Decreased Emergency Cholecystectomy and Case Fatality Rate, Not Explained by Expansion of Medicaid.

INTRODUCTION: Population data on longitudinal trends for cholecystectomies and their outcomes are scarce. We evaluated the incidence and case fatality rate of emergency and ambulatory cholecystectomies in New Jersey (NJ) and whether the Medicaid expansion changed trends. MATERIALS AND METHODS: A retrospective population cohort design was used to study the incidence of cholecystectomies and their case fatality rate from 2009 to 2018. Using linear and logistic regression we explored the trends of incidence and the odds of case fatality after versus before the January 1, 2014 Medicaid expansion. RESULTS: Overall, 93,423 emergency cholecystectomies were performed, with 644 fatalities; 87,239 ambulatory cholecystectomies were performed, with fewer than 10 fatalities. The 2009 to 2018 annual incidence of emergency cholecystectomies dropped markedly from 114.8 to 77.5 per 100,000 NJ population (P < 0.0001); ambulatory cholecystectomies increased from 93.5 to 95.6 per 100,000 (P = 0.053). The incidence of emergency cholecystectomies dropped more after than before Medicaid expansion (P < 0.0001). The odds ratio for case fatality among those undergoing emergency cholecystectomies after versus before expansion was 0.85 (95% CI, 0.72-0.99). This decrease in case fatality, apparent only in those over age 65, was not explained by the addition of Medicaid. CONCLUSIONS: A marked decrease in the incidence of emergency cholecystectomies occurred after Medicaid expansion, which was not accounted for by a minimal increase in the incidence of ambulatory cholecystectomies. Case fatality from emergency cholecystectomy decreased over time due to factors other than Medicaid. Further work is needed to reconcile these findings with the previously reported lack of decrease in overall gallstone disease mortality in NJ.

Abstract computation in schizophrenia detection through artificial neural network based systems.

Schizophrenia stands for a long-lasting state of mental uncertainty that may bring to an end the relation among behavior, thought, and emotion; that is, it may lead to unreliable perception, not suitable actions and feelings, and a sense of mental fragmentation. Indeed, its diagnosis is done over a large period of time; continuos signs of the disturbance persist for at least 6 (six) months. Once detected, the psychiatrist diagnosis is made through the clinical interview and a series of psychic tests, addressed mainly to avoid the diagnosis of other mental states or diseases. Undeniably, the main problem with identifying schizophrenia is the difficulty to distinguish its symptoms from those associated to different untidiness or roles. Therefore, this work will focus on the development of a diagnostic support system, in terms of its knowledge representation and reasoning procedures, based on a blended of Logic Programming and Artificial Neural Networks approaches to computing, taking advantage of a novel approach to knowledge representation and reasoning, which aims to solve the problems associated in the handling (i.e., to stand for and reason) of defective information.

Necrotizing soft tissue infections.

Necrotising soft tissue infection (NSTI) presents unique challenges in diagnosis and management. The key to a successful outcome is a high index of suspicion in appropriate clinical settings. Type II NSTI tends to occur on an extremity in younger, healthier patients with a history of known trauma, and to be monomicrobial. Type I NSTI tends to occur on the trunk of older, less healthy patients without an obvious history of trauma, and tends to be polymicrobial. Other, rarer types exist as well. The pathophysiology of both types involves superantigen acticivty, as well as a number of microbial byproducts which collectively decrease the viscosity of pus, facilitating its spread along deep tissue planes and ultimately causing diffuse deep thrombosis and aggressive systemic sepsis. The most important physical finding is tenderness to palpation beyond the area of redness, and the lack of crepitus should not be seen as a reassuring sign. Suspected cases should undergo early surgical exploration for diagnosis, which may be performed at bedside through a small incision. Most imaging techniques are not sufficiently specific to warrant a delay in surgical exploration. The Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) shows promise as a tool for excluding suspected cases. Successful outcomes in cases of NSTI require early and aggressive serial debridement and a multidisciplinary critical care approach.

Enhancing the tissue donor pool through donation after death in the field.

