Ubiquitin-Specific Protease 25 Aggravates Acute Pancreatitis and Acute Pancreatitis-Related Multiple Organ Injury by Destroying Tight Junctions Through Activation of The STAT3 Pathway

Ubiquitin-specific protease 25 (USP25) plays an important role in inflammation and immunity. However, the role of USP25 in acute pancreatitis (AP) is still unclear. To evaluate the role of USP25 in AP, we conducted research on clinical AP patients, USP25wild-type(WT)/USP25 knockout (USP25−/−) mice, and pancreatic acinar cells. Our results showed that serum USP25 concentration was higher in AP patients than in healthy controls and was positively correlated with disease severity. AP patients’ serum USP25 levels after treatment were significantly lower than that at the onset of AP. Moreover, USP25 expression was upregulated in cerulein-induced AP in mice, while USP25 deficiency attenuates AP and AP-related multiple organ injury. In vivo and in vitro studies showed that USP25 exacerbates AP by promoting the release of pro-inflammatory factors and destroying tight junctions of the pancreas. We showed that USP25 aggravates AP and AP-related multiple organ injury by activating the signal transducer and activator of transcription 3 (STAT3) pathway. Targeting the action of USP25 may present a potential therapeutic option for treating AP.

Proactive Management of Intraoperative Hypotension Reduces Biomarkers of Organ Injury and Oxidative Stress during Elective Non-Cardiac Surgery: A Pilot Randomized Controlled Trial

Background: Intraoperative hypotension is associated with increased postoperative morbidity and mortality. Methods: We randomly assigned patients undergoing major general surgery to early warning system (EWS) and hemodynamic algorithm (intervention group, n = 20) or standard care (n = 20). The primary outcome was the difference in hypotension (defined as mean arterial pressure < 65 mmHg) and as secondary outcome surrogate markers of organ injury and oxidative stress. Results: The median number of hypotensive episodes was lower in the intervention group (−5.0 (95% CI: −9.0, −0.5); p < 0.001), with lower time spent in hypotension (−12.8 min (95% CI: −38.0, −2.3 min); p = 0.048), correspondent to −4.8% of total surgery time (95% CI: −12.7, 0.01%; p = 0.048).The median time-weighted average of hypotension was 0.12 mmHg (0.35) in the intervention group and 0.37 mmHg (1.11) in the control group, with a median difference of −0.25 mmHg (95% CI: −0.85, −0.01; p = 0.025). Neutrophil Gelatinase-Associated Lipocalin (NGAL) correlated with time-weighted average of hypotension (R = 0.32; p = 0.038) and S100B with number of hypotensive episodes, absolute time of hypotension, relative time of hypotension and time-weighted average of hypotension (p < 0.001 for all). The intervention group showed lower Neuronal Specific Enolase (NSE) and higher reduced glutathione when compared to the control group. Conclusions: The use of an EWS coupled with a hemodynamic algorithm resulted in reduced intraoperative hypotension, reduced NSE and oxidative stress.

Inhibition of the JAK/STAT pathway with baricitinib reduces the multiple organ dysfunction caused by hemorrhagic shock in rats

Objective: The aim of this study was to investigate (a) the effects of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway inhibitor (baricitinib) on the multiple organ dysfunction syndrome (MODS) in a rat model of hemorrhagic shock (HS) and (b) whether treatment with baricitinib attenuates the activation of JAK/STAT, NF-κB and NLRP3 caused by HS. Background: Post-traumatic MODS, which is in part due to excessive systemic inflammation, is associated with high morbidity and mortality. The JAK/STAT pathway is a regulator of numerous growth factor and cytokine receptors and, hence, is considered a potential master regulator of many inflammatory signaling processes. However, its role in trauma-hemorrhage is unknown. Methods: An acute HS rat model was performed to determine the effect of baricitinib on MODS. The activation of JAK/STAT, NF-κB and NLRP3 pathways were analyzed by western blotting in the kidney and liver. Results: We demonstrate here for the first time that treatment with baricitinib (during resuscitation following severe hemorrhage) attenuates the organ injury and dysfunction and the activation of JAK/STAT, NF-κB and NLRP3 pathways caused by HS in the rat. Conclusions: Our results point to a role of the JAK/STAT pathway in the pathophysiology of the organ injury and dysfunction caused by trauma/hemorrhage and indicate that JAK inhibitors, such as baricitinib, may be repurposed for the treatment of the MODS after trauma and/or hemorrhage.

