Pediatric wound infections following 2023 Kahramanmaras earthquakes: case series.

BACKGROUND: The Kahramanmaras earthquakes in Turkey on February 6, 2023, resulted in more than 100 000 injuries and 50 500 deaths. The main causes of morbidity and mortality in earthquake-affected patients include crush syndrome, trauma-related extremity injuries, and wound infections. OBJECTIVE: To investigate infective complications, causative microorganisms, treatments, and treatment responses in pediatric patients. METHODS: The case series involved 12 earthquake victims admitted to a tertiary treatment center between February 9 and 24, 2023. Wound sample cultures were obtained from patients with infected wounds via wound secretions and tissue samples collected during surgery. RESULTS: Nine patients were male (75%), and the mean age of patients was 12.6 ± 3.7 years. Seven patients (58.3%) experienced crush syndrome. Seven patients (58.3%) underwent fasciotomy operations. The main infectious complications were wound infections (58.3%) and urinary tract infections (25%). Nine different organisms were found to cause wound infection, with Enterococcus faecium (41.6%), Acinetobacter baumanii (33.3%), and Pseudomonas aeruginosa (16.6%) being the major bacterial isolates. All Acinetobacter strains were multidrug-resistant (MDR). CONCLUSION: Major disasters such as earthquakes are rare, and infections are the major complications that increase morbidity and mortality. Initial appropriate treatment contributes to improved outcomes, as MDR strains are common pathogens in these patients.

Mortality risk factors for crush syndrome after an earthquake in Türkiye: Do systemic inflammatory parameters play any role?

BACKGROUND: The aim of our study is to assess the prognostic impact of the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) on 28-day mortality in patients admitted to the intensive care unit with crush syndrome following the Kahramanmaras earthquake in Türkiye. METHODS: A total of 63 adult patients with crush syndrome admitted to the intensive care unit after the earthquake were enrolled in this study. The medical records of the patients were examined using follow-up forms and the hospital data system. RESULTS: The mean age of the patients was 38.9±17.3 years, and the median time under debris was 31.5 hours. The 28-day mortality rate was 27%. In univariate generalized estimating equations (GEE) and other analyses, variables that are significant (or candidate variables) between 28-day mortality groups included age as a biological factor. These variables were included in the multivariate GEE model. The effects of continuous renal replacement therapy (CRRT), serum sodium concentration, Sequential Organ Failure Assessment (SOFA) score, and PLR on mortality were statistically significant. CONCLUSION: Elevated SOFA scores, the necessity for CRRT, increased serum sodium levels, and decreased PLR values are associated with increased 28-day mortality in patients with crush syndrome after an earthquake.

Incidence and predictive factors of double crush syndrome in patients undergoing cervical surgery: a database study.

BACKGROUND: Double crush syndrome (DCS) is characterized by multiple compression sites along a single peripheral nerve. It commonly presents with persistent distal symptoms despite surgical treatment for cervical radiculopathy. Management typically involves nerve release of the most symptomatic site. However, due to overlapping symptoms with cervical radiculopathy, patients may undergo cervical surgery prior to DCS diagnosis. Due to its rarity and frequent misdiagnosis, the authors aim to utilize a large national database to investigate the incidence and associations of DCS. METHODS: The Pearldiver database was utilized to identify patients undergoing cervical surgery for the management of cervical radiculopathy. Patients were stratified into three cohorts based on their clinical course before and after cervical surgery. The primary outcome was the prevalence of DCS, and secondary outcomes included an evaluation of predictive factors for each Group, using a significance level of P < 0.05. RESULTS: Among 195,271 patients undergoing cervical surgery for cervical radiculomyelopathy, 97.95% were appropriately managed, 1.42% had potentially mids-diagnosed DCS, and 0.63% were treatment-resistant. Diabetes and obesity were significant predictors of potentially misdiagnosed DCS (P < 0.05). CONCLUSION: This study presents data indicating that 1.42% of patients who receive cervical surgery may have underlying DCS and potentially benefit from nerve release prior to undergoing surgery. A concurrent diagnosis of diabetes and obesity may predict an underlying DCS.