INTRODUCTION: Tissue transplantation is an important adjunct to modern medical care and is used daily to save or improve patient lives. Tissue allografts include bone, tendon, corneas, heart valves and others. Increasing utilization may lead to tissue shortages, and tissue procurement organizations continue to explore ways to expand the cadaveric donor pool. Currently more than half of all deaths occur outside the acute care setting. HYPOTHESIS: Many who suffer prehospital deaths might be eligible for non-organ tissue donation. METHODS: A retrospective review of electronic prehospital medical records was conducted from May 1, 2008 through December 31, 2009. All prehospital deaths were included irrespective of cause. Once identified, additional medical history was obtained from prehospital, inpatient, and emergency department records. Age, medical history, and time of death were compared to exclusion criteria for four tissue procurement organizations (MTF, LifeNet, LifeCell, EyeBank). After analysis, percentages of eligible donors were calculated. RESULTS: Over 50,000 prehospital records were reviewed; 432 subjects died in the field and were eligible for analysis. Ages ranged from four to 103 years of age; the average was 68.3 (SD = 20.1) years. After exclusion for age, medical conditions, and time of death, 185 unique patients (42.8%) were eligible for donation to at least one of the four tissue procurement organizations (range 11.6%-34.3%). CONCLUSIONS: After prehospital death, many individuals may be eligible for tissue donation. These findings suggest that future prospective studies exploring tissue donation after prehospital death are indicated. These studies should aim to clarify eligibility criteria, create protocols and infrastructure, and explore the ethical implications of expanding tissue donation to include this population.

Ten-Year Trends of Persistent Mortality With Gallstone Disease: A Retrospective Cohort Study in New Jersey.

BACKGROUND AND AIMS: Recent trends in mortality with gallstone disease remain scarce in the United States. Yet multiple changes in clinical management, such as rates of endoscopy, cholecystectomy, and cholecystostomy, and insurance access at the state level, may have occurred. Thus, we evaluated recent secular trends of mortality with gallstone disease in New Jersey. METHODS: We performed a retrospective, cohort study of mortality from 2009 to 2018 using the National Center for Health Statistics, Restricted Mortality Files. The primary outcome was any death with an International Classifications of Disease, 10th Revision, Clinical Modification diagnosis code of gallstone disease in New Jersey. Simple linear regression was used to model trends of incidence of death. RESULTS: 1580 deaths with diagnosed gallstone disease (dGD) occurred from 2009 to 2018. The annual trend of incidence of death was flat over 10 years. The incidence of death with dGD relative to all death changed only from 0.21% to 0.20% over 10 years. These findings were consistent also in 18 of 20 subgroup combinations, although the trend of death with dGD in Latinos 65 years or older increased [slope estimate 0.93, 95% confidence limit 0.42-1.43, P = .003]. CONCLUSION: The rate of death with dGD showed little change over the recent 10 years in New Jersey. This needs to be reproduced in other states and nationally. A closer examination of the changes in clinical care and insurance access is needed to help understand why they did not result in a positive change in this avoidable cause of death.

Use of a New Prevention Model in Acute Care Surgery: A Population Approach to Preventing Emergency Surgical Morbidity and Mortality.

Whether patients undergo the more morbid and costly emergent rather than an elective type of surgery, may depend on many factors. Since tertiary prevention (preventing poor outcomes from emergency surgery) carries a much higher mortality than secondary prevention (preventing emergency surgery) or primary prevention (preventing the disease requiring surgery), the overall United States mortality might be reduced significantly, if emergency surgery could be avoided via high-quality primary prevention and non-surgical therapy or increasing elective surgery at the expense of emergency procedures, e.g., secondary prevention. The practice and study of acute care surgery then has the potential to broaden from a focus on the patient in the hospital emergency and operating rooms to the patient who no longer requires either, whose disease is treated or prevented in his/her/their community.

Proteinuria in early referral to spectral domain optical coherence tomography for macular edema detection in type 2 diabetes individuals: results from the Brazilian diabetes study.

