated with the anti-malarial drug pyrimethamine. Our earlier study revealed a significant decrease in the capacity of conventional dendritic cells (cDCs) to produce cytokines upon stimulation in infection-cured mice. In the present study, we aimed to further elucidate the modulation of cDC functionality during repeated infection-cure cycles by examining their phagocytic capacity. Administering fluorescent beads to mice resulted in no significant difference in the total number of bead-positive cells within the spleens of both uninfected and 3-cure (three cycles of infection-cure) mice. However, the proportion of the CD11c+F4/80- population within bead-positive cells was notably higher in 3-cure mice compared to uninfected mice. Subsequent in vitro analysis of bead phagocytosis by purified CD11c+cDCs revealed that the cDC2 subset from 3-cure mice exhibited significantly enhanced phagocytic capacity in comparison to their uninfected counterparts. These findings underscore the substantial impact of repeated infection-cure cycles on various facets of cDC function, potentially influencing the trajectory of immune responses against subsequent malaria infections.

Evaluation of Malarial Var2CSA-Displaying Baculovirus Vector in Transduction Efficiency in Human Cancer Cells.

Baculovirus vectors (BVs) are able to use for gene transduction in mammalian cells and are recognized as growing viral vectors for cancer gene therapy applications. The transduction efficiency of BVs varies among cancer cell types. To improve the transduction efficiency of BVs in human cancer cells, BV displaying malarial variant surface antigen 2-chondroitin sulfate A (var2CSA) molecules was developed in this study. Var2CSA plays a critical role in the sequestration of Plasmodium falciparum-infected erythrocytes in the placenta. Moreover, var2CSA binds to cancer cells via placenta-like chondroitin sulfate A (CSA), but not to non-cancer cells. Var2CSA BV showed significantly higher gene transduction than control BV in HepG2 and Huh7 cells, human hepatic cancer cells as well as AsPC-1 cells, human pancreatic cancer cells. The transduction efficiency of var2CSA BV was significantly inhibited by the anti-gp64 antibody, free heparin, and CSA. The results of this study suggest that var2CSA BV would be an improved vector for cancer gene therapies, especially in the treatment of hepatic and pancreatic cancers.

Ureteral rupture with retroperitoneal urinoma caused by peritoneal metastases of gastric cancer.

We describe the rare case of a patient with ureteric rupture during systemic drug treatment for peritoneal metastases of gastric cancer, who underwent double-J stent placement. A 66-year-old man with gastric cancer was referred to the authors' hospital. Esophagogastroduodenoscopy showed an irregular elevated lesion with thickened gastric folds, and biopsy specimens revealed a poorly differentiated adenocarcinoma. Abdominal contrast-enhanced computed tomography (CT) revealed extensive wall thickening with homogeneous enhancement of the stomach, enlarged lymph nodes in the perigastric area, and nodules in the peritoneal cavity, suggesting peritoneal metastases. The clinical diagnosis was cT4N2M1 with peritoneal metastases, and the patient received chemotherapy (S-1 plus oxaliplatin). After six courses of chemotherapy, the patient presented to the emergency outpatient department with a complaint of acute severe pain in the left lower back. Emergency abdominal contrast-enhanced CT showed extravasation of the contrast medium from the left upper ureter in the periureter area along with the retroperitoneum, and there was no mass lesion or stone in the kidney, ureter, or bladder. A double-J stent was placed under cystoscopic guidance, and no resistance was felt when the stent was inserted. The patient's postprocedural course was uneventful, and he received ramucirumab in combination with paclitaxel after double-J stent placement. However, 2 months later, systemic drug treatment was discontinued because of loss of appetite and increased general fatigue and changed to the best supportive care. His general condition gradually deteriorated, and he died 3 months after the ureteral rupture. Prompt interventions, including retrograde placement of ureteral stents with concurrent use of antibiotics, will reduce mortality and morbidity in this rare entity.

