Crush Syndrome Research Articles

Salvianolic acid B improves the survival rate, acute kidney dysfunction, inflammation and NETosis-mediated antibacterial action in a crush syndrome rat model.

Crush syndrome (CS) is a potentially lethal condition characterized by muscle cell damage resulting from decompression following compression. Patients with CS can develop cardiac failure, kidney dysfunction, shock, systemic inflammation and sepsis. Salvianolic acid B (SalB) has cardiac and kidney protective effects and anti-oxidative, anti-inflammatory, anti-apoptotic and anti-bacterial properties. The present study aimed to demonstrate the survival benefit of SalB in the CS rat model, which comprised anesthetized rats with bilateral hindlimb compression by a rubber tourniquet for 5 h. The rats examined were randomly divided into four groups: i) Sham; ii) sham treated with SalB; iii) CS rat model without treatment; and iv) CS rat model treated with SalB. Under continuous monitoring and recording of arterial blood pressures, blood and tissue samples were collected for biochemical analyses at designated timepoints before and after reperfusion. SalB administration improved the survival rate, kidney function (by treating shock and metabolic acidosis) and inflammation (by reducing mitochondrial dysfunction and endothelial damage). Reduced incidence of cardiac failure due to hyperkalemia was associated with reduced muscle injury via the prevention of mitochondrial dysfunction. Additionally, indirect antibacterial action by the neutrophil extracellular trap system (NETs) was observed. SalB administration to the CS rat model led to a substantial improvement in survival following CS by decreasing kidney and cardiac dysfunctions, inflammation, and endothelial dysfunction by improving the mitochondrial function and through antibacterial effects via NETs.

Postoperative Functional Analysis of Double Crush Versus Single Peripheral Nerve Decompression: A Retrospective Study.

Double crush (DC) syndrome patients presenting with C6-7 radiculopathy and median nerve compression in the carpal tunnel report greater nerve irritability and weakness postdecompression than isolated peripheral nerve decompression. We hypothesize that patient-reported outcome is inferior following release at both cervical spine and wrist versus a single site of decompression. Patients that underwent either anterior cervical decompression and fusion (ACDF) for C6-C7 radiculopathy, carpal tunnel release (CTR), or both within 5 years (DC) were identified. A total of 477 patients were analyzed (157 DC, 203 CTR, and 117 ACDF). Post-operative outcome Disabilities of the Arm, Shoulder, and Hand (QuickDASH), Neck Disability Index, and visual analog scale (VAS) scores were collected at an average of 2 years postoperatively. QuickDASH scores were higher in the DC group versus CTR group (36 vs 22, P < .0002). Postoperative disability in the ACDF group was significantly higher than the DC group (50 vs 36, P < .017). There were no differences between ACDF and DC groups in arm pain intensity, but the CTR group demonstrated significantly greater arm pain intensity than the DC group (5.7 vs 3.6, 10-point scale, P < .01). Patients undergoing ACDF and CTR have greater postoperative disability than those undergoing CTR alone, but less postoperative functional disability and pain than ACDF alone, indicating cervical radiculopathy may contribute a greater proportion of long-term disability postoperatively. Additionally, CTR had greater postoperative arm pain than DC patients, potentially indicating high rates of undiagnosed cervical radiculopathy or other sources of arm pain in these patients.

Morphological features of heart remodeling in the postcompression period of crush syndrome

