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Abstract Background Sympathetic nerve activity (SNA) plays a central role in the pathogenesis of several diseases such as sepsis and chronic kidney disease (CKD). Activation of microglia in the paraventricular nucleus of the hypothalamus (PVN) has been implicated in SNA. The mechanisms responsible for the adverse prognosis observed in sepsis associated with CKD remain to be determined. Therefore, we aimed to clarify the impact of increased SNA resulting from microglial activation on hemodynamics and organ damage in sepsis associated with CKD. Methods and results In protocol 1, male Sprague–Dawley rats underwent either nephrectomy (Nx) or sham surgery followed by cecal ligation and puncture (CLP) or sham surgery. After CLP, Nx-CLP rats exhibited decreased blood pressure, increased heart rate, elevated serum creatinine and bilirubin levels, and decreased platelet count compared to Nx-Sham rats. Heart rate variability analysis revealed an increased low to high frequency (LF/HF) ratio in Nx-CLP rats, indicating increased SNA. Nx-CLP rats also had higher creatinine and bilirubin levels and lower platelet counts than sham-CLP rats after CLP. In protocol 2, Nx-CLP rats were divided into two subgroups: one received minocycline, an inhibitor of microglial activation, while the other received artificial cerebrospinal fluid (CSF) intracerebroventricularly via an osmotic minipump. The minocycline-treated group (Nx-mino-CLP) showed attenuated hypotensive and increased heart rate responses compared to the CSF-treated group (Nx-CSF-CLP), and the LF/HF ratio was also decreased. Echocardiography showed larger left ventricular dimensions and inferior vena cava in the Nx-mino-CLP group. In addition, creatinine and bilirubin levels were lower and platelet counts were higher in the Nx-mino-CLP group compared to the Nx-CSF-CLP group. Conclusions In septic rats with concomitant CKD, SNA was significantly enhanced and organ dysfunction was increased. It has been suggested that the mechanism of exacerbated organ dysfunction in these models may involve abnormal systemic hemodynamics, possibly triggered by activation of the central sympathetic nervous system through activation of microglia in the PVN.

Pelvic fractures, accounting for 2–8% of skeletal injuries, present a significant burden in patients with trauma. High-energy incidents often result in severe pelvic trauma accompanied by comorbidities leading to high mortality rates. Managing these complications adds complexity to the treatment process, particularly in older patients who experience longer recovery times and higher injury severity. To improve the long-term quality of life, a multidisciplinary approach is essential. However, rehabilitation feasibility is influenced by the patient’s condition and pelvic fixation stability, necessitating individualized treatment. This study investigated the rehabilitation status and long-term outcomes of older patients with severe polytrauma and pelvic ring fractures caused by high-energy trauma. The results revealed that 79.2% of the patients achieved full weight-bearing, with a median time of 41.5 days, and eventually 58.3% were discharged home. Complications were observed in 83.3% of the patients, with various challenges affecting successful home discharge. Multidisciplinary rehabilitation programs are promising for optimizing outcomes and facilitating recovery in vulnerable patient populations. Still, larger, more focused studies are needed to gain more comprehensive insights into the treatment and recovery of older patients with pelvic ring fractures and severe polytrauma. Understanding these factors is crucial for guiding clinical decision-making and improving long-term outcomes in this population.

Recombinant antithrombin gamma (rAT) is reported as an effective drug for patients with disseminated intravascular coagulation (DIC) in Japan. As the appropriate dose and targeted AT activity remain unknown, this study aimed to determine these aspects for sepsis-induced DIC. Thirty-one patients with septic shock and DIC with AT levels

