Comparative study of the prevalence of organ injury in placenta accreta spectrum disorder between posterior colpotomy and conventional peripartum hysterectomies at a single referral center in southern Thailand.

OBJECTIVE: To compare the prevalence of adjacent organ injury in placenta accreta spectrum disorder (PAS) between the posterior colpotomy approach and conventional peripartum hysterectomy. METHODS: This retrospective study analyzed the data of pregnant women diagnosed with PAS who underwent peripartum hysterectomy at Songklanagarind Hospital between January 2006 and December 2021. The patients were divided into two groups: posterior colpotomy and conventional approaches. The characteristics and surgical and obstetric outcomes were compared. Univariate and multivariate logistic regression was used to identify factors and risk of organ injury. RESULTS: Among 174 patients, 64 underwent conventional peripartum hysterectomy, and 110 underwent the posterior colpotomy approach. The overall incidence of adjacent organ injury was 17.82%. Organ injury prevalence was lower in the posterior colpotomy group (10%) than in the conventional group (31.25%), with no difference in operative time. Multivariate analysis showed that posterior colpotomy reduced adjacent organ injury (odds ratio [OR] 0.18, 95% confidence interval [CI] 0.06-0.54, P = 0.002). Placenta percreta was associated with increased injury risk (OR 6.83, 95% CI 2.53-18.44, P < 0.002). Subgroup analysis showed that the posterior approach reduced bladder injury in placenta increta (OR 0.14, 95% CI 0.04-0.57, P = 0.003) and percreta (OR 0.19, 95% CI 0.05-0.77, P = 0.017). CONCLUSION: Compared with conventional peripartum hysterectomy, the posterior colpotomy approach in patients with PAS reduced the risk of adjacent organ injury, particularly for placenta increta and percreta. This technique should be considered in PAS cases, but further investigations with a prospective study design are needed.

Outcomes of Nonoperative Management of Penetrating Abdominal Trauma Injury: A Retrospective Study.

BACKGROUND: The treatment of penetrating abdominal injuries has changed in recent years with more focus on "nonoperative management" (NOM) to avoid unnecessary laparotomies while identifying injuries early. Although the NOM approach is widely used for stab wounds, its effectiveness in managing abdominal gunshot wounds is controversial. NOM of penetrating abdominal injuries is becoming more dependent on hemodynamic stability and improved noninvasive radiological interventions. The role of NOM is significantly underreported and underestimated in developing countries, particularly in fragile and conflict-affected states such as Yemen. The present study aims to evaluate the clinical outcomes of NOM in penetrating abdominal trauma injury patients and identify factors associated with NOM failure in a low-resource setting. METHODS: A retrospective study from January 2021 to December 2022 including patients diagnosed with penetrating abdominal trauma at the General Military Hospital, Sana'a, Yemen, was conducted. Hemodynamically stable patients without peritonitis or clear indications for immediate laparotomy were candidates for NOM and were included in the study. Patients with blunt abdominal injuries, penetrating wounds outside the abdomen, particularly head injury, eviscerated structures, and gastrointestinal hemorrhage, or those pronounced dead on arrival were excluded. The primary outcome was the success and failure rate of NOM necessitating laparotomy. The secondary outcome was the factors associated with NOM failure. RESULTS: During the study, 256 patients with penetrating abdominal injury were admitted, with 222 (86.7%) undergoing immediate laparotomy and 34 (13.3%) treated with NOM. The mean age was 27.6±7.4 years. Bump explosions, mostly sharp objects (secondary blast injuries), were the main causes of injury (n=18, 52.9%). Other causes were low-velocity gunshot wounds, stab wound injuries, and shotgun injuries in 14 (41.2%), one (2.9%), and one (2.9%), respectively. The majority of patients (n=25, 55.9%) were admitted within 6-24 hours of the incident. The abdominal computed tomography (CT) scan revealed various injuries in all patients, including hemoperitoneum in 11 (32.4%), pneumoperitoneum in five (14.7%), liver injury in 15 (44.1%), foreign body attached to the wall colon in 23 (67.6%), kidney injury in two (5.9%), and splenic injury in one (2.9%). NOM was successful in 31 (91.2%) patients. NOM failed in three (8.8%). One patient was treated via the laparoscopic procedure, and two patients were treated with laparotomy procedures. Five (14.7%) cases required intensive care unit (ICU) admission, with no deaths or major complications. In univariate analysis, the presence of free intra-abdominal fluid (pneumoperitoneum) on the initial CT scan and the need for ICU admission were associated with NOM failure and were statistically significant (p<0.05). CONCLUSION: Our findings support that some penetrating abdominal trauma patients can benefit from NOM. The goal of preventing unnecessary laparotomies should be aligned with a comprehensive comprehension of the clinical signs and symptoms of NOM failure and the necessity for surgical intervention. Serial abdominal examinations remain the foundation of selected NOM; nevertheless, radiological and laboratory tests can be important tools in decision-making. In this study, free intra-abdominal fluid on the initial CT scan and the need for ICU admission were associated with NOM failure.

