Incidence of cervical spine fractures on CT: a study in a large level I trauma center.

INTRODUCTION/PURPOSE: Though spinal fractures constitute a minority of all traumas, the financial burden imposed is immense especially following cervical spine trauma. There have been several papers in the past describing the incidence of cervical spine fractures. In this paper, we report the incidence of cervical spine fractures and correlate with demographic information and cause of injury and review the mechanism of fractures. MATERIALS AND METHODS: We performed retrospective analysis of 934 patients who had undergone CT scan for cervical spine trauma at our institute which includes 16 hospitals and one level I trauma center over a period of 2 years. This list was created from a wider database of 13,512 patients imaged for suspected cervical spine injury. All patients who had at least one positive finding on CT were included in this study irrespective of any demographic difference. Each patient was analyzed by reviewing the medical records, and correlation was sought between demographics and cause of injury. RESULTS: In our study, the peak incidence of cervical spine trauma was in the age group of 21-30 years followed by 31-40 years with a male:female ratio of 2.1. The major cause of injury in the study population was motor vehicle accidents (66.1%), followed by fall from height of less than 8 ft (12.2%). With regard to the ethnic distribution, Caucasians (46.9%) constituted the major population followed by Hispanic population (23.3%). C1 and C2 were observed to be more frequently fractured as compared with the subaxial spine. Incidence of C2 fractures (188 levels) was higher as compared with C1 (102 levels). Incidence of body and lateral mass fractures was marginally higher as compared with odontoid fractures. C7 (50 levels) was the most fractured vertebral body in the subaxial spine followed by C6 (35 levels) and C5. CONCLUSION: Spinal trauma is on the rise and it helps to know the factors which can guide us for better management of these patients. We can utilize these results to prognosticate and streamline clinical management of these patients.

Lipopolysaccharide-induced lung injury involves the nitration-mediated activation of RhoA.

Acute lung injury (ALI) is characterized by increased endothelial hyperpermeability. Protein nitration is involved in the endothelial barrier dysfunction in LPS-exposed mice. However, the nitrated proteins involved in this process have not been identified. The activation of the small GTPase RhoA is a critical event in the barrier disruption associated with LPS. Thus, in this study we evaluated the possible role of RhoA nitration in this process. Mass spectroscopy identified a single nitration site, located at Tyr(34) in RhoA. Tyr(34) is located within the switch I region adjacent to the nucleotide-binding site. Utilizing this structure, we developed a peptide designated NipR1 (nitration inhibitory peptide for RhoA 1) to shield Tyr(34) against nitration. TAT-fused NipR1 attenuated RhoA nitration and barrier disruption in LPS-challenged human lung microvascular endothelial cells. Further, treatment of mice with NipR1 attenuated vessel leakage and inflammatory cell infiltration and preserved lung function in a mouse model of ALI. Molecular dynamics simulations suggested that the mechanism by which Tyr(34) nitration stimulates RhoA activity was through a decrease in GDP binding to the protein caused by a conformational change within a region of Switch I, mimicking the conformational shift observed when RhoA is bound to a guanine nucleotide exchange factor. Stopped flow kinetic analysis was used to confirm this prediction. Thus, we have identified a new mechanism of nitration-mediated RhoA activation involved in LPS-mediated endothelial barrier dysfunction and show the potential utility of "shielding" peptides to prevent RhoA nitration in the management of ALI.

Association between mechanical ventilation parameters and mortality in children with respiratory failure on ECMO: a systematic review and meta-analysis.

