Cardiac Injuries at Estonian Major Trauma Facilities: A 23-year Perspective.

BACKGROUND AND AIMS: Cardiac injuries are highly lethal lesions following trauma and most of the patients decease in pre-hospital settings. However, studies on cardiac trauma in Estonia are scarce. Thus, we set out to study cardiac injuries admitted to Estonian major trauma facilities during 23 years of Estonian independence. MATERIALS AND METHODS: After the ethics review board approval, all consecutive patients with cardiac injuries per ICD-9 (861.0 and 861.1) and ICD-10 codes (S.26) admitted to the major trauma facilities between 1 January 1993 and 31 July 2016 were retrospectively reviewed. Cardiac contusions were excluded. Data collected included demographics, injury profile, and in-hospital outcomes. Primary outcome was mortality. Secondary outcomes were cardiac injury profile and hospital length of stay. RESULTS: During the study period, 37 patients were included. Mean age was 33.1 ± 12.0 years and 92% were male. Penetrating and blunt trauma accounted for 89% and 11% of the cases, respectively. Thoracotomy and sternotomy rates for cardiac repair were 80% and 20%, respectively. Most frequently injured cardiac chamber was left ventricle at 49% followed by right ventricle, right atrium, and left atrium at 34%, 17%, and 3% of the patients, respectively. Multi-chamber injury was observed at 5% of the cases. Overall hospital length of stay was 13.5 ± 16.7 days. Overall mortality was 22% (n = 8) with uniformly fatal outcomes following left atrial and multi-chamber injuries. CONCLUSION: Overall, 37 patients with cardiac injuries were hospitalized to national major trauma facilities during the 23-year study period. The overall in-hospital mortality was 22% comparing favorably with previous reports. Risk factors for mortality were initial Glasgow Coma Scale < 9, pre-hospital cardiopulmonary resuscitation, and alcohol intoxication.

Population-Based Autopsy Study of Traumatic Fatalities.

BACKGROUND: Injuries result in 5.8 million global fatalities annually and are the leading cause of death in younger individuals. Nevertheless, population-based autopsy investigations on traumatic deaths are scarce. We set out to study all consecutive autopsies on traumatic fatalities performed in a 5-year time segment in Estonia. METHODS: After the ethics review board approval, all consecutive autopsies after blunt or penetrating deaths occurring in prehospital or in-hospital settings between January 1, 2009, and December 31, 2013, were retrospectively reviewed using the National Forensic Medicine Database. Fatalities due to suffocation, intoxication, burns, or freezing were excluded. Data collection included demographics, mechanism of injuries, cause of death, and a detailed injury profile. Primary outcome was cause of death. Secondary outcomes included injury patterns. RESULTS: Overall, 1344 autopsies were included. 75.7% of deaths were following blunt trauma. Mean age was 50.4 ± 18.5 years, and 77.1% were male. A total of 71.8% of deaths occurred in the prehospital setting. Accidents, assaults, and suicides constituted 64.4, 20.5, and 15.2% of deaths, respectively. A total of 51.1% of injury fatalities had a positive blood alcohol level (BAL). Mean injury severity score was 39.7 ± 23.9. Most common cause of death was due to head injuries at 50.5% followed by hemorrhage at 30.4%. Cardiac and aortic injuries were the predominant cause of hemorrhage-related fatalities. CONCLUSIONS: The current population-based investigation documented brain injury as the predominant cause of death followed by cardiac and aortic injuries. High incidence of positive BAL among injury fatalities requires national initiatives for alcohol harm reduction and law enforcement efforts.

Synthesis, hydrolysis and anti-EBV activity of a series of 3'-modified cycloSal-BVDUMP pronucleotides.