Unveiling thioacetamide-induced toxicity: Multi-organ damage and omitted bone toxicity.

Thioacetamide (TAA), a widely employed hepatotoxic substance, has gained significant traction in the induction of liver failure disease models. Upon administration of TAA to experimental animals, the production of potent oxidative derivatives ensues, culminating in the activation of oxidative stress and subsequent infliction of severe damage upon multiple organs via dissemination through the bloodstream. This review summarized the various organ damages and corresponding mechanistic explanations observed in previous studies using TAA in toxicological animal experiments. The principal pathological consequences arising from TAA exposure encompass oxidative stress, inflammation, lipid peroxidation, fibrosis, apoptosis induction, DNA damage, and osteoclast formation. Recent in vivo and in vitro studies on TAA bone toxicity have confirmed that long-term high-dose use of TAA not only induces liver damage in experimental animals but also accompanies bone damage, which was neglected for a long time. By using TAA to model diseases in experimental animals and controlling TAA dosage, duration of use, and animal exposure environment, we can induce various organ injury models. It should be noted that TAA-induced injuries have a time-dependent effect. Finally, in our daily lives, especially for researchers, we should take precautions to minimize TAA exposure and reduce the probability of related organ injuries.

Reduction of lymphocyte count at early stage elevates severity and death risk of COVID-19 patients: a hospital-based case-cohort study.

Introduction: Several reports have noted that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) induced lymphopenia in coronavirus disease 2019 (COVID-19) patients. However, the clinical significance of lymphopenia remains unclear. The objective of this study was to analyze the association between lymphopenia at an early stage and the prognosis of COVID-19 patients. Material and methods: All 192 hospitalized patients with COVID-19 were enrolled. Demographic data and clinical characteristics were collected and patient's prognosis was followed up. Results: On admission, 84 (43.8%) patients suffered from lymphopenia among COVID-19 patients. The count and percentage of lymphocytes on admission were lower among patients over 70 years old than those of younger patients. Multivariate logistic regression revealed that older age was a risk factor of lymphopenia. Of interest, chest CT score, a key marker of lung injury, was increased among COVID-19 patients with lymphopenia. By contrast, PaCO2, SpO2 and oxygenation index, several respiratory function markers, were decreased in COVID-19 patients with lymphopenia. Moreover, total bilirubin (TBIL) and direct bilirubin (DBIL), two markers of hepatic injury, creatinine and urea nitrogen, two indices of renal function, and creatine kinase, AST and LDH, three myocardial enzymes, were elevated in COVID-19 patients with lymphopenia. Among 84 COVID-19 patients with lymphopenia, 32.1% died. The fatality rate was obviously higher in COVID-19 patients with lymphopenia. Conclusions: Older COVID-19 patients are more susceptible to lymphopenia. Multiple organ injuries were more serious in COVID-19 patients with lymphopenia. Lymphopenia at an early stage aggravates the severity and elevates the death risk of COVID-19 patients.

Apolipoprotein M bound sphingosine 1-phosphate suppresses NETosis through activating S1P1 and S1P4.

