Patterns of on-scene and healthcare system trauma deaths in the Western Cape of South Africa.

BACKGROUND: Injuries account for 8% or 4.4 million deaths annually worldwide, with 90% of injury deaths occurring in low- and middle-income countries. Inter-personal violence and road traffic injuries account for most injury deaths in South Africa, with rates among the highest globally. Understanding the location, timing, and factors of trauma deaths can identify opportunities to strengthen care. METHODS: This is a retrospective cross-sectional secondary analysis of trauma deaths from 2021 to 2022 in the Western Cape of South Africa. Healthcare system trauma deaths were identified from a multicenter study paired with a dataset for on-scene (i.e., prior to ambulance or hospital) trauma deaths in the same jurisdictions. We describe locations, timing, injury factors, and cause of death. We assess associations between those factors. RESULTS: There were 2418 deaths, predominantly young men, with most (2274, 94.0%) occurring on-scene. The most frequent mechanism of injury for all deaths was firearms (32.6%), followed by road traffic collisions (17.8%). On-scene deaths (33.2%) were significantly more likely to be injured by firearms compared to healthcare system deaths (23.6%) (p-value <0.01). Most healthcare system deaths within 4-24 h of injury occurred in a hospital emergency center. Among healthcare system decedents, half died in the emergency unit. CONCLUSIONS: We identified a large burden of deaths from interpersonal violence and road traffic collisions, mostly on-scene. In addition to primary prevention, shortening delays to care can improve mortality outcomes especially for deaths occurring within 4-24 h in emergency centers.

Biological Activities of Bismuth Compounds: An Overview of the New Findings and the Old Challenges Not Yet Overcome.

Bismuth-based drugs have been used primarily to treat ulcers caused by Helicobacter pylori and other gastrointestinal ailments. Combined with antibiotics, these drugs also possess synergistic activity, making them ideal for multiple therapy regimens and overcoming bacterial resistance. Compounds based on bismuth have a low cost, are safe for human use, and some of them are also effective against tumoral cells, leishmaniasis, fungi, and viruses. However, these compounds have limited bioavailability in physiological environments. As a result, there is a growing interest in developing new bismuth compounds and approaches to overcome this challenge. Considering the beneficial properties of bismuth and the importance of discovering new drugs, this review focused on the last decade's updates involving bismuth compounds, especially those with potent activity and low toxicity, desirable characteristics for developing new drugs. In addition, bismuth-based compounds with dual activity were also highlighted, as well as their modes of action and structure-activity relationship, among other relevant discoveries. In this way, we hope this review provides a fertile ground for rationalizing new bismuth-based drugs.

L-carnitine added to post-thawed semen acts as an antioxidant and a stimulator of equine sperm metabolism.

The objective of this study was to enhance the in vitro sperm quality and in vivo fertility of frozen-thawed equine semen by the addition of l-carnitine (LC) to post-thawed semen. Different concentrations of LC were added to thawed samples to obtain four treatments control and 0.5, 1 and 2 mM LC. In the in vitro experiments, sperm motility and kinematics, membrane integrity and intracellular calcium ion concentration ([Ca2+ ]i ) were investigated, and the antioxidant bioactivity of LC was assessed by measuring hydrogen peroxide and nitrite concentrations (NO2 - ). The fertility rate was assessed via the artificial insemination of mares. The treatment with 1 mM LC increased sperm [Ca2+ ]i (60.6 ± 0.05 AU), reduced nitrite concentration (39.1 ± 14.9 µM/µg protein), increased the sperm straightness percentage (STR: 78.3 ± 5.3%) and increased the pregnancy rate (75%) as compared to the control ([Ca2+ ]i 48.4 ± 0.05 AU, NO2 - concentration 63.1 ± 14.4 µM/µg protein, STR 67.5 ± 7.9%, 12.5% pregnancy rate, p < 0.05). These results suggest that 1 mM LC acts as an antioxidant and stimulator of sperm metabolism in post-thawed equine semen, increasing the fertility rate. Thus, addition of LC might be an alternative to improve the fertility of poor quality post-thawed equine semen.

HPV73 a nonvaccine type causes cervical cancer.

