Unicompartmental Knee Arthroplasty for Osteoarthritis Eliminates Lateral Thrust: Associations between Lateral Thrust Detected by Inertial Measurement Units and Clinical Outcomes.

The purpose of this study was to investigate the relationship between clinical outcomes and lateral thrust before and after unicompartmental knee arthroplasty (UKA) using inertial measurement sensor units. Eleven knees were evaluated with gait analysis. The varus angular velocity was used to evaluate lateral thrust. The femorotibial angle (FTA) and hip-knee-ankle angle (HKA) were used to evaluate lower-limb alignment, and the Oxford Knee Score (OKS) and Japanese Orthopaedic Association Score (JOA) were used to evaluate clinical outcomes. The mean pre-UKA peak varus velocity was 37.1 ± 9.8°/s, and that for post-UKA was 28.8 ± 9.1°/s (p = 0.00003), such that instabilities clearly improved. Assuming the definition of lateral thrust is when the varus angular velocity is more than 28.1°/s, 81.8% of patients had lateral thrust preoperatively, but this decreased to 55.6% postoperatively, such that the symptoms and objective findings improved. Both OKS and JOA improved after surgery. In addition, HKA was -7.9° preoperatively and -5.8° postoperatively (p = 0.024), and FTA was 181.4° preoperatively and 178.4° postoperatively (p = 0.012). There was a positive correlation between postoperative JOA and FTA, indicating that changes in postoperative alignment affected clinical outcomes. This study quantitatively evaluated the disappearance of lateral thrust by UKA, and it found that the stability can be achieved by UKA for unstable knees with lateral thrust.

Postoperative intravenous patient-controlled analgesia improves pain management after subcutaneous implantable defibrillator implantation.

Objective: Postoperative pain is a major issue with subcutaneous implantable cardioverter defibrillators (S-ICD). In 2020, we introduced intravenous patient-controlled analgesia (IV-PCA) in addition to the conventional, request-based analgesia for postoperative pain control in S-ICD. To determine the effect and safety, we quantitatively assessed the effect of IV-PCA after S-ICD surgery over conventional methods. Methods: During the study period, a total of 113 consecutive patients (age, 50.1 ± 15.5 years: males, 101) underwent a de novo S-ICD implantation under general anesthesia. While the postoperative pain was addressed with either request-based analgesia (by nonsteroid anti-inflammatory drugs, N = 68, dubbed as "PCA absent") or fentanyl-based IV-PCA in addition to the standard care (N = 45, dubbed as "PCA present"). The degree of postoperative pain from immediately after surgery to 1 week were retrospectively investigated by the numerical rating scale (NRS) divided into four groups at rest and during activity (0: no pain, 1-3: mild pain, 4-6: moderate pain, 7-10: severe pain). Results: Although IV-PCA was removed on Day 1, it was associated with continued better pain control compared to PCA absent group. At rest, the proportion of patients expressing pain (mild or more) was significantly lower in the PCA present group from Day 0 to Day 4. In contrast to at rest, a better pain control continued through the entire study period of 7 days. No serious adverse events were observed. A few patients experienced nausea in both groups and the inter-group difference was not found significant. Conclusion: IV-PCA suppresses postoperative pain in S-ICD without major safety concerns.