Predictive factors for acute kidney injury and amputation in crush injuries from the Kahramanmaras earthquakes.

BACKGROUND: Crush syndrome (CS) is characterized by high morbidity and mortality due to severe electrolyte disorders, circulatory dysfunction, and multiple organ failure, secondary to severe rhabdomyolysis and reperfusion injuries. Acute kidney injury (AKI) related to crush syndrome is one of the life-threatening complications and is the most frequent cause of death following earthquakes, other than trauma. We conducted a retrospective study to identify predictive parameters from clinical and laboratory data that aid in recognizing CS, assessing its severity, and evaluating acute kidney injury and amputation indications in patients. METHODS: We retrospectively evaluated the clinical data and laboratory follow-up of 33 patients treated for crush syndrome within the first two weeks following the February 6, 2023 earthquake. Patients who underwent surgery for crush syndrome but could not be followed post-surgery were excluded. Laboratory parameters were analyzed upon admission and then daily over an average seven-day follow-up. A p-value of <0.05 was considered statistically significant. Data analysis was performed using IBM SPSS Statistics 26.0 and R Studio software. RESULTS: Of the 33 patients, 17 were male and 16 were female. The incidence of AKI was 35.7%, 66.7%, and 100% in patients with injuries to one, two, and three extremities, respectively. A significant correlation was observed between total entrapment time and the duration of required dialysis days; AKI risk significantly increased with more than six hours of total entrapment time. Regarding the initial blood values upon hospital admission, a myoglobin level exceeding 2330 mg/dL demonstrated the highest sensitivity for predicting AKI. An initial uric acid level (>6.36 mg/dL) on admission had the highest specificity for predicting AKI. The initial myoglobin level (>3450 mg/dL) showed the highest sensitivity in predicting the need for amputation. Meanwhile, the mean creatine kinase (CK) level (>34800 U/L) exhibited the highest specificity but the lowest sensitivity for amputation prediction. CONCLUSION: The study analyzed the effectiveness and predictability of clinical and laboratory findings concerning amputation and acute kidney injury in crush syndrome resulting from earthquakes. Effective amputation management is a crucial factor influencing prognosis and survival in patients with earthquake-induced crush syndrome.

Double entrapment neuropathy of the ulnar nerve at the elbow and the wrist : double crush syndrome?

BACKGROUND: Double crush syndrome refers to a nerve in the proximal region being compressed, affecting its proximal segment. Instances of this syndrome involving ulnar and cubital canals during ulnar neuropathy are rare. Diagnosis solely through clinical examination is challenging. Although electromyography (EMG) and nerve conduction studies (NCS) can confirm neuropathy, they do not incorporate inching tests at the wrist, hindering diagnosis confirmation. We recently encountered eight cases of suspected double compression of ulnar nerve, reporting these cases along with a literature review. METHODS: The study included 5 males and 2 females, averaging 45.6 years old. Among them, 4 had trauma history, and preoperative McGowan stages varied. Ulnar neuropathy was confirmed in 7 cases at both cubital and ulnar canal locations. Surgery was performed for 4 cases, while conservative treatment continued for 3 cases. RESULTS: In 4 cases with wrist involvement, 2 showed ulnar nerve compression by a fibrous band, and 1 had nodular hyperplasia. Another case displayed ulnar nerve swelling with muscle covering. Among the 4 surgery cases, 2 improved from preoperative McGowan stage IIB to postoperative stage 0, with significant improvement in subjective satisfaction. The remaining 2 cases improved from stage IIB to IIA, respectively, with moderate improvement in subjective satisfaction. In the 3 cases receiving conservative treatment, satisfaction was significant in 1 case and moderate in 2 cases. Overall, there was improvement in hand function across all 7 cases. CONCLUSION: Typical outpatient examinations make it difficult to clearly differentiate the two sites, and EMG tests may not confirm diagnosis. Therefore, if a surgeon lacks suspicion of this condition, diagnosis becomes even more challenging. In cases with less than expected postoperative improvement in clinical symptoms of cubital tunnel syndrome, consideration of double crush syndrome is warranted. Additional tests and detailed EMG tests, including inching tests at the wrist, may be necessary. We aim to raise awareness double crush syndrome with ulnar nerve, reporting a total of 7 cases to support this concept.