Successful treatment of diabetic ketoacidosis secondary to fulminant type 1 diabetes mellitus using a closed-loop artificial pancreas in a pediatric patient.

Diabetic ketoacidosis (DKA) is a life-threatening complication of pediatric diabetes mellitus (DM). A bedside closed-loop artificial pancreas (AP) (STG-55; NIKKISO, Tokyo, Japan) maintains the blood glucose (BG) levels within the target range via automatic infusion of insulin and glucose. We report the application of the closed-loop AP to safely control the BG levels of a pediatric patient with DKA. A 12-year-old child with an unremarkable medical history presented with fever and restlessness. The patient was diagnosed with DKA secondary to fulminant type 1 DM and was treated with insulin infusion. He presented with Glasgow Coma Scale of E2V3M4. Arterial blood gas analysis revealed metabolic acidosis and BG levels of 489 mg/dL. His urine test was positive for ketones. Along with infusion therapy, automatic BG control using a closed-loop AP was initiated after ICU admission. This was adjusted to maintain BG levels within 100 mg/dL/6 h or less. After 24 h in the ICU, the patient regained consciousness and recovered from the metabolic acidosis. His general condition improved, and he was prescribed a diet treatment. The treatment was shifted to continuous insulin infusion, and he was transferred to the general ward, and was discharged on the 33rd day of hospitalization. The closed-loop AP prevented repetitive blood extractions, achieved prompt glycemic control, and prevented cerebral edema in a pediatric patient with DKA. This is the first report of successful treatment of DKA using a bedside closed-loop AP.

Impact of Energy and Protein Delivery to Critically Ill Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Optimal energy and protein delivery goals for critically ill patients remain unknown. The purpose of this systematic review and meta-analysis was to compare the impact of energy and protein delivery during the first 4 to 10 days of an ICU stay on physical impairments. We performed a systematic literature search of MEDLINE, CENTRAL, and ICHUSHI to identify randomized controlled trials (RCTs) that compared energy delivery at a cut-off of 20 kcal/kg/day or 70% of estimated energy expenditure or protein delivery at 1 g/kg/day achieved within 4 to 10 days after admission to the ICU. The primary outcome was activities of daily living (ADL). Secondary outcomes were physical functions, changes in muscle mass, quality of life, mortality, length of hospital stay, and adverse events. Fifteen RCTs on energy delivery and 14 on protein were included in the analysis. No significant differences were observed in any of the outcomes included for energy delivery. However, regarding protein delivery, there was a slight improvement in ADL (odds ratio 21.55, 95% confidence interval (CI) −1.30 to 44.40, p = 0.06) and significantly attenuated muscle loss (mean difference 0.47, 95% CI 0.24 to 0.71, p < 0.0001). Limited numbers of RCTs were available to analyze the effects of physical impairments. In contrast to energy delivery, protein delivery ≥1 g/kg/day achieved within 4 to 10 days after admission to the ICU significantly attenuated muscle loss and slightly improved ADL in critically ill patients. Further RCTs are needed to investigate their effects on physical impairments.

Evaluation of Combinatory Effects of Plasmodium Circumsporozoite Protein and Complement Regulatory Protein Expression of Recombinant Baculovirus Vectors.

