Boldine Attenuates Synaptic Failure and Mitochondrial Deregulation in Cellular Models of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common cause of senile dementia worldwide, characterized by both cognitive and behavioral deficits. Amyloid beta peptide (Aß) oligomers (AßO) have been found to be responsible for several pathological mechanisms during the development of AD, including altered cellular homeostasis and synaptic function, inevitably leading to cell death. Such AßO deleterious effects provide a way for identifying new molecules with potential anti-AD properties. Available treatments minimally improve AD symptoms and do not extensively target intracellular pathways affected by AßO. Naturally-derived compounds have been proposed as potential modifiers of Aß-induced neurodysfunction and cytotoxicity based on their availability and chemical diversity. Thus, the aim of this study was to evaluate boldine, an alkaloid derived from the bark and leaves of the Chilean tree Peumus boldus, and its capacity to block some dysfunctional processes caused by AßO. We examined the protective effect of boldine (1-10 µM) in primary hippocampal neurons and HT22 hippocampal-derived cell line treated with AßO (24-48 h). We found that boldine interacts with Aß in silico affecting its aggregation and protecting hippocampal neurons from synaptic failure induced by AßO. Boldine also normalized changes in intracellular Ca2+ levels associated to mitochondria or endoplasmic reticulum in HT22 cells treated with AßO. In addition, boldine completely rescued the decrease in mitochondrial membrane potential (ΔΨm) and the increase in mitochondrial reactive oxygen species, and attenuated AßO-induced decrease in mitochondrial respiration in HT22 hippocampal cells. We conclude that boldine provides neuroprotection in AD models by both direct interactions with Aß and by preventing oxidative stress and mitochondrial dysfunction. Additional studies are required to evaluate the effect of boldine on cognitive and behavioral deficits induced by Aß in vivo.

Publicly funded interfacility ambulance transfers for surgical and obstetrical conditions: A cross sectional analysis in an urban middle-income country setting.

INTRODUCTION: Interfacility transfers may reflect a time delay of definitive surgical care, but few studies have examined the prevalence of interfacility transfers in the urban low- and middle-income (LMIC) setting. The aim of this study was to determine the number of interfacility transfers required for surgical and obstetric conditions in an urban MIC setting to better understand access to definitive surgical care among LMIC patients. METHODS: A retrospective analysis of public interfacility transfer records was conducted from April 2015 to April 2016 in Cali, Colombia. Data were obtained from the single municipal ambulance agency providing publicly funded ambulance transfers in the city. Interfacility transfers were defined as any patient transfer between two healthcare facilities. We identified the number of transfers for patients with surgical conditions and categorized transfers based on patient ICD-9-CM codes. We compared surgical transfers from public vs. private healthcare facilities by condition type (surgical, obstetric, nonsurgical), transferring physician specialty, and transfer acuity (code blue, emergent, urgent and nonurgent) using logistic regression. RESULTS: 31,659 patient transports occurred over the 13-month study period. 22250 (70.2%) of all transfers were interfacility transfers and 7777 (35%) of transfers were for patients with surgical conditions with an additional 2,244 (10.3%) for obstetric conditions. 49% (8660/17675) of interfacility transfers from public hospitals were for surgical and obstetric conditions vs 32% (1466/4580) for private facilities (P<0.001). The most common surgical conditions requiring interfacility transfer were fractures (1,227, 5.4%), appendicitis (913, 4.1%), wounds (871, 3.9%), abdominal pain (818, 3.6%), trauma (652, 2.9%), and acute abdomen (271, 1.2%). CONCLUSION: Surgical and obstetric conditions account for nearly half of all urban interfacility ambulance transfers. The most common reasons for transfer are basic surgical conditions with public healthcare facilities transferring a greater proportion of patient with surgical conditions than private facilities. Timely access to an initial healthcare facility may not be a reliable surrogate of definitive surgical care given the substantial need for interfacility transfers.

Comparison of Epidemiology of the Injuries and Outcomes in Two First-Level Trauma Centers in Colombia Using the Pan-American Trauma Registry System.