Summary. In the postcompression period of crush syndrome regenerative processes develop restorative processes in target organs, in particular in the heart. However, the dynamics of myocardial regenerative changes in the postcompression period in crush syndrome is insufficiently covered in professional literature and requires comprehension study and clarified. The aim of the study – to find out features of regenerative changes in heart of laboratory rats in the dynamics in the postcompression period of crush syndrome. Materials and Methods. Light-optical and polarization were performed examination of the myocardium of 48 laboratory rats after 1, 3, 7 and 14 days (12 animals in each period) after cessation of 6 hour compression of the thigh right pelvic limb. Crush syndrome was modeled under anesthesia by intraperitoneal input of ketamine hydrochloride (100 mg/kg body weight) in a specially designed device, the compression force was 7 kg/cm2, the compressive surface area – 5 cm2. The control group consisted of 12 animals. Results. The stages of myocardial remodeling in the postcompression period are noted, reflecting its structural recovery. In the early postcompression period light-optical disorders predominated microcirculation and alternate changes in acquired cardiomyocytes maximum development after 3 days. After 7 days in myocardial stroma registered cellular infiltrates in which predominate lymphocytes and fybroblasts. Cardiomyocytes lose a compact, gait cells became fortuous, microfoci of contractures were detected and fragmentation, there was a weak proliferation of collagen fibers. After 14 days in the late postcompression period the manifestation do not fade microcirculation disorders. Processes were registered in some areas collagen formation. Conclusions. In the first three days after the cessation of compression of compression of the lower extremity dystrophic–necrotic changes of the myocardium persist in combination with microcirculatory disorders. After 7 days the development of interstitial lympho–histiocytic infiltration is observed against the background of a gradual decrease alternative and hemodynamic processes. After 14 days registration a restoration of myocardial histostructure with residual processes of microfocal contracture of cardiomyocyte degeneration and increased collagen formation are registere

Myoglobin promotes macrophage polarization to M1 type and pyroptosis via the RIG-I/Caspase1/GSDMD signaling pathway in CS-AKI

Crush syndrome (CS) is a life-threatening illness in traffic accidents and earthquakes. Crush syndrome-induced acute kidney injury (CS-AKI) is considered to be mainly due to myoglobin (Mb) circulation and deposition after skeletal muscle ruptures and releases. Macrophages are the primary immune cells that fight foreign substances and play critical roles in regulating the body’s natural immune response. However, what effect does myoglobin have on macrophages and the mechanisms involved in the CS-AKI remain unclear. This study aims to look into how myoglobin affects macrophages of the CS-AKI model. C57BL/6 mice were used to construct the CS-AKI model by digital crush platform. Biochemical analysis and renal histology confirmed the successful establishment of the CS-AKI mouse model. Ferrous myoglobin was used to treat Raw264.7 macrophages to mimic the CS-AKI cell model in vitro. The macrophage polarization toward M1 type and activation of RIG-I as myoglobin sensor were verified by real-time quantitative PCR (qPCR), Western blotting (WB), and immunofluorescence (IF). Macrophage pyroptosis was observed under light microscopy. The interaction between RIG-I and caspase1 was subsequently explored by co-immunoprecipitation (Co-IP) and IF. Small interfering RNA (siRIG-I) and pyroptosis inhibitor dimethyl fumarate (DMF) were used to verify the role of macrophage polarization and pyroptosis in CS-AKI. In the kidney tissue of CS-AKI mice, macrophage infiltration and M1 type were found. We also detected that in the cell model of CS-AKI in vitro, ferrous myoglobin treatment promoted macrophages polarization to M1. Meanwhile, we observed pyroptosis, and myoglobin activated the RIG-I/Caspase1/GSDMD signaling pathway. In addition, pyroptosis inhibitor DMF not only alleviated kidney injury of CS-AKI mice but also inhibited macrophage polarization to M1 phenotype and pyroptosis via the RIG-I/Caspase1/GSDMD signaling pathway. Our research found that myoglobin promotes macrophage polarization to M1 type and pyroptosis via the RIG-I/Caspase1/GSDMD signaling pathway in CS-AKI.

Remote ischemic postconditioning protects against crush-induced acute kidney injury via down-regulation of apoptosis and senescence