Association between regional critical care capacity and the incidence of invasive mechanical ventilation for coronavirus disease 2019: a population-based cohort study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has exposed critical care supply shortages worldwide. This study aimed to investigate the association between regional critical care capacity and the incidence of invasive mechanical ventilation following novel COVID-19 during the pandemic in Japan, a country with a limited intensive care unit (ICU) bed capacity of a median of 5.1 ICU beds per 100,000 individuals. METHODS: This population-based cohort study used data from the CRoss Icu Searchable Information System database and publicly available databases provided by the Japanese government and Japanese Society of Intensive Care Medicine. We identified patients recently diagnosed with COVID-19, those who received invasive mechanical ventilation, and those who received extracorporeal membrane oxygenation (ECMO) between February 2020 and March 2023. We analyzed the association between regional critical care capacity (ICU beds, high-dependency care unit (HDU) beds, resource-rich ICU beds, and intensivists) and the incidence of invasive mechanical ventilation, ECMO, and risk-adjusted mortality across 47 Japanese prefectures. RESULTS: Among the approximately 127 million individuals residing in Japan, 33,189,809 were recently diagnosed with COVID-19, with 12,203 and 1,426 COVID-19 patients on invasive mechanical ventilation and ECMO, respectively, during the study period. Prefecture-level linear regression analysis revealed that the addition of ICU beds, resource-rich ICU beds, and intensivists per 100,000 individuals increased the incidence of IMV by 5.37 (95% confidence interval, 1.99-8.76), 7.27 (1.61-12.9), and 13.12 (3.48-22.76), respectively. However, the number of HDU beds per 100,000 individuals was not statistically significantly associated with the incidence of invasive mechanical ventilation. None of the four indicators of regional critical care capacity was statistically significantly associated with the incidence of ECMO and risk-adjusted mortality. CONCLUSIONS: The results of prefecture-level analyses demonstrate that increased numbers of ICU beds, resource-rich ICU beds, and intensivists are associated with the incidence of invasive mechanical ventilation among patients recently diagnosed with COVID-19 during the pandemic. These findings have important implications for healthcare policymakers, aiding in efficiently allocating critical care resources during crises, particularly in regions with limited ICU bed capacities. Registry and the registration no. of the study/trial The approval date of the registry was August 20, 2020, and the registration no. of the study was lUMIN000041450.

Pharmacological Inhibition of Epidermal Growth Factor Receptor Prevents Intracranial Aneurysm Rupture by Reducing Endoplasmic Reticulum Stress.

BACKGROUND: Multiple pathways and factors are involved in the rupture of intracranial aneurysms. The EGFR (epidermal growth factor receptor) has been shown to mediate inflammatory vascular diseases, including atherosclerosis and aortic aneurysm. However, the role of EGFR in mediating intracranial aneurysm rupture and its underlying mechanisms have yet to be determined. Emerging evidence indicates that endoplasmic reticulum (ER) stress might be the link between EGFR activation and the resultant inflammation. ER stress is strongly implicated in inflammation and apoptosis of vascular smooth muscle cells, both of which are key components of the pathophysiology of aneurysm rupture. Therefore, we hypothesized that EGFR activation promotes aneurysmal rupture by inducing ER stress. METHODS: Using a preclinical mouse model of intracranial aneurysm, we examined the potential roles of EGFR and ER stress in developing aneurysmal rupture. RESULTS: Pharmacological inhibition of EGFR markedly decreased the rupture rate of intracranial aneurysms without altering the formation rate. EGFR inhibition also significantly reduced the mRNA (messenger RNA) expression levels of ER-stress markers and inflammatory cytokines in cerebral arteries. Similarly, ER-stress inhibition also significantly decreased the rupture rate. In contrast, ER-stress induction nullified the protective effect of EGFR inhibition on aneurysm rupture. CONCLUSIONS: Our data suggest that EGFR activation is an upstream event that contributes to aneurysm rupture via the induction of ER stress. Pharmacological inhibition of EGFR or downstream ER stress may be a promising therapeutic strategy for preventing aneurysm rupture and subarachnoid hemorrhage.

Association of initial lactate levels and red blood cell transfusion strategy with outcomes after severe trauma: a post hoc analysis of the RESTRIC trial.