Evaluation of pediatric trauma score and pediatric age-adjusted shock index in pediatric patients admitted to the hospital after an earthquake.

BACKGROUND: In our earthquake-prone country, it is crucial to gather data from regional hospitals following earthquakes. This information is essential for preparing for future disasters and enhancing healthcare services for those affected by earthquakes. This study aimed to evaluate the Pediatric Trauma Score (PTS) and the Shock Index, Pediatric Age-Adjusted (SIPA), in children affected by earthquakes, to provide clinicians with insights into the severity of trauma and hemodynamic stability. METHODS: The study included patients admitted to our hospital's pediatric emergency service within the three weeks following the earthquake. We evaluated their age, sex, admission vital signs, mechanical ventilation requirements, development of crush syndrome, length of hospital stay, PTS, and SIPA. RESULTS: Our study included 176 children (89 females and 87 males) with trauma. Fifty-eight (32.95%) children had crush syndrome, and 87 (49.43%) were hospitalized. The median PTS was 10 (ranging from -3 to 12), and the median SIPA was 1.00 (ranging from 0.57 to 2.10). We observed a negative correlation between the time spent under debris and PTS (r=-0.228, p=0.002) and a positive correlation with the SIPA score (r=0.268, p<0.001). The time spent under debris (p<0.001) and SIPA score (p<0.001) were significantly higher in hospitalized children. PTS was significantly lower in hospitalized children than in others. A PTS cutoff point of 7.5, and a SIPA cutoff point of 1.05, predicted hospitalization in all children. Time spent under debris and SIPA were significantly higher in children with crush syndrome than in others (p<0.001). PTS at a cutoff point of 8.5 and SIPA at a cutoff point of 1.05 predicted crush syndrome in all children. CONCLUSION: PTS and SIPA are important practical scoring systems that can be used to predict the severity of trauma, hospitalization, crush syndrome, and the clinical course in pediatric patients admitted to the hospital due to earthquake trauma.

Mortality Factors in Crush Syndrome.

BACKGROUND: Crush Syndrome is a major cause of morbidity and mortality following large-scale catastrophic earthquakes. Since there are no randomized controlled studies on Crush Syndrome, knowledge on this subject is limited to expert experience. The primary objective is to analyze the epidemiological and demographic characteristics, clinical outcomes, and mortality factors of earthquake victims after the Pazarcik and Elbistan earthquakes on February 6, 2023. METHODS: This cross-sectional and observational retrospective study evaluated 610 earthquake victims who presented to our center between February 6 and April 30, 2023. Among these patients, 128 with Crush Syndrome were included in the study. Patient information was gathered from hospital records during their stay and from national registries upon referral. The primary outcome was to identify risk factors for mortality. Demographic and laboratory data were analyzed by acute kidney injury (AKI) stages; mortality-affecting factors were identified through regression analysis. RESULTS: Of the 128 Crush Syndrome patients (100 adults, 28 children), 64 were female. The AKI rate was 32.8%. Among patients with AKI, the frequency of hemodialysis requirement was 69%, and the mortality rate was 14.2%. The overall mortality rate for patients with Crush Syndrome was 4.6%, compared to 3.9% (19/482) in earthquake victims without Crush Syndrome (p=0.705). Notably, low systolic blood pressure at admission was the only factor significantly affecting mortality in Crush Syndrome patients (Hazard Ratio [HR]: 1.088, p=0.021, 95% Confidence Interval [CI]). CONCLUSION: Our study highlights low systolic blood pressure upon admission as a significant risk factor for increased mortality in Crush Syndrome patients. This finding may contribute to the literature by emphasizing the importance of monitoring blood pressure under rubble and administering more aggressive fluid therapy to patients with low systolic blood pressure.