HPV73 is classified as possibly oncogenic. It is neither routinely evaluated in HPV screening, nor covered by any of the prophylactic vaccines. We sought to investigate the carcinogenic characteristics of HPV73. Molecular studies were performed on eight cervix cancer biopsy specimens containing HPV73 from a cross-sectional cancer cohort of 590 women referred to the National Cancer Institute in Rio de Janeiro, Brazil. Transcriptional activity of HPV73 was evaluated by detection of spliced transcripts of E6/E6* and E1^E4 in cDNA created from RNA isolated from fresh tissue. Disruption of viral E1 and E2 genes in the tumor DNA was assessed by overlapping PCR amplification. Evaluation of viral integration was performed using a customized capture panel and next-generation sequencing, and an in-house bioinformatic pipeline. HPV73 E6/E6* transcripts were found in 7/7 specimens with available RNA, and three also had HPV73 E1^E4 transcripts. Disruption of E1 and E2 genes was observed in 4/8 specimens. Integration of HPV73 sequences into the cancer cell genomes was identified in all cervix cancer tissues. These results provide evidence that HPV73 is an oncogenic virus that can cause invasive cervix cancer. With current molecular screening and HPV vaccination, not all cervix cancers will be prevented.

BRCA1, BRCA2, and TP53 germline and somatic variants and clinicopathological characteristics of Brazilian patients with epithelial ovarian cancer.

BACKGROUND: Approximately 3/4 of ovarian cancers are diagnosed in advanced stages, with the high-grade epithelial ovarian carcinoma (EOC) accounting for 90% of the cases. EOC present high genomic instability and somatic loss-of-function variants in genes associated with homologous recombination mutational repair pathway (HR), such as BRCA1 and BRCA2, and in TP53. The identification of germline variants in HR genes in EOC is relevant for treatment of platinum resistant tumors and relapsed tumors with therapies based in synthetic lethality such as PARP inhibitors. Patients with somatic variants in HR genes may also benefit from these therapies. In this work was analyzed the frequency of somatic variants in BRCA1, BRCA2, and TP53 in an EOC cohort of Brazilian patients, estimating the proportion of variants in tumoral tissue and their association with progression-free survival and overall survival. METHODS: The study was conducted with paired blood/tumor samples from 56 patients. Germline and tumoral sequences of BRCA1, BRCA2, and TP53 were obtained by massive parallel sequencing. The HaplotypeCaller method was used for calling germline variants, and somatic variants were called with Mutect2. RESULTS: A total of 26 germline variants were found, and seven patients presented germline pathogenic or likely pathogenic variants in BRCA1 or BRCA2. The analysis of tumoral tissue identified 52 somatic variants in 41 patients, being 43 somatic variants affecting or likely affecting protein functionality. Survival analyses showed that tumor staging was associated with overall survival (OS), while the presence of somatic mutation in TP53 was not associated with OS or progression-free survival. CONCLUSION: Frequency of pathogenic or likely pathogenic germline variants in BRCA1 and BRCA2 (12.5%) was lower in comparison with other studies. TP53 was the most altered gene in tumors, with 62.5% presenting likely non-functional or non-functional somatic variants, while eight 14.2% presented likely non-functional or non-functional somatic variants in BRCA1 or BRCA2.

Improving prehospital traumatic shock care: implementation and clinical effectiveness of a pragmatic, quasi-experimental trial in a resource-constrained South African setting.

OBJECTIVES: This project seeks to improve providers' practices and patient outcomes from prehospital (ie, ambulance-based) trauma care in a middle-income country using a novel implementation strategy to introduce a bundled clinical intervention. DESIGN: We conduct a two-arm, controlled, mixed-methods, hybrid type II study. SETTING: This study was conducted in the Western Cape Government Emergency Medical Services (EMS) system of South Africa. INTERVENTIONS: We pragmatically implemented a simplified prehospital bundle of trauma care (with five core elements) using a novel workplace-based, peer-to-peer, rapid training format. We assigned the intervention and control sites. OUTCOME MEASURES: We assessed implementation effectiveness among EMS providers and stakeholders, using the RE-AIM framework. Clinical effectiveness was assessed at the patient level, using changes in Shock Index x Age (SIxAge). Indices and cut-offs were established a priori. We performed a difference-in-differences (D-I-D) analysis with a multivariable mixed effects model. RESULTS: 198 of 240 (82.5%) EMS providers participated, 93 (47%) intervention and 105 (53%) control, with similar baseline characteristics. The overall implementation effectiveness was excellent (80.6%): reach was good (65%), effectiveness was excellent (87%), implementation fidelity was good (72%) and adoption was excellent (87%). Participants and stakeholders generally reported very high satisfaction with the implementation strategy citing that it was a strong operational fit and effective educational model for their organisation. A total of 770 patients were included: 329 (42.7%) interventions and 441 (57.3%) controls, with no baseline differences. Intervention arm patients had more improved SIxAge compared with control at 4 months, which was not statistically significant (-1.4 D-I-D; p=0.35). There was no significant difference in change of SIxAge over time between the groups for any of the other time intervals (p=0.99). CONCLUSIONS: In this quasi-experimental trial of bundled care using the novel workplace rapid training approach, we found overall excellent implementation effectiveness but no overall statistically significant clinical effectiveness.