BACKGROUND: The appropriateness of a restrictive transfusion strategy for those with active bleeding after traumatic injury remains uncertain. Given the association between tissue hypoxia and lactate levels, we hypothesized that the optimal transfusion strategy may differ based on lactate levels. This post hoc analysis of the RESTRIC trial sought to investigate the association between transfusion strategies and patient outcomes based on initial lactate levels. METHODS: We performed a post hoc analysis of the RESTRIC trial, a cluster-randomized, crossover, non-inferiority multicenter trials, comparing a restrictive and liberal red blood cell transfusion strategy for adult trauma patients at risk of major bleeding. This was conducted during the initial phase of trauma resuscitation; from emergency department arrival up to 7 days after hospital admission or intensive care unit (ICU) discharge. Patients were grouped by lactate levels at emergency department arrival: low (< 2.5 mmol/L), middle (≥ 2.5 and < 4.0 mmol/L), and high (≥ 4.0 mmol/L). We compared 28 days mortality and ICU-free and ventilator-free days using multiple linear regression among groups. RESULTS: Of the 422 RESTRIC trial participants, 396 were analyzed, with low (n = 131), middle (n = 113), and high (n = 152) lactate. Across all lactate groups, 28 days mortality was similar between strategies. However, in the low lactate group, the restrictive approach correlated with more ICU-free (ß coefficient 3.16; 95% CI 0.45 to 5.86) and ventilator-free days (ß coefficient 2.72; 95% CI 0.18 to 5.26) compared to the liberal strategy. These findings persisted even after excluding patients with severe traumatic brain injury. CONCLUSIONS: Our results suggest that restrictive transfusion strategy might not have a significant impact on 28-day survival rates, regardless of lactate levels. However, the liberal transfusion strategy may lead to shorter ICU- and ventilator-free days for patients with low initial blood lactate levels.

Vitamin D deficiency promotes intracranial aneurysm rupture.

Intracranial aneurysm rupture causes severe disability and high mortality. Epidemiological studies show a strong association between decreased vitamin D levels and an increase in aneurysm rupture. However, the causality and mechanism remain largely unknown. In this study, we tested whether vitamin D deficiency promotes aneurysm rupture and examined the underlying mechanism for the protective role of vitamin D against the development of aneurysm rupture utilizing a mouse model of intracranial aneurysm. Mice consuming a vitamin D-deficient diet had a higher rupture rate than mice with a regular diet. Vitamin D deficiency increased proinflammatory cytokines in the cerebral arteries. Concurrently, vitamin D receptor knockout mice had a higher rupture rate than the corresponding wild-type littermates. The vitamin D receptors on endothelial and vascular smooth muscle cells, but not on hematopoietic cells, mediated the effect of aneurysm rupture. Our results establish that vitamin D protects against the development of aneurysmal rupture through the vitamin D receptors on vascular endothelial and smooth muscle cells. Vitamin D supplementation may be a viable pharmacologic therapy for preventing aneurysm rupture.

Low-flow time and outcomes in out-of-hospital cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation.

INTRODUCTION: In out-of-hospital cardiac arrest (OHCA) patients with extracorporeal cardiopulmonary resuscitation (ECPR), the association between low-flow time, the duration between the initiation of conventional cardiopulmonary resuscitation and the establishment of ECPR, and outcomes has not been clearly determined. METHODS: This was a secondary analysis of the retrospective multicenter registry in Japan. This study registered patients ≥18 years old who were admitted to the emergency department for OHCA and underwent ECPR between January, 2013 and December, 2018. Low-flow time was defined as the time from initiation of conventional cardiopulmonary resuscitation to the establishment of ECPR, and patients were categorized into two groups according to the visualized association of the restricted cubic spline curve. The primary outcome was survival discharge. Cubic spline analyses and multivariable logistic regression analyses were performed to assess the nonlinear associations between low-flow time and outcomes. RESULTS: A total of 1,524 patients were included. The median age was 60 years, and the median low-flow time was 52 (42-53) mins. The overall survival at hospital discharge and favorable neurological outcomes were 27.8% and 14.2%, respectively. The cubic spline analysis showed a decreased trend of survival discharge rates and favorable neurological outcomes with shorter low-flow time between 20 and 60 mins, with little change between the following 60 and 80 mins. The multivariable logistic regression analyses showed that patients with long low-flow time (>40 mins) compared to those with short low-flow time (0-40 mins) had significantly worse survival (adjusted odds ratio 0.42; 95% confidence intervals, 0.31-0.57) and neurological outcomes (0.65; 0.45-0.95, respectively). CONCLUSIONS: The survival discharge and neurological outcomes of patients with low-flow time shorter than 40 min are better than those of patients with longer low-flow time.