Objective This study was performed to evaluate the correlation between parameters measured by bedside ultrasonography and detection of intracranial organic lesions in patients with impaired consciousness in an intensive care unit (ICU) setting. Methods We retrospectively reviewed the medical records of patients who were admitted to our ICU from April 2017 to July 2019. Patients who underwent computed tomography or magnetic resonance imaging examination and measurement of the flow velocity of the carotid and intracranial arteries and the optic nerve sheath diameter by ultrasonography were selected for analysis. Results In total, 64 patients were analyzed in this study. Of these, intracranial lesions were detected by computed tomography or magnetic resonance imaging in 17 (27%) patients. The left:right ratio of the end-diastolic velocity of the bilateral common carotid artery (CCA-ED ratio) and the pulsatility index of the middle cerebral artery (MCA-PI) were significantly higher in patients with than in those without intracranial lesions. The cut-off value of the CCA-ED ratio was 1.55 (sensitivity, 66.7%; specificity, 81.6%), and that of the MCA-PI was 1.21 (sensitivity, 57.1%; specificity, 76.7%). Conclusion Bedside ultrasonography is useful for predicting intracranial lesions requiring therapeutic intervention in ICU patients with impaired consciousness.

Abstract Background Patients with rheumatoid arthritis (RA) have high mortality risk and are frequently treated in intensive care units (ICUs). Methods This was a retrospective observational study. This study included 67 patients (20 males, 47 females) with RA who were admitted at the ICU of our institution for ≥48 h between January 2008 and December 2017. We analyzed the 30-day mortality of these patients and the investigated prognostic factors in RA patients admitted to our ICU. Results Upon admission, the median age was 70 (range, 33–96) years, and RA duration was 10 (range, 0–61) years. The 5-year survival after ICU admission was 47%, and 30-day, 90-day, and 1-year mortality rates were 22, 27, and 37%, respectively. The major reasons for ICU admission were cardiovascular complications (24%) and infection (40%) and the most common ICU treatments were mechanical ventilation (69%), renal replacement (25%), and vasopressor (78%). In the 30-day mortality group, infection led to a fatal outcome in most cases (67%), and nonsurvival was associated with a significantly higher glucocorticoid dose, updated Charlson’s comorbidity index (CCI), and acute physiology and chronic health evaluation (APACHE) II score. Laboratory data obtained at ICU admission showed that lower platelet number and total protein and higher creatinine and prothrombin time international normalized ratio (PT-INR) indicated significantly poorer prognosis. The multivariate Cox proportional hazard model revealed that nonuse of csDMARDs, high updated CCI, increased APACHE II score, and prolonged PT-INR were associated with a higher risk of mortality after ICU admission. Conclusion Our study demonstrated that the nonuse of csDMARDs, high updated CCI, elevated APACHE II score, and coagulation abnormalities predicted poorer prognosis in RA patients admitted to the ICU.

Abstract Background Mesenchymal stem cells (MSCs), including adipose-derived mesenchymal stem cells (ADSCs), have been shown to attenuate organ damage in acute respiratory distress syndrome (ARDS) and sepsis; however, the underlying mechanisms are not fully understood. In this study, we aimed to explore the potential roles and molecular mechanisms of action of ADSCs in histone-induced endothelial damage. Methods Male C57BL/6 N mice were intravenously injected with ADSCs, followed by histones or a vehicle. The mice in each group were assessed for survival, pulmonary vascular permeability, and histological changes. A co-culture model with primary human umbilical vein endothelial cells (HUVECs) exposed to histones was used to clarify the paracrine effect of ADSCs. Overexpression and inhibition of miR-126 ADSCs were also examined as causative factors for endothelial protection. Results The administration of ADSCs markedly improved survival, inhibited histone-mediated lung hemorrhage and edema, and attenuated vascular hyper-permeability in mice. ADSCs were engrafted in the injured lung and attenuated histone-induced endothelial cell apoptosis. ADSCs showed endothelial protection (via a paracrine effect) and Akt phosphorylation in the histone-exposed HUVECs. Notably, increased Akt phosphorylation by ADSCs was mostly mediated by exosomes in histone-induced cytotoxicity and lung damage. Moreover, the expression of miR-126 was increased in exosomes from histone-exposed ADSCs. Remarkably, the inhibition of miR-126 in ADSCs failed to increase Akt phosphorylation in histone-exposed HUVECs. Conclusion ADSC-derived exosomes may exert protective effects on endothelial cells via activation of the PI3K/Akt pathway.