Baculovirus vectors (BVs) are safely able to transduce foreign genes and express them in mammalian cells. However, the transduction activity of BVs is strongly reduced by the attack of serum complement, which is one of the major obstacles in the use of BVs for in vivo gene transfer. One strategy to overcome this problem is the display of complement regulatory proteins (CRPs) on BV virions. We previously developed CD46-decay accelerating factor (DAF)-CD59 triple fusion type BV showing potent complement resistance. We also developed BVs expressing Plasmodium circumsporozoite protein (CSP) to enhance transduction efficacy in hepatic cells. In this study, we investigated the combination of CSP and CRPs in a BV system to evaluate transduction efficacy along with complement resistance. To accomplish the combination of CSP and CRPs, we generated insect Sf9 cells stably expressing CRPs, to which CSP type BV was infected. The BVs collected from these infected cells were confirmed to possess both CSP and CRPs in virions. We demonstrated that CSP-CD46-DAF-CD59 type BV, containing both CSP and CD46-DAF-CD59, showed a significant increase in transduction efficacy in human hepatoma HepG2 cells under intact serum exposure compared with control type BV or CSP type BV, retaining both advantages of CSP and CD46-DAF-CD59. Collectively, these results demonstrated that the utilization of stably expressing Sf9 cells to introduce the protein products of interest, e.g., CRPs into BVs, would be useful strategy to generate BVs with novel functions such as resistance against serum complement attack.

Plasmodium infection cure cycles induce modulation of conventional dendritic cells.

Malaria is one of the most widespread human infectious diseases worldwide and a cause of mortality. It is difficult to induce immunological memory against the malarial parasite Plasmodium. The immunity to clinical malaria disease is acquired with multiple infection and treatment cycles, along with substantial reduction in parasite burden. However, the mechanism of the acquired immunity remains largely unclear. Conventional DCs (cDCs) play a pivotal role in orchestration of immune responses. The purpose of this study is to analyze the characterization of cDCs after the infection and cure treatment cycles. Mice were infected with the lethal rodent malarial parasite Plasmodium berghei ANKA, which was followed by cure treatment with the antimalarial drug pyrimethamine. This was then followed by a challenge with live parasites. The mice that went through infection cure cycles showed significant immune response, demonstrating robust immunological memory against malaria parasites. We investigated the cytokine production capacity of splenic cDCs in both naive and infection cure mice by stimulating purified splenic cDCs with LPS (TLR4 agonist) or CpG (TLR9 agonist). The capacity of cytokine production was found to be significantly decreased in infection cure mice. The suppression of cytokine production was sustained for a long term (6 months). Moreover, the surface expression of MHC Class II molecules was significantly lower in infection cure mice than in naive mice. These results suggest that Plasmodium infection and cure treatment resulted in strong immunological memory and modulation of full functionality of cDCs.

Influence of nutrition support therapy on readmission among patients with acute heart failure in the intensive care unit: A single-center observational study.

BACKGROUND & AIMS: The effect of nutrition support therapy on prevention of readmission among patients with acute heart failure (HF) in an intensive care unit (ICU) setting remains unclear. We hypothesized that nutrition support therapy might decrease the readmission rate among these patients. Thus, we conducted a single-center prospective observational study to verify this hypothesis. METHODS: Patients diagnosed with acute HF admitted to the ICU for more than 14 days between April 2016 and March 2017 were included in the analysis. The primary outcome was the relationship between nutritional intake and HF-related hospital readmission due to HF at 180 days after discharge. We divided the participants into 2 groups: patients who were not readmitted to hospital within 180 days after discharge (non-readmission group) and patients who were readmitted within this timeframe (HF-related readmission group). Data were expressed as median (interquartile range). RESULTS: Sixty patients required readmission due to HF-related events (HF-related readmission group). On the other hand, 127 patients did not require readmission (non-readmission group). The calorie and protein intake on day 3 after ICU admission in the HF-related readmission group was significantly higher than that in the non-readmission group [20.5 (14.2, 27.8) vs. 27.7 (22.5, 31.2) kcal/kg/day, p < 0.001; 0.7 (0.5, 0.9) vs. 0.9 (0.7, 1.2) g/kg/day, p < 0.001, respectively]. Similarly, the protein intake values on day 7 were also significantly higher in the HF-related readmission group [0.8 (0.6, 1.0) vs. 0.9 (0.7, 1.2) g/kg/day, p = 0.04]. Multivariate analysis indicated that total caloric intake on day 3 was an independent factor affecting readmission (odds ratio = 1.05, 95% confidence interval = 1.01-1.09, p = 0.006). In addition, when the cut off value of calorie intake was set to 18 kcal/kg/day, the group ingesting ≥18 kcal/kg/day on day 3 had a significantly higher readmission rate within 180 days after discharge. CONCLUSIONS: Our data showed that total calorie intake ≥18 kcal/kg/day on day 3 might increase the readmission rate among patients with acute HF.

