Somatically Acquired LINE‐1 Insertions in Normal Esophagus Undergo Clonal Expansion in Esophageal Squamous Cell Carcinoma

Squamous cell carcinoma of the esophagus (SCC) is the most common form of esophageal cancer in the world and is typically diagnosed at an advanced stage when successful treatment is challenging. Understanding the mutational profile of this cancer may identify new treatment strategies. Because somatic retrotransposition has been shown in tumors of the gastrointestinal system, we focused on LINE‐1 (L1) mobilization as a source of genetic instability in this cancer. We hypothesized that retrotransposition is ongoing in SCC patients. The expression of L1 encoded proteins is necessary for retrotransposition to occur; therefore, we evaluated the expression of L1 open reading frame 1 protein (ORF1p). Using immunohistochemistry, we detected ORF1p expression in all four SCC cases evaluated. Using L1‐seq, we identified and validated 74 somatic insertions in eight tumors of the nine evaluated. Of these, 12 insertions appeared to be somatic, not genetically inherited, and sub‐clonal (i.e., present in less than one copy per genome equivalent) in the adjacent normal esophagus (NE), while clonal in the tumor. Our results indicate that L1 retrotransposition is active in SCC of the esophagus and that insertion events are present in histologically NE that expands clonally in the subsequent tumor.     

Patients with Acute Lacunar Infarction Have Benefit from Intravenous Thrombolysis

Introduction: Usefulness of intravenous thrombolysis in patients with acute lacunar cerebral infarction is questionable. The aim of this study was to evaluate the efficacy and safety of intravenous thrombolysis in patients with lacunar infarction in comparison with patients with nonlacunar infarction as well as with patients with lacunar infarction who were not treated with intravenous thrombolysis. Materials and methods: In the first part of the study, among patients with acute ischemic stroke treated with intravenous thrombolysis, characteristics and outcomes of 46 patients with lacunar and 221 patients with nonlacunar infarction were compared. In the second part, 46 patients with lacunar infarction treated with intravenous thrombolysis were compared with 45 lacunar infarction patients who were not treated with intravenous thrombolysis. Results: Patients with lacunar infarction had a lower National Institutes of Health Stroke Scale score (9.2 versus 13.9, P < .001), a greater Alberta Stroke Program Early computed tomography (CT) score (9.7 versus 9.2, P?=?.002), a lower prevalence of atrial fibrillation (6.5% versus 41.2%, P < .001), and significantly more frequently an excellent outcome after 3 months (76.1% versus 36.2%, P < .001) compared with patients with nonlacunar infarction. Among patients with lacunar infarction, an excellent outcome at discharge was significantly more frequent in the intravenous thrombolysis group (41.3% versus 15.6%, P?=?.01), and the length of hospitalization was significantly shorter (9.5 days versus 14.3 days, P?=?.002). There was no hemorrhagic transformation among patients with lacunar infarction treated with intravenous thrombolysis. Conclusion: Intravenous thrombolysis has proven to be effective and safe in patients with lacunar infarction and should always be applied if there are no absolute contraindications.     

Musculoskeletal ultrasonography in routine rheumatology practice: data from Central and Eastern European countries

The main aim was to gain structured insight into the use of musculoskeletal ultrasonography (MSUS) in routine rheumatology practices in Central and Eastern European (CEE) countries. In a cross-sectional, observational, international, multicenter survey, a questionnaire was sent to investigational sites in CEE countries. Data on all subsequent routine MSUS examinations, site characteristics, MSUS equipment, and investigators were collected over 6 months or up to 100 examinations per center. A total of 95 physicians at 44 sites in 9 countries provided information on a total of 2810 MSUS examinations. The most frequent diagnoses were rheumatoid arthritis (RA) and spondyloarthritis (34.8 and 14.9 % of cases, respectively). Mean number of joints examined was 6.8. MSUS was most frequently performed for diagnostic purposes (58 %), particularly in patients with undifferentiated arthritis, suspected soft tissue disorders, or osteoarthritis (73.0–85.3 %). In RA patients, 56.3 % of examinations were conducted to monitor disease activity. Nearly all investigations (99 %) had clinical implications, while the results of 78.6 % of examinations (51.6–99.0 %) were deemed useful for patient education. This first standardized multicountry survey performed in CEEs provided a structured documentation of the routine MSUS use in participating countries. The majority of MSUS examinations were performed for diagnostic purposes, whereas one-third was conducted to monitor disease activity in RA. A majority of examinations had an impact on clinical decision making and were also found to be useful for patient education.     