A series of cycloSal-BVDUMP phosphate triesters has been prepared. The prototype compound was 3-methyl-cycloSal-BVDUMP 2. Furthermore, a series of 3'-O-acyl-modified derivatives having carboxylic acids with different lipophilicity or a L-configurated alpha-amino acid (phenylalanine) was prepared. The hydrolysis properties in phosphate buffer PBS as well as in PBS containing pig liver esterase (PLE) will be described. Finally, the biological activity against EBV has been determined.

Inhibitory effect of cycloSaligenyl-nucleoside monophosphates (cycloSal-NMP) of acyclic nucleoside analogues on HSV-1 and EBV.

The in vitro antiviral activity of a new series of cycloSal-pro-nucleotides derived from the acyclic nucleoside analogues aciclovir and penciclovir against herpes simplex virus type 1 (HSV-1), thymidine kinase deficient (TK-) HSV-1, and Epstein-Barr virus (EBV) was evaluated. Using the XTT-based tetrazolium reduction assay EZ4U, the cycloSal derivatives were examined for their antiviral and cytotoxic effects in HSV-1 as well as HSV-1-TK--infected Vero cells. The anti-EBV activity was assessed by means of an EBV DNA hybridization assay using a digoxigenin-labeled probe specific for the Bam H1-W-fragment of the EBV genome and by measuring viral capsid antigen (VCA) expression in P3HR-1 cells by indirect immunofluorescence. Among the new cycloSal-phosphotriesters the three aciclovir monophosphates proved to be potent and selective inhibitors of HSV-1 replication, EBV DNA synthesis and EB-VCA expression. Of interest is the retention of activity of the aciclovir monophosphates in HSV-1-TK--infected cells. Particularly 3-methyl-cycloSal-aciclovir monophosphate retained the same effectiveness, as compared to the wild type virus strain. In contrast to the aciclovir pro-nucleotides the penciclovir cycloSal-phosphotriesters exhibited at best only a marginal antiviral effect on HSV and EBV replication.

Evidence for cyclophosphate formation during hydrolysis of 3-methyl-cycloSal-PCVMP.

A hydrolysis study of 3-methyl-cycloSal-PCVMP 2 is described. Surprisingly, phosphotriester 5 released in this study not the expected PCVMP, but cycloPCVMP.

Chemistry and anti-herpes simplex virus type 1 evaluation of cycloSal-nucleotides of acyclic nucleoside analogues.

The synthesis of different cycloSal-phosphotriesters of the acyclic nucleoside analogues acyclovir (ACV), penciclovir (PCV) and T-penciclovir (T-PCV) as potential new lipophilic, membrane-soluble pronucleotides is described. The introduction of the cycloSal moiety was achieved by using reactive cyclic chlorophosphane reagents. In addition to the cycloSal-PCV monophosphate (MP) phosphotriesters, a second derivative bearing an acetyl group at the second primary alcohol function was prepared. In hydrolysis studies the cycloSal-ACVMPs showed the expected range of hydrolytic stability dependent on the substituent in the masking group (8-17 h). In contrast, the cycloSal-PCVMP derivatives exhibited a 11- to 15-fold increase in hydrolytic lability as compared to the corresponding cycloSal-ACVMP derivatives. We demonstrated that the free primary alcohol group is responsible for this rate acceleration because cycloSal-OAc-PCVMP, in which the hydroxyl group was blocked by acetylation, did not show the aforementioned acceleration. Unexpectedly, the hydrolysis product was not PCVMP but according to NMR and mass spectrometry it was cycloPCVMP (cPCVMP). The title compounds were evaluated in vitro for their ability to inhibit herpes simplex virus type 1 (HSV-1) and thymidine kinase-negative (TK-) HSV-1 replication in Vero cells. The cycloSal-ACVMP compounds exhibited high antiviral activity in HSV-1-infected cells. More importantly, one derivative retained all activity from the wild-type virus strain in HSV-1/TK(-)-infected Vero cells. The PCV derivatives were markedly less active. The reason for the failure of the cycloSal-PCVMPs seems to be due to the formation of cPCVMP instead of the desired PCVMP.