Glucose control using a closed-loop device decreases inflammation after cardiovascular surgery without increasing hypoglycemia risk.

Although tight glucose control might reduce inflammation after cardiac surgery, it remains unclear whether inflammation can be controlled by maintaining glucose levels within 110-180 mg/dL. We hypothesized that a glucose target range of 110-180 mg/dL decreases inflammation after cardiovascular surgery. This retrospective study included 72 cardiovascular surgery patients divided into two groups according to the glucose control approach. Patients allocated to the closed-loop group received closed-loop glucose control (target glucose levels at 110-180 mg/dL) from admission to the intensive care unit until 9 a.m. on postoperative day (POD) 1. Patients allocated to the conventional group received conventional glucose control using a sliding scale method to maintain blood glucose levels < 200 mg/dL. Primary outcomes were C-reactive protein (CRP) levels on PODs 1, 2, and 7. Data were reported as mean ± standard deviation. Comparisons were performed using the chi-squared test and unpaired t test, with p < 0.05 indicating statistical significance. The closed-loop group had significantly lower average glucose levels (169 ± 24 vs. 201 ± 36 mg/dL, p < 0.001) and standard deviation of glucose levels (22 ± 13 vs. 44 ± 20 mg/dL; p < 0.001). The CRP levels on PODs 2 and 7 were significantly lower in the closed-loop group than in the conventional group (10.8 ± 5.6 vs. 14.1 ± 5.7 mg/dL, p = 0.02; 4.6 ± 2.5 vs. 7.3 ± 4.0 mg/dL, p < 0.001; respectively). Our findings suggest that glucose control using a closed-loop device might decrease inflammation after cardiovascular surgery without increasing hypoglycemia risk.

Prognostic significance of serum alkaline phosphatase and lactate dehydrogenase levels in patients with unresectable advanced gastric cancer.

BACKGROUND: This study evaluated the prognostic value of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) together with host-related factors in patients with unresectable advanced gastric cancer. METHODS: The study enrolled 262 patients who received chemotherapy for unresectable advanced gastric cancer at Kochi Medical School from 2007 to 2015. Clinicopathological information and systemic inflammatory response data were analyzed for associations between baseline cancer-related prognostic variables and survival outcomes. RESULTS: The median survival time was significantly lower for patients with high ALP, high LDH, high total bilirubin, high aspartate aminotransferase, high alanine transaminase, high gamma-glutamyltransferase, high creatinine, a Glasgow prognostic score (GPS) of 1 or 2 score compared to GPS 0, higher compared to lower neutrophil to lymphocyte ratio (NLR) 3.9, lower compared to higher prognostic nutrition index 36.1, T3-4 compared to T1-2 tumor and diffuse-type compared to intestinal-type histology. Multivariate survival analysis identified high ALP 322 (HR 1.808; 95% CI 1.015-3.220; P = 0.044), T2-3 (HR 2.622; 95% CI 1.224-5.618; P = 0.013), and diffuse-type gastric cancer (HR 2.325; 95% CI 1.341-4.032; P = 0.003) as significant independent predictors of worse prognosis in the studied group of cancer patients. CONCLUSIONS: High level of ALP is an independent, worse prognosis factor for patients receiving chemotherapy for unresectable and recurrent gastric cancer.

Gastric outlet obstruction caused by metastatic tumor of the stomach originating from primary breast cancer: A case report.