Hemoperitoneum Due to Penetrating Intercostal Artery Injury: A Case Report of a Rare and Still Understudied Entity

Intercostal artery injury may be life-threatening and usually presents as hemothorax. We report a unique case of penetrating injury, causing hemoperitoneum due to intercostal artery injury, without thoracic involvement. During urgent laparotomy, no intra-abdominal organ injury was found. Hemostasis was successfully achieved via suturing through an additional lateral 10cm incision through the left thorax.

Left atrial Appendage Rupture Following Intraoperative Hypertensive Crisis

The acute and severe rise in systemic blood pressure during or after cardiac operations may be life-threatening and result in end-organ injury. This case is the first report of spontaneous left atrial appendage rupture following the hypertensive crisis in cardiac surgery

Intravital microscopic observation of the microvasculature during hemodialysis in healthy rats

Hemodialysis (HD) provides life-saving treatment for kidney failure. Patient mortality is extremely high, with cardiovascular disease (CVD) being the leading cause of death. This results from both a high underlying burden of cardiovascular disease, as well as additional physiological stress from the HD procedure itself. Clinical observations indicate that HD is associated with microvascular dysfunction (MD), underlining the need for a fundamental pathophysiological assessment of the microcirculatory consequences of HD. We therefore successfully developed an experimental small animal model, that allows for a simultaneous real-time assessment of the microvasculature. Using in-house built ultra-low surface area dialyzers and miniaturized extracorporeal circuit, we successfully dialyzed male Wistar Kyoto rats and combined this with a simultaneous intravital microscopic observation of the EDL microvasculature. Our results show that even in healthy animals, a euvolemic HD procedure can induce a significant systemic hemodynamic disturbance and induce disruption of microvascular perfusion (as evidence by a reduction in the proportion of the observed microcirculation receiving blood flow). This study, using a new small animal hemodialysis model, has allowed direct demonstration that microvascular blood flow in tissue in skeletal muscle is acutely reduced during HD, potentially in concert with other microvascular beds. It shows that preclinical small animal models can be used to further investigate HD-induced ischemic organ injury and allow rapid throughput of putative interventions directed at reducing HD-induced multi-organ ischemic injury.

Nutritional Status Disorders and Selected Risk Factors of Ventilator-Associated Pneumonia (VAP) in Patients Treated in the Intensive Care Ward—A Retrospective Study

Introduction: The development of pneumonia in patients treated in intensive care wards is influenced by numerous factors resulting from the primary health condition and co-morbidities. The aim of this study is the determination of the correlation between nutritional status disorders and selected risk factors (type of injury, epidemiological factors, mortality risk, inflammation parameters, age, and gender) and the time of pneumonia occurrence in patients mechanically ventilated in intensive care wards. Material and method: The study included 121 patients with injuries treated in the intensive care ward who had been diagnosed with pneumonia related to mechanical ventilation. The data were collected using the method of retrospective analysis of patients’ medical records available in the electronic system. Results: Ventilator-associated pneumonia (VAP) occurred more frequently in patients over 61 years of age (40.4%), men (67.8%), after multiple-organ injury (45.5%), and those with a lower albumin level (86%), higher CRP values (83.5%), and leukocytes (68.6%). The risk of under-nutrition assessed with the NRS-2002 system was confirmed in the whole study group. The statistical analysis demonstrated a correlation between the leukocytes level (p = 0.012) and epidemiological factors (p = 0.035) and the VAP contraction time. Patients infected with Staphylococcus aureus had 4% of odds for the development of late VAP in comparison to Acinetobacter baumannii (p < 0.001), whereas patients infected by any other bacteria or fungi had about four times lower odds of the development of late VAP in comparison to Acinetobacter baumannii (p = 0.02). Patients with results in APACHE from 20 to 24 and from 25 to 29 had 13% and 21%, respectively, odds of the development of late VAP in comparison to patients with APACHE II scores ranging from 10 to 19 (respectively, p = 0.006; p = 0.028). Conclusions: The development of VAP is impacted by many factors, the monitoring of which has to be included in prophylactics and treatment.