BackgroundAcute renal failure due to crush syndrome is one of the leading causes of death in disasters. Ischemic Postconditioning (IPC) is a potentially effective strategy to protect against ischemic reperfusion injury, but a few studies noted its protective effect in crush induced acute kidney injury (AKI). Hence, this study investigated the optimal IPC strategy to prevent crush induced AKI and reveal related cellular mechanisms. MethodsThe right lower extremities of rabbits were constantly compressed for 8 h and then performed five cycles of clamping and releasing the femoral artery and vein before depression using a clip. In terms of the duration of clamping and releasing, the animals were randomly divided into 5 groups, Control, IPC-5sec, IPC-30sec, IPC-1min, and IPC-5min groups; 6 rabbits for each group. Biomarkers of inflammation, renal function, renal tubular injury, and muscular injury, apoptosis, and cellular senescence in kidney were detected. ResultsSix hours after decompression, the levels of Serum Creatine (SCr), Blood Urea Nitrogen (BUN), K+, and Interleukin-6 (IL-6) in IPC-1min and IPC-5min groups were lower than Control, with a statistically significant difference. The morphological study of Periodic Acid-Schiff (PAS) staining demonstrated that 6 h after decompression, IPC-1min can attenuate renal tubular damage renal tubule. Meanwhile, the level of Neutrophil Gelatinase-Associated Lipocalin (NGAL) in circulation in the IPC-30sec, IPC-1min, and IPC-5min groups was significantly decreased compared with the Control group, 2 h after decompression. On the other hand, the levels of serum Creatine Kinase (CK) and Myoglobin (Mb), and the morphological change of muscular damage detected by hematoxylin and eosin (H&E) staining in IPC-1min-treated group were significantly lower than Control group 6 hours after decompression. Further results of the cellular mechanism showed that the apoptotic markers of Terminal deoxynucleotidyl Transferase-mediated dUTP Nick End Labeling (TUNEL) and Caspase3 and the cell senescent markers of senescence-associated β-galactosidase (SA-β-Gal) and nuclear LAMNB1 have changed significantly in the IPC-1min group, compared with the control group. ConclusionsPerforming 5 cycles of 1-min IPC would be a convenient, time-saving, and effective method to prevent crush-induced AKI by attenuating the release of nephrotoxic substances after decompression and downregulation of the expression of apoptosis and cellular senescence biomarkers.

Strategies for the Long-Term Preservation of Site for Future Implantation of Cardiac Implantable Electronic Devices (CIEDs): Two Decades of Experience.

IntroductionImplantation of cardiac implantable electronic devices (CIEDs) is an art of science. As the volume of implantation has increased worldwide, so has the rate of complications. Infection, fibrosis, lead and device erosion, lead displacement, right ventricle perforation, lead fracture, and insulation break are the common complications in the implantation process. This exposes the patient for reopening and threatens the implantation for further complication due to infection, fibrosis of veins, failure to retrieve the implanted wire, and failure to re-implant the device on the same site. We slightly changed our implantation technique to preserve the implantation site for future implantation and reduce the rate of complication in the index implantation.MethodsThis randomized control trial was conducted from January 2016 to September 2019 at Hayatabad Medical Complex Peshawar, Pakistan. A consecutive sampling technique was used to obtain a sample size of 602 patients keeping a 95% confidence interval and a 5% margin error. We adopted a strategy to take prick, for implantation of devices, inside the pocket, which reduces the number of sutures, hastens the procedure, prevents erosion, and minimizes the chance of subclavian crush syndrome and insulation break. We also selected the minimum possible length of leads. This will possibly decrease the chances of cumbersome fibrosis around the lead and device and will make future implantation convenient.ResultsThere was a total of 602 procedures in the study period. About 253 (42%) procedures were done in the newly adopted strategy and 349 (58%) were performed in the conventional way. Our complication rate grossly reduces in the novel way of implantation in which we took our prick inside the pocket.ConclusionA slight modification in the implantation of CIEDs not only prevents the rate of complication in the index implantation but will also possibly preserve the site for future implantation.

HP41: Idiopathic systemic capillary leak syndrome with severe peripheral nervous system involvement. Case report