Multiple stabbing in sex-related homicides

It is possible that sexually driven homicides are the consequence of sexual deviation, but more often than not the main cause of such homicides stems from a non-paraphilic person’s emotional component. It is known that homicides which involve multiple stabbing are very often the result of the assailant’s highly expressed affect. This study tries to establish whether such homicides are essentially related to the sexual motives of the murderer. This paper is conducted through a retrospective autopsy study that includes 766 cases of homicides. These were reviewed and analysed according to the motive of the homicide, as well as by method, age, and gender of the victim, and the relationship between the victim and the assailant. The motives of homicides are classified as non-sexual and sexual, including homicides related to rape, jealousy, amorous affairs outside of an established relationship, deviant sexual behaviour of psychiatric patients, paraphilia, and disturbed emotional relationships between the victim and the assailant. Cases include both hetero- and homosexual relationships. Multiple stabbing occurs significantly more frequently in sex-related homicides (≥3 stab wounds) than in other homicide types. When the criteria for multiple stabbing are changed (≥4, 5, or 25 stab wounds), the percentage of sex-related homicides rises in every group in relation to the increased number of wounds. Sensitivity and specificity are represented by ROC curves for 3, 5 and 7 stab wounds. The correlation coefficients between multiple stabbing and sex-related homicides regarding gender are all near 0.9. For female victims, all homicides committed by 25 and more stab wounds were found to be sex-related. Statistically, jealousy was the most frequent motive for sex-related multiple stabbing homicides. Regardless of age, homicides involving multiple stabbings should be considered sex-related, especially when the victim is female.     

Craniocerebral injuries in traffic accidents with fatal outcomes

Research into crainiocerebral injury (CCI) characteristics of traffic accidents with fatal outcomes, as well as certain types of CCIs and defined categories of traffic participants, has been conducted. The research data were obtained from autopsy protocols at the Institute of Forensic Medicine in Serbia. Out of the 202 cases of individuals who had been fatally injured in traffic accidents, CCIs were diagnosed in 82.7% of them. The highest percentage of CCIs was established for front-seat passengers (95%), while for drivers it was 86.2%, pedestrians 78%, and 76% for rear-seat passengers. The domination of males among the deceased was also found, mostly as drivers (92%). The majority of individuals who experienced a CCI were in the age group of 21 to 30 years old, while pedestrians were commonly older than 60. In these cases, a high frequency of skull fractures was usually localized in different cranial regions (67.7%). In the majority of cases with CCIs (81.4%), these injuries contributed to an ultimate fatal outcome, mainly in pedestrians (93%). Fatal and non-fatal CCIs resulting from traffic accidents can result in significant socio-economic consequences for the individual and society as a whole that include specifically the ongoing costs and outcomes in cases from non-fatal injuries.     

Are COX‐2 inhibitors preferable to combined NSAID and PPI in countries with moderate health service expenditures?

Rationale In developed countries, cyclooxygenase 2 (COX‐2) inhibitors were shown to be less costly than the combination of non‐steroidal anti‐inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) in treatment of patients with high risk of serious gastrointestinal (GI) adverse effects. It is questionable if such results apply to developing countries where health service costs are lower and there is high discrepancy between generic and patent protected drug prices. We analysed the direct cost of treatment with generic NSAIDs in combination with PPIs versus branded COX‐2 inhibitors in patients with high risk of serious GI adverse effects from the perspective of the public health service in Serbia. Methods Total cost of treatment of serious GI complications and the use of NSAID+PPI versus COX‐2 inhibitors were calculated. A model for estimation of cost of treatment of NSAID+PPI versus COX‐2 inhibitors which included the probability of developing serious GI adverse effects was developed. Results Total cost of treatment of serious GI adverse effects resulted in an average of $814/patient. Considering the relative risk of such adverse effects for patients with four or more risk factors, the least costly treatment over 6 months was the use of celecoxib ($487). Compared with diclofenac+omeprazole, cost savings were estimated at $59 and $22 per patient with celecoxib and etoricoxib, respectively. Conclusion Cost savings may be achieved by using COX‐2 inhibitors in patients at high risk of GI adverse effects even in countries with moderate health care service expenditures. Such possibility requires further investigation.