Simultaneous Versus Staged Surgery for Double Crush Syndrome of Cervical Radiculopathy and Peripheral Nerve Compression at the Wrist: A Retrospective Single-Center Study.

STUDY DESIGN: Retrospective single-center study. OBJECTIVES: To evaluate the results of surgical treatment in patients with double crush syndrome associated with cervical radiculopathy and upper limb peripheral nerve compression after staged and simultaneous operations. SUMMARY OF BACKGROUND DATA: Currently, choosing the optimal diagnostic and therapeutic modalities for treating patients with double crush syndrome remains unresolved. METHODS: The study included 79 patients with double crush syndrome (cervical radiculopathy and syndrome of Guyon's canal or Carpal tunnel syndrome). Two independent groups were studied: In the Staged Group (n=35), we performed a cervical decompression with stabilization and peripheral nerve decompression at separate days due to ongoing clinical symptoms (average interval between interventions being 22 (18;26) days). In the simultaneous group (n=33), we performed both the cervical spine surgery as well as the peripheral nerve procedures in one surgical session. Total operative time, estimated blood loss, length of hospitalization, complications, and clinical data (NDI score, SF-36, VAS neck pain score, VAS arm pain score, Disabilities of Arm, Shoulder, and Hand (DASH) score, and Macnab scale) were compared. We used the Mann-Whitney (MW) test for intergroup comparisons, the Wilcoxon criterion for dependent samples, and the Fisher exact test for binomial parameters. RESULTS: There was a significantly lower operative time, duration of inpatient treatment, and temporary disability in the simultaneous group (P=0.01, P=0.04, and P=0.006, respectively). Comparative analysis did not reveal significant intergroup differences using NDI, VAS, and DASH ( P >0.05), whereas, at discharge, significantly better clinical parameters were appreciated for the simultaneous group using SF-36 and Macnab scores ( P =0.04 and P =0.03, respectively). At the last follow-up, an intra-group analysis revealed comparable clinical effectiveness between the two approaches ( P >0.05). CONCLUSION: Comparison of the effectiveness of simultaneous and staged surgery revealed comparable long-term clinical outcomes. However, simultaneous surgery conveys clinically important advantages in terms of surgical time, anesthesia duration, length of hospitalization, and patient disability. LEVEL OF EVIDENCE: 3.

Pediatric kidney care experience after the 2023 Türkiye earthquake.

BACKGROUND: Two earthquakes on 6 February 2023 destroyed 10 cities in Türkiye. We report our experience with pediatric victims during these catastrophes, with a focus on crush syndrome related-acute kidney injury (Crush-AKI) and death. METHOD: Web-based software was prepared. Patient demographics, time under rubble (TUR), admission laboratory data, dialysis, and kidney and overall outcomes were recorded. RESULTS: A total of 903 injured children (median age 11.62 years) were evaluated. Mean TUR was 13 h (interquartile range 32.5, max 240 h). Thirty-one of 32 patients with a TUR of >120 h survived. The patient who was rescued after 10 days survived. Two-thirds of the patients were given 50 mEq/L sodium bicarbonate in 0.45% sodium chloride solution on admission day. Fifty-eight percent of patients were given intravenous fluid (IVF) at a volume of 2000-3000 mL/m2 body surface area (BSA), 40% at 3000-4000 mL/m2 BSA and only 2% at >4000 mL/m2 BSA. A total of 425 patients had surgeries, and 48 suffered from major bleeding. Amputations were recorded in 96 patients. Eighty-two and 66 patients required ventilator and inotropic support, respectively. Crush-AKI developed in 314 patients (36% of all patients). In all, 189 patients were dialyzed. Age >15 years, creatine phosphokinase (CK) ≥20 950 U/L, TUR ≥10 h and the first-day IVF volume <3000-4000 mL/m2 BSA were associated with Crush-AKI development. Twenty-two deaths were recorded, 20 of 22 occurring in patients with Crush-AKI and within the first 4 days of admission. All patients admitted after 7 days survived. CONCLUSIONS: These are the most extensive pediatric kidney disaster data obtained after an earthquake. Serum CK level was significantly associated with Crush-AKI at the levels of >20 950 U/L, but not with death. Adolescent age and initial IVF of less than 3000-4000 mL/m2 BSA were also associated with Crush-AKI. Given that mildly injured victims can survive longer periods in the disaster field, we suggest uninterrupted rescue activity for at least 10 days.

