Aberrant accumulation of TMEM43 accompanied by perturbed transmural gene expression in arrhythmogenic cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) caused by TMEM43 p.S358L is a fully penetrant heart disease that results in impaired cardiac function or fatal arrhythmia. However, the molecular mechanism of ACM caused by the TMEM43 variant has not yet been fully elucidated. In this study, we generated knock-in (KI) rats harboring a Tmem43 p.S358L mutation and established induced pluripotent stem cells (iPSCs) from patients based on the identification of TMEM43 p.S358L variant from a family with ACM. The Tmem43-S358L KI rats exhibited ventricular arrhythmia and fibrotic myocardial replacement in the subepicardium, which recapitulated the human ACM phenotype. The four-transmembrane protein TMEM43 with the p.S358L variant (TMEM43S358L ) was found to be modified by N-linked glycosylation in both KI rat cardiomyocytes and patient-specific iPSC-derived cardiomyocytes. TMEM43S358L glycosylation increased under the conditions of enhanced endoplasmic reticulum (ER) stress caused by pharmacological stimulation or age-dependent decline of the ER function. Intriguingly, the specific glycosylation of TMEM43S358L resulted from the altered membrane topology of TMEM43. Moreover, unlike TMEM43WT , which is mainly localized to the ER, TMEM43S358L accumulated at the nuclear envelope of cardiomyocytes with the increase in glycosylation. Finally, our comprehensive transcriptomic analysis demonstrated that the regional differences in gene expression patterns between the inner and outer layers observed in the wild type myocardium were partially diminished in the KI myocardium prior to exhibiting histological changes indicative of ACM. Altogether, these findings suggest that the aberrant accumulation of TMEM43S358L underlies the pathogenesis of ACM caused by TMEM43 p.S358L variant by affecting the transmural gene expression within the myocardium.

Intraocular penetration of liposomal amphotericin B after intravenous injection in inflamed human eyes.

PURPOSE: To determine the intraocular penetration of amphotericin B (AMPH-B) after an intravenously injection of liposomal amphotericin B (L-AMB) in inflamed human eyes. METHODS: Seven eyes of 5 patients with fungal eye diseases (endophthalmitis in 6 eyes and keratitis in 1 eye) were treated with intravenous injections of 100-250 mg/day of L-AMB. Samples of blood, corneal button, aqueous humor, and vitreous humor were collected and assessed for AMPH-B. RESULTS: The AMPH-B level in the cornea (604.0 µg/g) of the case with fungal keratitis exceeded the minimum inhibitory concentration. However, the levels in the aqueous and vitreous humors of the cases with fungal endophthalmitis were lower, e.g., 0.02 ± 0.01 µg/ml (0.09% of serum level) in the aqueous humor and 0.05 ± 0.08 µg/ml (0.17% of serum level) in the vitreous humor. CONCLUSIONS: The AMPH-B levels administered intravenously were very low in the aqueous and vitreous humors. Our findings indicate that intravenous L-AMB can be considered only for patients with mild endogenous fungal endophthalmitis, e.g., isolated chorioretinitis without vitreous extensions.

Validity and risk factor analysis for helicopter emergency medical services in Japan: a pilot study.

BACKGROUND: Some emergency departments use triage scales, such as the Canadian Triage and Acuity Scale and Japan Urgent Stroke Triage Score, to detect life-threatening situations. However, these protocols have not been used for aeromedical services. Therefore, we investigated the factors predicting these life-threatening situations in aeromedical services as a pilot study for establishing the protocol. METHOD: We retrospectively evaluated helicopter emergency medical service cases from 1 April 2015 to 31 March 2020 at Gifu University Hospital using the mission records. We only evaluated cases dealing with suggested internal medicine issues. We excluded cases influenced by external factors such as trauma or cases that included hospital-to-hospital transportation, focusing only on prehospital care. We evaluated the validity of the medical emergencies based on the needs for emergency interventions and hospital admission and of the suggested diagnoses and associated risk factors. RESULT: A total of 451 cases were suitable for inclusion in the study. In the analysis for all emergency calls, 235 (52.11%) cases needed emergency intervention and 300 (64.4%) required hospital admission. The suggested diagnosis was valid for 261 (57.87%) cases. After the first assessment by emergency medical technicians, 75 cases were removed. Analysis after this first assessment found that 52.31% cases required emergency intervention, 70.26% needed admission, and the suggested diagnosis was valid for 69.41% of cases. In the analysis of emergency calls, the multivariate analysis of some key variables identified age, playing sports, and gasping as risk factors for emergency intervention. Hospital admission risk factors included being age only. The suggested diagnosis was valid only for sports situations. In the analysis after the first assessment by an emergency medical technician, risk factors for emergency intervention included being age being male, playing sports, and gasping, and those for hospital admission was being age, being male, and experiencing stroke symptoms and/or disturbance of consciousness. The suggested diagnosis was valid only for sports situations. CONCLUSION: Some 'second' keywords/phrases predict medical emergencies. Therefore, the dispatch commander should gather these keyword/phrases to assess.