A Comparison of Hidden Blood Loss Between Multilevel Posterior Lumbar Interbody Fusion and Lateral Lumbar Interbody Fusion in Adult Spinal Deformity Patients.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: This study aimed to compare transfusion and blood loss volumes, particularly hidden blood loss volume, in adult spinal deformity patients undergoing lateral lumbar interbody fusion (LLIF) and posterior lumbar interbody fusion (PLIF). Corrective surgery for adults with spinal deformity patients can be performed via the traditional posterior approach (PLIF) or minimally invasive lateral approach (LLIF). LLIF is associated with longer or comparable operation times and lower intraoperative blood loss. However, hidden blood loss has not been compared between the two procedures. METHODS: We compared hidden blood loss and other blood loss volumes, transfusion volume, operation time, and radiographic surgical outcomes between LLIF patients (n = 71) and PLIF patients (n = 33) who underwent surgery in our institution from September 2011 to June 2018. All patients provided informed consent in accordance with the Declaration of Helsinki. Institutional ethics committee conducted this study approval was obtained. RESULTS: Transfusion volume and intraoperative and total blood loss volumes were significantly higher in the PLIF group. Operation time and HBL did not significantly differ. The hidden blood loss-to-intraoperative blood loss ratio was significantly higher in the LLIF group (113% vs 60%; P = .004). Radiographic measures of outcome were significantly better after surgery than before in both groups. CONCLUSIONS: Although intraoperative blood loss was less with LLIF than PLIF, HBL was similar between the approaches. Patients undergoing LLIF should be followed closely for postoperative anemia even if intraoperative blood loss is low.

Age-dependent contribution of intrinsic mechanisms to sinoatrial node function in humans.

Average beat interval (BI) and beat interval variability (BIV) are primarily determined by mutual entrainment between the autonomic-nervous system (ANS) and intrinsic mechanisms that govern sinoatrial node (SAN) cell function. While basal heart rate is not affected by age in humans, age-dependent reductions in intrinsic heart rate have been documented even in so-called healthy individuals. The relative contributions of the ANS and intrinsic mechanisms to age-dependent deterioration of SAN function in humans are not clear. We recorded ECG on patients (n = 16 < 21 years and n = 23 41-78 years) in the basal state and after ANS blockade (propranolol and atropine) in the presence of propofol and dexmedetomidine anesthesia. Average BI and BIV were analyzed. A set of BIV features were tested to designated the "signatures" of the ANS and intrinsic mechanisms and also the anesthesia "signature". In young patients, the intrinsic mechanisms and ANS mainly contributed to long- and short-term BIV, respectively. In adults, both ANS and intrinsic mechanisms contributed to short-term BIV, while the latter also contributed to long-term BIV. Furthermore, anesthesia affected ANS function in young patients and both mechanisms in adult. The work also showed that intrinsic mechanism features can be calculated from BIs, without intervention.

Two Cases of Degenerative Cervical Spondylotic Myelopathy in Adults with Athetoid and Dystonic Cerebral Palsy.

BACKGROUND Patients with athetoid and dystonic cerebral palsy (ADCP) may develop degenerative changes in the cervical spine that can aggravate their neurological symptoms in adulthood. This report is of 2 cases of ADCP associated with degenerative cervical spondylotic myelopathy in a 39-year-old woman and a 52-year-old man, requiring different surgical treatments. CASE REPORT Case 1. The patient was a 39-year-old woman who had fallen down 7 years before surgery and had since been walking with a cane. Her gait disturbance had worsened in the 2 years prior to surgery, and numbness in her upper limbs appeared. In the year before surgery, spasticity and numbness in the lower limbs worsened, and fine motor impairment also appeared. Because of mild involuntary movements of the neck, cervical laminoplasty from C3 to C6 was performed, and her symptoms remained stable until the last follow-up 4.5 years after surgery. Case 2. The patient was a 52-year-old man who had fallen down 7 years before surgery, resulting in transient limb weakness. In the year before surgery, he had developed fine motor impairment. He subsequently developed gait disturbance and requested cervical surgery. Because of involuntary movements involving the neck and trunk, he underwent cervical posterior fusion from C2 to T1. Six months after surgery, the gait disturbance had improved. CONCLUSIONS This report describes 2 adults with a history of ADCP since birth and highlights that degenerative changes of the cervical spine can occur at a relatively early age in adulthood, requiring an individualized approach to management.