The pleiotropic effects of high-density lipoprotein (HDL), including its protective properties against sepsis, are attributed to the sphingosine 1-phosphate and apolipoprotein M (ApoM) that are carried on the lipoproteins. In this study, we attempted to elucidate the possible mechanisms underlying the sepsis coagulopathic state by considering the modulation of NETosis. Our results revealed that in a lipopolysaccharide-induced sepsis mouse model, the levels of NETosis markers, such as plasma DNA and histone, were elevated in ApoM-knockout (KO) mice and attenuated in ApoM-overexpressing mice. In ApoM-KO mice, the survival rate decreased and the occurrence rates of coagulopathy and organ injury increased following the administration of histone. Treatment with a conditioned medium of ApoM-overexpressing cells attenuated the observed NETosis in HL-60S cells that differentiated into neutrophils and were inhibited through the suppression of S1P1 or S1P4. The attenuation of PKCδ and PKCα/ß by S1P1 and S1P4 activation may also be involved. In ApoM-overexpressing mice, coagulopathy and organ injuries were attenuated following an injection of histone; these effects were partially inhibited by S1P1, 3, S1P4, or S1P1 antagonists. Furthermore, the exogenous administration of ApoM protected ApoM-KO mice that were challenged with histone from developing NETosis. In conclusion, the ApoM/S1P axis protects against NETosis through the attenuation of PKC activation by S1P1 and S1P4. The development of drugs targeting the ApoM/S1P axis may be beneficial for the treatment of pathological conditions involving uncontrolled NETosis, such as sepsis.

Saudi Critical Care Society clinical practice guidelines on the prevention of venous thromboembolism in adults with trauma: reviewed for evidence-based integrity and endorsed by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine.

BACKGROUND: To develop evidence-based clinical practice guidelines on venous thromboembolism (VTE) prevention in adults with trauma in inpatient settings. METHODS: The Saudi Critical Care Society (SCCS) sponsored guidelines development and included 22 multidisciplinary panel members who completed conflict-of-interest forms. The panel developed and answered structured guidelines questions. For each question, the literature was searched for relevant studies. To summarize treatment effects, meta-analyses were conducted or updated. Quality of evidence was assessed using the Grading Recommendations, Assessment, Development, and Evaluation (GRADE) approach, then the evidence-to-decision (EtD) framework was used to generate recommendations. Recommendations covered the following prioritized domains: timing of pharmacologic VTE prophylaxis initiation in non-operative blunt solid organ injuries; isolated blunt traumatic brain injury (TBI); isolated blunt spine trauma or fracture and/or spinal cord injury (SCI); type and dose of pharmacologic VTE prophylaxis; mechanical VTE prophylaxis; routine duplex ultrasonography (US) surveillance; and inferior vena cava filters (IVCFs). RESULTS: The panel issued 12 clinical practice recommendations-one, a strong recommendation, 10 weak, and one with no recommendation due to insufficient evidence. The panel suggests starting early pharmacologic VTE prophylaxis for non-operative blunt solid organ injuries, isolated blunt TBIs, and SCIs. The panel suggests using low molecular weight heparin (LMWH) over unfractionated heparin (UFH) and suggests either intermediate-high dose LMWH or conventional dosing LMWH. For adults with trauma who are not pharmacologic candidates, the panel strongly recommends using mechanical VTE prophylaxis with intermittent pneumatic compression (IPC). The panel suggests using either combined VTE prophylaxis with mechanical and pharmacologic methods or pharmacologic VTE prophylaxis alone. Additionally, the panel suggests routine bilateral lower extremity US in adults with trauma with elevated risk of VTE who are ineligible for pharmacologic VTE prophylaxis and suggests against the routine placement of prophylactic IVCFs. Because of insufficient evidence, the panel did not issue any recommendation on the use of early pharmacologic VTE prophylaxis in adults with isolated blunt TBI requiring neurosurgical intervention. CONCLUSION: The SCCS guidelines for VTE prevention in adults with trauma were based on the best available evidence and identified areas for further research. The framework may facilitate adaptation of recommendations by national/international guideline policymakers.