Idiopathic systemic capillary leak syndrome (ISCLS) a rare condition characterised by repeated relapses of leaking of plasma from blood vessels into body cavities and muscles. In one third of cases the disease is associated with variable severity peripheral nervous system damage. 26 years old male was admitted to hospital after repeated fainting with complains about progressive pain and numbness in lower limbs. In the hospital symptoms were rapidly progressing and patient developed asymmetrical painful tetraparesis (muscle strength in legs 0-1, muscle strength in arms 4). Systemic manifestations included hypotension, tachycardia, hemoconcentration, hypoalbuminemia, cardiac tamponade, crush syndrome. On 5th day from symptom onset treatment with intravenous immunoglobulin (IvIg) was started. After first IVIG treatment course systemic symptoms had resolved. Patient continued to receive IvIg monthly as a prophylactic treatment. After two courses of IvIg pain ceased, muscle strength improved (arm muscles 5, leg muscles 4). Patient died 20 months after symptom onset due to repeated systemic relapses. Electrodiagnostic study (EMG/NCS) was performed 3 times (on 3rd day from symptom onset, after first and second IvIg course). First EMG/NCS showed severe axonal motor and sensory neuropathy in legs, mild motor axonal damage in arms with massive spontaneous activity in all examined muscles. After repeated IvIg courses NCS in arms become normal, in legs tibial and peroneal MUAP remained absent, sural SNAP became normal; EMG showed slight evidence of reinnervation process without signs of active denervation. Conclusion. ISCLS can be considered in patients with rapidly progressive axonal polyradiculoneuritis with autonomic signs.

Systemic Review of Animal Models Used in the Study of Crush Syndrome.

Crush syndrome (CS), also known as traumatic rhabdomyolysis, is the leading cause of death following extrication from structural collapse due to earthquakes. Due to the unfeasibility of human studies, animal models are used to study crush syndrome pathophysiology, including biochemistry and treatment regimes. The aim of this systematic literature review was to identify the differences and benefits of various animal models used in the study of CS and provide valuable information for design of future research. A systematic search was conducted in two methods: with the filters "(crush syndrome) AND (crush muscle injury)" and with the keywords "(crush syndrome) AND (animal model)" covering all articles in the PubMed databases. The search generated 378 articles. After screening abstracts, 91 articles were retrieved and read, then 11 repeated articles were removed and 2 reference papers were included. We finally reviewed 82 original articles. There appear to be two primary methods employed for inducing crush syndrome in animal models, which are chemically induced injury and physically induced injury. Chemical method mainly includes intramuscular (IM) injection of tissue extract solution and IM injection of 50% glycerine. Physical method can be classified into invasive and non-invasive physical compression by elasticated material, inflatable band and heavy load. Various species of animals have been used to study CS, including mice (13.4%), rats (68.3%), rabbits (11.0%), canines (4.9%), goats (1.2%), and pigs (1.2%). Small animals are suitable for researches exploring the mechanism of disease or drug efficacy while large animals can work better with clinical application-related researches. In regard to the choice of modeling method, compressing the certain muscle of animals by heavy things is superior to others to cause systemic trauma-related rhabdomyolysis signs. In addition, due to the significant burden of crush injuries on animals, further attention shall be paid to the selection of the most suitable anesthetics and appropriate analgesics.

Anti-high-mobility group box-1 (HMGB1) mediates the apoptosis of alveolar epithelial cells (AEC) by receptor of advanced glycation end-products (RAGE)/c-Jun N-terminal kinase (JNK) pathway in the rats of crush injuries

ObjectivesThe lung injury is often secondary to severe trauma. In the model of crush syndrome, there may be secondary lung injury. We hypothesize that high-mobility group box 1 (HMGB1), released from muscle tissue, mediates the apoptosis of alveolar epithelial cells (AEC) via HMGB1/Receptor of advanced glycation end-products (RAGE)/c-Jun N-terminal kinase (JNK) pathway. The study aimed to investigate how HMGB1 mediated the apoptosis of AEC in the rat model.MethodsSeventy-five SD male rats were randomly divided into five groups: CS, CS + vehicle, CS + Ethyl pyruvate (EP), CS + FPS-ZM1 group, and CS + SP600125 groups. When the rats CS model were completed after 24 h, the rats were sacrificed. We collected the serum and the whole lung tissues. Inflammatory cytokines were measured in serum samples. Western blot and RT-qPCR were used to quantify the protein and mRNA. Lastly, apoptotic cells were detected by TUNEL. We used SPSS 25.0 for statistical analyses.ResultsNine rats died during the experiments. Dead rats were excluded from further analysis. Compared to the CS group, levels of HMGB1 and inflammatory cytokines in serum were downregulated in CS + EP, CS + FPS-ZM1, and CS + SP600125 groups. Western blot and RT-qPCR analysis revealed a significant downregulation of HMGB1, RAGE, and phosphorylated-JNK in CS + EP, CS + FPS-ZM1, and CS + SP600125 groups, compared with the CS groups, excluding total-JNK mRNA. Apoptosis of AEC was used TUNEL to assess. We found the TUNEL-positive cells were downregulated in CS + EP, CS + FPS-ZM1, and CS + SP600125 groups.ConclusionThe remote lung injury begins early after crush injuries. The HMGB1/RAGE/JNK signaling axis is an attractive target to abrogate the apoptosis of AEC after crush injuries.