Neurological Analysis Based on the Terminal End of the Spinal Cord and the Narrowest Level of Injured Spine in Thoracolumbar Spinal Injuries.

This study aimed to clarify neurological differences among the epiconus, conus medullaris, and cauda equina syndromes. Eighty-seven patients who underwent surgery for acute thoracolumbar spinal injuries were assessed. We defined the epiconus as the region from the terminal end of the spinal cord to the proximal 1.0 to 2.25 vertebral bodies, the conus medullaris as the region proximal to < 1.0 vertebral bodies, and the cauda equina as the distal part of the nerve roots originating from the spinal cord. On the basis of the distance from the terminal end of the spinal cord to the narrowest level of the spinal canal, the narrowest levels were ordered as follows: the epiconus followed by the conus medullaris and cauda equina. The narrowest levels were the epiconus in 22 patients, conus medullaris in 37 patients, and cauda equina in 25 patients. On admission, significantly more patients had a narrowed epiconus of Frankel grades A-C than a narrowed cauda equina. At the final follow-up, there were no significant differences in neurological recovery among those with epiconus, conus medullaris, or cauda equina syndrome. Anatomically classifying the narrowest lesion is useful for clarifying the differences and similarities among these three syndromes.

The Restrictive Red Blood Cell Transfusion Strategy for Critically Injured Patients (RESTRIC) trial: a cluster-randomized, crossover, non-inferiority multicenter trial of restrictive transfusion in trauma.

BACKGROUND: The efficacies of fresh frozen plasma and coagulation factor transfusion have been widely evaluated in trauma-induced coagulopathy management during the acute post-injury phase. However, the efficacy of red blood cell transfusion has not been adequately investigated in patients with severe trauma, and the optimal hemoglobin target level during the acute post-injury and resuscitation phases remains unclear. Therefore, this study aimed to examine whether a restrictive transfusion strategy was clinically non-inferior to a liberal transfusion strategy during the acute post-injury phase. METHODS: This cluster-randomized, crossover, non-inferiority multicenter trial was conducted at 22 tertiary emergency medical institutions in Japan and included adult patients with severe trauma at risk of major bleeding. The institutions were allocated a restrictive or liberal transfusion strategy (target hemoglobin levels: 7-9 or 10-12 g/dL, respectively). The strategies were applied to patients immediately after arrival at the emergency department. The primary outcome was 28-day survival after arrival at the emergency department. Secondary outcomes included transfusion volume, complication rates, and event-free days. The non-inferiority margin was set at 3%. RESULTS: The 28-day survival rates of patients in the restrictive (n = 216) and liberal (n = 195) strategy groups were 92.1% and 91.3%, respectively. The adjusted odds ratio for 28-day survival in the restrictive versus liberal strategy group was 1.02 (95% confidence interval: 0.49-2.13). Significant non-inferiority was not observed. Transfusion volumes and hemoglobin levels were lower in the restrictive strategy group than in the liberal strategy group. No between-group differences were noted in complication rates or event-free days. CONCLUSIONS: Although non-inferiority of the restrictive versus liberal transfusion strategy for 28-day survival was not statistically significant, the mortality and complication rates were similar between the groups. The restrictive transfusion strategy results in a lower transfusion volume. TRIAL REGISTRATION NUMBER: umin.ac.jp/ctr: UMIN000034405, registration date: 8 October 2018.

How Much Experience is Required to Acquire the Skills to Independently Perform Spine Surgery? What Milestones are Needed for Successful Surgery?