Saudi Critical Care Society clinical practice guidelines on the prevention of venous thromboembolism in adults with trauma: reviewed for evidence-based integrity and endorsed by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine

To develop evidence-based clinical practice guidelines on venous thromboembolism (VTE) prevention in adults with trauma in inpatient settings. The Saudi Critical Care Society (SCCS) sponsored guidelines development and included 22 multidisciplinary panel members who completed conflict-of-interest forms. The panel developed and answered structured guidelines questions. For each question, the literature was searched for relevant studies. To summarize treatment effects, meta-analyses were conducted or updated. Quality of evidence was assessed using the Grading Recommendations, Assessment, Development, and Evaluation (GRADE) approach, then the evidence-to-decision (EtD) framework was used to generate recommendations. Recommendations covered the following prioritized domains: timing of pharmacologic VTE prophylaxis initiation in non-operative blunt solid organ injuries; isolated blunt traumatic brain injury (TBI); isolated blunt spine trauma or fracture and/or spinal cord injury (SCI); type and dose of pharmacologic VTE prophylaxis; mechanical VTE prophylaxis; routine duplex ultrasonography (US) surveillance; and inferior vena cava filters (IVCFs). The panel issued 12 clinical practice recommendations­one, a strong recommendation, 10 weak, and one with no recommendation due to insufficient evidence. The panel suggests starting early pharmacologic VTE prophylaxis for non-operative blunt solid organ injuries, isolated blunt TBIs, and SCIs. The panel suggests using low molecular weight heparin (LMWH) over unfractionated heparin (UFH) and suggests either intermediate­high dose LMWH or conventional dosing LMWH. For adults with trauma who are not pharmacologic candidates, the panel strongly recommends using mechanical VTE prophylaxis with intermittent pneumatic compression (IPC). The panel suggests using either combined VTE prophylaxis with mechanical and pharmacologic methods or pharmacologic VTE prophylaxis alone. Additionally, the panel suggests routine bilateral lower extremity US in adults with trauma with elevated risk of VTE who are ineligible for pharmacologic VTE prophylaxis and suggests against the routine placement of prophylactic IVCFs. Because of insufficient evidence, the panel did not issue any recommendation on the use of early pharmacologic VTE prophylaxis in adults with isolated blunt TBI requiring neurosurgical intervention. The SCCS guidelines for VTE prevention in adults with trauma were based on the best available evidence and identified areas for further research. The framework may facilitate adaptation of recommendations by national/international guideline policymakers.

Successful non-operative management of multiple intra-abdominal solid organ injury after blunt abdominal trauma: a case report.

Injuries to the solid abdominal viscera are common after blunt trauma. The success of non-operative management of these injuries has led to recent extensions of this approach to managing higher-grade, more complicated injuries that are typically treated operatively. We reported a 19-year-old male who presented with abdominal pain and gross hematuria during the late hours due to a motor vehicle accident. Abdominal computed tomography scan revealed moderate hemoperitoneum, extensively devascularized spleen with laceration extending into the hilum, multiple tears in the left kidney extended to the hilum, and large perinephric hematoma suggestive of Grade V injuries (shattered spleen and left kidney). We managed the patient non-operatively until he improved and became ready for discharge from the hospital in stable good health status. In conclusion, this case brings to light a unique instance where severe grade multiple solid organ injury was successfully managed with a conservative approach.

Long non-coding RNA plasmacytoma variant translocation 1 correlates with higher inflammation, multiple organ injury and mortality risk in acute pancreatitis, especially in severe acute pancreatitis.