The most common sites of breast cancer metastasis are the bone, liver, lung and brain, while gastrointestinal metastasis from breast cancer is rare. We herein present the case of a 68-year-old woman who was admitted to our department with nausea and appetite loss. The patient's medical history included right mastectomy with sentinel lymph node biopsy 5 years earlier for invasive lobular carcinoma, measuring 6.2 cm in greatest diameter, without lymphovascular invasion. Two years after the surgery, the patient developed brain metastasis and underwent metastasectomy to control the neurological symptoms, including unsteadiness and asthenia. After the second surgery, the patient received systemic chemotherapy using S-1, followed by bevacizumab plus paclitaxel. However, due to bevacizumab-related cardiotoxicity, the treatment was switched to eribulin. On esophagogastroduodenoscopy, an elevated lesion was identified in the antrum, causing severe narrowing of the gastric outlet. Biopsy and histological examination of the tumor revealed infiltration of the gastric wall by undifferentiated neoplastic cells with poor adhesion, morphologically similar to invasive lobular carcinoma, and immunohistochemical staining was positive for estrogen receptor, mammaglobin and GATA3. Finally, 18F-2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography combined with computed tomography imaging revealed FDG uptake across the thickness of the antral wall. The patient was diagnosed with gastric metastasis from the original breast cancer and subsequently underwent endoscopic self-expandable metallic stent (SEMS) placement. There were no procedure-related adverse events, and the patient remained alive under best supportive care 4 months after SEMS placement. To the best of our knowledge, this is the first reported case of gastric outlet obstruction caused by metastatic breast carcinoma managed by SEMS placement. While such a diagnosis is rare, clinicians treating patients with gastric metastases should be aware of possible gastric outlet obstruction and SEMS placement as an effective palliative intervention.

Protection of Baculovirus Vectors Expressing Complement Regulatory Proteins against Serum Complement Attack.

Baculovirus vectors (BVs) enable safe and efficient gene delivery to mammalian cells and are useful in a wide range of applications, including gene therapy and in vivo analysis of gene functions. We previously developed BVs expressing malaria sporozoite surface proteins for targeting liver cells or hepatocytes. However, BVs are known to be very vulnerable to complement attack and efforts to overcome their inactivation based on complement are important. In this study, BVs expressing complement regulatory proteins (CRPs) on the surfaces of virions were developed to inhibit complement reactions. Decay accelerating factor (DAF; CD55)-type BVs exhibited significantly higher complement resistance than control BVs without any CRPs in HepG2 cells transduction, although the transduction efficacy of DAF-type BV was low. In contrast, CD46-DAF-CD59 fusion type BVs showed significantly higher transduction efficacy and complement resistance than both control and DAF-type BVs. DAF-type and CD46-DAF-CD59 type BVs repressed formation of the membrane attack complex, a terminal product of complement reaction cascades, induced by BVs. These results suggest that the CD46-DAF-CD59 fusion construct confers complement protection ability superior to that of the DAF construct in gene delivery under complement active serum.

Treatment of bimaxillary protrusion with temporary anchorage devices.

For treatment of severe bimaxillary protrusion in adults, a condition known to be among the most difficult to manage, both the maxillary and mandibular anterior teeth must be fully retracted using all the extraction space available. This article reports the treatment of an adult with severe high-angle bimaxillary protrusion. To correct the protrusion of the anterior teeth, orthodontic anchor screws (OASs) were used to provide absolute anchorage during anterior retraction. Acceptable occlusion, facial profile, and balance were achieved. OASs appear to be very useful for treatment of severe bimaxillary protrusion in adults.

Mortality and physical status at hospital discharge in Japanese elderly critically ill patients: a single-center retrospective study.