BACKGROUND: Measurement of retinal thickness by optical coherence tomography (OCT) shows higher diagnostic accuracy for diabetic macular edema (DME) than fundus photography alone. The expanding gap between the rising number of type 2 diabetes (T2D) individuals and the availability of OCT devices demands a targeted selection of individuals at higher risk of DME who would benefit the most from early referral. We sought to appraise if proteinuria should be considered in a targeted referral of T2D individuals to OCT examination. METHODS: This study was a cross-sectional analysis of 576 consecutive patients enrolled in the Brazilian Diabetes Study between June/2016 and December/2021 who underwent OCT exam and urinalysis to assess ME and proteinuria status, respectively. Differences in the prevalence of DME between proteinuria groups and across a range of diabetic retinopathy (DR) stages were evaluated. RESULTS: Among 1134 eyes included in this analysis, the prevalence of proteinuria was 22% and 18.2% of eyes had DME. Proteinuria was related to an increased prevalence of DME (13.2% vs 38.7% for control vs proteinuria, respectively; p < .001), with an OR of 4.08 [95% confidence interval (CI): 2.50-6.64, p < .001), after adjustment for covariates. Proteinuria was independently related to DME also among eyes with non-apparent DR [OR: 2.82; 95%CI: 1.34-5.93; p = .003] and non-proliferative DR (OR of 5.94, 95%CI 2.13-16.62, p < .001). Fundus photography spotted only half of the DME cases detected by OCT. CONCLUSION: In T2D individuals, early referral to OCT examination should be pursued for all individuals with concurrent proteinuria. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04949152.

A longitudinal surgical systems strengthening research program for medical students: the exploration of a model for global health education.

BACKGROUND: In response to the staggering global burden of conditions requiring emergency and essential surgery, the development of international surgical system strengthening (SSS) is fundamental to achieving universal, timely, quality, and affordable surgical care. Opportunity exists in identifying optimal collaborative processes that both promote global surgery research and SSS, and include medical students. This study explores an education model to engage students in academic global surgery and SSS via institutional support for longitudinal research. OBJECTIVES: We set out to design a program to align global health education and longitudinal health systems research by creating an education model to engage medical students in academic global surgery and SSS. PROGRAM DESIGN AND IMPLEMENTATION: In 2015, medical schools in the United States and Colombia initiated a collaborative partnership for academic global surgery research and SSS. This included development of two longitudinal academic tracks in global health medical education and academic global surgery, which we differentiated by level of institutional resourcing. Herein is a retrospective evaluation of the first two years of this program by using commonly recognized academic output metrics. MAIN ACHIEVEMENTS: In the first two years of the program, there were 76 total applicants to the two longitudinal tracks. Six of the 16 (37.5%) accepted students selected global surgery faculty as mentors (Acute Care Surgery faculty participating in SSS with Colombia). These global surgery students subsequently spent 24 total working weeks abroad over the two-year period participating in culminating research experiences in SSS. As a quantitative measure of the program's success, the students collectively produced a total of twenty scholarly pieces in the form of accepted posters, abstracts, podium presentations, and manuscripts in partnership with Colombian research mentors. POLICY IMPLICATIONS: The establishment of scholarly global health education and research tracks has afforded our medical students an active role in international SSS through participation in academic global surgery research. We propose that these complementary programs can serve as a model for disseminated education and training of the future global systems-aware surgeon workforce with bidirectional growth in south and north regions with traditionally under-resourced SSS training programs.

DNA Barcoding of Mosquitoes from the Pantanos de Centla Biosphere Reserve, Southeastern Mexico.

Accurate identification of mosquito species is essential to support programs that involve the study of distribution and mosquito control. Numerous mosquito species are difficult to identify based only on morphological characteristics, due to the morphological similarities in different life stages and large numbers of some species that are members of morphologically similar species complexes. In the present study, the mosquitoes collected in the Pantanos de Centla Biosphere Reserve, southeastern Mexico, were evaluated using a combination of morphological and molecular approaches (mitochondrial cytochrome c oxidase subunit I [COI] DNA barcode). A total of 1,576 specimens of 10 genera and 35 species, mostly adult stages, were collected. A total of 225 COI DNA barcode sequences were analyzed; most species formed well-supported groups in the neighbor joining, maximum likelihood, and Bayesian inference trees. The intraspecific Kimura 2-parameter (K2P) genetic distance averaged 1.52%. An intraspecific K2P distance of 6.20% was observed in Anopheles crucians s.l., while a deep split was identified in Culex erraticus and Cx. conspirator. This study showed that COI DNA barcodes offer a reliable approach to support mosquito species identification in Mexico.