Mutant KCNJ3 and KCNJ5 Potassium Channels as Novel Molecular Targets in Bradyarrhythmias and Atrial Fibrillation.

BACKGROUND: Bradyarrhythmia is a common clinical manifestation. Although the majority of cases are acquired, genetic analysis of families with bradyarrhythmia has identified a growing number of causative gene mutations. Because the only ultimate treatment for symptomatic bradyarrhythmia has been invasive surgical implantation of a pacemaker, the discovery of novel therapeutic molecular targets is necessary to improve prognosis and quality of life. METHODS: We investigated a family containing 7 individuals with autosomal dominant bradyarrhythmias of sinus node dysfunction, atrial fibrillation with slow ventricular response, and atrioventricular block. To identify the causative mutation, we conducted the family-based whole exome sequencing and genome-wide linkage analysis. We characterized the mutation-related mechanisms based on the pathophysiology in vitro. After generating a transgenic animal model to confirm the human phenotypes of bradyarrhythmia, we also evaluated the efficacy of a newly identified molecular-targeted compound to upregulate heart rate in bradyarrhythmias by using the animal model. RESULTS: We identified one heterozygous mutation, KCNJ3 c.247A>C, p.N83H, as a novel cause of hereditary bradyarrhythmias in this family. KCNJ3 encodes the inwardly rectifying potassium channel Kir3.1, which combines with Kir3.4 (encoded by KCNJ5) to form the acetylcholine-activated potassium channel ( IKACh channel) with specific expression in the atrium. An additional study using a genome cohort of 2185 patients with sporadic atrial fibrillation revealed another 5 rare mutations in KCNJ3 and KCNJ5, suggesting the relevance of both genes to these arrhythmias. Cellular electrophysiological studies revealed that the KCNJ3 p.N83H mutation caused a gain of IKACh channel function by increasing the basal current, even in the absence of m2 muscarinic receptor stimulation. We generated transgenic zebrafish expressing mutant human KCNJ3 in the atrium specifically. It is interesting to note that the selective IKACh channel blocker NIP-151 repressed the increased current and improved bradyarrhythmia phenotypes in the mutant zebrafish. CONCLUSIONS: The IKACh channel is associated with the pathophysiology of bradyarrhythmia and atrial fibrillation, and the mutant IKACh channel ( KCNJ3 p.N83H) can be effectively inhibited by NIP-151, a selective IKACh channel blocker. Thus, the IKACh channel might be considered to be a suitable pharmacological target for patients who have bradyarrhythmia with a gain-of-function mutation in the IKACh channel.

Novel Synthetic, Host-defense Peptide Protects Against Organ Injury/Dysfunction in a Rat Model of Severe Hemorrhagic Shock.

