Circulating lipopolysaccharide (LPS) concentrations are often elevated in patients with sepsis or various endogenous diseases related to bacterial translocation from the gut. Systemic inflammatory responses induced by endotoxemia induce severe involuntary loss of skeletal muscle, termed muscle wasting, which adversely affects the survival and functional outcomes of these patients. Currently, no drugs are available for the treatment of endotoxemia-induced skeletal muscle wasting. Here, we tested the effects of TAK-242, a Toll-like receptor 4 (TLR4)-specific signalling inhibitor, on myotube atrophy in vitro and muscle wasting in vivo induced by endotoxin. LPS treatment of murine C2C12 myotubes induced an inflammatory response (increased nuclear factor-κB activity and interleukin-6 and tumour necrosis factor-α expression) and activated the ubiquitin–proteasome and autophagy proteolytic pathways (increased atrogin-1/MAFbx, MuRF1, and LC-II expression), resulting in myotube atrophy. In mice, LPS injection increased the same inflammatory and proteolytic pathways in skeletal muscle and induced atrophy, resulting in reduced grip strength. Notably, pretreatment of cells or mice with TAK-242 reduced or reversed all the detrimental effects of LPS in vitro and in vivo. Collectively, our results indicate that pharmacological inhibition of TLR4 signalling may be a novel therapeutic intervention for endotoxemia-induced muscle wasting.

Circulating lipopolysaccharide (LPS) concentrations are often elevated in patients with sepsis or with various endogenous diseases that are associated with metabolic endotoxemia. Involuntary loss of skeletal muscle, termed muscle wasting, is commonly observed in these conditions, suggesting that circulating LPS might play an essential role in its development. Although impairment of muscle regeneration is an important determinant of skeletal muscle wasting, it is unclear whether LPS affects this process and, if so, by what mechanism. Here, we used the C2C12 myoblast cell line to investigate the effects of LPS on myogenesis. C2C12 myoblasts were grown to 80% confluence and induced to differentiate in the absence or presence of LPS (0.1 or 1 μg/mL); TAK-242 (1 μM), a specific inhibitor of Toll-like receptor 4 (TLR4) signaling; and a tumor necrosis factor (TNF)-α neutralizing antibody (5 μg/mL). Expression of a skeletal muscle differentiation marker (myosin heavy chain II), two essential myogenic regulatory factors (myogenin and MyoD), and a muscle negative regulatory factor (myostatin) was analyzed by western blotting. Nuclear factor-κB (NF-κB) DNA-binding activity was measured using an enzyme-linked immunosorbent assay. LPS dose-dependently and significantly decreased the formation of multinucleated myotubes and the expression of myosin heavy chain II, myogenin, and MyoD, and increased NF-κB DNA-binding activity and myostatin expression. The inhibitory effect of LPS on myogenic differentiation was reversible, suggesting that it was not caused by nonspecific toxicity. Both TAK-242 and anti-TNF-α reduced the LPS-induced increase in NF-κB DNA-binding activity, downregulation of myogenic regulatory factors, and upregulation of myostatin, thereby partially rescuing the impairment of myogenesis. Our data suggest that LPS inhibits myogenic differentiation via a TLR4–NF-κB-dependent pathway and an autocrine/paracrine TNF-α-induced pathway. These pathways may be involved in the development of muscle wasting caused by sepsis or metabolic endotoxemia.