The prevalence of double- and multiple crush syndromes in patients surgically treated for peripheral nerve compression in the upper limb.

OBJECTIVE: The double crush syndrome describes a condition characterized by multifocal entrapment of a nerve. In the upper limb, the high prevalence of carpal tunnel syndrome makes it a common diagnosis of assumption in the setting of median neuropathy. More proximal compressions may tend to be overlooked, under-diagnosed and under-treated in the population. This study aims to map the prevalence of peripheral upper limb nerve compressions among patients undergoing peripheral nerve decompression. METHODS: A prospective case series was conducted on 183 patients undergoing peripheral nerve decompression in a private hand surgery clinic. Level(s) of nerve compression in the median, ulnar and radial nerves were determined by history and physical examination. The prevalence of each nerve compression syndrome or combination of syndromes was analyzed. RESULTS: A total of 320 upper limbs in 183 patients were analyzed. A double crush of the median nerve at the levels of the lacertus fibrosus and carpal tunnel was identified in 78% of upper limbs with median neuropathy, whereas isolated lacertus syndrome and carpal tunnel syndrome were present in only 5% and 17% of affected limbs respectively. Cubital tunnel syndrome affected 12.5% of upper limbs, and 80% of these had concomitant lacertus and carpal tunnel syndromes, compared to only 7.5% with isolated cubital tunnel syndrome. CONCLUSION: A high prevalence should prompt clinicians towards more routine assessment for double crush syndrome to avoid misdiagnosis, inadequate treatment, recurrence, and revision surgeries.

Thromboprophylaxis in pediatric patients with earthquake-related crush syndrome: a single centre experience.

PURPOSE: Injuries increase the risk of venous thromboembolism (VTE). However, the literature on the management of anticoagulant therapy in pediatric patients with crush injury is limited. In this study, we aimed to share our experience about anticoagulant thromboprophylaxis in pediatric patients with earthquake-related crush syndrome. METHODS: This study included patients who were evaluated for VTE risk after the Turkey-Syria earthquake in 2023. Since there is no specific pediatric guideline for the prevention of VTE in trauma patients, risk assessment for VTE and decision for thromboprophylaxis was made by adapting the guideline for the prevention of perioperative VTE in adolescent patients. RESULTS: Forty-nine patients [25 males and 24 females] with earthquake-related crush syndrome had participated in the study. The median age of the patients was 13.5 (8.8-15.5) years. Seven patients (14.6%) who had no risk factors for thrombosis were considered to be at low risk and did not receive thromboprophylaxis. Thirteen patients (27.1%) with one risk factor for thrombosis were considered to be at moderate risk and 28 patients (58.3%) with two or more risk factors for thrombosis were considered to be at high risk. Moderate-risk patients (n = 8) and high-risk patients aged < 13 years (n = 11) received prophylactic enoxaparin if they could not be mobilized early, while all high-risk patients aged ≥ 13 years (n = 13) received prophylactic enoxaparin. CONCLUSION: With the decision-making algorithm for thyromboprophylaxis we used, we observed a VTE rate of 2.1% in pediatric patients with earthquake-related crush syndrome.