Management of Severe Crush Injuries in Austere Environments: A Special Operations Perspective.

Crush injuries present a challenging case for medical providers and require knowledge and skill to manage the subsequent damage to multiple organ systems. In an austere environment, in which resources are limited and evacuation time is extensive, a medic must be prepared to identify trends and predict outcomes based on the mechanism of injury and patient presentation. These injuries occur in a variety of environments from motor vehicle accidents (at home or abroad) to natural disasters and building collapses. Crush injury can lead to compartment syndrome, traumatic rhabdomyolysis, arrythmias, and metabolic acidosis, especially for patients with extended treatment and extrication times. While crush syndrome occurs due to the systemic effects of the injury, the onset can be as early as 1 hour postinjury. With a comprehensive understanding of the pathophysiology, diagnosis, management, and tactical considerations, a prehospital provider can optimize patient outcomes and be prepared with the tools they have on hand for the progression of crush injury into crush syndrome.

A medical approach to the 2020 Elazig earthquake

Objective: Besides their direct effects, earthquakes may cause death by Crush syndrome and renal factors. In this study we aimed to evaluate the medical results of 2020 Elazig earthquake. Methods: We obtained the medical data from the National Medical Rescue Team (UMKE) and hospital records. Results: There were 1063 injured, 45 victims who were pulled out from the rubble and 41 deaths due to 2020 Elazig earthquake. Of the hospitalized patients 33% were treated with Crush/ compartment syndrome diagnosis. Conclusion: Catastrophic effects and collapsing buildings due to earthquakes, threat human life. In Elazig earthquake, none of the 48 hospitalized patients required dialysis probably due to early treatment and transfer to the hospital. Renal care and treatment such as fluid replacement, dialysis are as important as traumatological services in earthquakes in terms of increasing survival.

SUBCLAVIAN CRUSH SYNDROME AND INAPPROPRIATE SHOCKS IN PATIENT WITH IMPLANTABLE CARDIOVERTER DEFIBRILATOR

Subclavian crush syndrome may occur when the lead from cardiovascular implantable electronic device (CIED) is trapped between the clavicle and the first rib and the insulation layer is damaged, or conductor has been fractured. This complication carries an even greater risk if it involves a defibrillation electrode. Case report: We describe a case of&nbsp;a 68year old male patient with sudden onset of Implantable cardioverter defibrillator (ICD) activation- shocks delivery,&nbsp;more than ten times in the period of two hours, right before the admission to the emergency unit department. His ECG on admission shows rhythm of pacemaker with normal ventricular capture. The device interrogation revealed 53 episodes of ventricular fibrillation- false detection and delivery of multiple inappropriate shocks. Low impedance was detected of pace/sense electrodes &lt;200Ω, rise in shock impedance, ventricular oversensing episodes, and high pacing threshold. Due to Inappropriate ICD therapy the detection was turned off. Radiography findings have shown interruption of electrode – continuity in a position corresponding to subclavian crush syndrome, thereby implantation of the new system was indicated. The intervention of new system implantation was performed&nbsp;without any complication in standard procedure, using left axillary vein approach. We inserted a new ventricular single coil defibrillation electrode and new ICD device. The patient was discharged&nbsp;in a good clinical condition. Physicians must demonstrate excellent understanding of lead designs, mechanism of lead fracture, diagnosis and management, in order to make the best decision for every individual patient. Inappropriate shocks are medical emergency and must be treated immediately. Individual approach in every patient should be mandatory. Keywords:subclavian crush syndrome, Implantable cardioverter defibrillator, lead fracture.