Because most community hospitals in Japan do not maintain 24-h availability of in-house anesthesiologists, surgeons, and interventional radiologists, staffing dramatically declines during off hours. It is unclear whether, in such under-resourced hospitals, trauma patients presenting during off hours and requiring subspecialty intervention have worse outcomes than those who present during business hours. This was a retrospective cohort study at a community hospital in Japan. Participants were all injured patients requiring emergency trauma surgery or transarterial embolization who presented from January 2002 to December 2013. We investigated whether outcomes of these patients differed between business hours (8:01 AM to 6:00 PM weekdays) and off hours (6:01 PM to 8:00 AM weekdays plus all weekend hours). The primary outcome measure was mortality rate, and the secondary outcome measures were duration of emergency room (ER) stay; unexpected death (death/probability of survival > 0.5); and adverse events occurring in the ER. We adjusted for potential confounders of age, sex, Injury Severity Score (ISS), Revised Trauma Score, presentation phase (2002–2005, 2006–2009, and 2010–2013), Charlson Comorbidity Index, and injury type (blunt or penetrating) using logistic regression models. Of the 805 patients included, 379 (47.1%) presented during business hours and 426 (52.9%) during off hours. Off-hours presentation was associated with longer ER stays for patients with systolic blood pressure < 90 mmHg on admission (p = 0.021), ISS >15 (p = 0.047), and pelvic fracture requiring transarterial embolization (p < 0.001). Off-hours presentation was also associated with increased risk of adverse events in the ER (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.1–2.7, p = 0.020). After adjustment for confounders, an increased risk of adverse events (OR 1.6, 95% CI 1.1–2.7, p = 0.049) persisted, but no differences were detected in mortality (p = 0.80) and unexpected death (p = 0.44) between off hours and business hours. At a community hospital in Japan, presentation during off hours was associated with a longer ER stay for severely injured patients and increased risk of adverse events in the ER. However, these disadvantages did not impact mortality or unexpected outcome.

The genus Chromobacterium consists of 7 recognized species. Among those, only C. violaceum, commonly found in the soil and water of tropical and subtropical regions, has been shown to cause human infection. Although human infection is rare, C. violaceum can cause life-threatening sepsis, with metastatic abscesses, most frequently infecting those who are young and healthy.

The aim of this study was to determine complication rates and possible risk factors of expert-performed endotracheal intubation (ETI) in patients with trauma, in both the prehospital setting and the emergency department. We also investigated how the occurrence of ETI-related complications affected the survival of trauma patients. This single-center retrospective observational study included all injured patients who underwent anesthesiologist-performed ETI from 2007 to 2017. ETI-related complications were defined as hypoxemia, unrecognized esophageal intubation, regurgitation, cardiac arrest, ETI failure rescued by emergency surgical airway, dental trauma, cuff leak, and mainstem bronchus intubation. Of the 537 patients included, 23.5% experienced at least one complication. Multivariable logistic regression analysis revealed that low Glasgow Coma Scale Score (adjusted odds ratio [AOR], 0.93; 95% confidence interval [CI], 0.88–0.98), elevated heart rate (AOR, 1.01; 95% CI, 1.00–1.02), and three or more ETI attempts (AOR, 15.71; 95% CI, 3.37–73.2) were independent predictors of ETI-related complications. We also found that ETI-related complications decreased the likelihood of survival of trauma patients (AOR, 0.60; 95% CI, 0.38–0.95), independently of age, male sex, Injury Severity Score, Glasgow Coma Scale Score, and off-hours presentation. Our results suggest that airway management in trauma patients carries a very high risk; this finding has implications for the practice of airway management in injured patients.

Scrub typhus is an infectious disease that is caused by Orientia tsutsugamushi. The authors describe an autopsied case of scrub typhus complicated with severe disseminated intravascular coagulation (DIC). An 82‐year‐old man complained of fever 4 days after climbing a mountain. The patient was admitted to an urban hospital, and meropenem and ceftriaxone were administered. The patient's condition deteriorated and he was transferred to a second hospital. On physical examination, a black scab was found and scrub typhus was suspected. Despite intensive treatment, the patient died on the fifth day. High levels of O. tsutsugamushi IgM antibody were confirmed. An autopsy revealed systemic vasculitis and perivasculitis. The endothelial tissue of the white pulp of the spleen was markedly infiltrated by plasma cells. The authors speculated that a severe immune reaction against O. tsutsugamushi enhanced an inflammatory response, leading to DIC. This case is a warning to doctors who are not familiar with scrub typhus.