To investigate if toll-like receptor (TLR) 4/nuclear factor-kappa B (NF-κB) signaling pathways mediated crush injury induced acute kidney injury (AKI) in rats, and if TAK-242 (a specific inhibitor of TLR4) attenuates the injury through inhibiting the signaling pathways.

This study was divided into two parts: (1) Establish the crush injury model: 50 rats were randomly divided into control group and four crush injury groups (n = 10/group). Crush injury groups were given 3kg pressure for eight hours and were sacrificed at the time points of 0h, 6h, 12h, and 24h after relieving pressure. And (2) Select the most obvious injury group (12h group) for drug intervention group. Thirty rats were randomly divided into control group, 12h group, and 12h+TAK-242 group (n = 10/group). Two parts detection were as follows: pathological changes of kidney tissues were observed in Haematoxylin and Eosin (HE) staining. Serum creatinine, blood urea nitrogen (BUN), myoglobin (Mb), and blood potassium were examined by automatic biochemical analysis instrument. Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). The TLR4 messenger ribonucleic acid (mRNA), TLR4, and P65 were detected by real-time polymerase chain reaction (PCR), western blot, immunohistochemistry staining.

Compared with the control group, kidney tissues were damaged in crush injury groups, and most obvious in the 12h group. The level of serum creatinine, BUN, Mb, blood potassium, IL-6, TNF-α, and TLR4mRNA were increased in the crush injury groups and significantly increased in the 12h group (P <.05). The TLR4 and P65 were significantly increased in the 12h group (P <.05). Compared with the 12h group, kidney tissue damage was significantly reduced in the TAK-242 group (P <.05). The level of serum creatinine, BUN, Mb, blood potassium, IL-6, TNF-α, TLR4mRNA, TLR4, and P65 in the TAK-242 group were significantly reduced (P <.05).

The present findings conclude that TLR4/NF-κB signaling pathways mediated crush injury induced AKI in rats, and TAK-242 attenuates the injury through inhibiting the signaling pathways.

During disasters and complex emergencies, environmental conditions can adversely affect the performance of point-of-care (POC) testing. Knowledge of these conditions can help device developers and operators understand the significance of temperature and humidity limits necessary for use of POC devices. First responders will benefit from improved performance for on-site decision making.

To create dynamic temperature and humidity profiles that can be used to assess the environmental robustness of POC devices, reagents, and other resources (eg, drugs), and thereby, to improve preparedness.

Surface temperature and humidity data from the National Climatic Data Center (Asheville, North Carolina USA) was obtained, median hourly temperature and humidity were calculated, and then mathematically stretched profiles were created to include extreme highs and lows. Profiles were created for: (1) Banda Aceh, Indonesia at the time of the 2004 Tsunami; (2) New Orleans, Louisiana USA just before and after Hurricane Katrina made landfall in 2005; (3) Springfield, Massachusetts USA for an ambulance call during the month of January 2009; (4) Port-au-Prince, Haiti following the 2010 earthquake; (5) Sendai, Japan for the March 2011 earthquake and tsunami with comparison to the colder month of January 2011; (6) New York, New York USA after Hurricane Sandy made landfall in 2012; and (7) a 24-hour rescue from Hawaii USA to the Marshall Islands. Profiles were validated by randomly selecting 10 days and determining if (1) temperature and humidity points fell inside and (2) daily variations were encompassed. Mean kinetic temperatures (MKT) were also assessed for each profile.

Profiles accurately modeled conditions during emergency and disaster events and enclosed 100% of maximum and minimum temperature and humidity points. Daily variations also were represented well with 88.6% (62/70) of temperature readings and 71.1% (54/70) of relative humidity readings falling within diurnal patterns. Days not represented well primarily had continuously high humidity. Mean kinetic temperature was useful for severity ranking.

Simulating temperature and humidity conditions clearly reveals operational challenges encountered during disasters and emergencies. Understanding of environmental stresses and MKT leads to insights regarding operational robustness necessary for safe and accurate use of POC devices and reagents. Rescue personnel should understand these principles before performing POC testing in adverse environments.

FergusonWJ , LouieRF , TangCS , Paw UKT , KostGJ . Dynamic Temperature and Humidity Environmental Profiles: Impact for Future Emergency and Disaster Preparedness and Response. Prehosp Disaster Med. 2014;29(1):1-8.

Serum creatine kinase and myoglobin elevation has been described involving muscle manipulation after surgery and also after bariatric, urologic and gynaecologic procedures. It encompasses a wide range of severity, reflecting in the worst cases true rhabdomyolysis. We occasionally noted creatine kinase elevations after intracranial neurosurgery, an occurrence that has not yet been described. To assess whether the issue of postoperative muscle enzyme elevation is relevant to neurosurgery, we prospectively measured serum creatine kinase and myoglobin in a series of neurosurgical patients submitted to craniotomy.

We studied 30 patients aged 22–69 yr submitted to craniotomy. Blood samples were taken prior to the procedure, at the end of anaesthesia and on the first, second and third postoperative days. Blood was checked for creatine kinase, myoglobin, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, creatinine and serum electrolytes. We recorded the patient’s age, sex, height, weight and body mass index. Throughout surgery, we recorded the highest and the lowest body temperature and sampled the mean arterial pressure at 5 min intervals. We performed backwards stepwise logistic regression analysis to identify the elements that best correlate with the development of cell muscle damage.

On the first postoperative day creatine kinase peaked from baseline (305 (107–1306) UI L−1 vs. 59 (42–94) UI L−1; P < 0.001) while myoglobin rose significantly from baseline to the end of surgery (70 (42–147) ng mL−1 vs. 36 (30–44) ng mL−1; P = 0.002). Logistic regression showed that length of surgery was the only factor clearly influencing peak creatine kinase (P < 0.001; R2 0.7) and myoglobin (P = 0.011; R2 0.41) concentration.

Creatine kinase and myoglobin elevation may occur after intracranial neurosurgery. In our series, length of surgery was a risk factor.

Cardiac marker sensitivity depends on chest pain duration at the time of sampling. Our objective was to estimate the sensitivity, specificity, and likelihood ratios of early CK–MB and myoglobin assays in patients presenting to the emergency department (ED) with nondiagnostic ECGs, stratified by the duration of ongoing chest pain at the time of ED assessment.

This was a prospective observational study carried out in 10 US and 2 Canadian EDs. Patients >25 years of age with ongoing chest pain and nondiagnostic ECGs were stratified by pain duration (0–4 h, 4–8 h, 8–12 h, >12 h). CK–MB and myoglobin assays were drawn at T = 0 (ED assessment) and T = 1 hr. Patients were followed for 7–14 days to identify all cases of acute myocardial infarction (AMI). ED test results were correlated with patient outcomes.

Of 5005 eligible patients, 565 had AMI. Pain duration was 0–4 h in 3014 patients, 4–8 h in 961, 8–12 h in 487, and >12 h in 543. Marker sensitivity increased with pain duration, ranging from 28%–77% for CK–MB and 39%–73% for myoglobin. The maximal sensitivity achieved by a T = 0 assay was 73%, and this was in patients with 8–12 or >12 h of ongoing pain. No combination of tests achieved 90% sensitivity in any pain duration strata.

Regardless of chest pain duration, single assays and early serial markers (0+1 hr) do not rule out AMI; therefore, serial assays over longer observation periods are required. Likelihood ratios derived in this study will help physicians who use Bayesian analysis to determine post-test AMI likelihood in patients with chest pain.