OBJECTIVE: To evaluate (1) levels of the host-defense/antimicrobial peptide LL-37 in patients with trauma and hemorrhagic shock (HS) and (2) the effects of a synthetic host-defense peptide; Pep19-4LF on multiple organ failure (MOF) associated with HS. BACKGROUND: HS is a common cause of death in severely injured patients. There is no specific therapy that reduces HS-associated MOF. METHODS: (1) LL-37 was measured in 47 trauma/HS patients admitted to an urban major trauma center. (2) Male Wistar rats were submitted to HS (90 min, target mean arterial pressure: 27-32 mm Hg) or sham operation. Rats were treated with Pep19-4LF [66 (n = 8) or 333 µg/kg ·â€Šh (n = 8)] or vehicle (n = 12) for 4 hours following resuscitation. RESULTS: Plasma LL-37 was 12-fold higher in patients with trauma/HS compared to healthy volunteers. HS rats treated with Pep19-4LF (high dose) had a higher mean arterial pressure at the end of the 4-hour resuscitation period (79 ±â€Š4 vs 54 ±â€Š5 mm Hg) and less renal dysfunction, liver injury, and lung inflammation than HS rats treated with vehicle. Pep19-4LF enhanced (kidney/liver) the phosphorylation of (1) protein kinase B and (2) endothelial nitric oxide synthase. Pep19-4LF attenuated the HS-induced (1) translocation of p65 from cytosol to nucleus, (2) phosphorylation of IκB kinase on Ser, and (3) phosphorylation of IκBα on Ser resulting in inhibition of nuclear factor kappa B and formation of proinflammatory cytokines. Pep19-4LF prevented the release of tumor necrosis factor alpha caused by heparan sulfate in human mononuclear cells by binding to this damage-associated molecular pattern. CONCLUSIONS: Trauma-associated HS results in release of LL-37. The synthetic host-defense/antimicrobial peptide Pep19-4LF attenuates the organ injury/dysfunction associated with HS.

Artesunate Protects Against the Organ Injury and Dysfunction Induced by Severe Hemorrhage and Resuscitation.

OBJECTIVE: To evaluate the effects of artesunate on organ injury and dysfunction associated with hemorrhagic shock (HS) in the rat. BACKGROUND: HS is still a common cause of death in severely injured patients and is characterized by impairment of organ perfusion, systemic inflammatory response, and multiple organ failure. There is no specific therapy that reduces organ injury/dysfunction. Artesunate exhibits pharmacological actions beyond its antimalarial activity, such as anticancer, antiviral, and anti-inflammatory effects. METHODS: Rats were submitted to HS. Mean arterial pressure was reduced to 30 mm Hg for 90 minutes, followed by resuscitation. Rats were randomly treated with artesunate (2.4 or 4.8 mg/kg i.v.) or vehicle upon resuscitation. Four hours later, parameters of organ injury and dysfunction were assessed. RESULTS: Artesunate attenuated the multiple organ injury and dysfunction caused by HS. Pathway analysis of RNA sequencing provided good evidence to support an effect of artesunate on the Akt-survival pathway, leading to downregulation of interleukin-1 receptor-associated kinase 1. Using Western blot analysis, we confirmed that treatment of HS rats with artesunate enhanced the phosphorylation (activation) of Protein kinase B (Akt) and endothelial nitric oxide synthase and the phosphorylation (inhibition) of glycogen synthase kinase-3ß (GSK-3ß). Moreover, artesunate attenuated the HS-induced activation of nuclear factor kappa B and reduced the expression of proinflammatory proteins (inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin 6). CONCLUSIONS: Artesunate attenuated the organ injury/dysfunction associated with HS by a mechanism that involves the activation of the Akt-endothelial nitric oxide synthase survival pathway, and the inhibition of glycogen synthase kinase-3ß and nuclear factor kappa B. A phase II clinical trial evaluating the effects of good manufacturing practice-artesunate in patients with trauma and severe hemorrhage is planned.

Hyperbaric oxygenation therapy for crush injuries reduces the risk of complications: research report.

BACKGROUND: Hyperbaric oxygen (HBO2) therapy has been adopted for crush injuries, but there are few studies supporting its use. We therefore investigated the effects of HBO2 on management of patients with complicated crush injuries. METHODS: This historic cohort study included patients with crush injuries and open fractures with severities greater than or equal to Gustilo class IIIA. We divided the patients into two groups: Control and HBO2. The control group received conventional treatment, while the HBO2 group received conventional treatment plus HBO2. We compared the groups with respect to the incidence of infection, need for additional surgery, and length of intensive care unit (ICU) and hospital stays. RESULTS: There were 16 patients in the HBO2 group and 13 in the control group. There were no patients with infections in the HBO2 group, whereas in the control group six patients had infections and five needed another drainage procedure. These incidences were significantly lower in the HBO2 group (p = 0.003 and 0.013). However, the durations of ICU and hospital stays were similar across the two groups. CONCLUSIONS: HBO2 is effective in the management of crush injuries from the viewpoint of reducing complications and reoperations. These observations should be verified in additional studies with larger sample sizes because the patient number is limited.