BACKGROUND: Long non-coding RNA plasmacytoma variant translocation 1 (lnc-PVT1) possesses a good ability to regulate inflammation as well as multiple organ injury via multiple pathways, and clinically exacerbates severe acute pancreatitis (SAP) via autophagy. This study aimed to further assess the correlation of lnc-PVT1 with inflammation, multiple disease assessment scales, and prognostication in acute pancreatitis (AP) patients. METHODS: Peripheral blood mononuclear cell (PBMC) samples were collected from 98 AP patients (within 24 h after admission) and 50 healthy controls (HCs). lnc-PVT1 in PBMC samples was examined by reverse transcription-quantitive polymerase chain reaction. Multiple AP assessments, C-reactive protein (CRP) level, and in-hospital deaths were evaluated or recorded. RESULTS: lnc-PVT1 was overexpressed in AP patients compared with HCs; it was also positively correlated with Ranson's score, acute pathologic and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, and CRP level in AP patients. Besides, lnc-PVT1 disclosed a good predictive value for higher in-hospital mortality in AP patients (the area under the curve: 0.838, 95% confidence interval: 0.708-0.968). Lastly, lnc-PVT1 was generally correlated with CRP level as well as SOFA score among mild AP, moderate-severe AP, and SAP subgroups, especially in SAP subgroup; it was also correlated with higher mortality risk in SAP subgroup, but not in mild AP or moderate-severe AP subgroup. CONCLUSION: lnc-PVT1 is associated with CRP level, SOFA score, and higher mortality risk in AP patients, especially in SAP patients, indicating its potential as a biomarker for AP.

The role of PD-L1 in the immune dysfunction that mediates hypoxia-induced multiple organ injury.

Hypoxia is a pathological condition common to many diseases, although multiple organ injuries induced by hypoxia are often overlooked. There is increasing evidence to suggest that the hypoxic environment may activate innate immune cells and suppress adaptive immunity, further stimulating inflammation and inhibiting immunosurveillance. We found that dysfunctional immune regulation may aggravate hypoxia-induced tissue damage and contribute to secondary injury. Among the diverse mechanisms of hypoxia-induced immune dysfunction identified to date, the role of programmed death-ligand 1 (PD-L1) has recently attracted much attention. Besides leading to tumour immune evasion, PD-L1 has also been found to participate in the progression of the immune dysfunction which mediates hypoxia-induced multiple organ injury. In this review, we aimed to summarise the role of immune dysfunction in hypoxia-induced multiple organ injury, the effects of hypoxia on the cellular expression of PD-L1, and the effects of upregulated PD-L1 expression on immune regulation. Furthermore, we summarise the latest information pertaining to the involvement, diagnostic value, and therapeutic potential of immunosuppression induced by PD-L1 in various types of hypoxia-related diseases, including cancers, ischemic stroke, acute kidney injury, and obstructive sleep apnoea. Video Abstract.

Automated segmentation of the injured kidney due to abdominal trauma.

The objective of this study is to propose and validate a computer-aided segmentation system which performs the automated segmentation of injured kidney in the presence of contusion, peri-, intra-, sub-capsular hematoma, laceration, active extravasation and urine leak due to abdominal trauma. In the present study, total multi-phase CT scans of thirty-seven cases were used; seventeen of them for the development of the method and twenty of them for the validation of the method. The proposed algorithm contains three steps: determination of the kidney mask using Circular Hough Transform, segmentation of the renal parenchyma of the kidney applying the symmetry property to the histogram, and estimation of the kidney volume. The results of the proposed method were compared using various metrics. The kidney quantification led to 92.3 ± 4.2% Dice coefficient, 92.8 ± 7.4%/92.3 ± 5.1% precision/sensitivity, 1.4 ± 0.6 mm/2.0 ± 1.0 mm average surface distance/root-mean-squared error for intact and 87.3 ± 8.4% Dice coefficient, 84.3 ± 13.8%/92.2 ± 3.8% precision/sensitivity and 2.4 ± 2.2 mm/4.0 ± 4.2 mm average surface distance/root-mean-squared error for injured kidneys. The segmentation of the injured kidney was satisfactorily performed in all cases. This method may lead to the automated detection of renal lesions due to abdominal trauma and estimate the intraperitoneal blood amount, which is vital for trauma patients.

Comparison of American guidelines for field triage and Polish criteria as qualification to a trauma center.