General Microbiota of the Soft Tick Ornithodoros turicata Parasitizing the Bolson Tortoise (Gopherus flavomarginatus) in the Mapimi Biosphere Reserve, Mexico.

The general bacterial microbiota of the soft tick Ornithodoros turicata found on Bolson tortoises (Gopherus flavomarginatus) were analyzed using next generation sequencing. The main aims of the study were to establish the relative abundance of bacterial taxa in the tick, and to document the presence of potentially pathogenic species for this tortoise, other animals, and humans. The study was carried-out in the Mapimi Biosphere Reserve in the northern-arid part of Mexico. Bolson tortoises (n = 45) were inspected for the presence of soft ticks, from which 11 tortoises (24.4%) had ticks in low loads (1-3 ticks per individual). Tick pools (five adult ticks each) were analyzed through 16S rRNA V3-V4 region amplification in a MiSeq Illumina, using EzBioCloud as a taxonomical reference. The operational taxonomic units (OTUs) revealed 28 phyla, 84 classes, 165 orders, 342 families, 1013 genera, and 1326 species. The high number of taxa registered for O. turicata may be the result of the variety of hosts that this tick parasitizes as they live inside G. flavomarginatus burrows. While the most abundant phyla were Proteobacteria, Actinobacteria, and Firmicutes, the most abundant species were two endosymbionts of ticks (Midichloria-like and Coxiella-like). Two bacteria documented as pathogenic to Gopherus spp. were registered (Mycoplasma spp. and Pasteurella testudinis). The bovine and ovine tick-borne pathogens A. marginale and A. ovis, respectively, were recorded, as well as the zoonotic bacteria A. phagocytophilum,Coxiella burnetii, and Neoehrlichia sp. Tortoises parasitized with O. turicata did not show evident signs of disease, which could indicate a possible ecological role as a reservoir that has yet to be demonstrated. In fact, the defense mechanisms of this tortoise against the microorganisms transmitted by ticks during their feeding process are still unknown. Future studies on soft ticks should expand our knowledge about what components of the microbiota are notable across multiple host-microbe dynamics. Likewise, studies are required to better understand the host competence of this tortoise, considered the largest terrestrial reptile in North America distributed throughout the Chihuahuan Desert since the late Pleistocene.

An Integrated Molecular Approach to Untangling Host-Vector-Pathogen Interactions in Mosquitoes (Diptera: Culicidae) From Sylvan Communities in Mexico.

There are ~240 species of Culicidae in Mexico, of which some are vectors of arthropod-borne viruses such as Zika virus, dengue virus, chikungunya virus, and West Nile virus. Thus, the identification of mosquito feeding preferences is paramount to understanding of vector-host-pathogen interactions that, in turn, can aid the control of disease outbreaks. Typically, DNA and RNA are extracted separately for animal (insects and blood meal hosts) and viral identification, but this study demonstrates that multiple organisms can be analyzed from a single RNA extract. For the first time, residual DNA present in standard RNA extracts was analyzed by DNA barcoding in concert with Sanger and next-generation sequencing (NGS) to identify both the mosquito species and the source of their meals in blood-fed females caught in seven sylvan communities in Chiapas State, Mexico. While mosquito molecular identification involved standard barcoding methods, the sensitivity of blood meal identification was maximized by employing short primers with NGS. In total, we collected 1,634 specimens belonging to 14 genera, 25 subgenera, and 61 morphospecies of mosquitoes. Of these, four species were new records for Mexico (Aedes guatemala, Ae. insolitus, Limatus asulleptus, Trichoprosopon pallidiventer), and nine were new records for Chiapas State. DNA barcode sequences for >300 bp of the COI gene were obtained from 291 specimens, whereas 130 bp sequences were recovered from another 179 specimens. High intraspecific divergence values (>2%) suggesting cryptic species complexes were observed in nine taxa: Anopheles eiseni (5.39%), An. pseudopunctipennis (2.79%), Ae. podographicus (4.05%), Culex eastor (4.88%), Cx. erraticus (2.28%), Toxorhynchites haemorrhoidalis (4.30%), Tr. pallidiventer (4.95%), Wyeomyia adelpha/Wy. guatemala (7.30%), and Wy. pseudopecten (4.04%). The study increased the number of mosquito species known from 128 species to 138 species for Chiapas State, and 239 for Mexico as a whole. Blood meal analysis showed that Aedes angustivittatus fed on ducks and chicken, whereas Psorophora albipes fed on humans. Culex quinquefasciatus fed on diverse hosts including chicken, human, turkey, and Mexican grackle. No arbovirus RNA was detected by reverse transcriptase-polymerase chain reaction in the surveyed specimens. This study demonstrated, for the first time, that residual DNA present in RNA blood meal extracts can be used to identify host vectors, highlighting the important role of molecular approaches in both vector identification and revealing host-vector-pathogen interactions.