Hospital crisis management after a disaster: from the epicenter of 2023 Türkiye-Syria earthquake.

BACKGROUND: In such cases where sudden destruction and injury are very high, search and rescue teams and hospitals can be the most important determining factors between people's lives and deaths. METHODS: This study was conducted retrospectively, after the two catastrophic earthquakes (Türkiye-Syria Earthquakes) by taking the records of the patients who admitted to our hospital. Patients' admission times, diagnoses, demographic data, triage codes, medical interventions, hemodialysis needs, crush syndrome and mortality rates were analyzed. RESULTS: In the first 5 days after the earthquake, 247 earthquake-related patients were admitted to our hospital. The most intense period of admission to the emergency department was the first 24 h. The most intensive period of surgical procedures was 24-48 h. It was observed that Orthopedic surgical procedures were applied most frequently and the most common cause of mortality was crush syndrome. CONCLUSION: In terms of preparations for earthquakes, especially in hospitals in the earthquake zone it will be beneficial for each hospital to make hospital disaster plans. For this reason, we thought it would be useful to share our experiences during this disaster.

6 February 2023, orthopedic experience in Kahramanmaras earthquake and surgical decision in patients with crush syndrome.

BACKGROUND: The decision of fasciotomy or amputation in crush syndrome is controversial and challenging for surgeons. We aimed to share our experiences after the Kahramanmaras earthquake, to predict the severity of crush syndrome and mortality, and to guide the surgical decision. METHODS: The clinical data of patients during their first week of hospitalization were analyzed retrospectively. Totally, 233 crush syndrome patients were included. Demographic data, physical and laboratory findings, surgical treatments, and outcomes were recorded. RESULTS: The mean time under the rubble was 41.89 ± 29.75 h. Fasciotomy and amputation were performed in 41 (17.6%) and 72 (30.9%) patients. One hundred and two patients (56.7%) underwent hemodialysis. Fifteen patients (6.4%) died. Lower extremity injury, abdominal trauma, and thoracic trauma were associated with mortality. Mortality was significantly increased in patients with thigh injuries (p = 0.028). The mean peak CK concentration was 69.817.69 ± 134.812.04 U/L. Peak CK concentration increased substantially with amputation (p = 0.002), lower limb injury (p < 0.001), abdominal trauma (p = 0.011), and thoracic trauma (p = 0.048). CONCLUSIONS: Thigh injury is associated with the severity of crush syndrome and mortality. Late fasciotomy should not be preferred in crush syndrome. Amputation is life-saving, especially in desperate lower extremity injuries.

Evaluation of the 2023 Kahramanmaras earthquake from the perspective of Plastic Surgery Department: A single-center experience.

OBJECTIVES: The aim of this study was to evaluate the treatment management and demographic data of earthquake victims admitted to Plastic Surgery Department of our center after the 2023 Kahramanmaras earthquake. PATIENTS AND METHODS: Between February 6th, 2023 and February 15th, 2023, a total of 120 patients (65 males, 55 females; mean age: 36.3±17.3 years; range, 85 to 88 years) who were consulted to the Plastic Surgery Department of our center were included. Demographic data of the patients, time to admission to the emergency room, removal time under the rubble, type of injury, emergency operation requirement, fasciotomy requirement, hyperbaric oxygen therapy administration, and length of stay in the intensive care unit were evaluated. After the first intervention, patients with compartment syndrome underwent emergency fasciotomy immediately. Perioperative laboratory values of the patients were followed closely to prevent the development of crush syndrome. RESULTS: Due to stay under the rubble, upper extremity soft tissue injury was seen in 46.2% of the patients. The pelvic and abdominal region were the least affected soft tissues in 1.7% patients. Fasciotomy was performed in 75 patients who stayed under the rubble. Hyperbaric oxygen therapy was applied to 21 of 75 patients who underwent fasciotomy. Amputation was performed in four patients, three of which were in the upper extremity and one in the lower extremity, during follow-up after fasciotomy. A total of 10.83% of the patients were treated conservatively and 11.67% of them were reconstructed with free flaps. Totally 7.5% of the patients who stayed under the rubble were hospitalized in our clinic for maxillofacial injuries. A total of 66.6% of these patients were treated surgically, while 33.3% of them were further treated conservatively. CONCLUSION: Proper triage, proper fasciotomy, and appropriate surgical interventions reduce the amputation rate, yielding clinically satisfactory results.

