Stimulation of Wnt/beta-catenin signaling pathway with Wnt agonist reduces organ injury after hemorrhagic shock

BACKGROUND: Hemorrhagic shock is a leading cause of morbidity and mortality in surgery and trauma patients. Despite a large number of preclinical trials conducted to develop therapeutic strategies against hemorrhagic shock, there is still an unmet need for effective therapy for hemorrhage patients. Wnt/beta-catenin signaling controls developmental processes and cellular regeneration owing to its central role in cell survival and proliferation. We therefore hypothesized that the activation of Wnt signaling reduces systemic injury caused by hemorrhagic shock. METHODS: Adult male Sprague-Dawley rats underwent hemorrhagic shock by controlled bleeding of the femoral artery to maintain a mean arterial pressure of 30 mm Hg for 90 minutes, followed by resuscitation with crystalloid equal to two times the shed blood volume. After resuscitation, animals were infused with Wnt agonist (5 mg/kg) or vehicle (20% dimethyl sulfoxide in saline). Blood and tissue samples were collected 6 hours after resuscitation for analysis. RESULTS: Hemorrhagic shock increased serum levels of aspartate aminotransferase, lactate, and lactate dehydrogenase. Treatment with Wnt agonist significantly reduced these levels by 40%, 36%, and 77%, respectively. Wnt agonist also decreased blood urea nitrogen and creatinine by 34% and 56%, respectively. The treatment reduced lung myeloperoxidase activity and interleukin 6 messenger RNA by 55% and 68%, respectively, and significantly improved lung histology. Wnt agonist treatment increased Bcl-2 protein to sham values and decreased cleaved caspase 3 by 46%, indicating attenuation of hemorrhage-induced apoptosis in the lungs. Hemorrhage resulted in significant reductions of A-catenin protein levels in the lungs as well as down-regulation of a Wnt target gene, cyclin D1, while Wnt agonist treatment preserved these levels. CONCLUSION: The administration of Wnt agonist attenuated hemorrhage-induced organ injury, inflammation, and apoptosis. This was correlated with the preservation of the Wnt signaling pathway. Thus, Wnt/beta-catenin activation could be protective in hemorrhagic shock. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved

Competence acquisition for single-incision laparoscopic cholecystectomy

BACKGROUND AND OBJECTIVES: Within the past few years, there has been a push for an even more minimally invasive approach to biliary disease with the adoption of single-incision laparoscopic cholecystectomy. We sought to compare 4 individual surgeon experiences to define whether there exists a learning curve for performing single-incision laparoscopic cholecystectomy. METHODS: We performed a retrospective review 290 single-incision laparoscopic cholecystectomies performed by a group of general surgeons, with varying levels of experience and training, at 3 institutions between May 2008 and September 2010. The procedure times were recorded for each single-incision laparoscopic cholecystectomy, ordered chronologically for each surgeon, and subsequently plotted on a graph. The patients were also combined into cohorts of 5 and 10 cases to further evaluate for signs of improvement in operative efficiency. RESULTS: Of the 4 surgeons involved in the study, only 1 (surgeon 4, laparoscopic fellowship trained with \u3c5 \u3eyears\u27 experience) confirmed the presence of a learning curve, reaching proficiency within the first 15 cases performed. The other surgeons had more variable procedure times, which did not show a distinct trend. When we evaluated the cases by cohorts of 5 cases, surgeon 4 had a significant difference between the first and last cohort. Increased body mass index resulted in a slightly longer operative time (P \u3c .0063). The conversion rate to multiport laparoscopic surgery was 3.1%. CONCLUSIONS: Our results indicate that among experienced general surgeons, there does not seem to be a significant learning curve when transitioning from conventional laparoscopic cholecystectomy to single-incision laparoscopic cholecystectomy. The least experienced surgeon in the group, surgeon 4, appeared to reach proficiency after 15 cases. Greater than 5 years of experience in laparoscopic surgery appears to provide surgeons with a sufficient skill set to obviate the need for a single-incision laparoscopic cholecystectomy learning curve

Growth arrest-specific protein 6 protects against renal ischemia-reperfusion injury

BACKGROUND: Renal injury caused by ischemia-reperfusion (I/R) often occurs after shock or transplantation. Growth arrest-specific protein 6 (Gas6) is a secreted protein that binds to the TAM-Tyro3, Axl, Mer-family tyrosine kinase receptors, which modulate the inflammatory response and activate cell survival pathways. We hypothesized that Gas6 could have a protective role in attenuating the severity of renal injury after I/R. MATERIALS AND METHODS: Adult mice were subjected to 45 min of bilateral renal ischemia. Recombinant mouse Gas6 (rmGas6, 5 mug per mouse) or normal saline (vehicle) was administered intraperitoneally 1 h before ischemia and all subjects were sacrificed at 23 h after I/R for blood and tissue analysis. The expression of protein and messenger RNA (mRNA) was assessed by Western blotting and quantitative polymerase chain reaction, respectively. RESULTS: Treatment with rmGas6 significantly decreased serum levels of creatinine and blood urea nitrogen by 29% and 27%, respectively, improved the renal histologic injury index, and reduced the apoptosis in the kidneys, compared with the vehicle. Renal mRNA levels of interleukin 1beta, interleukin 6, tumor necrosis factor alpha, keratinocyte-derived chemokine and macrophage inflammatory protein 2 were decreased significantly by 99%, 60%, 53%, 58%, and 43%, with rmGas6 treatment, respectively. After I/R, renal I-kappa-B alpha levels were reduced by 40%, whereas they returned to sham levels with rmGas6 treatment. The mRNA levels of inducible nitric oxide synthase and cyclooxygenase 2 were reduced by 79% and 70%, respectively, whereas the expression of cyclin D1 was increased by 2.1-fold in the rmGas6-treated group, compared with the vehicle. CONCLUSIONS: Gas6 suppresses the nuclear factor kappaB pathway and promotes cell proliferation, leading to the reduction of inflammation and protection of renal injury induced by I/R