INTRODUCTION: The aim of this study was to compare the epidemiology of traumatic injuries and mortality outcomes between two tertiary-care trauma centers in Colombia using data from Pan-American Trauma Registry (PATR). METHODS: January 1-December 31, 2012, data from the Hospital Universitario del Valle (HUV, public) and Fundacion Valle del Lili (FVL, private) in Cali, Colombia, were considered. Differences in demographic and clinical information were compared using descriptive statistics. Propensity score matching was used to match patients on age, gender, and ISS. Within matched cohorts, multivariable logistic regression models were used to assess for differences in in-hospital mortality, further adjusting for insurance type, employment, heart rate, presence of hypotension (SBP < 90), and GCS score. RESULTS: HUV (8539; 78% male) and FVL (10,456; 60% male) had a combined total of 18,995 trauma cases in 2012 with comparable mean ages of 29.7 years. There were significant differences in insurance status, injury severity, and mechanism of injury between patients at HUV and FLV. On risk-adjusted logistic regression analyses with propensity score matched cohorts, the odds of death in HUV was higher compared to patients presenting at FVL hospital (OR [95% CI]:4.93 [3.37-7.21], p < 0.001). CONCLUSION: The study established the utility of the PATR and revealed important trends in patient demographics, injury epidemiology, and mortality outcomes, which can be used to target trauma initiatives throughout the region. It underscores the profound importance that differences in case mix play in the risk of trauma-related mortality, further emphasizing the need to monitor and evaluate unique aspects of trauma in LMIC. LEVEL OF EVIDENCE: III.

Computed tomography in hemodynamically unstable severely injured blunt and penetrating trauma patients.

BACKGROUND: Dynamic and efficient resuscitation strategies are now being implemented in severely injured hemodynamically unstable (HU) patients as blood products become readily and more immediately available in the trauma room. Our ability to maintain aggressive resuscitation schemes in HU patients allows us to complete diagnostic imaging studies before rushing patients to the operating room (OR). As the criteria for performing computed tomography (CT) scans in HU patients continue to evolve, we decided to compare the outcomes of immediate CT versus direct admission to the OR and/or angio suite in a retrospective study at a government-designated regional Level I trauma center in Cali, Colombia. METHODS: During a 2-year period (2012-2013), blunt and penetrating trauma patients (≥ 15 years) with an Injury Severity Score (ISS) greater than 15 who met criteria of hemodynamic instability (systolic blood pressure [SBP] <100 mm Hg and/or heart rate >100 beats/min and/or ≥ 4 U of packed red blood cells transfused in the trauma bay) were included. Isolated head trauma and patients who experienced a prehospital cardiac arrest were excluded. The main study outcome was mortality. RESULTS: We reviewed 171 patients. CT scans were performed in 80 HU patients (47%) immediately upon arrival (CT group); the remaining 91 patients (53%) went directly to the OR (63 laparotomies, 20 thoracotomies) and/or 8 (9%) to the angio suite (OA group). Of the CT group, 43 (54%) were managed nonoperatively, 37 (46%) underwent surgery (15 laparotomies, 3 thoracotomies), and 2 (5%) underwent angiography (CT OA subgroup). None of the mortalities in the CT group occurred in the CT suite or during their intrahospital transfers. CONCLUSION: There was no difference in mortality between the CT and OA groups in HU patients. CT scan was attainable in 47% of HU patients and avoided surgery in 54% of the cases. Furthermore, CT scan was helpful in deciding definitive/specific surgical management in 46% scanned HU patients who necessitated surgery after CT. LEVEL OF EVIDENCE: Therapy/care management study, level IV.

Complex penetrating duodenal injuries: less is better.

BACKGROUND: The traditional management of complex penetrating duodenal trauma (PDT) has been the use of elaborate temporizing and complex procedures such as the pyloric exclusion and duodenal diverticulization. We sought to determine whether a simplified surgical approach to the management of complex PDT injuries improves clinical outcome. METHODS: A retrospective review of all consecutive PDT from 2003 to 2012 was conducted. Patients were divided into three groups according to a simplified surgical algorithm devised following the local experience at a regional Level I trauma center. Postoperative duodenal leaks were drained externally either via traditional anterior drainage or via posterior "retroperitoneal laparostomy" as an alternate option. RESULTS: There were 44 consecutive patients with PDT, and 41 of them (93.2%) were from gunshot wounds. Seven patients were excluded owing to early intraoperative death secondary to associated devastating traumatic injuries. Of the remaining 36 patients, 7 (19.4%) were managed with single-stage primary duodenal repair with definitive abdominal wall fascial closure (PDR + NoDC group). Damage-control laparotomy was performed in 29 patients, (80.5%) in which primary repair was performed in 15 (51.7%) (PDR + DC group), and the duodenum was over sewn and left in discontinuity in 14 (48.3%). Duodenal reconstruction was performed after primary repair in 2 of 15 cases and after left in discontinuity in 13 of 14 cases (DR + DC group). The most common complication was the development of a duodenal fistula in 12 (33%) of 36 cases. These leaks were managed by traditional anterior drainage in 9 (75%) of 12 cases and posterior drainage by retroperitoneal laparostomy in 3 (25%) of 12 cases. The duodenal fistula closed spontaneously in 7 (58.3%) of 12 cases. The duodenum-related mortality rate was 2.8%, and the overall mortality rate was 11.1%. CONCLUSION: An application of basic damage-control techniques for PDT leads to improved survival and an acceptable incidence of complications. LEVEL OF EVIDENCE: Therapeutic study, level IV.