INTRODUCTION: Trauma is the third cause of death among the general population in Poland, and the first in people aged 1-44 years. Trauma centers are hospitals dedicated to treating patients with multiple organ injuries, in a complex way that endeavours to ensure a lower mortality rate, shorter hospital stay and better outcomes if the patients are transferred to such a center. Worldwide, there are many models on how to treat a trauma patient, but them to be qualified for the procedure, the selection of potential patients is crucial. OBJECTIVE: The aim of the study was to compare the Polish model for qualification to a trauma center and American Guidelines for Field Triage. MATERIAL AND METHODS: Retrospective analysis of medical documentation recorded between 1 January 2014 - 31 December 2014 was undertaken. The study concerned trauma patients admitted to the Emergency Department of the Regional Trauma Center at the Copernicus Memorial Hospital in Lódz, Poland. Inclusion criterion was initial diagnosis 'multiple-organ injury' among patients transported by the Emergency Medical Service (EMS). RESULTS: In the period indicated, 3,173 patients were admitted to the Emergency Department at the Copernicus Memorial Hospital. From among them, 159 patients were included in the study. Only 13.2% of the patients fulfilled the Polish Qualification Criteria to Trauma Center in comparison to 87.4% who fulfilled the American Guidelines for Field Triage. CONCLUSIONS: Polish qualification criteria do not consider the large group of patients with severe injuries (ISS>15), but indicate patients with minimal chance of survival. Polish criteria do not consider the mechanism of injury, which is a relevant predictive indicator of severe or extremely severe injuries (ISS>15). Further studies should be undertaken to improve the qualification and treatment of trauma patients in Poland.

[Treatment and nursing of one patient with burns on perineal region and complicated by secondary multiple organ injuries by exposing to paraquat fluid].

On March 18, 2016, one 53 years old man with burns on perineal region and complicated by secondary multiple organ injuries by exposing to paraquat fluid was admitted to our department. Comprehensive treatment measures including protective mechanical ventilation, intensive care, vacuum sealing drainage, anti-infection, and organ protection were conducted sequentially. Through 33 days of comprehensive treatment and nursing, the patient's condition substantially improved and he left hospital. This case presents that paraquat fluid absorption through skin and mucosa can also lead to severe systemic poisoning, and multiple organ protection is the key to improve the prognosis of this patient.

Intravenous injection of post-hemorrhagic shock mesenteric lymph induces multiple organ injury in rats.

Post-hemorrhagic shock mesenteric lymph (PHSML) has an important role in the multiple organ injuries caused by severe shock. The current study investigated whether intravenous injection of PHSML induces organ injury in normal rats. Following the establishment of hemorrhagic shock in donor rats (40±2 mmHg, 3 h), PHSML was drained during hypotension at 1-3 h and then injected to normal rats through the femoral vein within 30 min. The mean arterial pressure (MAP) was measured, and samples were obtained for analysis of histology and biochemical indices at 2.5 h post-PHSML administration. PHSML administration resulted in a significant decrease in MAP at the early and late stage of the experiment. Structural damage of the lung, kidney, heart and liver was also observed, and the levels of urea, creatinine, aspartate aminotransferase, total bile acid and creatine kinase MB isoenzyme were increased in the plasma. Additionally, PHSML injection significantly increased the levels of trypsin, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 and receptor of advanced glycation end-products in the plasma, malondialdehyde in the lung and myocardium, and TNF-α in the lung, kidney, myocardium and liver. Intravenous injection of PHSML induced multiple organ injury in normal rats via increases in trypsin activity, inflammatory factors and free radical production. The findings indicate that PHSML return is an important contributor to organ damage following hemorrhagic shock.

Automated computer-aided diagnosis of splenic lesions due to abdominal trauma.