Double Crush Syndrome of the Upper Extremity.

The double crush hypothesis originally proposed that compression of a peripheral nerve at a proximal site increases its susceptibility to additional distal lesions. The etiology of double crush syndrome is likely multifactorial as mechanical, systemic, pharmacologic, or environmental factors may increase a patient's susceptibility to this syndrome. To date, there remains no standardized definition of double crush syndrome, and there is no consensus on its exact pathophysiology or diagnostic criteria. Patients with double crush syndrome should be counseled that surgical repair may produce inferior outcomes compared with those who are treated for isolated entrapment neuropathies.

Survey of Molecular Mechanisms of Hyperbaric Oxygen in Tissue Repair.

For more than six decades, hyperbaric oxygen (HBO) has been used for a variety of indications involving tissue repair. These indications comprise a wide range of diseases ranging from intoxications to ischemia-reperfusion injury, crush syndrome, central nervous injury, radiation-induced tissue damage, burn injury and chronic wounds. In a systematic review, the molecular mechanisms triggered by HBO described within the last two decades were compiled. They cover a wide range of pathways, including transcription, cell-to-cell contacts, structure, adhesion and transmigration, vascular signaling and response to oxidative stress, apoptosis, autophagy and cell death, as well as inflammatory processes. By analyzing 71 predominantly experimental publications, we established an overview of the current concepts regarding the molecular mechanisms underlying the effects of HBO. We considered both the abovementioned pathways and their role in various applications and indications.

The Myth of Median Nerve in Forearm and Its Role in Double Crush Syndrome: A Cadaveric Study.

Purpose: This study aims to histologically compare the median nerve in the arm, forearm, and wrist, to help understand how cervical radiculopathy in a double crush phenomenon causes distal nerve dysfunction at the carpal tunnel and median nerve with concurrent absence of symptoms at the forearm.Methods: The study was performed on 12 fresh cadaveric upper limbs free from any injury or operation. Male cadavers in the age range of 35–40 years were used. The dissection of the median nerve and the histological examination of the specimens from the arm, forearm, and wrist were conducted to evaluate variations in the epineurium thickness (μm), perineurium thickness (μm), number of fascicles per nerve trunk, area percent of myelin covering, and area percent of neurolemmal sheath.Results: Morphometric and statistical results of the cadaveric median nerve trunk revealed that the mean epineurium and perineurium thickness measured in H&E-stained sections in the forearm were significantly greater than those in the arm and wrist specimens. Further, the mean percent area of the myelin covering in the forearm was significantly lower than that in the arm and wrist specimens in the sections stained with osmium oxide (p < 0.001). There were, however, no significant differences in the neurolemmal sheath among the arm, forearm, and wrist specimens in the silver-stained sections.Conclusion: The histological differences explained the high concomitant occurrence of carpal tunnel syndrome (CTS) and cervical radiculopathy and the concurrent absence of symptoms at the forearm. Hence, we suggest cautious evaluation of patients with upper limb symptoms, since the management of these conditions requires a different approach.

In Situ Neurolysis of Ulnar Nerve for Patients With Failed Anterior Subcutaneous Transposition - A Case Series.

BACKGROUNDVarious surgical techniques have been attempted to treat patients with failed anterior subcutaneous transposition performed for cubital tunnel syndrome.OBJECTIVETo analyze intraoperative findings of failed anterior subcutaneous transposition and to report the outcome of in Situ neurolysis of ulnar nerve.METHODSPatients who, under diagnosis of failed anterior subcutaneous transposition of ulnar nerve, underwent in Situ neurolysis between 2001 and 2018 were included in this study. We excluded patients with follow-up of less than one year, records of traumatic ulnar nerve injury, and concomitant double crush syndrome such as cervical spondylosis causing radicular pain, ulnar tunnel syndrome, or thoracic outlet syndrome. Surgical outcomes were evaluated using visual analog scale (VAS) pain score and Disabilities of the Arm, Shoulder, and Hand (DASH) score, which were assessed before and after surgery. A total of 28 elbows in 27 patients whose average age was 58.5 (range, 31-76) yr were enrolled, and the duration of follow-up was 5.8 (range, 1.0-14.9) yr.RESULTSThe most common pathologic finding identified during operation was severe adhesion of the transposed nerve in all elbows, followed by incomplete decompression of deep flexor-pronator aponeurosis in 26 elbows (93%). The average VAS pain score improved from 4.9 (range, 2-7) to 1.3 (range, 0-5), and the average DASH score from 31.7 (range, 18.1-66.7) to 14.1 (range, 5.0-46.6). Of the 28 elbows, 27 (96.4%) showed improvement of preoperative symptoms.CONCLUSIONIn Situ neurolysis of ulnar nerve for patients with failed anterior subcutaneous transposition resulted in satisfactory outcome.