Purpose: To assess the number of surgeries needed to acquire the necessary skills to perform spine surgery independently. Patients and Methods: A questionnaire on 12 different spinal procedures was sent to orthopedic surgeons affiliated with the spine teams of orthopedic departments at either the Akita University or Sapporo Medical University. Participants were asked to identify whether they (A) could independently perform each procedure, (B) could perform each procedure with the assistance of a senior doctor, or (C) were unable to perform each procedure. Those whose response was (A) were asked how many surgeries were required to acquire the necessary skills. Those who responded to (B) or (C) were asked how many surgeries they believed were required to acquire the skills necessary to operate independently. Participants also responded to 10 questions on surgical training techniques and rated the usefulness of each method. Results: A total of 55 spine surgeons responded to the questionnaire. Group A required significantly fewer surgeries in the following categories to become independent than required Group C: upper cervical spine surgery (7.3/19.3), anterior cervical decompression/fusion (6.7/28.8), posterior cervical decompression/fusion (9.5/27.3), lumbar discectomy (12.6/26.7), endoscopic lumbar discectomy (10.2/24.2), spinal tumor resection (6.5/37.2), and spinal kyphosis surgery (10.3/32.3). Over 80% of participants responded that the following were effective methods: "surgeries where a senior doctor is the main surgeon, and the respondent is the assistant and observer"; "surgeries where the respondent is the main surgeon, and a senior doctor is an assistant"; "self-study using surgery manuals, articles, and textbooks"; and "training through video surgery sessions". Conclusion: Surgeons who do not perform specific procedures independently require more surgical experience than those who operate independently. Our results may help develop more efficient training methods for spine surgeons.

Targeted therapy using polymyxin B hemadsorption in patients with sepsis: a post-hoc analysis of the JSEPTIC-DIC study and the EUPHRATES trial.

BACKGROUND: Polymyxin B hemadsorption (PMX-HA) reduces blood endotoxin levels, but characteristics of patients with sepsis likely to benefit from PMX-HA are not well known. We sought to identify patient subgroups likely to benefit from PMX-HA. METHODS: We retrospectively identified 1911 patients with sepsis from a retrospective observational study in Japan (the JSEPTIC-DIC study) and 286 patients with endotoxemic septic shock from a randomized controlled trial in North America that restricted patients to those with high endotoxin activity (the EUPHRATES trial). We applied the machine learning-based causal forest model to the JSEPTIC-DIC cohort to investigate heterogeneity in treatment effects of PMX-HA on 28-day survival after adjusting for potential confounders and ascertain the best criteria for PMX-HA use. The derived criteria for targeted therapy by PMX-HA were validated using the EUPHRATES trial cohort. RESULTS: The causal forest model revealed heterogeneity in treatment effects of PMX-HA. Since patients having higher treatment effects were more likely to have severe coagulopathy and hyperlactatemia, we identified the potential treatment targets of PMX-HA as patients with PT-INR > 1.4 or lactate > 3 mmol/L. In the EUPHRATES trial cohort, PMX-HA use on the targeted subpopulation (75% of all patients) was significantly associated with higher 28-day survival (PMX-HA vs. control, 68% vs. 52%; treatment effect of PMX-HA, + 16% [95% CI + 2.2% to + 30%], p = 0.02). CONCLUSIONS: Abnormal coagulation and hyperlactatemia in septic patients with high endotoxin activity appear to be helpful to identify patients who may benefit most from PMX-HA. Our findings will inform enrollment criteria for future interventional trials targeting patients with coagulopathy and hyperlactatemia.

Effects of Soft Tissue Sarcoma and Doxorubicin on Bone Metabolism in Mice.