Clinical impact of a prehospital trauma shock bundle of care in South Africa.

INTRODUCTION: Patients experiencing traumatic shock are at a higher risk for death and complications. We previously designed a bundle of emergency medical services traumatic shock care ("EMS-TruShoC") for prehospital providers in resource-limited settings. We assess how EMS-TruShoC changes clinical outcomes of critically injured prehospital patients. METHODS: This is a quasi-experimental educational implementation of a simplified bundle of care using a pre-post design with a control group. The intervention was delivered to EMS providers in Western Cape, South Africa. Delta shock index (heart rate divided by systolic blood pressure, reported as change from the scene to facility arrival) from the 13 months preceding intervention were compared to the 13 months post-implementation. A difference-in-differences analysis examined the difference in mean shock index change between the groups. RESULTS: Data were collected from 198 providers who treated 770 severe trauma patients. The patient groups had similar demographic and clinical characteristics at baseline. Over all time-points, both groups had an increase in mean delta shock index (worsening shock), with the largest difference occurring 4-months post-implementation (0.047 change in control arm, 0.004 change in intervention arm; -0.043 difference-in-differences, P = 0.27). In pre-specified subgroup analyses, there was a statistically significant improvement in delta shock index in the intervention arm in patients with penetrating trauma cared for by basic providers immediately post-implementation (-0.372 difference-in-differences, P = 0.02). DISCUSSION: Overall, there was no significant difference in delta shock index between the EMS-TruShoC intervention versus control groups. However, significant improvement in shock index in one subgroup suggests the intervention may be more likely to benefit penetrating trauma patients and basic providers.

A social network approach for the study of leprosy transmission beyond the household.

BACKGROUND: Mycobacterium leprae was the first microorganism directly associated with a disease, however, there are still important gaps in our understanding of transmission. Although household contacts are prioritized, there is evidence of the importance of extrahousehold contacts. The goal of this article is to contribute to our understanding of the transmission of leprosy ex-household. METHODS: We compare co-location data of 397 leprosy cases and 211 controls drawn from the Centro de Dermatologia Sanitária D. Libânia in Fortaleza, Brazil. We collected lifetime geolocation data related to residence, school attendance and workplace and developed novel methods to establish a critical distance (Rc) for exposure and evaluated the potential for transmission for residence, school and workplace. RESULTS: Our methods provide different threshold values of distance for residence, school and workplace. Residence networks demonstrate an Rc of about 500 m. Cases cluster in workplaces as well. Schools do not cluster cases. CONCLUSIONS: Our novel network approach offers a promising opportunity to explore leprosy transmission. Our networks confirm the importance of coresidence, provide a boundary and suggest a role for transmission in workplaces. Schools, on the other hand, do not demonstrate a clustering of cases. Our findings may have programmatic relevance.

Serum albumin and vascular endothelial growth factor in epithelial ovarian cancer: looking at adnexal tumor drainage.

PURPOSE: This study aims to analyze serum albumin levels (SAL) in relation to concentrations of vascular endothelial growth factor (VEGF) from peripheral plasma, infundibular plasma, peritoneal fluids and the peritoneal burden of VEGF of patients with epithelial ovarian cancer. METHODS: Exploratory analyses of SAL in 39 patients and its relation to mean concentrations of VEGF from the origins are described above. Statistical analyses comprised Student's t test, Mann-Whitney test and Pearson's and Spearman's correlation coefficient. RESULTS: Both infundibular concentrations of VEGF and the peritoneal burden of VEGF showed significant differences between SAL dichotomized at 3 g/dl. Concentrations of VEGF in peritoneal fluids were not significant in relation to SAL. Peripheral plasma VEGF levels did not show any linear correlation with SAL. Indeed, SAL showed a significant negative linear correlation (p < 0.001) to infundibular plasma as well as the peritoneal burden of VEGF (p = 0.004). CONCLUSIONS: Infundibular mean concentrations of VEGF may contribute to reduce SAL in advanced staging rather than the peripheral plasma concentrations of this glycoprotein. The peritoneal burden of VEGF may also aid in decreasing levels of serum albumin.