The Role of Alpha-1-Acid Glycoprotein in the Diagnosis and Treatment of Crush Syndrome-Induced Acute Kidney Injury.

Crush syndrome (CS) is the most common cause of deaths following earthquakes and other disasters. The pathogenesis of CS has yet to be fully elucidated. Thus, clinical choice of ideal drug treatments for CS remains deficient. In this study, we first evaluated the relation between extrusion force and the severities of CS. Rats were exposed to different extrusion forces: 1 kg, 3 kg, 5 kg, and 8 kg, respectively. Survival rates, crushed muscle tissue edema, serum biochemical parameters, and histopathological staining were used to assess severity. Our results showed that there were no statistical differences in survival rate or changes in thigh circumference among the different extrusion forces groups. However, serum levels of potassium, creatine kinase, blood urea nitrogen, creatinine, and myoglobin were elevated at 12- and 24-h post-decompression in 5 kg and 8 kg groups, compared with 1 kg and 3 kg groups. Histopathological staining demonstrated that the degree of organ damage to kidney, muscle, and lung tissues correlated with increasing extrusion force. We next analyzed changes in serum protein profiles in 3 kg or 5 kg extrusion pressure groups. A total of 76 proteins (20 upregulated, 56 downregulated) were found to be altered at all three time points (0, 12, and 72 h) post-decompression, compared with the control group. Three common upregulated proteins alpha-1-acid glycoprotein (α1-AGP), neutrophil gelatinase-associated lipocalin (NGAL), and Haptoglobin were selected for validation of increased expression. α1-AGP was explored as a treatment for CS-induced acute kidney injury (AKI). Intraperitoneal injection of α1-AGP protected kidneys from CS-induced AKI by regulating TNF-α and IL-6 production, attenuating neutrophil recruitment, and reducing renal cell apoptosis. Our findings demonstrated that the severity of crush injury is causally related to extrusion pressure and increase in blood serum markers. Our identification of the biomarker and treatment candidate, α1-AGP, suggests its implication in predicting the severity of CS and its use as a mediator of CS-induced AKI, respectively.

Prehospital treatment of rhabdomyolysis in people who fall

Of people aged 65 and older, 30% will fall at least once per year—for people aged over 80, this rises to 50%. Patients who remain on the floor for a long time are at risk of developing rhabdomyolysis. If a person cannot move or get off the floor, tissue necrosis can occur at the point of contact and skeletal muscle is destroyed, releasing its contents into the bloodstream. This can eventually lead to crush syndrome, which includes rhabdomyolysis, hyperkalemia, dysrhythmias and acute kidney injury, and can be fatal. There are no guidelines for a time period when rhabdomyolysis is more likely to occur nor international consensus on how to best treat this condition in and out of hospital. This article looks at rhabdomyolysis resulting from falls in elderly people, and how to recognise and manage it. The aim is to improve awareness of rhabdomyolysis among prehospital practitioners so they can improve its management and advise patients at home.