Background: In refractory respiratory failure (RF), extracorporeal membrane oxygenation (ECMO) is a salvage therapy that seeks to reduce lung injury induced by mechanical ventilation. The parameters of optimal mechanical ventilation in children during ECMO are not known. Pulmonary ventilatory management during this therapy may impact mortality. The objective of this study was to evaluate the association between ventilatory parameters in children during ECMO therapy and in-hospital mortality. Methods: A systematic search of PubMed/MEDLINE, Embase, Cochrane, and Google Scholar from January 2013 until May 2022 (PROSPERO 450744), including studies in children with ECMO-supported RF assessing mechanical ventilation parameters, was conducted. Risk of bias was assessed using the Newcastle-Ottawa scale; heterogeneity, with absence <25% and high >75%, was assessed using I2. Sensitivity and subgroup analyses using the Mantel-Haenszel random-effects model were performed to explore the impact of methodological quality on effect size. Results: Six studies were included. The median age was 3.4 years (IQR: 3.2-4.2). Survival in the 28-day studies was 69%. Mechanical ventilation parameters associated with higher mortality were a very low tidal volume ventilation (<4 ml/kg; OR: 4.70; 95% CI: 2.91-7.59; p < 0.01; I2: 38%), high plateau pressure (mean Dif: -0.70 95% CI: -0.18, -0.22; p < 0.01), and high driving pressure (mean Dif: -0.96 95% CI: -1.83, -0.09: p = 0.03). The inspired fraction of oxygen (p = 0.09) and end-expiratory pressure (p = 0.69) were not associated with higher mortality. Patients who survived had less multiple organ failure (p < 0.01). Conclusion: The mechanical ventilation variables associated with higher mortality in children with ECMO-supported respiratory failure are high plateau pressures, high driving pressure and very low tidal volume ventilation. No association between mortality and other parameters of the mechanical ventilator, such as the inspired fraction of oxygen or end-expiratory pressure, was found. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023450744, PROSPERO 2023 (CRD42023450744).

Prevalence and characteristics of chronic kidney disease in people with type 2 diabetes mellitus in the Autonomous Community of Aragon.

AIMS: The main objective in this study was to determine the prevalence of Chronic Kidney Disease (CKD) in people with Type 2 Diabetes Mellitus (T2DM) in the Autonomous Community (AC) of Aragon (Spain) and to detect whether or not there is under-registration in the patient's history. As a secundary objetive, it was proposed to study the most relevant demographic and clinical characteristics of people with CKD. METHODS: Observational and retrospective real world data study of the population over 18 years of age with a diagnosis of T2DM, between January 2017 and December 2021. A descriptive analysis of qualitative and quantitative variables, and a comparison using the parametric Student's t-test or the non-parametric Mann-Whitney U-test between both groups was performed. RESULTS: The prevalence of T2DM was 8.07 % and that of CKD 31.4 %, with an under-reporting of 47 %. The main risk factor associated with CKD was arterial hypertension (p<0.001), followed by dyslipidemia (p<0.001). The main treatment used for diabetes control was metformin, both in patients with and without CKD (p<0.001). A total of 56.81 % of people with T2DM and CKD did not undergo annual monitoring of their renal function (glomerular filtration rate) or determination of albuminuria. CONCLUSIONS: The prevalence of CKD increases in patients with T2DM (31.4 %), and in almost half of patients the diagnosis is not registered (47 %). This under-reporting delays the implementation of measures needed to prevent CKD progression.

Documento de consenso sobre tabaquismo y riesgo vascular.

Consensus statement on smoking and vascular risk About 22% of the Spanish population are daily smokers. Men are more likely to smoke than women. In Spain, women between 15-25 years of age smoke as much or more than men. Every smoker should be assessed for: physical dependence on nicotine (Fagerström test), social and psychological dependence (Glover Nilsson test), level of motivation to quit (Richmond test), probability of therapy success (Henri-Mondor and Michael-Fiore tests), and stage of behavioral change development (Prochaska and DiClementi). Advice on smoking cessation is highly cost-effective and should always be provided. Smoking is an enhancer of cardiovascular risk because it acts as a pathogen agent in the development of arteriosclerosis and is associated with ischemic heart disease, stroke, and peripheral artery disease. Smoking increases the risk of chronic lung diseases (COPD) and is related to cancers of the lung, female genitalia, larynx, oropharynx, bladder, mouth, esophagus, liver and biliary tract, and stomach, among others. Combined oral contraceptives should be avoided in women smokers older than 35 years of age due to the risk of thromboembolism. In smoking cessation, the involvement of physicians, nurses, psychologists, etc. is important, and their multidisciplinary collaboration is needed. Effective pharmacological treatments for smoking cessation are available. Combined treatments are recommended when smoker's dependence is high. For individuals who are unable to quit smoking, a strategy based on tobacco damage management with a total switch to smokeless products could be a less dangerous alternative for their health than continuing to smoke.