Prompt diagnosis and appropriate treatment of Japanese spotted fever: A report of three cases.

Background: Japanese Spotted Fever (JSF) is a Spotted Fever Group (SFG) rickettsiosis caused by Rickettsia japonica. More than 300 cases are diagnosed annually in Japan, and the number of reported cases has been increasing. Correct diagnoses depend on the triad of symptoms and signs, including fever, rash, and eschar, which can be seen at the site of vector bites. JSF is not life-threatening if treated appropriately without diagnostic delay but there are some fatal cases every year. This negligence leads to disseminated intravascular coagulation (DIC) and multiple organ failure (MOF), and poor prognoses, consequently. Prompt diagnosis of JSF is difficult when the aforementioned triad of signs and symptoms is not initially present. Case report: This report describes three JSF cases: an 87-year-old woman with fever, shock, pancytopenia, DIC, and MOF; a 79-year-old man with fever and difficulty in movement; and a 78-year-old man with fever, general fatigue, and appetite loss. All patients had a rash and eschar, which led to prompt diagnosis and appropriate treatment immediately. All patients were treated without any complications. Why should an emergency physician be aware of this?: As mentioned above, JFS can be fatal with delayed diagnoses and treatment initiations. The key for a prompt diagnosis is to recognize the triad of symptoms and signs, which are not often present initially, and it makes JSF diagnosis challenging. Repeated comprehensive physical examinations are essential for prompt diagnosis and improve prognosis of JSF.

Intraocular penetration of intravenous micafungin in inflamed human eyes.

Eight eyes of 7 patients with fungal disease received intravenous injections of 150 to 300 mg micafungin, and samples of blood, cornea, retina-choroid, aqueous humor, and vitreous humor were collected. The micafungin levels in all collected samples exceeded the MICs; however, the levels in the vitreous and aqueous humors were lower. Our findings suggest that intravenous micafungin should be given in combination with intravitreal antifungal agents after vitrectomy in severe cases of intraocular fungal diseases.

Inhibition of Macrophage Migration Inhibitory Factor Activity Attenuates Haemorrhagic Shock-Induced Multiple Organ Dysfunction in Rats.

Objective: The aim of this study was to investigate (a) macrophage migration inhibitory factor (MIF) levels in polytrauma patients and rats after haemorrhagic shock (HS), (b) the potential of the MIF inhibitor ISO-1 to reduce multiple organ dysfunction syndrome (MODS) in acute (short-term and long-term follow-up) HS rat models and (c) whether treatment with ISO-1 attenuates NF-κB and NLRP3 activation in HS. Background: The MODS caused by an excessive systemic inflammatory response following trauma is associated with a high morbidity and mortality. MIF is a pleiotropic cytokine which can modulate the inflammatory response, however, its role in trauma is unknown. Methods: The MIF levels in plasma of polytrauma patients and serum of rats with HS were measured by ELISA. Acute HS rat models were performed to determine the influence of ISO-1 on MODS. The activation of NF-κB and NLRP3 pathways were analysed by western blot in the kidney and liver. Results: We demonstrated that (a) MIF levels are increased in polytrauma patients on arrival to the emergency room and in rats after HS, (b) HS caused organ injury and/or dysfunction and hypotension (post-resuscitation) in rats, while (c) treatment of HS-rats with ISO-1 attenuated the organ injury and dysfunction in acute HS models and (d) reduced the activation of NF-κB and NLRP3 pathways in the kidney and liver. Conclusion: Our results point to a role of MIF in the pathophysiology of trauma-induced organ injury and dysfunction and indicate that MIF inhibitors may be used as a potential therapeutic approach for MODS after trauma and/or haemorrhage.

Loss-of-function mutations in the co-chaperone protein BAG5 cause dilated cardiomyopathy requiring heart transplantation.