Precision engineered peptide targeting leukocyte extracellular traps mitigate acute kidney injury in Crush syndrome.

Crush syndrome induced by skeletal muscle compression causes fatal rhabdomyolysis-induced acute kidney injury (RIAKI) that requires intensive care, including hemodialysis. However, access to crucial medical supplies is highly limited while treating earthquake victims trapped under fallen buildings, lowering their chances of survival. Developing a compact, portable, and simple treatment method for RIAKI remains an important challenge. Based on our previous finding that RIAKI depends on leukocyte extracellular traps (ETs), we aimed to develop a novel medium-molecular-weight peptide to provide clinical treatment of Crush syndrome. We conducted a structure-activity relationship study to develop a new therapeutic peptide. Using human peripheral polymorphonuclear neutrophils, we identified a 12-amino acid peptide sequence (FK-12) that strongly inhibited neutrophil extracellular trap (NET) release in vitro and further modified it by alanine scanning to construct multiple peptide analogs that were screened for their NET inhibition ability. The clinical applicability and renal-protective effects of these analogs were evaluated in vivo using the rhabdomyolysis-induced AKI mouse model. One candidate drug [M10Hse(Me)], wherein the sulfur of Met10 is substituted by oxygen, exhibited excellent renal-protective effects and completely inhibited fatality in the RIAKI mouse model. Furthermore, we observed that both therapeutic and prophylactic administration of M10Hse(Me) markedly protected the renal function during the acute and chronic phases of RIAKI. In conclusion, we developed a novel medium-molecular-weight peptide that could potentially treat patients with rhabdomyolysis and protect their renal function, thereby increasing the survival rate of victims affected by Crush syndrome.

Zinc chelator treatment in crush syndrome model mice attenuates ischemia-reperfusion-induced muscle injury due to suppressing of neutrophil infiltration.

In crush syndrome, massive muscle breakdown resulting from ischemia-reperfusion muscle injury can be a life-threatening condition that requires urgent treatment. Blood reperfusion into the ischemic muscle triggers an immediate inflammatory response, and neutrophils are the first to infiltrate and exacerbate the muscle damage. Since free zinc ion play a critical role in the immune system and the function of neutrophils is impaired by zinc depletion, we hypothesized that the administration of a zinc chelator would be effective for suppressing the inflammatory reaction at the site of ischemia-reperfusion injury and for improving of the pathology of crush syndrome. A crush syndrome model was created by using a rubber tourniquet to compress the bilateral hind limbs of mice at 8 weeks. A zinc chelator N,N,N',N'-tetrakis-(2-pyridylmethyl)-ethylenediamine (TPEN) was administered immediately after reperfusion in order to assess the anti-inflammatory effect of the chelator for neutrophils. Histopathological evaluation showed significantly less muscle breakdown and fewer neutrophil infiltration in TPEN administration group compared with control group. In addition, the expression levels of inflammatory cytokine and chemokine such as IL-6, TNFα, CXCL1, CXCL2, CXCR2, CCL2 in ischemia-reperfusion injured muscle were significantly suppressed with TPEN treatment. Less dilatation of renal tubules in histological evaluation in renal tissue and significantly better survival rate were demonstrated in TPEN treatment for ischemia-reperfusion injury in crush syndrome. The findings of our study suggest that zinc chelators contributed to the resolution of exacerbation of the inflammatory response and attenuation of muscle breakdown in the acute phase after crush syndrome. In addition, our strategy of attenuation of the acute inflammatory reaction by zinc chelators may provide a promising therapeutic strategy not only for crush syndrome, but also for other diseases driven by inflammatory reactions.