RIG-I, a novel DAMPs sensor for myoglobin, activates NF-\u03baB/caspase-3 signaling in CS-AKI model

BackgroundAcute kidney injury (AKI) is the main life-threatening complication of crush syndrome (CS), and myoglobin is accepted as the main pathogenic factor. The pattern recognition receptor retinoicacid-inducible gene I (RIG-I) has been reported to exert anti-viral effects function in the innate immune response. However, it is not clear whether RIG-I plays a role in CS-AKI. The present research was carried out to explore the role of RIG-I in CS-AKI.MethodsSprague-Dawley rats were randomly divided into two groups: the sham and CS groups (n = 12). After administration of anesthesia, the double hind limbs of rats in the CS group were put under a pressure of 3 kg for 16 h to mimic crush conditions. The rats in both groups were denied access to food and water. Rats were sacrificed at 12 h or 36 h after pressure was relieved. The successful establishment of the CS-AKI model was confirmed by serum biochemical analysis and renal histological examination. In addition, RNA sequencing was performed on rat kidney tissue to identify molecular pathways involved in CS-AKI. Furthermore, NRK-52E cells were treated with 200 μmol/L ferrous myoglobin to mimic CS-AKI at the cellular level. The cells and cell supernatant samples were collected at 6 h or 24 h. Small interfering RNAs (siRNA) was used to knock down RIG-I expression. The relative expression levels of molecules involved in the RIG-I pathway in rat kidney or cells samples were measured by quantitative Real-time PCR (qPCR), Western blotting analysis, and immunohistochemistry (IHC) staining. Tumor necrosis factor-α (TNF-α) was detected by ELISA. Co-Immunoprecipitation (Co-IP) assays were used to detect the interaction between RIG-I and myoglobin.ResultsRNA sequencing of CS-AKI rat kidney tissue revealed that the different expression of RIG-I signaling pathway. qPCR, Western blotting, and IHC assays showed that RIG-I, nuclear factor kappa-B (NF-κB) P65, p-P65, and the apoptotic marker caspase-3 and cleaved caspase-3 were up-regulated in the CS group (P < 0.05). However, the levels of interferon regulatory factor 3 (IRF3), p-IRF3 and the antiviral factor interferon-beta (IFN-β) showed no significant changes between the sham and CS groups. Co-IP assays showed the interaction between RIG-I and myoglobin in the kidneys of the CS group. Depletion of RIG-I could alleviate the myoglobin induced expression of apoptosis-associated molecules via the NF-κB/caspase-3 axis.ConclusionRIG-I is a novel damage-associated molecular patterns (DAMPs) sensor for myoglobin and participates in the NF-κB/caspase-3 signaling pathway in CS-AKI. In the development of CS-AKI, specific intervention in the RIG-I pathway might be a potential therapeutic strategy for CS-AKI.

Acute Kidney Injury in Crush Syndrome and Renal Disaster-Experience in Bangladesh after garment factory collapse

Background: Crush-syndrome usually resulting from earthquake and other natural disaster causes mortality and morbidity. A multistoried garment factory collapsed in Savar, Dhaka, Bangladesh on 24th April 2013 with about 4000 workers. Among the rescued victims, many of them develop crush – syndrome and AKI that led to a man-made renal disaster in Bangladesh. We analyzed outcome of severe AKI patient who required renal replacement therapy.&#x0D; Methods: Victims from accident site were first treated in primarily local hospital and primary care center. Suspected crush syndrome patients were rapidly transferred to tertiary hospital for dialysis and ICU support. We collect data of severe AKI patient by a standard questionnairebased onrenal disaster relief force – crush syndrome patient questionnaire.&#x0D; Results: We had experienced many AKI and crush syndrome after collapsed garment factory with 3500 workers which created a manmade renal disaster. We observed 27 severe AKI due to crush syndrome of Rana plaza with mean age 25.12 years, most of them were female (51.85%). Victims rescued as early as possible, average rescue time was 20.30 hours, 62.96% developed compartment syndrome and required fasciotomy. All of them got dialysis treatment; some of them required ICU support. Among all, 67% recovered completely and 26% died. Main causes of death were infection and DIC with MOF.&#x0D; Conclusions: Crush injury victims who developed severe AKI, required dialysis. Severe AKI patients who required dialysis had high mortality and morbidity. Early intervention to prevent AKI and complications may reduce mortality and morbidity.&#x0D; Bangladesh J Medicine July 2021; 32(2) : 107-112