BACKGROUND/AIM: This study aimed to evaluate the effects of doxorubicin (Dox) on bone microstructure and metabolism in a mouse model of soft tissue sarcoma. MATERIALS AND METHODS: CCRF S-180II cells (2-4×105 cells/0.2 ml) were injected subcutaneously into the back of mice. The mice were divided into four groups according to tumor and treatment status and were reared and sacrificed after 2 or 4 weeks. Micro-computed tomography (CT) was performed to calculate the architecture of the femoral bone. The proximal tibia was double stained with tartrate-resistant acid phosphatase (TRACP) and alkaline phosphatase (ALP), and bone morphometry was performed. RESULTS: Trabecular bone mass was significantly reduced in the Sarcoma and Sarcoma+Dox groups. Cortical bone thickness was reduced in the DOX group, with a stronger effect observed in the Sarcoma+Dox group. In bone morphometry, osteoclast number at the bone surface (Oc.N/BS) was significantly lower in the Dox, Sarcoma, and Sarcoma+Dox groups than in the Control group at 2 weeks. The osteoblast surface at the bone surface (Ob.S/BS) was significantly lower in the Dox and Sarcoma groups than in the Control group at 2 weeks. At 4 weeks, the differences were smaller for both Oc.N/BS and Ob.S/BS. CONCLUSION: The use of doxorubicin alone worsened the cortical bone structure; however, the presence of both soft-tissue sarcoma and doxorubicin use worsened both cortical and trabecular bone structures from an early stage.

Association of body mass index and hypoglycemia with mortality rates among sepsis patients: A retrospective sub-analysis of the FORECAST study.

Aim: Hypoglycemia at admission is associated with high mortality in sepsis patients. However, the influence of body mass index (BMI) on this association remains unknown. Therefore, this study assesses the association of hypoglycemia at admission with mortality in patients with sepsis according to BMI. Methods: This was a secondary analysis of a multicenter, prospective cohort study of 59 intensive care units in Japan. We included 1184 patients (age ≥16 years) with severe sepsis and excluded those with missing data on glucose level, BMI, or survival at discharge. The initial blood glucose level of <70 mg/dL was defined as hypoglycemia. Patients were assigned to the hypoglycemia or non-hypoglycemia group as per BMI category (<18.5 [low], 18.5-24.9 [normal], and ≥25 [high] kg/m2). The main outcome was in-hospital mortality. Multivariate logistic regression models were used to evaluate BMI category-by-hypoglycemia interactions. Results: Overall, 1103 patients, including 65 with hypoglycemia, were analyzed. In the normal BMI group, patients with hypoglycemia had a higher in-hospital mortality rate (18/38, 47.4%) than those without (119/584, 20.4%). There was a significant interaction between normal BMI and hypoglycemia affecting in-hospital mortality; however, this effect was not observed for other BMI categories (odds ratio, 2.32; 95% confidence interval, 1.05-5.07; p-value for interaction = 0.0476). Conclusion: The relationship between patients with sepsis and hypoglycemia on admission may differ according to BMI. Hypoglycemia on admission may be associated with high mortality in patients with normal BMI, but not in those with low or high BMI.

Mechanisms Underlying the Suppression of IL-1ß Expression by Magnesium Hydroxide Nanoparticles.

In recent years, magnesium hydroxide has been widely studied due to its bioactivity and biocompatibility. The bactericidal effects of magnesium hydroxide nanoparticles on oral bacteria have also been reported. Therefore, in this study, we investigated the biological effects of magnesium hydroxide nanoparticles on inflammatory responses induced by periodontopathic bacteria. Macrophage-like cells, namely J774.1 cells, were treated with LPS derived from Aggregatibacter actinomycetemcomitans and two different sizes of magnesium hydroxide nanoparticles (NM80/NM300) to evaluate their effects on the inflammatory response. Statistical analysis was performed using an unresponsive Student's t-test or one-way ANOVA followed by Tukey's post hoc test. NM80 and NM300 inhibited the expression and secretion of IL-1ß induced by LPS. Furthermore, IL-1ß inhibition by NM80 was dependent on the downregulation of PI3K/Akt-mediated NF-κB activation and the phosphorylation of MAPK molecules such as JNK, ERK1/2, and p38 MAPK. By contrast, only the deactivation of the ERK1/2-mediated signaling cascade is involved in IL-1ß suppression by NM300. Although the molecular mechanism involved varied with size, these results suggest that magnesium hydroxide nanoparticles have an anti-inflammatory effect against the etiologic factors of periodontopathic bacteria. These properties of magnesium hydroxide nanoparticles can be applied to dental materials.

Magnesium Hydroxide Nanoparticles Inhibit the Biofilm Formation of Cariogenic Microorganisms.