BACKGROUND: Because there is ongoing population aging, the age of patients admitted to the intensive care unit (ICU) is also higher. However, the evidence about outcomes in elderly patients is insufficient in Japan. Therefore, we conducted a retrospective study. METHOD: The study participants were consecutive patients who were admitted to our ICU and received mechanical ventilation for more than 24 h. We divided the patients into two groups, according to age. Patients in group A were 74 years old or younger, and those in group B were 75 years old or older. The major outcome was in-hospital mortality. FINDINGS: Two hundred and twenty patients met the inclusion criteria. There were 118 patients in group A and 102 patients in group B. The overall hospital mortality in both groups were similar (19 vs. 25%, p = 0.23). The proportion of patients who were discharged home and had good physical status at hospital discharge in group A were significantly higher than that in group B (72 vs. 37%, p < 0.0001; 91 vs. 74%, p = 0.004, respectively). CONCLUSION: The elderly population were associated with a twofold increase in the risk of discharged not to the home compared with others.

Easy Debonding of Ceramic Brackets Bonded with a Light-Cured Orthodontic Adhesive Containing Microcapsules with a CO2 Laser.

OBJECTIVE: An easy debonding method for ceramic brackets using a light-cured Bis-GMA resin containing heat-expandable microcapsules and CO2 laser was investigated. BACKGROUND: Ceramic brackets are used frequently in orthodontic treatment because of their desirable esthetic properties. However, the application of heavy force to ceramic brackets in debonding can fracture the tooth enamel and ceramic brackets, causing tooth pain. MATERIALS AND METHODS: In total, 60 freshly extracted bovine permanent mandibular incisors were divided randomly into 10 groups of 6 specimens each, corresponding to the number of variables tested. Ceramic brackets were bonded to bovine permanent mandibular incisors using an orthodontic bonding agent containing heat-expandable microcapsules at different levels (0-30 wt%) and resin composite paste, and cured by a curing device. The bond strengths were measured before and after CO2 laser irradiation, and the temperature increase in the pulp chamber in fresh human first premolars was also evaluated. RESULTS: With CO2 laser irradiation for 5 sec to the bracket, the bond strength in the 25% microcapsule group decreased significantly, to ∼0.17-fold, compared with that of the no-laser group (p < 0.05). The maximum temperature increase in the pulp chamber was 5.3°C with laser irradiation, which was less than the level that induces pulp damage. CONCLUSIONS: From these results, it seems likely that the combined use of a light-cured orthodontic bonding agent containing microcapsules and a CO2 laser is a simple debonding system for ceramic brackets, with less debonding time and enamel damage.

DAF-shielded baculovirus-vectored vaccine enhances protection against malaria sporozoite challenge in mice.

BACKGROUND: Previous studies have shown that the baculovirus-vectored vaccine based on the "baculovirus dual expression system (BDES)" is an effective vaccine delivery platform for malaria. However, a point of weakness remaining for use of this vaccine platform in vivo concerns viral inactivation by serum complement. In an effort to achieve complement resistance, the gene encoding the human decay-accelerating factor (hDAF) was incorporated into the BDES malaria vaccine expressing the Plasmodium falciparum circumsporozoite protein (PfCSP). RESULTS: The newly-developed BDES vaccine, designated BDES-sPfCSP2-Spider, effectively displayed hDAF and PfCSP on the surface of the viral envelope, resulting in complement resistance both in vitro and in vivo. Importantly, upon intramuscular inoculation into mice, the BDES-sPfCSP2-Spider vaccine had a higher protective efficacy (60%) than that of the control vaccine BDES-sPfCSP2-Spier (30%) against challenge with transgenic Plasmodium berghei sporozoites expressing PfCSP. CONCLUSION: DAF-shielded BDES-vaccines offer great potential for development as a new malaria vaccine platform against the sporozoite challenge.

Prevention of atrial fibrillation after cardiac surgery using low-dose landiolol: A systematic review and meta-analysis.