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.

OBJECTIVES: The 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. METHODS: Seventy-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. RESULTS: Nine 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. CONCLUSION: The 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.

ß1-Blocker improves survival and ventricular remodelling in rats with lethal crush injury.

BACKGROUND: Crush injury/crush syndrome (CI/CS) is the second most common cause of death during earthquakes. Most studies of CI/CS have mainly focused on kidney injury after decompression. Few studies have focused on myocardial injury caused by crush injury and its potential mechanisms. METHODS: We first verified cardiomyocyte injury during compression in rats with a crush injury. The survival rate, electrocardiographic results, histological results, catecholamine changes and cardiac ß1-AR expression were evaluated. Next, we explored the effects of pretreatment with a selective ß1-blocker (bisoprolol) with or without fluid resuscitation on rats with a crush injury. In addition to evaluating the survival rates, biochemical and histological analyses and echocardiographic measurements were also performed. RESULTS: Reduced heart rates, elevated ST segments, and tall-peaked T waves were observed in the rats with a crush injury. The changes in the myocardial enzymes and pathological results demonstrated that myocardial damage occurred during compression in rats with a crush injury. The levels of the catecholamine norepinephrine in both the serum and myocardial tissue were elevated during compression. Pretreatment with a selective ß1-blocker combined with fluid resuscitation significantly improved the survival rates of the rats with lethal crush injury. The myocardial enzymes and pathological results showed that the combined therapy decreased myocardial damage. The echocardiography measurements showed that the rats that received the combined therapy exhibited decreased left ventricular mass (LVM), left ventricular volume at end-systole (LVVs) and left ventricular internal diameter (LVID) compared with the rats with a crush injury. CONCLUSIONS: Our findings demonstrated the presence of myocardial injury in the early stage of compression in rats with a crush injury. Pretreatment with a ß1-blocker (bisoprolol) with fluid resuscitation significantly reduced mortality, decreased myocardial tissue damage, and improved ventricular remodelling in rats with a lethal crush injury.

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

BACKGROUND: Acute 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. METHODS: Sprague-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. RESULTS: RNA 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-ß) 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. CONCLUSION: RIG-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.

Double crush syndrome: Epidemiology, diagnosis, and treatment results.

BACKGROUND: Double Crush Syndrome (DCS) is a clinical condition that involves multiple compression sites along a single peripheral nerve. The present study aims to describe the epidemiology of DCS and surgical results. METHODS: A retrospective observational analytic study included patients with clinical diagnosis of cervical radiculopathy and carpal tunnel syndrome who underwent surgery between January 2009 and January 2019. General demographic characteristics were noted, and 3 groups were distinguished: spinal surgery, carpal tunnel release, and bimodal decompression (BD); statistical differences were analyzed between them. RESULTS: The sample comprised 32 patients. DCS prevalence was 10.29%. Mean age at presentation was 59.25±10.98 years. There was female predominance (75%). Paresthesia was the main symptom (65.6%). Post-surgical results of BD showed significant improvement in sensory nerve conduction velocity, motor nerve conduction velocity (both P=0.008), and disability on Douleur Neuropathique 4 questions, Neck Disability Index, and Boston Carpal Tunnel Questionnaire (P=0.001, 0.004, 0.008, respectively). CONCLUSIONS: Diagnosis and management of DCS are a challenge. It is necessary to determine the site with maximal compression and risk of complications to decide on treatment. If first-line surgery is adequate, proximal and distal symptomatology can be improved. To maximize success, we recommend BD, according to the present results.