Abstract Redox status influences the course of the inflammatory, metabolic, and proliferative liver diseases. Oxidative stress is thought to play a crucial and sustained role in the pathological progression of early steatosis to severe hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Oxidative stress induced by reactive oxygen species which are generated in the mitochondria can lead to chronic organelle damage in hepatocytes. Currently, the diagnosis of liver disease requires liver biopsy, which is invasive and associated with complications. The present report describes the development of a novel molecular probe, EDA-PROXYL, with higher reactivity and mitochondrial selectivity than standard carboxyl-PROXYL and carbamoyl-PROXYL probes. The membrane permeability of our probe improved in aqueous environments which led to increased accumulation in the liver and interaction of EDA-PROXYL with the carnitine transporter via the amine (NH3 +) group further increased accumulation. This increased mitochondrial sensitivity and enhanced accumulation highlight the potential of EDA-PROXYL as a molecular probe for determining metabolic reactions of the mitochondria. Thus, this novel probe could be a tool for the evaluation of redox status of the mitochondria to assess the degree of liver injury and, ultimately, the response to pharmacological therapy.

Abstract Background The management of cardiac trauma requires rapid intervention in the emergency room, facilitated by a surgeon with prior experience to have good outcomes. Many surgeons have little experience in the requisite procedures. We report here 4 patients who suffered cardiac trauma, and all 4 patients survived with good neurologic outcomes. Case presentations Patient 1 suffered blunt cardiac trauma from a motor vehicle accident and presented in shock. Cardiac tamponade was diagnosed and a cardiac rupture repaired with staples through a median sternotomy after rapid transport to the operating room. Patient 2 suffered blunt cardiac trauma and presented in shock with cardiac tamponade. Operating room median sternotomy allowed extraction of pericardial clot with recovery of physiologic stability. Patient 3 presented with self-inflicted stab wounds to the chest and was unstable. She was brought to the operating room and thoracotomy allowed identification of a left ventricle wound which was repaired with a suture. Patient 4 presented in cardiac arrest with multiple self-inflicted stab wounds to the chest. Emergency room thoracotomy allowed repair of a right ventricle laceration with recovery of vital signs. Conclusions The management of all 4 patients was according to the principles taught in the ATOM course. Three of the 4 surgeons had no prior experience with management of cardiac trauma and credited the good outcomes to taking the ATOM course. These are uncommon injuries and formal training in their management is beneficial to patients.

Background Open abdomen management (OAM) is used not only for trauma but also for treatment of peritonitis. However, the rate of successful fascial closure in patients with OAM remains low. Case Presentation The patient was a 38‐year‐old morbidly obese man who underwent laparoscopic sleeve gastrectomy. Twenty days after surgery, postoperative leakage resulted in panperitonitis. In this case, we undertook drainage by open laparotomy. The patient's status was generally unstable and he was treated with OAM. We used flexible silicone mesh as the dressing material for negative‐pressure wound therapy. Open abdominal management continued until status improvement (32 days). Fascial closure was eventually successful because of good granulation growth. Conclusion When combined with negative‐pressure wound therapy, silicone mesh prevents wound adhesions and infection after surgery. Silicone mesh is useful for patients with increased risk of infection, such as those with diffuse peritonitis.

Doxorubicin (DOX) induces dose-dependent cardiotoxicity via oxidative stress and abnormal mitochondrial function in the myocardium. Therefore, a noninvasive in vivo imaging procedure for monitoring the redox status of the heart may aid in monitoring diseases and developing treatments. However, an appropriate technique has yet to be developed. In this study, we demonstrate a technique for detecting and visualizing the redox status of the heart using in vivo dynamic nuclear polarization–magnetic resonance imaging (DNP–MRI) with 3-carbamoyl-PROXYL (CmP) as a molecular imaging probe. Male C57BL/6N mice were administered DOX (20 mg/kg) or saline. DNP–MRI clearly showed a slower DNP signal reduction in the DOX group than in the control group. Importantly, the difference in the DNP signal reduction rate between the two groups occurred earlier than that detected by physiological examination or clinical symptoms. In an in vitro experiment, KCN (an inhibitor of complex IV in the mitochondrial electron transport chain) and DOX inhibited the electron paramagnetic resonance change in H9c2 cardiomyocytes, suggesting that the redox metabolism of CmP in the myocardium is mitochondrion-dependent. Therefore, this molecular imaging technique has the potential to monitor the dynamics of redox metabolic changes in DOX-induced cardiomyopathy and facilitate an early diagnosis of this condition.