Detection of Rickettsia spp. in Rhipicephalus sanguineus (sensu lato) collected from free-roaming dogs in Coahuila state, northern Mexico.

BACKGROUND: The aim of this study was to detect and molecularly identify Rickettsia spp. in Rhipicephalus sanguineus (sensu lato) collected from free-roaming dogs in 30 communities from five municipalities in the south of Coahuila State, northern Mexico, where Rocky Mountain spotted fever is endemic. METHODS: In total, 60 dogs from each municipality were examined for engorged ticks. DNA was isolated from tick pools and conventional PCR assays targeting the 23S-5S ribosomal RNA intergenic spacer and outer membrane protein (ompA) gene of Rickettsia spp. were performed. RESULTS: All ticks (n = 1238) were morphologically identified as R. sanguineus (s.l.). Six pools (each with six engorged females) from four municipalities were positive to Rickettsia spp. DNA sequencing and phylogenetic analyses confirmed the presence of R. rickettsii and R. rhipicephali in R. sanguineus (s.l.) in these ticks. CONCLUSIONS: This study confirms the presence of R. rickettsii and R. rhipicephali in R. sanguineus (s.l.) from stray dogs in the south of Coahuila. This suggests that stray dogs may play a role in the inter-municipal dissemination of infected ticks in this region. Further research is required to assess whether ticks from stray dogs could serve as good indicators for the molecular xenomonitoring of R. rickettsii in this region. Considering that R. sanguineus (s.l.) is a proven vector of R. rickettsii in Mexico, increased awareness regarding permanent tick control in dogs is warranted.

The mosquitoes (Diptera: Culicidae) of Tabasco, Mexico.

To document and update the mosquito species of Tabasco, Mexico, field collection trips were conducted in the two physiographic regions of Tabasco: the coastal plain of the southern gulf and the mountains of Chiapas and Guatemala. Mosquitoes were collected as immature and adult stages during the dry and rainy seasons from 2014 through 2015. Additionally, the Reference Collection of Arthropods of Medical Importance (CAIM-InDRE) containing mosquitoes of Tabasco was re-examined. In total, 4,913 specimens were collected and examined, which are divided into seven tribes, 18 genera, 27 subgenera, and 104 species. Of these, one genus (Shannoniana Lane and Cerqueira), two subgenera (Georgecraigius Reinert, Harbach and Kitching, and Carrollia Lutz), and 21 species are new records for the mosquito fauna of Tabasco. Culex metempsytus Dyar is a new record for Mexico and Wyeomyia jocosa (Dyar and Knab) is removed from the Mexican mosquito fauna. Seventeen species historically reported were not found in the field collections conducted here. Taxonomic notes, new distribution limits, and comments about the medical importance of species of mosquitoes of Tabasco are discussed. Tabasco is the second state in Mexico with the largest mosquito richness (104 species), followed by Veracruz with 139 species.

Comparison of two DNA extraction methods from larvae, pupae, and adults of Aedes aegypti.