Measuring quality of pre-hospital traumatic shock care-development and validation of an instrument for resource-limited settings.

BACKGROUND AND AIMS: Improving the quality of pre-hospital traumatic shock care, especially in low- and middle-income countries, is particularly relevant to reducing the large global burden of disease from injury. What clinical interventions represent high-quality care is an actively evolving field and often dependent on the specific injury pattern. A key component of improving the quality of care is having a consistent way to assess and measure the quality of shock care in the pre-hospital setting. The objective of this study was to develop and validate a chart abstraction instrument to measure the quality of trauma care in a resource-limited, pre-hospital emergency care setting. METHODS: Traumatic shock was selected as the tracer condition. The pre-hospital quality of traumatic shock care (QTSC) instrument was developed and validated in three phases. A content development phase utilized a rapid literature review and expert consensus to yield the contents of the draft instrument. In the instrument validation phase, the QTSC instrument was created and underwent end user and content validation. A pilot-testing phase collected user feedback and performance characteristics to iteratively refine draft versions into a final instrument. Accuracy and inter- and intra-rater agreement were calculated. RESULTS: The final QTSC instrument contains 10 domains of quality, each with specific criteria that determine how the domain is measured and the level of quality of care rendered. The instrument is over 90% accurate and has good inter- and intra-rater reliability when used by trained pre-hospital provider users in South Africa. Pre-hospital provider user feedback indicates the tool is easy to learn and quick to use. CONCLUSION: We created and validated a novel chart abstraction instrument that can reliably and accurately measure the quality of pre-hospital traumatic shock care. We provide a systematic methodology for developing and validating a quality of care tool for resource-limited care settings.

A scoping review of worldwide studies evaluating the effects of prehospital time on trauma outcomes.

BACKGROUND: Annually, over 1 billion people sustain traumatic injuries, resulting in over 900,000 deaths in Africa and 6 million deaths globally. Timely response, intervention, and transportation in the prehospital setting reduce morbidity and mortality of trauma victims. Our objective was to describe the existing literature evaluating trauma morbidity and mortality outcomes as a function of prehospital care time to identify gaps in literature and inform future investigation. MAIN BODY: We performed a scoping review of published literature in MEDLINE. Results were limited to English language publications from 2009 to 2020. Included articles reported trauma outcomes and prehospital time. We excluded case reports, reviews, systematic reviews, meta-analyses, comments, editorials, letters, and conference proceedings. In total, 808 articles were identified for title and abstract review. Of those, 96 articles met all inclusion criteria and were fully reviewed. Higher quality studies used data derived from trauma registries. There was a paucity of literature from studies in low- and middle-income countries (LMIC), with only 3 (3%) of articles explicitly including African populations. Mortality was an outcome measure in 93% of articles, predominantly defined as "in-hospital mortality" as opposed to mortality within a specified time frame. Prehospital time was most commonly assessed as crude time from EMS dispatch to arrival at a tertiary trauma center. Few studies evaluated physiologic morbidity outcomes such as multi-organ failure. CONCLUSION: The existing literature disproportionately represents high-income settings and most commonly assessed in-hospital mortality as a function of crude prehospital time. Future studies should focus on how specific prehospital intervals impact morbidity outcomes (e.g., organ failure) and mortality at earlier time points (e.g., 3 or 7 days) to better reflect the effect of early prehospital resuscitation and transport. Trauma registries may be a tool to facilitate such research and may promote higher quality investigations in Africa and LMICs.

Investigating extradomiciliary transmission of tuberculosis: An exploratory approach using social network patterns of TB cases and controls and the genotyping of Mycobacterium tuberculosis.

Extradomiciliary contacts have been overlooked in the study of TB transmission due to difficulties in identifying actual contacts in large populations. Complex network analysis provides a framework to model the structure of contacts, specially extradomiciliary ones. We conducted a study of incident sputum-positive TB cases and healthy controls occurring in a moderate TB burden city. Cases and controls were interviewed to obtain data regarding the usual locations of residence, work, study, and leisure. Mycobacterium tuberculosis isolated from sputum was genotyped. The collected data were used to build networks based on a framework of putative social interactions indicating possible TB transmission. A user-friendly open source environment (GraphTube) was setup to extract information from the collected data. Networks based on the likelihood of patient-patient, patient-healthy, and healthy-healthy contacts were setup, depending on a constraint of geographical distance of places attended by the volunteers. Using a threshold for the geographical distance of 300 m, the differences between TB cases and controls are revealed. Several clusters formed by social network nodes with high genotypic similarity were characterized. The developed framework provided consistent results and can be used to support the targeted search of potentially infected individuals and to help to understand the TB transmission.

Extracorporeal membrane oxygenation: a literature review. / Oxigenação por membrana extracorpórea: revisão da literatura.

Extracorporeal membrane oxygenation is a modality of extracorporeal life support that allows for temporary support in pulmonary and/or cardiac failure refractory to conventional therapy. Since the first descriptions of extracorporeal membrane oxygenation, significant improvements have occurred in the device and the management of patients and, consequently, in the outcomes of critically ill patients during extracorporeal membrane oxygenation. Many important studies about the use of extracorporeal membrane oxygenation in patients with acute respiratory distress syndrome refractory to conventional clinical support, under in-hospital cardiac arrest and with cardiogenic refractory shock have been published in recent years. The objective of this literature review is to present the theoretical and practical aspects of extracorporeal membrane oxygenation support for respiratory and/or cardiac functions in critically ill patients.

A oxigenação por membrana extracorpórea é uma modalidade de suporte de vida extracorpóreo que possibilita suporte temporário à falência da função pulmonar e/ou cardíaca, refratária ao tratamento clínico convencional. Desde as primeiras descrições da oxigenação por membrana extracorpórea, melhorias significativas ocorreram no dispositivo, no manejo do paciente e, consequentemente, nos desfechos dos pacientes em oxigenação por membrana extracorpórea. Diversos estudos importantes sobre a utilização de oxigenação por membrana extracorpórea em pacientes com síndrome do desconforto respiratório agudo refratária ao suporte clínico convencional, em parada cardíaca intra-hospitalar e choque cardiogênico refratário foram publicados nos últimos anos. Dessa forma, o objetivo desta revisão é apresentar conceitos teóricos e práticos sobre a utilização da oxigenação por membrana extracorpórea em situações de falência pulmonar e/ou cardíaca refratária ao manejo clínico convencional em pacientes críticos.

Overexpression of HMGA1 Figures as a Potential Prognostic Factor in Endometrioid Endometrial Carcinoma (EEC).

Endometrioid endometrial carcinomas (EEC) are the most common malignant gynecologic tumors. Despite the increase in EEC molecular knowledge, the identification of new biomarkers involved in disease's development and/or progression would represent an improvement in its course. High-mobility group A protein (HMGA) family members are frequently overexpressed in a wide range of malignancies, correlating with a poor prognosis. Thus, the aim of this study was to analyze HMGA1 and HMGA2 expression pattern and their potential role as EEC biomarkers. HMGA1 and HMGA2 expression was initially evaluated in a series of 46 EEC tumors (stages IA to IV), and the findings were then validated in The Cancer Genome Atlas (TCGA) EEC cohort, comprising 381 EEC tumors (stages IA to IV). Our results reveal that HMGA1 and HMGA2 mRNA and protein are overexpressed in ECC, but only HMGA1 expression is associated with increased histological grade and tumor size. Moreover, HMGA1 but not HMGA2 overexpression was identified as a negative prognostic factor to EEC patients. Finally, a positive correlation between expression of HMGA1 pseudogenes-HMGA1-P6 and HMGA1-P7-and HMGA1 itself was detected, suggesting HMGA1 pseudogenes may play a role in HMGA1 expression regulation in EEC. Thus, these results indicate that HMGA1 overexpression possesses a potential role as a prognostic biomarker for EEC.

Early versus delayed initiation of renal replacement therapy for acute kidney injury: an updated systematic review, meta-analysis, meta-regression and trial sequential analysis of randomized controlled trials. / Início precoce em comparação ao início tardio da terapia de substituição renal para lesão renal aguda: revisão sistemática atualizada, metanálise, metarregressão e análise sequencial de ensaios clínicos randomizados e controlados.

OBJECTIVE: To evaluate whether early initiation of renal replacement therapy is associated with lower mortality in patients with acute kidney injury compared to delayed initiation. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials comparing early versus delayed initiation of renal replacement therapy in patients with acute kidney injury without the life-threatening acute kidney injury-related symptoms of fluid overload or metabolic disorders. Two investigators extracted the data from the selected studies. The Cochrane Risk of Bias Tool was used to assess the quality of the studies, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to test the overall quality of the evidence. RESULTS: Six randomized controlled trials (1,292 patients) were included. There was no statistically significant difference between early and delayed initiation of renal replacement therapy regarding the primary outcome (OR 0.82; 95%CI, 0.48 - 1.42; p = 0.488), but there was an increased risk of catheter-related bloodstream infection when renal replacement therapy was initiated early (OR 1.77; 95%CI, 1.01 - 3.11; p = 0.047). The quality of evidence generated by our meta-analysis for the primary outcome was considered low due to the risk of bias of the included studies and the heterogeneity among them. CONCLUSION: Early initiation of renal replacement therapy is not associated with improved survival. However, the quality of the current evidence is low, and the criteria used for -early- and -delayed- initiation of renal replacement therapy are too heterogeneous among studies.

OBJETIVO: Avaliar se, em comparação ao início tardio, o início precoce da terapia de substituição renal se associa com menor mortalidade em pacientes com lesão renal aguda. MÉTODOS: Conduzimos uma revisão sistemática e metanálise de ensaios clínicos randomizados e controlados, que compararam terapia de substituição renal com início precoce àquela com início tardio em pacientes com lesão renal aguda, sem sintomas relacionados à insuficiência renal aguda que oferecessem risco à vida, como sobrecarga hídrica ou distúrbios metabólicos. Dois investigadores extraíram os dados a partir de estudos selecionados. Utilizaram-se a ferramenta Cochrane Risk of Bias, para avaliar a qualidade dos estudos, e a abordagem Grading of Recommendations Assessment, Development and Evaluation (GRADE), para testar a qualidade geral da evidência. RESULTADOS: Incluíram-se seis estudos clínicos randomizados e controlados (1.292 pacientes). Não houve diferença estatisticamente significante entre o início precoce e tardio da terapia de substituição renal, no que se referiu ao desfecho primário (OR 0,82; IC95% 0,48 - 1,42; p = 0,488). Foi maior o risco de infecção da corrente sanguínea relacionada ao cateter quando a terapia de substituição renal foi iniciada precocemente (OR 1,77; IC95% 1,01 - 3,11; p = 0,047). A qualidade da evidência gerada por nossa metanálise para o desfecho primário foi considerada baixa, em razão do risco de viés dos estudos incluídos e da heterogeneidade entre eles. CONCLUSÃO: O início precoce da terapia de substituição renal não se associou com melhora da sobrevivência. Entretanto, a qualidade da evidência atual é baixa, e os critérios utilizados para início precoce e tardio da terapia de substituição renal foram demasiadamente heterogêneos entre os estudos.

Assessment of fluid responsiveness in spontaneously breathing patients: a systematic review of literature.

Patients who increase stoke volume or cardiac index more than 10 or 15% after a fluid challenge are usually considered fluid responders. Assessment of fluid responsiveness prior to volume expansion is critical to avoid fluid overload, which has been associated with poor outcomes. Maneuvers to assess fluid responsiveness are well established in mechanically ventilated patients; however, few studies evaluated maneuvers to predict fluid responsiveness in spontaneously breathing patients. Our objective was to perform a systematic review of literature addressing the available methods to assess fluid responsiveness in spontaneously breathing patients. Studies were identified through electronic literature search of PubMed from 01/08/2009 to 01/08/2016 by two independent authors. No restrictions on language were adopted. Quality of included studies was evaluated with Quality Assessment of Diagnostic Accuracy Studies tool. Our search strategy identified 537 studies, and 9 studies were added through manual search. Of those, 15 studies (12 intensive care unit patients; 1 emergency department patients; 1 intensive care unit and emergency department patients; 1 operating room) were included in this analysis. In total, 649 spontaneously breathing patients were assessed for fluid responsiveness. Of those, 340 (52%) were deemed fluid responsive. Pulse pressure variation during the Valsalva maneuver (∆PPV) of 52% (AUC ± SD: 0.98 ± 0.03) and passive leg raising-induced change in stroke volume (∆SV-PLR) > 13% (AUC ± SD: 0.96 ± 0.03) showed the highest accuracy to predict fluid responsiveness in spontaneously breathing patients. Our systematic review indicates that regardless of the limitations of each maneuver, fluid responsiveness can be assessed in spontaneously breathing patients. Further well-designed studies, with adequate simple size and power, are necessary to confirm the real accuracy of the different methods used to assess fluid responsiveness in this population of patients.

Prevalence of HLA DQB1*0602 allele in patients with migraine.

BACKGROUND: Studies have shown a high prevalence of migraine among narcoleptic patients. HLA-DQB1*0602 and HLA DRB1 alleles are closely associated with narcolepsy. An increase in the HLA-DRB1 allele frequency in patients with visual aura has raised greater awareness of the genetic background in migraine. PURPOSE: Since the regions DR and DQ of the HLA are in tightly linkage desiquilibrium we hypothesize that HLA-DQB1*0602 might be associated to the pathophysiology of migraine. METHOD: We analyzed the presence of HLA DQB1*0602 allele in 50 healthy subjects with no history of migraine, 53 patients with migraine without aura and 52 patients with migraine with aura. RESULTS: There was no difference in the frequency of HLA DQB1*0602 allele when control subjects and all patients were compared. We failed to note any difference in frequencies when comparing migraine patients with and without aura. CONCLUSION: Further studies with different patient populations, with other hypothalamic markers (melatonin, hypocretin) in migraine patients may shed light on to its pathophysiology.

A study of T CD4, CD8 and B lymphocytes in narcoleptic patients.

UNLABELLED: Narcolepsy is characterized by excessive daytime sleep and cataplexy. Little is known about the possible difference in pathophysiology between patients with or without cataplexy. OBJECTIVE: To quantify T CD4, T CD8 and B lymphocytes in subgroups of patients with narcolepsy and the presence or absence of the HLA-DQB1*0602 allele between groups. METHOD: Our study was prospective and controlled (transversal) with 22 narcoleptic patients and 23 health control subjects. Patients underwent an all-night polysomnographic recording (PSG) and a multiple sleep latency Test (MSLT). The histocompatibility antigen allele (HLA-DQB1*0602), T CD4, CD8 and B lymphocytes were quantified in control subjects and in narcoleptics. RESULTS: The HLA-DQB1*0602 allele was identified in 10 (62.5%) of our 16 cataplexic subjects and in 2 (33.3%) of the 6 patients without cataplexy (p=0.24). In control subjects, HLA-DQB1*0602 allele was identified in 5 (20%). A significant decrease in T CD4 and B lymphocytes was found in narcoleptic patients with recurrent cataplexy when compared with our patients without cataplexy. CONCLUSION: Autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis were associated with a decrease in sub-group of T CD4 and B lymphocytes. A drop in B lymphocytes count in reumathoid arthritis might, it is posited, be correlated to the presence of HLA-DRB1 allele along with an overall worsened outcome of the affliction. The theory of an increase in consumption of B lymphocytes over the maturation phase has likewise been put forward. Our study reinforces the view that narcolepsy should be considered from an immunological perspective.

Noncompaction of the left ventricle: a new cardiomyopathy is presented to the clinician.

Noncompaction of the left ventricular myocardium is a morphogenetic abnormality involving loss of compaction of the myocardial fiber meshwork during intrauterine life. It is an extremely rare condition, accounting for only 0.05% of the cases evaluated in databanks. It has been described in both genders, in many ethnic groups and at different ages. Recently published studies of case series have shown a high mortality rate among these patients during follow-up of up to 48 months. Many cases have so far been misdiagnosed due to poor knowledge of the findings relating to this syndrome. There needs to be an attempt at early and accurate diagnosis, because of the need to investigate the patients family upon such diagnosis, and today this can be achieved using echocardiographic criteria.

Sedation in mechanically ventilated patients-time to stay awake?

On June, 2016, Klompas and colleagues published an article in the Chest entitled "Associations between different sedatives and ventilator-associated events, length of stay, and mortality in patients who were mechanically ventilated", which investigated the effects of different sedatives on ventilator-associated events (VAEs), length of stay, and mortality in patients who were mechanically ventilated. This study used data of over 9,603 patients in order to investigate patients over the age of 18 who underwent mechanical ventilation for more than 3 days over a 7-year period in a large academic medical center. The investigators found that propofol and dexmedetomidine were associated with less time to extubation compared with benzodiazepines, but dexmedetomidine was also associated with less time to extubation vs. propofol. This study raises important questions about the sedation of critically ill patients.