Early-stage gastrointestinal cancer is often treated by endoscopic submucosal dissection (ESD) using a flexible endoscope. Compared with conventional percutaneous surgery, ESD is much less invasive and provides a high quality of life for the patient because it does not require a skin incision, and the organ is preserved. However, the operator must be highly skilled because ESD requires using a flexible endoscope with energy devices, which have limited degrees of freedom. To facilitate easier manipulation of these flexible devices, we developed a surgical robot comprising a flexible endoscope and two articulating instruments. The robotic system is based on a conventional flexible endoscope, and an extrapolated motor unit moves the endoscope in all its degrees of freedom. The instruments are thin enough to allow insertion of two instruments into the endoscope channel, and each instrument has a bending section that allows for up–down, right–left, and forward–backward motion. In this study, we performed an ex vivo feasibility evaluation using the proposed robotic system for ESD in a porcine stomach. The procedure was successfully performed by five novice operators without complications. Our findings demonstrated the feasibility of the proposed robotic system and, furthermore, suggest that even operators with limited experience can use this system to perform ESD.

Gastrointestinal cancer, when detected early, is treated by accessing the lesion through the natural orifice using flexible endoscopes. However, the limited degree-of-freedom (DOF) of conventional treatment devices and the narrow surgical view through the endoscope demand advanced techniques. In contrast, multi-DOF forceps systems are an excellent alternative; however, these systems often involve high fabrication costs because they require a large number of micro-parts. To solve this problem, we designed compact multi-DOF endoluminal forceps with a monolithic structure comprising compliant hinges. To allow an efficient stress dispersion at the base end when the hinge bends, we proposed a novel design method to obtain the hinge parameters using the beam of uniform strength theory. This method does not involve a high computational cost. The results show that the improved design with a variable hinge thickness can reduce the maximum bending stress, dispersing the stress in a larger area than that of the previous design considering a constant thickness of the hinge. Moreover, the experiments conducted in a prototype confirm that the radius of the curvature was significantly improved. The proposed method could aid in designing other continuum robots relying on compliant hinges.

Background and study aims The association of tumor hypoxia and vascularization with malignant progression is recognized, and detection by measuring tissue hemoglobin (Hb) saturation and concentration has attracted attention. In this study, we designed a simple algorithm and multispectral image-processing endoscopy system to map relative Hb concentration and Hb saturation for detection of tumors in small animal viscera in vivo. Materials and methods We designed and validated an optical filter-equipped endoscope system for two-dimensional visualization of Hb concentration and saturation maps and used it in a real-time video examination. A simplified method based on spectral data capture and analysis of defuse reflection of mucosa, including image capture and data processing of the spectral features of Hb oxygenation, was developed. Results An Hb saturation calibration curve was obtained. Then, differences in oxygenation levels between normal mucosa and in vivo tumors in a small animal model were determined by using the new method and endoscope system. Conclusions A multispectral image-processing endoscopic system with a mapping frame rate comparable to that of white light imaging systems (7.5 frames/second) was developed.

Case We report a 2‐year‐old boy with duodenal ulcer with active bleeding that occurred as a result of norovirus gastroenteritis. On admission, the patient presented with shock accompanied with vomiting and melena. Abdominal contrast enhanced computed tomography scan showed signs of duodenal bleeding. Outcome He was successfully treated with emergent transcatheter arterial embolization. After the treatment, endoscopic examination revealed duodenal ulcer and the stool norovirus antigen test was found to be positive. The patient recovered completely without any sequelae. Conclusion Life‐threatening duodenal ulcer bleeding in children can be caused by viral gastroenteritis. When endoscopic therapy is unsuccessful or difficult, in cases of small children, angiographic intervention can be a safe alternative treatment option of gastrointestinal bleeding.