Dermatofibrosarcoma Protuberans of the Face.

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive tumor with high rate of local recurrence but low metastatic potential. Its high-grade fibrosarcomatous variant and occurrence on the head and neck are rare findings associated with increased morbidity and mortality. The most significant prognostic feature of DFSP is obtaining tumor free surgical margins. As such, accurate recognition and proper management of this uncommon and locally aggressive malignancy is especially crucial in head and neck surgery.

Purification and functional analysis of protein kinase G-1α using a bacterial expression system.

3',5' Cyclic guanosine monophosphate (cGMP)-dependent protein kinase G-1α (PKG-1α) is an enzyme that is a target of several anti-hypertensive and erectile dysfunction drugs. Binding of cGMP to PKG-1α produces a conformational change that leads to enzyme activation. Activated PKG-1α performs important roles both in blood vessel vasodilation and in maintaining the smooth muscle cell in a differentiated contractile state. Recombinant PKG-1α has been expressed and purified using Sf9-insect cells. However, attempts at purifying full length protein in a soluble and active form in prokaryotes have thus far been unsuccessful. These attempts have been hampered by the lack of proper eukaryotic protein folding machinery in bacteria. In this study, we report the successful expression and purification of PKG-1α using a genetically engineered Escherichia coli strain, Rosetta-gami 2(DE3), transduced with full-length human PKG-1α cDNA containing a C-terminal histidine tag. PKG-1α was purified to homogeneity using sequential nickel affinity chromatography, gel filtration and ion exchange MonoQ columns. Protein identity was confirmed by immunoblot analysis. N-terminal sequencing using Edman degradation demonstrated that the purified protein was full length. Analysis of enzyme kinetics, using a nonlinear regression curve, identified that, at constant cGMP levels (10µM) and varying ATP concentrations, PKG-1α had a maximal velocity (V(max)) of 5.02±0.25pmol/min/µg and a Michaelis-Menten constant (K(m)) of 11.78±2.68µM ATP. Recent studies have suggested that endothelial function can be attenuated by oxidative and/or nitrosative stress but the role of PKG-1α under these conditions is unclear. We found that PKG-1α enzyme activity was attenuated by exposure to the NO donor, spermine NONOate, hydrogen peroxide, and peroxynitrite but not by superoxide, suggesting that the attenuation of PKG-1α activity may be an under-appreciated mechanism underlying the development of endothelial dysfunction in a number of cardiovascular diseases.

Comparison of two approaches to prevention of mental health problems in college students: Enhancing coping and executive function skills.

OBJECTIVE: College students face a significant number of stressors, increasing risk for internalizing and externalizing psychopathology. The current study examines two promising avenues of intervention aimed to reduce stress and prevent psychopathology in this population: a coping skills group and a cognitive training program. PARTICIPANTS: 62 undergraduate students from two universities were recruited from 2013 to 2015. METHODS: Students were randomized to a 6-week coping skills group or cognitive training program and completed measures of stress, coping, executive function, and symptoms of anxiety, depression and Attention-Deficit Hyperactivity Disorder (ADHD) at pre- and post-intervention. RESULTS: Participants in both conditions reported significant decreases in social stress, executive function difficulties, and anxiety symptoms post-intervention. Students in the cognitive program improved significantly more on measures of behavior regulation and ADHD symptoms compared to the coping group at post-intervention. CONCLUSIONS: Brief stress management interventions targeting coping and executive function may benefit college students at risk for psychopathology.