Although various caries-preventive agents have been developed, dental caries is still a leading global disease, mostly caused by biological factors such as mutans streptococci. Magnesium hydroxide nanoparticles have been reported to exhibit antibacterial effects; however, they are rarely used in oral care practical applications. In this study, we examined the inhibitory effect of magnesium hydroxide nanoparticles on biofilm formation by Streptococcus mutans and Streptococcus sobrinus-two typical caries-causing bacteria. Three different sizes of magnesium hydroxide nanoparticles (NM80, NM300, and NM700) were studied, all of which inhibited biofilm formation. The results showed that the nanoparticles were important for the inhibitory effect, which was not influenced by pH or the presence of magnesium ions. We also determined that the inhibition process was mainly contact inhibition and that medium (NM300) and large (NM700) sizes were particularly effective in this regard. The findings of our study demonstrate the potential applications of magnesium hydroxide nanoparticles as caries-preventive agents.

Aerosolized antibiotics therapy for infected traumatic pulmonary pseudocysts: A case report.

Background: Traumatic pulmonary pseudocysts are caused after thoracic trauma. They do not usually require specific therapy when no complications arise, such as infection and bleeding. Complicated pulmonary pseudocysts, however, can be life threatening and require specific treatment. Although treatments of systemic antibiotics and surgery for infected cysts have been reported, to the best of our knowledge, there are no reports on aerosolized antibiotics therapy for infected traumatic pulmonary pseudocysts. Case presentation: We present the case of a 31-year-old woman who was severely injured and suffered a blunt thoracic trauma in a vehicular accident, and required ventilator management in a previous hospitalization. Seven days later, she developed acute respiratory distress syndrome and was transferred to our department. We were unable to maintain proper oxygenation with ventilator management alone and established venous-venous extracorporeal membrane oxygenation. She then developed persistent bacteremia of Pseudomonas aeruginosa owing to infected traumatic pulmonary pseudocysts. On the 21st day of her hospitalization, the drainage for the enlarged cyst led to minor improvements in her respiratory condition. On the 32nd day of hospitalization, in addition to systemic antibiotics therapy, the aerosolized antibiotics therapy (inhalation of tobramycin (135 mg) every 12 h) was administered for the treatment of resistant infected pseudocysts. Her respiratory condition gradually improved, and the infected pseudocysts shrank. On the 43rd day of hospitalization, she was successfully removed from extracorporeal membrane oxygenation. Conclusions: Aerosolized antibiotics therapy may be a potential option for patients with infected traumatic pulmonary pseudocysts when conventional therapies are not successful.

Changes in Corticospinal Excitability and Motor Control During Cerebellar Transcranial Direct Current Stimulation in Healthy Individuals.

Cerebellar transcranial direct current stimulation (ctDCS) modulates the primary motor cortex (M1) via cerebellar brain inhibition (CBI), which affects motor control in humans. However, the effects of ctDCS on motor control are inconsistent because of an incomplete understanding of the real-time changes in the M1 excitability that occur during ctDCS, which determines motor output under regulation by the cerebellum. This study investigated changes in corticospinal excitability and motor control during ctDCS in healthy individuals. In total, 37 healthy individuals participated in three separate experiments. ctDCS (2 mA) was applied to the cerebellar hemisphere during the rest condition or a pinch force-tracking task. Motor-evoked potential (MEP) amplitude and the F-wave were assessed before, during, and after ctDCS, and pinch force control was assessed before and during ctDCS. The MEP amplitudes were significantly decreased during anodal ctDCS from 13 min after the onset of stimulation, whereas the F-wave was not changed. No significant changes in MEP amplitudes were observed during cathodal and sham ctDCS conditions. The MEP amplitudes were decreased during anodal ctDCS when combined with the pinch force-tracking task, and pinch force control was impaired during anodal ctDCS relative to sham ctDCS. The MEP amplitudes were not significantly changed before and after all ctDCS conditions. Motor cortical excitability was suppressed during anodal ctDCS, and motor control was unskilled during anodal ctDCS when combined with a motor task in healthy individuals. Our findings provided a basic understanding of the clinical application of ctDCS to neurorehabilitation.