Mosquitoes are the most important arthropods from the point of view of public health, due to the fact that they can transmit a large number of pathogens which can cause diseases to humans and animals. Aedes aegypti (L.) is one of the most important vector species in the world, since it can transmit numerous pathogens such as dengue, Zika, and chikungunya. Therefore, studies involving the molecular aspects of this and other mosquitoes species are currently increasing. In this report, we describe the comparison between two DNA extraction techniques, Chelex and cetyltrimethylammonium bromide (CTAB), for carrying out DNA extraction in larvae, pupae and adult female of Ae. aegypti. The Chelex technique was superior in the amount and purity of DNA as compared to the CTAB technique in the three life stages we tested.

Assessment of dapagliflozin effect on diabetic endothelial dysfunction of brachial artery (ADDENDA-BHS2 trial): rationale, design, and baseline characteristics of a randomized controlled trial.

BACKGROUND: Endothelial dysfunction (ED) is a hallmark in type 2 diabetes mellitus (T2DM) that favor both atherogenesis and ischemia and reperfusion injury (IRI). Sodium-glucose-2 co-transporter inhibitors (SGLT2i) may hypothetically improve microvascular and macrovascular functions via a broad spectrum of mechanisms, being superior to traditional antidiabetic therapy such as sulfonylurea, even in subjects under equivalent glycemic control. Hence, the present clinical trial was designed to compare the effect of these two treatments on markers of arterial wall function and inflammation in T2DM patients as well as on the potential mediating parameters. METHOD AND RESULTS: ADDENDA-BHS2 is a prospective, single-center, active-controlled, open, randomized trial. Ninety-eight participants (40-70 years old) with HbA1c 7-9% were randomized (1:1, stratified by gender, BMI and HbA1c levels) to either dapagliflozin 10 mg/day or glibenclamide 5 mg/day on top of metformin. The primary endpoint was the change of flow-mediated dilation (FMD) after a 12-week period of treatment evaluated at rest and after IRI between dapagliflozin and glibenclamide arms. Secondary outcomes were defined as the difference between treatments regarding: plasma nitric oxide (NO) change after FMD, plasma isoprostane, plasma levels of vascular inflammatory markers and systemic inflammatory markers, plasma levels of adipokines, anthropometric measures, glucose control parameters, office and ambulatory BP control. Safety endpoints were defined as systolic and diastolic function assessed by echocardiography and retinopathy change. Serious adverse events were recorded. The study protocol was approved by the Independent Scientific Advisory Committee. CONCLUSION: The ADDENDA-BHS2 trial is an investigator-initiated clinical trial comparing the effect of dapagliflozin versus glibenclamide on several aspects of vascular function in high cardiovascular risk T2DM patients. Besides, a large clinical and biochemical phenotype assessment will be obtained for exploring potential mediations and associations.Trial registration Clinical trial registration: NCT02919345 (September, 2016).

Transfusion of fresh frozen plasma in critically ill surgical patients is associated with an increased risk of infection.

OBJECTIVE: To determine whether there is an association between transfusion of fresh frozen plasma and infection in critically ill surgical patients. DESIGN: Retrospective study. SETTING: A 24-bed surgical intensive care unit in a university hospital. PATIENTS: A total of 380 non-trauma patients who received fresh frozen plasma from 2004 to 2005 were compared with 2,058 nontrauma patients who did not receive fresh frozen plasma. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We calculated the relative risk of infectious complication for patients receiving and not receiving fresh frozen plasma. T-test allowed comparison of average units of fresh frozen plasma transfused to patients with and without infectious complications to describe a dose-response relationship. We used multivariate logistic regression analysis to evaluate the association between fresh frozen plasma and infectious complication, controlling for the effect of red blood cell transfusion, Acute Physiology and Chronic Health Evaluation II, and patient age. A significant association was found between transfusion of fresh frozen plasma and ventilator-associated pneumonia with shock (relative risk 5.42, 2.73-10.74), ventilator-associated pneumonia without shock (relative risk 1.97, 1.03-3.78), bloodstream infection with shock (relative risk 3.35, 1.69-6.64), and undifferentiated septic shock (relative risk 3.22, 1.84-5.61). The relative risk for transfusion of fresh frozen plasma and all infections was 2.99 (2.28-3.93). The t-test revealed a significant dose-response relationship between fresh frozen plasma and infectious complications (p = .02). Chi-square analysis showed a significant association between infection and transfusion of fresh frozen plasma in patients who did not receive concomitant red blood cell transfusion (p < .01), but this association was not significant in those who did receive red blood cells in addition to fresh frozen plasma. The association between fresh frozen plasma and infectious complications remained significant in the multivariate model, with an odds ratio of infection per unit of fresh frozen plasma transfused equal to 1.039 (1.013-1.067). This odds ratio resembled that noted for each unit of packed red blood cells, 1.074 (1.043-1.106). CONCLUSIONS: Transfusion of fresh frozen plasma is associated with an increased risk of infection in critically ill patients.