STUDY OBJECTIVE: Atrial fibrillation (AF) is associated with mortality after cardiac surgery. Several studies have reported that landiolol might help to prevent postoperative AF. The objective of this study was to investigate whether low-dose landiolol is useful in terms of balance of benefit and risk. DESIGN: We conducted a meta-analysis after systematically searching the PubMed, the Cochrane library and the ICHUSHI to identify randomized, controlled trials investigating the preventive effect of landiolol on incidence of AF after cardiac surgery. PATIENTS: Six randomized trial with 571 patients were included. MEASUREMENTS: The primary outcome was incidence of AF after surgery, while secondary outcomes were mortality and complications. MAIN RESULTS: Incidence of AF within 1week after surgery was significantly lower in the landiolol group than in the control group (odds ratio, 0.27; 95% confidence interval, 0.18-0.42; p<0.001). Three of the 6 studies reported data regarding in-hospital mortality and complications, showing no significant differences between groups (0.7 vs 3.0%; OR, 0.45; 95% CI, 0.07-2.74; p=0.39; and 4.5 vs 9.7%; OR, 0.45; 95% CI, 0.16-1.23; p=0.12, respectively). CONCLUSIONS: Our systematic review revealed that low-dose landiolol might help to prevent AF after cardiac surgery and further large trials are needed to evaluate safety because mortality and morbidity rate were very low in included studies.

Influence of saline-based hydroxyethyl starch on umbilical cord blood electrolytes.

Hydroxyethyl starch (HES) is widely used to prevent and treat spinal anesthesia-induced hypotension during cesarean section. However, the use of saline-based HES may lead to hyperchloremia. This study aimed to clarify the effects of saline-based HES on umbilical cord chloride level at delivery. We retrospectively analyzed 93 consecutive single-pregnancy patients who underwent cesarean section with combined spinal-epidural anesthesia. The patients were divided into two groups, depending on the use of 6% HES 130/0.4: group A (461 ± 167 ml of saline-based HES was administered; 43 patients) and group B (HES not administered; 50 patients). The major outcome was umbilical cord chloride level at delivery. The volume infused from operating room admission until delivery was not significantly different between groups. The umbilical cord chloride level at delivery was statistically significantly higher in group A than in group B, but clinically similar (108 ± 2 vs. 107 ± 2 mmol/l, P = 0.02). No differences were observed in the Apgar score or other umbilical cord laboratory data at delivery (Na+, K+, pH, base excess). In conclusion, we suggest that although the use of up to 500 ml of saline-based HES during cesarean section influences umbilical cord blood electrolytes, the effect is not of a clinically significant magnitude.

Influence of dexmedetomidine on cognitive function in volunteers.

STUDY OBJECTIVE: Some outpatient procedures are performed under sedation with dexmedetomidine, although the effect of dexmedetomidine on cognitive function remains unclear. This study investigated the effect of dexmedetomidine on cognitive function in healthy volunteers. DESIGN: Observation study in volunteers. SETTING: University-affiliated teaching hospital. PATIENTS: Six healthy volunteers. INTERVENTIONS: After infusion of a 6-µg/kg per hour loading dose of dexmedetomidine for 10 minutes, a maintenance infusion of 0.4 µg/kg per hour was administered for 4 hours. MEASUREMENTS: Cognitive function was evaluated before infusion (baseline) and at 2, 4, 6, and 8 hours after infusion. Cognitive function, response speed, accuracy, and consistency were measured by CogHealth. Depth of sedation was evaluated at 1-hour intervals by evaluating the Bispectral Index. Data are presented as the change from baseline. MAIN RESULTS: The Bispectral Index value was significantly lower from 10 minutes to 6 hours after infusion versus the pre-infusion value. Response speed was also significantly lower at 2 hours and 4 hours after infusion (92 ± 8%, P< .0001; 93 ± 6%, P< .0001), as was consistency (96 ± 7%, P= .0009; 96 ± 5%, P= .0003). Response accuracy was unaltered by the infusion. CONCLUSIONS: Dexmedetomidine slightly reduced response speed and consistency, but did not affect response accuracy. Cognitive function was restored to pre-administration values 2 hours after the infusion of dexmedetomidine was discontinued.