Actualidad de los Inhibidores de la PCSK9 / Current state of PCSK9 inhibitors

Hasta hace poco los fármacos hipolipemiantes que habían demostrado, de manera consistente y reproducible, capacidad para prevenir la aparición de las enfermedades cardiovasculares, sobre todo de la cardiopatía isquémica, tanto en prevención primaria como secundaria, eran las estatinas. En España, hay comercializadas siete y todas tienen estudios de reducción de eventos clínicos frente a placebo y, en algunos casos de prevención secundaria, de tratamiento intensivo frente al convenciona, menos la pitavastatina que solo cuenta con un estudio que compara dosis altas con dosis bajas de la misma estatina. Tras los fracasos en la prevención cardiovascular del ácido nicotínico, actualmente no comercializado en España, la limitada utilidad de los fibratos y de los ácidos grasos omega 39, solo nos quedan como tratamiento para asociar a las estatinas las resinas de intercambio iónico, habitualmente mal toleradas, y ezetimiba, fármaco que solo tiene estudios de reducción de eventos en asociación con estatinas en pacientes con insuficiencia renal y con síndrome coronario agudo

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Enfermedad de Rosai-Dorfman (ERD) con compromiso exclusivo del sistema nervioso central. Presentación de caso y revisión de literatura / Rosai-Dorfman Disease (RDD) With Isolated Compromise of the Central Nervous System. Case Report and Literature Review

La enfermedad de Rosai-Dorfman (ERD) o histiocitosis sinusal con linfadenopatía masiva (HSLM) es una entidad histiocítica benigna rara, que usualmente afecta los ganglios linfáticos. Se han descrito algunos casos en el sistema nervioso central, y son excepcionales los que aparecen sin afección nodular concomitante. La falta de patrones imaginológicos cerebrales típicos puede llevar a una cirugía por un diagnóstico erróneo, con causas atribuidas a un probable origen maligno. Usualmente, el diagnóstico histopatológico se realiza después del procedimiento quirúrgico. Esta entidad clínico-patológica carece de consenso en diagnóstico, curso clínico y tratamiento. Se presenta un caso de ERD con extensión intracraneal, con la lectura retrospectiva de los estudios imaginológicos.

Rosai-Dorfman Disease (RDD) or Sinus Histiocytosis with Massive Lymphadenopathy (SHML) is a rare benign histiocytic disorder, usually affecting the lymph nodes. Intracranial involvement is an uncommon variant of the disease; however, intracranial lesions without concomitant nodular involvement is exceptional. The lack of typical brain imaging patterns can lead to surgery due to misdiagnosis, with causes attributed to a probable malignant origin. Histopathological diagnosis is usually made after the surgical procedure. There is no consensus related to diagnosis, clinical course and treatment of this disease. A case report is presented on isolated intracranial RDD, with a retrospective reading of the imaging studies.

Endothelin-1 stimulates catalase activity through the PKCδ-mediated phosphorylation of serine 167.

Our previous studies have shown that endothelin-1 (ET-1) stimulates catalase activity in endothelial cells and in lambs with acute increases in pulmonary blood flow (PBF), without altering gene expression. The purpose of this study was to investigate the molecular mechanism by which this occurs. Exposing pulmonary arterial endothelial cells to ET-1 increased catalase activity and decreased cellular hydrogen peroxide (H2O2) levels. These changes correlated with an increase in serine-phosphorylated catalase. Using the inhibitory peptide δV1.1, this phosphorylation was shown to be protein kinase Cδ (PKCδ) dependent. Mass spectrometry identified serine 167 as the phosphorylation site. Site-directed mutagenesis was used to generate a phospho-mimic (S167D) catalase. Activity assays using recombinant protein purified from Escherichia coli or transiently transfected COS-7 cells demonstrated that S167D catalase had an increased ability to degrade H2O2 compared to the wild-type enzyme. Using a phospho-specific antibody, we were able to verify that pS167 catalase levels are modulated in lambs with acute increases in PBF in the presence and absence of the ET receptor antagonist tezosentan. S167 is located on the dimeric interface, suggesting it could be involved in regulating the formation of catalase tetramers. To evaluate this possibility we utilized analytical gel filtration to examine the multimeric structure of recombinant wild-type and S167D catalase. We found that recombinant wild-type catalase was present as a mixture of monomers and dimers, whereas S167D catalase was primarily tetrameric. Further, the incubation of wild-type catalase with PKCδ was sufficient to convert wild-type catalase into a tetrameric structure. In conclusion, this is the first report indicating that the phosphorylation of catalase regulates its multimeric structure and activity.