Aim Sarcopenia has been increasingly reported as a prognostic factor for outcome in settings such as cirrhosis, liver transplantation, and emergent surgery. We aimed to elucidate the significance of sarcopenia in severe blunt trauma patients. Methods We retrospectively analyzed 84 patients emergently admitted to the intensive care unit at Kyushu University Hospital (Fukuoka, Japan) from May 2012 to April 2015. We assessed the amount of skeletal muscle present according to computed tomography and its relevance to ventilation‐free days, patients' length of stay in the intensive care unit, and 28‐day mortality. Results Twenty‐five (29.7%) patients were defined as sarcopenic. Sixteen (19.7%) patients required 15 days or more in the intensive care unit. The major reason was a prolonged ventilation requirement due to flail chest (n = 7) or pneumonia (n = 3). Sarcopenic patients' stays in intensive care were significantly longer than those of non‐sarcopenic patients (18.7 versus 6.4 days, respectively; P < 0.001). Univariate and multivariate analyses showed sarcopenia to be a significant risk factor for prolonged intensive care unit stay. Conclusion Sarcopenia is a risk factor that predicts prolonged intensive care unit stay in high‐energy blunt trauma patients.

The functions of genes involved in idiopathic portal hypertension (IPH) remain unidentified. The present study was undertaken to identify the functions of genes expressed in blood samples from patients with IPH through comprehensive analysis of gene expression using DNA microarrays. The data were compared with data from healthy individuals to explore the functions of genes showing increased or decreased expression in patients with IPH. In cluster analysis, no dominant probe group was shown to differ between patients with IPH and healthy controls. In functional annotation analysis using the Database for Annotation Visualization and Integrated Discovery tool, clusters showing dysfunction in patients with IPH involved gene terms related to the immune system. Analysis using network-based pathways revealed decreased expression of adenosine deaminase, ectonucleoside triphosphate diphosphohydrolase 4, ATP-binding cassette, subfamily C, member 1, transforming growth factor-β, and prostaglandin E receptor 2; increased expression of cytochrome P450, family 4, subfamily F, polypeptide 3, and glutathione peroxidase 3; and abnormalities in the immune system, nucleic acid metabolism, arachidonic acid/leukotriene pathways, and biological processes. These results suggested that IPH involved compromised function of immunocompetent cells and that such dysfunction may be associated with abnormalities in nucleic acid metabolism and arachidonic acid/leukotriene-related synthesis/metabolism.

Stenotrophomonas maltophilia is an important nosocomial bacterial pathogen, as is Pseudomonas aeruginosa. Differentiation of these bacteria as bacteremic agents is critical in the clinical setting and to define a therapeutic strategy; however, the associated factors and prognosis for S. maltophilia bacteremia have not been fully evaluated to adequately characterize these factors. We first conducted a matched case-control study to clarify these questions. A total of 30 case patients with S. maltophilia bacteremia were compared with 30 control patients with P. aeruginosa bacteremia between January 2005 and August 2014, according to matching criteria based on underlying disease, age, and gender. The 30-day mortality rate for the case patients (53.3%) was significantly higher than that of the control group (30.0%) (P = 0.047, using the log-rank test). Conditional logistic regression analysis showed that the predisposing factors specific for the detection of S. maltophilia bacteremia were indwelling artificial products other than a central venous catheter, ICU stay, and previous use of anti-MRSA drugs. The high severity of illness was associated with mortality in both case and control patients. Interestingly, inappropriate antimicrobial treatment was an additional independent risk factor for mortality in only the case patients with S. maltophilia bacteremia (odds ratio = 13.64, P = 0.048). Monotherapy with fluoroquinolones inactive against the S. maltophilia isolates was mainly responsible for the inappropriate treatment. These results suggest that more precise prediction and more appropriate treatment might improve the prognosis of patients with S. maltophilia bacteremia.