Dilated cardiomyopathy (DCM) is a major cause of heart failure, characterized by ventricular dilatation and systolic dysfunction. Familial DCM is reportedly caused by mutations in more than 50 genes, requiring precise disease stratification based on genetic information. However, the underlying genetic causes of 60 to 80% of familial DCM cases remain unknown. Here, we identified that homozygous truncating mutations in the gene encoding Bcl-2­associated athanogene (BAG) co-chaperone 5 (BAG5) caused inherited DCM in five patients among four unrelated families with complete penetrance. BAG5 acts as a nucleotide exchange factor for heat shock cognate 71 kDa protein (HSC70), promoting adenosine diphosphate release and activating HSC70-mediated protein folding. Bag5 mutant knock-in mice exhibited ventricular dilatation, arrhythmogenicity, and poor prognosis under catecholamine stimulation, recapitulating the human DCM phenotype, and administration of an adeno-associated virus 9 vector carrying the wild-type BAG5 gene could fully ameliorate these DCM phenotypes. Immunocytochemical analysis revealed that BAG5 localized to junctional membrane complexes (JMCs), critical microdomains for calcium handling. Bag5-mutant mouse cardiomyocytes exhibited decreased abundance of functional JMC proteins under catecholamine stimulation, disrupted JMC structure, and calcium handling abnormalities. We also identified heterozygous truncating mutations in three patients with tachycardia-induced cardiomyopathy, a reversible DCM subtype associated with abnormal calcium homeostasis. Our study suggests that loss-of-function mutations in BAG5 can cause DCM, that BAG5 may be a target for genetic testing in cases of DCM, and that gene therapy may potentially be a treatment for this disease.

Distribution of micafungin in the tissue fluids of patients with invasive fungal infections.

The distribution of micafungin (MCFG) in tissue fluids, such as cerebrospinal fluid (CSF), pleural effusions, ascites, and wound tissue fluids, was examined in seven patients with invasive fungal infections. MCFG (100-300 mg) was administered once daily over a 1-h intravenous infusion. Blood and tissue fluid samples were collected from 1 to 24 h after infusion. Although two patients had similar MCFG concentrations in their plasma, the concentrations in the CSF differed between these two patients. The concentration in the CSF of one patient was much higher than the MIC(90) for Candida albicans, Candida glabrata, and Aspergillus fumigatus, whereas the MCFG concentration in the CSF of the other patient was comparable to the MIC(90). By contrast, MCFG concentrations in pleural effusions, ascites, and wound tissue fluids were above the MIC(90). These results suggest that intravenous MCFG may be effective to treat invasive fungal infections that invade the organs and tissues.

Severe heat stroke complicated by multiple cerebral infarctions: a case report.

BACKGROUND: Heat-related illnesses include symptoms such as heat syncope/cramps, heat exhaustion, and life-threatening heat stroke. Usually, a heat stroke causes cerebellar ataxia, cognitive impairment, dysphagia, and aphasia. We report a very rare case of a patient who developed severe heat stroke complicated by multiple cerebral infarctions. CASE PRESENTATION: An 80-year-old Asian woman was found lying unconscious at her house, with no air conditioner and closed windows; the highest outside temperature was 36.1 °C. She was brought to our hospital unconscious with a high bladder temperature (42.5 °C) and disseminated intravascular coagulation (DIC score 4). She was diagnosed with severe heat stroke and managed with rapid cooling, intravenous fluids therapy, antibiotic therapy, and anti-coagulation therapy for DIC. Anti-coagulation therapy consisted of treatment with recombinant thrombomodulin for 4 days (days 1-4) and recombinant antithrombin for 1 day (day 1). A head computed tomography (CT) and magnetic resonance imaging (MRI) examination were performed on day 3, because she was still unconscious. Diffuse-weighted imaging showed high-signal intensities, indicating multiple lesions. An intracranial magnetic resonance angiography showed normal results. Imaging indicated new multiple cerebellar infarctions complicated with DIC. A tracheotomy was performed on day 9 because her conscious condition had not improved. She was transferred to another hospital for subacute care on day 23. CONCLUSIONS: Early management of heat stroke using anti-DIC, anti-bacterial, and fluid resuscitation therapy can help prevent complications such as intracranial hemorrhaging.

Diffuse midline glioma in the spinal cord with rapid respiratory deterioration.