BACKGROUND: Computer-aided detection in the setting of trauma presents unique challenges due to variations in shape and attenuation of the injured organs based on the timing and severity of the injury.  We developed and validated an automated computer-aided diagnosis algorithm to detect splenic lesions such as laceration, contusion, subcapsular hematoma, perisplenic hematoma, and active extravasation using computed tomography (CT) images in patients sustaining blunt or penetrating abdominal trauma. METHODS: We categorized the splenic pathologies into three groups: contusion/laceration, hematoma, and active extravasation. We first analyzed the spleen and perisplenic region by estimating the mean value and standard deviation of the spleen. We determined adaptive threshold values based on the histogram of the area and detected the lesions after morphological operations and volumetric comparisons. RESULTS: The overall performance of the three computer-aided diagnosis (CAD) algorithms is an accuracy of 0.80, sensitivity of 0.95, specificity of 0.67, and a diagnostic odds ratio (DOR) of 40 with a 95 % confidence interval (CI): 14 to 117. The CAD of perisplenic hematoma had the highest diagnosis rates with an accuracy of 0.90, a sensitivity of 0.95,  specificity of 0.80, and DOR of 76 with a 95 % CI:  13 to 442. CONCLUSIONS: We developed a new algorithm to detect post-traumatic splenic lesions automatically and with high accuracy. Our method could potentially lead to the automated diagnosis of all traumatic abdominal pathologies. HIPPOKRATIA 2018, 22(2): 80-85.

Combined Hemorrhagic Shock and Unilateral Common Carotid Occlusion Induces Neurological Injury in Adult Male Rats.

Background: Clinical assessment reveals that patients after surgery of cardiopulmonary bypass or coronary bypass experience postoperative cognitive dysfunction. This study aimed to investigate whether resuscitation after a hemorrhagic shock (HS) and/or mild cerebral ischemia caused by a unilateral common carotid artery occlusion (UCCAO) can cause brain injury and concomitant neurological dysfunction, and explore the potential mechanisms. Methods: Blood withdrawal (6 mL/100 g body weight) for 60 min through the right jugular vein catheter-induced an HS. Immediately after the termination of HS, we reinfused the initially shed blood volumes to restore and maintain the mean arterial blood pressure (MABP) to the original value during the 30-min resuscitation. A cooling water blanket used to induce whole body cooling for 30 min after the end of resuscitation. Results: An UCCAO caused a slight cerebral ischemia (cerebral blood flow [CBF] 70%) without hypotension (MABP 85 mmHg), systemic inflammation, multiple organs injuries, or neurological injury. An HS caused a moderate cerebral ischemia (52% of the original CBF levels), a moderate hypotension (MABP downed to 22 mmHg), systemic inflammation, and peripheral organs injuries. However, combined an UCCAO and an HS caused a severe cerebral ischemia (18% of the original CBF levels), a moderate hypotension (MABP downed to 17 mmHg), systemic inflammation, peripheral organs damage, and neurological injury, which can be attenuated by whole body cooling. Conclusions: When combined with an HS, an UCCAO is associated with ischemic neuronal injury in the ipsilateral hemisphere of adult rat brain, which can be attenuated by therapeutic hypothermia. A resuscitation from an HS regards as a reperfusion insult which may induce neurological injury in patients with an UCCAO disease.

Advances and New Concepts in Alcohol-Induced Organelle Stress, Unfolded Protein Responses and Organ Damage.

Alcohol is a simple and consumable biomolecule yet its excessive consumption disturbs numerous biological pathways damaging nearly all organs of the human body. One of the essential biological processes affected by the harmful effects of alcohol is proteostasis, which regulates the balance between biogenesis and turnover of proteins within and outside the cell. A significant amount of published evidence indicates that alcohol and its metabolites directly or indirectly interfere with protein homeostasis in the endoplasmic reticulum (ER) causing an accumulation of unfolded or misfolded proteins, which triggers the unfolded protein response (UPR) leading to either restoration of homeostasis or cell death, inflammation and other pathologies under severe and chronic alcohol conditions. The UPR senses the abnormal protein accumulation and activates transcription factors that regulate nuclear transcription of genes related to ER function. Similarly, this kind of protein stress response can occur in other cellular organelles, which is an evolving field of interest. Here, I review recent advances in the alcohol-induced ER stress response as well as discuss new concepts on alcohol-induced mitochondrial, Golgi and lysosomal stress responses and injuries.