The impact of development of acute lung injury on hospital mortality in critically ill trauma patients.

OBJECTIVE: The additional impact of development of acute lung injury on mortality in severely-injured trauma patients beyond baseline severity of illness has been questioned. We assessed the contribution of acute lung injury to in-hospital mortality in critically ill trauma patients. DESIGN: Prospective cohort study. The contribution of acute lung injury to in-hospital mortality was evaluated in two ways. First, multivariable logistic regression models were used to test the independent association of acute lung injury with in-hospital mortality while adjusting for baseline confounding variables. Second, causal pathway models were used to estimate the amount of the overall association of baseline severity of illness with in-hospital mortality that is attributable to the interval development of acute lung injury. SETTING: Academic level 1 trauma center. PATIENTS: Two hundred eighty-three critically ill trauma patients without isolated head injury and with an Injury Severity Score > or = 16 were evaluated for development of acute lung injury in the first 5 days after trauma. MEASUREMENTS AND MAIN RESULTS: Of the 283 patients, 38 (13.4%) died. The unadjusted mortality rate was nearly three-fold greater in the acute lung injury group (23.9% vs. 8.4%; odds ratio = 3.36; 95% confidence interval 1.67-6.77; p = 0.001). Acute lung injury remained an independent risk factor for death after adjustment for age, baseline Acute Physiologic and Chronic Health Evaluation III score, Injury Severity Score, and blunt mechanism of injury (odds ratio = 2.87; 95% confidence interval 1.29-6.37; p = 0.010). Forty percent of the total association of the baseline Acute Physiologic and Chronic Health Evaluation III score with mortality occurred via an indirect association through acute lung injury, and the remaining 60% via a direct effect. CONCLUSIONS: Development of acute lung injury in critically ill trauma patients without isolated head injury contributes independently to in-hospital mortality beyond baseline severity of illness measures. In addition, a significant portion of the association between baseline illness severity and risk of death in these patients might be explained by the interval development of acute lung injury.

Methylene blue and vasoplegia: who, when, and how?

Systemic inflammatory response can be associated with clinically significant and, at times, refractory hypotension. Despite the lack of uniform definitions, this condition is frequently called vasoplegia or vasoplegic syndrome (VS), and is thought to be due to dysregulation of endothelial homeostasis and subsequent endothelial dysfunction secondary to direct and indirect effects of multiple inflammatory mediators. Vasoplegia has been observed in all age groups and in various clinical settings, such as anaphylaxis (including protamine reaction), sepsis, hemorrhagic shock, hemodialysis, and cardiac surgery. Among mechanisms thought to be contributory to VS, the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway appears to play a prominent role. In search of effective treatment for vasoplegia, methylene blue (MB), an inhibitor of nitric oxide synthase (NOS) and guanylate cyclase (GC), has been found to improve the refractory hypotension associated with endothelial dysfunction of VS. There is evidence that MB may indeed be effective in improving systemic hemodynamics in the setting of vasoplegia, with reportedly few side effects. This review describes the current state of clinical and experimental knowledge relating to MB use in the setting of VS, highlighting the potential risks and benefits of therapeutic MB administration in refractory hypotensive states.