BACKGROUND: Neurogenic acute respiratory failure is usually caused by either infection or vascular insufficiency. We report the case of a patient who developed acute respiratory failure secondary to a spinal tumor. CASE PRESENTATION: A 32-year-old man, presenting with numbness and muscle weakness in his legs for 2 weeks, was transferred to our hospital with worsening quadriplegia and development of respiratory symptoms. We carried out emergent spinal decompression and initiated steroid pulse therapy, with no resolution of symptoms; a tumor incision biopsy after contrast cervical magnetic resonance imaging revealed an intraspinal tumor with a pathological diagnosis of World Health Organization grade IV glioma. The patient developed bradycardia, severe sepsis, status epilepticus, and cardiopulmonary arrest due to hypoxemia and was treated with chemoradiotherapy under mechanical ventilation. He was later transferred to another hospital for subacute care. CONCLUSION: Acute respiratory failure caused by spinal tumors is uncommon. However, acute care practitioners should be mindful of neoplastic lesions as a potential cause.

Recombinant thrombomodulin protects against LPS-induced acute respiratory distress syndrome via preservation of pulmonary endothelial glycocalyx.

BACKGROUND AND PURPOSE: Disruption of the endothelial glycocalyx is causally related to microvascular endothelial dysfunction, a characteristic of sepsis-induced acute respiratory distress syndrome (ARDS). Recombinant human thrombomodulin (rhTM) attenuates vascular endothelial injuries, but the underlying mechanism remains elusive. Here, we investigated the structural basis and molecular mechanisms of rhTM effects on vascular endothelial injury in a model of sepsis. EXPERIMENTAL APPROACH: LPS (20 mg·kg-1 ) was intraperitoneally injected into 10-week-old male C57BL6 mice, and saline or rhTM was intraperitoneally injected 3 and 24 h after LPS injection. Using serum and/or lung tissue, histological, ultrastructural, and microarray analyses were performed. KEY RESULTS: Survival rate of rhTM-treated mice was significantly higher than that of control mice 48 h after LPS injection. Serum concentrations of IL-6 and high-mobility group box 1 were lower in the rhTM-treated group than in the control. Injury to the endothelial glycocalyx in pulmonary capillaries was attenuated by rhTM treatment. Gene set enrichment analysis revealed up-regulation of gene sets corresponding to cell proliferation/differentiation and anti-inflammation, such as the TGF-ß pathway, and negative regulation of IL-6, upon rhTM treatment. Gene expression of heparan sulfate 6-O-sulfotransferase 1 and endothelial cell-specific molecule 1 (components of the endothelial glycocalyx) was significantly preserved by rhTM treatment, and their protein expression levels were maintained in endothelial cells. CONCLUSION AND IMPLICATIONS: Our findings show that rhTM treatment affected inflammation, cell proliferation/differentiation, and glycocalyx synthesis in serum and lung tissue, subsequently attenuating ARDS caused by endothelial injury.

Neutrophil Elastase Inhibition Ameliorates Endotoxin-induced Myocardial Injury Accompanying Degradation of Cardiac Capillary Glycocalyx.

Myocardial injury in sepsis may be caused by a burst of several inflammatory mediators, leading to vascular endothelial injuries. However, the contribution of neutrophil elastase (NE) to myocardial injury in sepsis is still unknown. We aimed to evaluate whether endotoxemia-induced myocardial injury is associated with NE. Lipopolysaccharide (LPS) was injected intraperitoneally at a dose of 20 mg/kg into granulocyte-colony-stimulating-factor knockout mice (G-CSF-KO), which have few neutrophils, and littermate control mice. The survival rate of G-CSF-KO mice 48 hours after LPS injection was significantly greater than that of control mice. The serum level of troponin I in G-CSF-KO mice was significantly lower than that in control mice. In addition, the concentration of inflammatory cytokine interleukin-6 (IL-6) was significantly decreased 6 and 12 hours after LPS administration compared with that in control mice. Ultrastructural analysis revealed that vascular endothelial structures and the endothelial glycocalyx in G-CSF-KO mice were clearly preserved. Next, mice were injected with 0.2 mg/kg sivelestat (an NE inhibitor) after LPS administration. The survival rate was significantly higher and the serum level of troponin I was lower in sivelestat-injected mice than in control mice, respectively. Furthermore, IL-6 levels were significantly decreased 6 and 12 hours after LPS administration compared with those in control mice. Vascular endothelial structures and the endothelial glycocalyx in sivelestat-treated mice were clearly preserved at the ultrastructural level. In conclusion, NE is significantly associated with myocardial injury in endotoxemia. Inhibition of NE may be a useful tool for the management of endotoxemia.