A comprehensive five-step surgical management approach to penetrating liver injuries that require complex repair.

BACKGROUND: The objective of this study was to describe a comprehensive five-step surgical management approach for patients with penetrating liver trauma based on our collective institutional experience. METHODS: A prospective consecutive study of all penetrating liver traumas from January 2003 to December 2011 at a regional Level I trauma center in Cali, Colombia, was conducted. RESULTS: A total of 538 patients with penetrating thoracoabdominal trauma were operated on at our institution. Of these, 146 had penetrating liver injuries that satisfied the inclusion criteria for surgical intervention to manage their hepatic and/or associated injuries. Eighty-eight patients (60%) had an American Association for the Surgery of Trauma-Organ Injury Scale (AAST-OIS) of Grade III (54 patients, 37%), Grade IV (24 patients, 16%), and Grade V (10 patients, 7%). This group of patients required advanced "complex" techniques of hemostasis such as the Pringle maneuver (PM), perihepatic liver packing (PHLP), and/or hepatotomy with selective vessel ligation (SVL). The focus of our study was this subgroup of patients, which we further divided into two as follows: those who required only PM + PHLP (55 patients, 63%) to obtain control of their liver hemorrhage and those who required PM + PHLP + SVL (33 patients, 37%). Of the patients who required PM + PHLP + SVL, 10 (27%) required ligation of major intrahepatic branches, which included suprahepatic veins (n = 4), portal vein (n = 4), retrohepatic vena cava (n = 1), and hepatic artery (n = 1). The remaining 23 patients (73%) required direct vessel ligation of smaller intraparenchymal vessels. The overall mortality was 15.9% (14 of 88), with 71.4% (10 of 14) related to coagulopathy. Mortality rates for Grade III was 3.7% (2 of 54), for Grade IV was 20.8% (5 of 24), and for Grade V was 70% (7 of 10). The mortality in the PM + PHLP + SVL group was higher compared with the PM + PHLP group (12 [36.4%] vs. 2 [3.6%], p = 0.001]. CONCLUSION: For those patients who fail to respond to PM + PHLP and/or those who have AAST-OIS penetrating liver injuries, Grades IV and V would benefit from immediate intraparenchymal exploration and SVL.

Safety of performing a delayed anastomosis during damage control laparotomy in patients with destructive colon injuries.

BACKGROUND: Recent studies report the safety and feasibility of performing delayed anastomosis (DA) in patients undergoing damage control laparotomy (DCL) for destructive colon injuries (DCIs). Despite accumulating experience in both civilian and military trauma, questions regarding how to best identify high-risk patients and minimize the number of anastomosis-associated complications remain. Our current practice is to perform a definitive closure of the colon during DCL, unless there is persistent acidosis, bowel wall edema, or evidence of intra-abdominal abscess. In this study, we evaluated the safety of this approach by comparing outcomes of patients with DCI who underwent definitive closure of the colon during DCL versus patients managed with colostomy with or without DCL. METHODS: We performed a retrospective chart review of patients with penetrating DCI during 2003 to 2009. Severity of injury, surgical management, and clinical outcome were assessed. RESULTS: Sixty patients with severe gunshot wounds and three patients with stab wounds were included in the analysis. DCL was required in 30 patients, all with gunshot wounds. Three patients died within the first 48 hours, three underwent colostomy, and 24 were managed with DA. Thirty-three patients were managed with standard laparotomy: 26 patients with primary anastomosis and 7 with colostomy. Overall mortality rate was 9.5%. Three late deaths occurred in the DCL group, and only one death was associated with an anastomotic leak. CONCLUSIONS: Performing a DA in DCI during DCL is a reliable and feasible approach as long as severe acidosis, bowel wall edema, and/or persistent intra-abdominal infections are not present.