A comparison of regional and general anesthesia in patients undergoing carotid endarterectomy

AbstractPurpose: The optimal anesthetic for use during carotid endarterectomy is controversial. Advocates of regional anesthesia suggest that it may reduce the incidence of perioperative complications in addition to decreasing operative time and hospital costs. To determine whether the anesthetic method correlated with the outcome of the operation, a retrospective review of 3975 carotid operations performed over a 32-year period was performed.Methods: The records of all patients who underwent carotid endarterectomy at our institution from 1962 to 1994 were retrospectively reviewed. Operations performed with the patient under regional anesthesia were compared with those performed with the patient under general anesthesia with respect to preoperative risk factors and perioperative complications.Results: Regional anesthesia was used in 3382 operations (85.1%). There were no significant differences in the age, gender ratio, or the rates of concomitant medical illnesses between the two patient populations. The frequency of perioperative stroke in the series was 2.2%; that of myocardial infarction, 1.7%; and that of perioperative death, 1.5%. There were no statistically significant differences in the frequency of perioperative stroke, myocardial infarction, or death on the basis of anesthetic technique. A trend toward higher frequencies of perioperative stroke (3.2% vs 2.0%) and perioperative death (2.0% vs 1.4%) in the general anesthesia group was noted. In examining operative indications, however, there was a significant increase in the percentage of patients receiving general anesthesia who had sustained preoperative strokes when compared with the regional anesthesia patients (36.1% vs 26.4%; p < 0.01). There was also a statistically significant higher frequency of contralateral total occlusion in the general anesthesia group (21.8% vs 15.4%; p = 0.001). The trend toward increased perioperative strokes in the general anesthesia group may be explicable either by the above differences in the patient populations or by actual differences based on anesthetic technique that favor regional anesthesia.Conclusions: In a retrospective review of a large series of carotid operations, regional anesthesia was shown to be applicable to the vast majority of patients with good clinical outcome. Although the advantages over general anesthesia are perhaps small, the versatility and safety of the technique is sufficient reason for vascular surgeons to include it in their armamentarium of surgical skills. Considering that carotid endarterectomy is a procedure in which complication rates are exceedingly low, a rigidly controlled, prospective randomized trial may be required to accurately assess these differences. (J Vasc Surg 1996;24;946-56.

Acute Arterial Thromboembolism in Patients with COVID-19 in the New York City Area

© 2020 Elsevier Inc. Background: Coronavirus disease 2019 (COVID-19) predisposes to arterial and venous thromboembolic complications. We describe the clinical presentation, management, and outcomes of acute arterial ischemia and concomitant infection at the epicenter of cases in the United States. Methods: Patients with confirmed COVID-19 infection between March 1, 2020 and May 15, 2020 with an acute arterial thromboembolic event were reviewed. Data collected included demographics, anatomical location of the thromboembolism, treatments, and outcomes. Results: Over the 11-week period, the Northwell Health System cared for 12,630 hospitalized patients with COVID-19. A total of 49 patients with arterial thromboembolism and confirmed COVID-19 were identified. The median age was 67 years (58–75) and 37 (76%) were men. The most common preexisting conditions were hypertension (53%) and diabetes (35%). The median D-dimer level was 2,673 ng/mL (723–7,139). The distribution of thromboembolic events included upper 7 (14%) and lower 35 (71%) extremity ischemia, bowel ischemia 2 (4%), and cerebral ischemia 5 (10%). Six patients (12%) had thrombus in multiple locations. Concomitant deep vein thrombosis was found in 8 patients (16%). Twenty-two (45%) patients presented with signs of acute arterial ischemia and were subsequently diagnosed with COVID-19. The remaining 27 (55%) developed ischemia during hospitalization. Revascularization was performed in 13 (27%) patients, primary amputation in 5 (10%), administration of systemic tissue‐ plasminogen activator in 3 (6%), and 28 (57%) were treated with systemic anticoagulation only. The rate of limb loss was 18%. Twenty-one patients (46%) died in the hospital. Twenty-five (51%) were successfully discharged, and 3 patients are still in the hospital. Conclusions: While the mechanism of thromboembolic events in patients with COVID-19 remains unclear, the occurrence of such complication is associated with acute arterial ischemia which results in a high limb loss and mortality

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic