Marcin Fudalej

Clinical and Genetic Risk Factors for Suicide under the Influence of Alcohol in a Polish Sample

AIMS Despite the large number of suicides that occur with intoxication, little is known about the unique predictors of suicide after alcohol consumption. The goal of this study was to examine clinical and genetic risk factors for alcohol-related suicide. METHODS Data on 162 suicide victims were obtained from post-mortem examinations, police and prosecution inquiries, autopsy protocols and available medical records. Four single nucleotide polymorphisms in the central serotonin system and the renin-angiotensin system related genes previously found to be associated with suicide, alcohol dependence or depression were genotyped. RESULTS The strongest predictor of suicide under the influence of alcohol was alcohol dependence (OR = 4.63). Those who did not drink alcohol before suicide were more likely to have a diagnosis of major depressive disorder in their medical record and more often had the TT genotype of the tryptophan hydroxylase 2 gene. CONCLUSIONS Suicide under the influence of alcohol is strongly connected with alcohol dependence. The TPH2 gene may play an important role in suicide vulnerability especially in individuals who did not drink alcohol before suicide.

Possible association between suicide committed under influence of ethanol and a variant in the AUTS2 gene

Background rs6943555 in AUTS2 has been shown to modulate ethanol consumption. We hypothesized that rs6943555 might be associated with completed suicide. Methods We genotyped rs6943555 in 625 completed suicides and 3861 controls using real-time TaqMan Allelic Discrimination Assay. All individuals were Polish Caucasians. Results We detected an association between suicide and rs6943555 A allele (OR = 1.17, P = 0.018 for allelic comparison, OR = 1.24, P = 0.013 for dominant, and OR = 1.18, P = 0.020 for co-dominant model of inheritance). The association remained significant after adjusting for age and gender (co-dominant: P = 0.002 and dominant model: P = 0.001). After stratifying suicides according to blood ethanol concentration (BAC≤ 20 mg/dl and BAC > 20 mg/dl) the association remained significant only for cases who committed suicide under influence of alcohol (co-dominant: OR  =  1.37, P = 0.004 and dominant model: OR = 1.45, P = 0.006). To validate this finding we genotyped another cohort of 132 cases. We reproduced the association between rs6943555 A allele and suicide under influence of ethanol (allelic comparison: OR = 1.55, P = 0.023; co-dominant : OR = 1.54, P = 0.031; dominant model: OR = 1.84, P = 0.015). Analyzing pooled suicides with BAC >20 mg/dl (N = 300) we found the association of rs6943555 A allele not only vs. controls (allelic OR = 1.41, P = 0.00029) but also vs. cases with BAC ≤ 20 mg/dl (N = 449, allelic OR = 1.33, P = 0.019). Conclusions In our study rs6943555 A allele is associated with suicide committed after drinking ethanol shortly before death. The rs6943555 A allele may be linked to adverse emotional reaction to ethanol, which could explain the association with lower consumption in general population as well as the predisposition to suicide under influence of ethanol.

Angiotensin-Converting Enzyme Polymorphism and Completed Suicide: An Association in Caucasians and Evidence for a Link with a Method of Self-Injury

Background/Aims: An association between the II genotype of the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism and suicide was found among Japanese men. Our purpose was to replicate this finding in Caucasians and explore other putative genotypic associations among suicides. Methods: The ACE genotypes were studied by a 2-stage PCR method in 150 completed suicides and 165 age- and sex-matched controls. Results: We found an increase in the frequency of the ACEI allele among male victims of suicide compared to male controls (odds ratio, OR = 1.69, p < 0.006), female suicides (OR = 2.01, p = 0.006) and pooled controls (OR = 1.77, p = 0.001). Analysis of genotype distribution showed that the codominant model had the best fit (p = 0.7) whereas the recessive model could be rejected (p = 0.04). Among males we found an association between the number of the ACE I allele and the method of suicide: OR = 17.98, pcorrected = 0.00003, for jumping from a height; OR = 0.36, pcorrected = 0.048, for hanging. We also observed a trend for a negative effect of the number of copies of the ACE I allele on prevalence of depression (OR = 0.36, p = 0.013) and a trend for an effect on age at death (p = 0.021). Conclusions: Our results suggest that low ACE activity associated with the I allele is a risk factor for suicide, especially in a subset of males. This may be of concern given the widespread use of drugs lowering ACE activity.

A comparison of a traditional endotracheal tube versus Etview Sl in endotracheal intubation during different emergency conditions: A randomized, crossover cadaver trial

Background:Airway management is a crucial skill essential to paramedics and personnel working in Emergency Medical Services and Emergency Departments: Lack of practice, a difficult airway, or a trauma situation may limit the ability of paramedics to perform direct laryngoscopy during cardiopulmonary resuscitation. Videoscope devices are alternatives for airway management in these situations. The ETView VivaSight SL (ETView; ETView Ltd., Misgav, Israel) is a new, single-lumen airway tube with an integrated high-resolution imaging camera. To assess if the ETView VivaSight SL can be a superior alternative to a standard endotracheal tube for intubation in an adult cadaver model, both during and without simulated CPR. Methods:ETView VivaSight SL tube was investigated via an interventional, randomized, crossover, cadaver study. A total of 52 paramedics participated in the intubation of human cadavers in three different scenarios: a normal airway at rest without concomitant chest compression (CC) (scenario A), a normal airway with uninterrupted CC (scenario B) and manual in-line stabilization (scenario C). Time and rate of success for intubation, the glottic view scale, and ease-of-use of ETView vs. sETT intubation were assessed for each emergency scenario. Results:The median time to intubation using ETView vs. sETT was compared for each of the aforementioned scenarios. For scenario A, time to first ventilation was achieved fastest for ETView, 19.5 [IQR, 16.5–22] sec, when compared to that of sETT at 21.5 [IQR, 20–25] sec (p = .013). In scenario B, the time for intubation using ETView was 21 [IQR, 18.5–24.5] sec (p < .001) and sETT was 27 [IQR, 24.5–31.5] sec. Time to first ventilation for scenario C was 23.5 [IQR, 19–25.5] sec for the ETView and 42.5 [IQR, 35–49.5] sec for sETT. Conclusions:In normal airways and situations with continuous chest compressions, the success rate for intubation of cadavers and the time to ventilation were improved with the ETView. The time to glottis view, tube insertion, and cuff block were all found to be shorter with the ETView. Trial Registration:clinicaltrials.gov Identifier: NCT02733536.

A Randomized Cadaver Study Comparing First-Attempt Success Between Tibial and Humeral Intraosseous Insertions Using NIO Device by Paramedics: A Preliminary Investigation.

Abstract Medical personnel may encounter difficulties in obtaining intravenous (IV) access during cardiac arrest. The 2015 American Heart Association guidelines and the 2015 European Resuscitation Council guidelines for cardiopulmonary resuscitation (CPR) suggest that rescuers establish intraosseous (IO) access if an IV line is not easily obtainable. The aim of the study was to compare the success rates of the IO proximal tibia and proximal humerus head access performed by paramedics using the New Intraosseous access device (NIO; Persys Medical, Houston, TX, USA) in an adult cadaver model during simulated CPR. In an interventional, randomized, crossover, single-center cadaver study, a semi-automatic spring-load driven NIO access device was investigated. In total, 84 paramedics with less than 5-year experience in Emergency Medical Service participated in the study. The trial was performed on 42 adult cadavers. In each cadaver, 2 IO accesses to the humerus head, and 2 IO accesses to the proximal tibia were obtained. The success rate of the first IO attempt was 89.3% (75/84) for tibial access, and 73.8% (62/84) for humeral access (P = 0.017). The procedure times were significantly faster for tibial access [16.8 (interquartile range, IQR, 15.1–19.9] s] than humeral access [26.7 (IQR, 22.1–30.9) s] (P < 0.001). Tibial IO access is easier and faster to put in place than humeral IO access. Humeral IO access can be an alternative method to tibial IO access. Trial Registration: clinicaltrials.gov Identifier: NCT02700867.

Ability of paramedics to perform endotracheal intubation during continuous chest compressions: a randomized cadaver study comparing Pentax AWS and Macintosh laryngoscopes☆☆☆★

OBJECTIVE The aim of the trial was to compare the time parameters for intubation with the use of the Macintosh (MAC) laryngoscope and Pentax AWS-S100 videolaryngoscope (AWS; Pentax Corporation, Tokyo, Japan) with and without chest compression (CC) by paramedics during simulated cardiopulmonary resuscitation in a cadaver model. METHODS This was a randomized crossover cadaver trial. Thirty-five paramedics with no experience in videolaryngoscopy participated in the study. They performed intubation in two emergency scenarios: scenario A, normal airway without CC; scenario B, normal airway with continuous CC. RESULTS The median time to first ventilation with the use of the AWS and the MAC was similar in scenario A: 25 (IQR, 22-27) seconds vs. 24 (IQR, 22.5-26) seconds (P=.072). A statistically significant difference in TTFV between AWS and MAC was noticed in scenario B (P=.011). In scenario A, the first endotracheal intubation (ETI) attempt success rate was achieved in 97.1% with AWS compared with 94.3% with MAC (P=.43). In scenario B, the success rate after the first ETI attempt with the use of the different intubation methods varied and amounted to 88.6% vs. 77.1% for AWS and MAC, respectively (P=.002). CONCLUSIONS The Pentax AWS offered a superior glottic view as compared with the MAC laryngoscope, which was associated with a higher intubation rate and a shorter intubation time during an uninterrupted CC scenario. However, in the scenario without CC, the results for AWS and MAC were comparable.

Analysis of four genes involved in the neurodevelopment shows association of rs4307059 polymorphism in the cadherin 9/10 region with completed suicide.

Background: We hypothesized that DNA variants affecting neurodevelopment such as rs4307059 (CDH10/CDH9), rs930752 (NRXN1), rs6265 (BDNF) or rs10868235 (NTRK2) may predispose to completed suicide. Methodology: We used a case-control two-stage approach based on a discovery cohort (557 cases and ∼550 controls) and replication cohort (159 cases and 186 controls). The suicides were ascertained as consecutive cases autopsied at the Department of Forensic Medicine, Medical University of Warsaw, Poland. Results: In the discovery cohort we found an association between suicide and the CC genotype in the rs4307059 polymorphism (OR 1.64, p = 0.012). The trend for an overrepresentation of the CC homozygotes among suicides was replicated in the second cohort (OR 1.97, p = 0.056). Analysis in the pooled cohorts showed that rs4307059 CC was associated with completed suicide (OR 1.71, p = 0.002) also after Bonferroni correction (pcor. = 0.024). In an exploratory search for genotype-phenotype correlation we found that males with the rs4307059 CC genotype committed suicide earlier than those with CT/TT genotypes (p = 0.049). Conclusions: The CC genotype of rs4307059 located in the region between CDH9 and CDH10 is associated with completed suicide in a Polish cohort.

No association between MTHFR C677T polymorphism and completed suicide

MTHFR C677T polymorphism (rs1801133) was associated with numerous psychiatric conditions but no prior study investigated whether it predisposes to completed suicide. We typed rs1801133 in 692 suicide victims and 3257 controls representative of a Polish adult population (the WOBASZ cohort). Although we had a power of 0.8 to detect (at alpha 0.05) an allelic OR=1.19, we did not find significant difference among suicides vs. controls in the prevalence of the MTHFR 677T allele (OR=1.02, p=0.759) or the TT genotype (OR=1.01, p=0.926). Since among controls we found an association between TT and depression defined by Beck Depression Inventory (BDI, OR=1.61, p=0.049) we also compared suicides with controls without signs of depression (BDI ≤ 11) but found no association (OR=1.0, p=0.976). Analyses within suicides showed trends (not significant after Bonferroni correction) for correlations between the dose of the T allele and age at death among males and blood ethanol concentration among females, who committed suicide under the influence of alcohol. We conclude that MTHFR C677T polymorphism is not a risk factor for completed suicide. The sex-specific trends for correlations between rs1801133 and age at death, and blood ethanol concentration should be studied further.

LC-MS/MS method development and validation for quantitative analyses of 2-aminothiazoline-4-carboxylic acid--a new cyanide exposure marker in post mortem blood.

2-aminothiazoline-4-carboxylic acid (ATCA) is a hydrogen cyanide metabolite that has been found to be a reliable biomarker of cyanide poisoning, because of its long-term stability in biological material. There are several methods of ATCA determination; however, they are restricted to extraction on mixed mode cation exchange sorbents. To date, there has been no reliable method of ATCA determination in whole blood, the most frequently used material in forensic analysis. This novel method for ATCA determination in post mortem specimen includes protein precipitation, and derivatization of interfering compounds and their later extraction with ethyl acetate. ATCA was quantitatively analyzed via high performance liquid chromatography-tandem mass spectrometry with positive electrospray ionization detection using a hydrophilic interaction liquid chromatography column. The method satisfied all validation criteria and was tested on the real samples with satisfactory results. Therefore, this analytical approach has been proven to be a tool for measuring endogenous levels of ATCA in post mortem specimens. To conclude, a novel, accurate and sensitive method of ATCA determination in post mortem blood was developed. The establishment of the method provides new possibilities in the field of forensic science.

Ability of paramedics to perform intraosseous access. A randomized cadaver study comparing EZ-IO® and NIO® devices

We have read with great interest the article entitled ‘EZ-IO® ntraosseous access teaching in the workplace using a mobile “tea rolley” training method’ by Penketh et al.,1 describing a novel echnique for technical skill training. The success rate and time eeded for intravascular access are crucial during cardiopulmonary esuscitation (CPR), in order to administer fluids and drugs, in articular in case of trauma and non-shockable rhythms. Accordng to the 2015 European Resuscitation Council (ERC) Guidelines, ntraosseous (IO) access should be applied in adults if it is difficult r impossible to establish a peripheral venous access for CPR or ven in paediatrics as a first intravascular access method.2,3 As a onsequence, paramedics should be skilled in the use of IO devices. We have carried out a trial to evaluate the ability of paramedics o obtain an IO access during simulated CPR in an adult cadaver odel with the EZ-IO® as compared with the NIO® (NIO; Persys edical, Houston, TX, USA; Fig. 1) device. This prospective ranomized crossover cadaver study was approved by the Bioethics ommittee of the Medical University of Warsaw, Poland (approval o.: KB/22/2015) and it was conducted from November 2015 to ebruary 2016, as a complement of related previous studies.4,5 hirty-eight voluntary paramedics participated in the trial after iven their informed consent. None of them had previous experince with IO access devices. In a random order, they used the tested evices to perform IO access through proximal tibia in fresh adult 18–65 years old at the time of death up to 72 h after death) cadavers vailable thanks to the collaboration of the Department of Forensic edicine, Medical University of Warsaw, Poland (Supplementary ata: Fig. 2). Prior to the trial, all participants received a 5-minute