Factors Enhancing Serum Syndecan-1 Concentrations: A Large-Scale Comprehensive Medical Examination.

Endothelial disorders are related to various diseases. An initial endothelial injury is characterized by endothelial glycocalyx injury. We aimed to evaluate endothelial glycocalyx injury by measuring serum syndecan-1 concentrations in patients during comprehensive medical examinations. A single-center, prospective, observational study was conducted at Asahi University Hospital. The participants enrolled in this study were 1313 patients who underwent comprehensive medical examinations at Asahi University Hospital from January 2018 to June 2018. One patient undergoing hemodialysis was excluded from the study. At enrollment, blood samples were obtained, and study personnel collected demographic and clinical data. No treatments or exposures were conducted except for standard medical examinations and blood sample collection. Laboratory data were obtained by the collection of blood samples at the time of study enrolment. According to nonlinear regression, the concentrations of serum syndecan-1 were significantly related to age (p = 0.016), aspartic aminotransferase concentration (AST, p = 0.020), blood urea nitrogen concentration (BUN, p = 0.013), triglyceride concentration (p < 0.001), and hematocrit (p = 0.006). These relationships were independent associations. Endothelial glycocalyx injury, which is reflected by serum syndecan-1 concentrations, is related to age, hematocrit, AST concentration, BUN concentration, and triglyceride concentration.

Sternoclavicular joint septic arthritis with chest wall abscess in a healthy adult: a case report.

BACKGROUND: Septic arthritis of the sternoclavicular joint is rare. It can be associated with serious complications such as osteomyelitis, chest wall abscess, and mediastinitis. In this report, we describe a case of an otherwise healthy adult with septic arthritis of the sternoclavicular joint with chest wall abscess. CASE PRESENTATION: A 68-year-old Japanese man presented to our hospital complaining of pain and erythema near the right sternoclavicular joint. Despite 1 week of oral antibiotics, his symptoms did not improve. Computed tomography revealed an abscess with air around the right pectoralis major muscle. After being transferred to a tertiary hospital, emergency surgery was performed. Operative findings included necrotic tissue around the right sternoclavicular joint and sternoclavicular joint destruction, which was debrided and packed open. Methicillin-susceptible Staphylococcus aureus was identified in blood and wound cultures. Negative pressure wound therapy and hyperbaric oxygen therapy were performed for infection control and wound healing. The patient's general condition improved, and good granulation tissue developed. The wound was closed using a V-Y flap on hospital day 48. The patient has been free of relapse for 3 years. CONCLUSIONS: Septic arthritis of the sternoclavicular joint is an unusual infection, especially in otherwise healthy adults. Because it is associated with serious complications such as chest wall abscess, prompt diagnosis and appropriate treatment are required.

Preliminary experience with air transfer of patients for rescue endovascular therapy after failure of intravenous tissue plasminogen activator.

The present report describes our experience with air transfer of patients with acute ischemic stroke in whom intravenous tissue plasminogen activator (IV t-PA) failed for rescue endovascular therapy (EVT). Twenty-three consecutive patients in whom IV t-PA failed were transferred to our hospital for rescue EVT between February 2011 and April 2013. The amount of time required for transfer, distance, clinical outcomes, and complications were compared between patients transferred by ground (TG group; n = 17) and by air (TA group; n = 6). Computed tomography imaging on arrival revealed hemorrhagic transformation in 1 (5.9%) patient in the TG group, whereas none of the patients in the TA group developed any type of complication. The remaining 22 patients received rescue EVT. The elapsed time from the request call to arrival at our hospital did not significantly differ between the TG and TA groups (45.8 ± 4.9 min vs. 41.6 ± 2.3 min). However, the distance from the primary hospital to our institution was significantly longer for the TA group than for the TG group (38.8 ± 10.4 km vs. 13.5 ± 1.2 km, p = 0.001). The frequency of favorable outcomes (modified Rankin Scale 0-1 at 90 days after onset) in the TG and TA groups were 25.0% and 50.0%, respectively (p = 0.267). Air transfer for patients after IV t-PA failure allowed for more rapid delivery of patients over longer distances than ground transfer.