Protein engineering to develop a redox insensitive endothelial nitric oxide synthase.

The zinc tetrathiolate (ZnS4) cluster is an important structural feature of endothelial nitric oxide synthase (eNOS). The cluster is located on the dimeric interface and four cysteine residues (C94 and C99 from two adjacent subunits) form a cluster with a Zn ion in the center of a tetrahedral configuration. Due to its high sensitivity to oxidants this cluster is responsible for eNOS dimer destabilization during periods of redox stress. In this work we utilized site directed mutagenesis to replace the redox sensitive cysteine residues in the ZnS4 cluster with redox stable tetra-arginines. Our data indicate that this C94R/C99R eNOS mutant is active. In addition, this mutant protein is insensitive to dimer disruption and inhibition when challenged with hydrogen peroxide (H2O2). Further, the overexpression of the C94R/C99R mutant preserved the angiogenic response in endothelial cells challenged with H2O2. The over-expression of the C94R/C99R mutant preserved the ability of endothelial cells to migrate towards vascular endothelial growth factor (VEGF) and preserved the endothelial monolayer in a scratch wound assay. We propose that this dimer stable eNOS mutant could be utilized in the treatment of diseases in which there is eNOS dysfunction due to high levels of oxidative stress.

Risk factors associated with postoperative seizures in patients undergoing cardiac surgery who received tranexamic acid: a case-control study.

Antifibrinolytic agents are used during cardiac surgery to minimize bleeding and reduce exposure to blood products. Several reports suggest that tranexamic acid (TA) can induce seizure activity in the postoperative period. To examine factors associated with postoperative seizures in patients undergoing cardiac surgery who received TA. University-affiliated hospital. Case-control study. Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) between January 2008 and December 2009 were identified. During this time, all patients undergoing heart surgery with CPB received TA. Cases were defined as patients who developed seizures that required initiation of anticonvulsive therapy within 48 h of surgery. Exclusion criteria included subjects with preexisting epilepsy and patients in whom the convulsive episode was secondary to a new ischemic lesion on brain imaging. Controls who did not develop seizures were randomly selected from the initial cohort. From an initial cohort of 903 patients, we identified 32 patients with postoperative seizures. Four patients were excluded. Twenty-eight cases and 112 controls were analyzed. Cases were more likely to have a history of renal impairment and higher preoperative creatinine values compared with controls (1.39 ± 1.1 vs. 0.98 ± 0.02 mg/dL, P = 0.02). Significant differences in the intensive care unit, postoperative and total lengths of stay were observed. An association between high preoperative creatinine value and postoperative seizure was identified. TA may be associated with the development of postoperative seizures in patients with renal dysfunction. Doses of TA should be reduced or even avoided in this population.

eNOS activation and NO function: structural motifs responsible for the posttranslational control of endothelial nitric oxide synthase activity.

Rather than being a constitutive enzyme as was first suggested, endothelial nitric oxide synthase (eNOS) is dynamically regulated at the transcriptional, posttranscriptional, and posttranslational levels. This review will focus on how changes in eNOS function are conferred by various posttranslational modifications. The latest knowledge regarding eNOS targeting to the plasma membrane will be discussed as the role of protein phosphorylation as a modulator of catalytic activity. Furthermore, new data are presented that provide novel insights into how disruption of the eNOS dimer prevents eNOS uncoupling and the production of superoxide under conditions of elevated oxidative stress and identifies a novel regulatory region we have termed the 'flexible arm'.

Comparison of two protective lung ventilatory regimes on oxygenation during one-lung ventilation: a randomized controlled trial.

BACKGROUND: The efficacy of protective ventilation in acute lung injury has validated its use in the operating room for patients undergoing thoracic surgery with one-lung ventilation (OLV). The purpose of this study was to investigate the effects of two different modes of ventilation using low tidal volumes: pressure controlled ventilation (PCV) vs. volume controlled ventilation (VCV) on oxygenation and airway pressures during OLV. METHODS: We studied 41 patients scheduled for thoracoscopy surgery. After initial two-lung ventilation with VCV patients were randomly assigned to one of two groups. In one group OLV was started with VCV (tidal volume 6 mL/kg, PEEP 5) and after 30 minutes ventilation was switched to PCV (inspiratory pressure to provide a tidal volume of 6 mL/kg, PEEP 5) for the same time period. In the second group, ventilation modes were performed in reverse order. Airway pressures and blood gases were obtained at the end of each ventilatory mode. RESULTS: PaO2, PaCO2 and alveolar-arterial oxygen difference did not differ between PCV and VCV. Peak airway pressure was significantly lower in PCV compared with VCV (19.9 ± 3.8 cmH2O vs 23.1 ± 4.3 cmH2O; p < 0.001) without any significant differences in mean and plateau pressures. CONCLUSIONS: In patients with good preoperative pulmonary function undergoing thoracoscopy surgery, the use of a protective lung ventilation strategy with VCV or PCV does not affect the oxygenation. PCV was associated with lower peak airway pressures.

Metodo de identificación de Flavivirus endemicos que afectan a la población humana: uso de bovinos / Identification method of endemic Flavivirus affecting the human population: use of bovines

Se investigaron infecciones por flavivirus en una muestra de 1279 sueros bovinos correspondientes a 8 tambos, 3 rodeos de cría e invernada y 2 cabañas, mostrándose que tanto ILH como SLE producen infecciones en estos animales con diferentes prevalencias de acuerdo a grupos etarios y a manejo de explotación. Se hacen analogías entre agrupamiento de poblaciones humanas y de animales tendientes a considerar modelos epidemiológicos de estos dos virus endémicos: Ilheus y Encefalitis de San Luis que aislados en la Pcia. de Buenos Aires en 1963 se los ha encontrado asociados a patologías del niño y del adulto

Flavivirus: encuesta serológica en equinos del partido de Tandil / Flavivirus: serological survey in horses from Tandil county

Se obtivieron 282 sueros de equinos cuyas edades oscilan entre 45 días y 27 años provenientes del partido de Tandil y alrededores para investigar anticuerpos contra 3 flavivirus: Ilheus (ILH), Encefalitis de San Luis (SLE) y Fiebre amarilla (YF) mediante las técnicas de inhibición de la hemaglutinación (IH), fijación de complemento (FC) y neutralización (NT). Las muestras se recolectaron entre el 20-3-79 y el 25-11-80. Cuarenta y nueve sueron reaccionaron positivamente contra uno o más de los flavivirus usados por IH y/o FC, representando una prevalencia del 17,4% para este complemento antigénico. Veinticuartro de ellos neutralizaron ILH, 6 SLE, y de ellos, 2 neutralizaron simultáneamente a ambos virus. Veintiún sueros no neutralizaron ni ILH ni SLE, por cual no podemos atribuir los anticuerpos específicamente a estos virus, sino a alguno/s con ellos relacionados, que podrían corresponder a flavivirus presentes en el medio ambiente pero no en nuestras pruebas. Otros 12 sueron negativos para los tres antígenos por IH y/o FC tampoco neutralizaron SLE o ILH. Los resultaods muestran que ILH y SLE, ambos virus aislados años atrás en Argentina, son endémicos en el área bajo estudio y que los mismos infectan a equinos, quinzás sin oroducirles enfermedades detectables, ya que no han sido reportadas epizzotias equinas en la población investigada, atribuidas a SLE o ILH