Splenic Artery Angioembolization is Associated with Increased Venous Thromboembolism.

BACKGROUND: Angioembolization has become an increasingly utilized adjunct for splenic preservation after trauma. Embolization of the splenic artery may produce a transient systemic hypercoagulable state. This study was designed to determine the risk of venous thromboembolism (VTE) in blunt trauma patients managed nonoperatively with splenic angioembolization, relative to those managed without. METHOD: Retrospective review of the American College of Surgeons Trauma Quality Improvement Performance (TQIP) Database from 2013 to 2016. Adult (>16 years) patients with isolated, severe (Grades III-V) blunt splenic injuries managed nonoperatively who received pharmacological VTE prophylaxis formed the study population. Outcomes included deep venous thrombosis (DVT), pulmonary embolism (PE), or any VTE. RESULTS: A total of 2643 patients met inclusion criteria (69.1% Grade III, 26.5% Grade IV, 4.5% Grade V). The incidence of DVT was 4.5% in patients who underwent angioembolization, compared to 1.4% in patients who did not (p<0.001). Multivariable analysis showed that angioembolization was an independent risk factor for both DVT (OR 2.65, p = 0.006) and any VTE (OR 2.04, p = 0.01). Analysis according to splenic injury Grades showed that angioembolization remained an independent risk factor for DVT (p = 0.004) in the Grade IV-V injury group, and for VTE (p<0.01) in the Grade III injury group. Initiation of pharmacological VTE prophylaxis 48 h after admission was associated with increased VTE rates in comparison to early initiation (OR 1.75, p = 0.02) CONCLUSIONS: Splenic artery angioembolization may be an independent risk factor for VTE events in isolated, severe blunt splenic trauma managed nonoperatively. Early prophylaxis with LMWH after intervention should be strongly considered.

Ocular swabs on exhumed bodies: An alternative to the collection of "classical" tissue samples in forensic genetics.

We present the results obtained on DNA extracted from ocular (scleral/corneal) swabs collected from exhumed bodies at different times of burial. To our knowledge, there are no publications in the scientific forensic literature dealing with sclera/cornea as a source of DNA in the forensic laboratory. The obtained results demonstrate that cornea/sclera swabbing might be a promising alternative to the sampling of other tissues for DNA extraction even in highly putrefied bodies.

Effect of whole body vibration frequency on neuromuscular activity in ACL-deficient and healthy males.

Whole-body vibration (WBV) has been shown to enhance muscle activity via reflex pathways, thus having the potential to contrast muscle weakness in individuals with rupture of the anterior cruciate ligament (ACL). The present study aimed to compare the magnitude of neuromuscular activation during WBV over a frequency spectrum from 20 to 45 Hz between ACL-deficient and healthy individuals. Fifteen males aged 28±4 with ACL rupture and 15 age-matched healthy males were recruited. Root mean square (RMS) of the surface electromyogram from the vastus lateralis in both limbs was computed during WBV in a static half-squat position at 20, 25, 30, 35, 40 and 45 Hz, and normalized to the RMS while maintaining the half-squat position without vibration. The RMS of the vastus lateralis in the ACL-deficient limb was significantly greater than in the contralateral limb at 25, 30, 35 and 40 Hz (P<0.05) and in both limbs of the healthy participants (dominant limb at 25, 30, 35, 40 and 45 Hz, P<0.05; non dominant limb at 20, 25, 30, 35, 40 and 45 Hz, P<0.05). The greater neuromuscular activity in the injured limb compared to the uninjured limb of the ACL-deficient patients and to both limbs of the healthy participants during WBV might be due to either augmented excitatory or reduced inhibitory neural inflow to motoneurons of the vastus lateralis through the reflex pathways activated by vibratory stimuli. The study provides optimal WBV frequencies which might be used as reference values for ACL-deficient patients.

Analysis of risk factors for pharyngocutaneous fistula after total laryngectomy with particular focus on nutritional status.

Pharyngocutaneous fistula (PCF) is the most common complication following total laryngectomy and the most difficult to manage. It often causes increased morbidity, delays starting adjuvant therapy, prolongs hospitalisation, increases treatment costs and reduces the quality of life (QoL). The objective of this study is to analyse the predisposing factors and the most important nutritional parameters related to the development of PCF in patients undergoing total laryngectomy and to suggest medical alternatives that might improve results. We performed a retrospective study of 69 patients who underwent either primary or salvage total laryngectomy in our department between January 2008 and January 2012. Risk factors for fistula formation were analysed including tumour characteristics (histology, grading, AJCC stage), treatment (primary or salvage surgery, extent of resection, flap reconstruction, preoperative radiotherapy), comorbidity and nutritional status (preoperative haemoglobin, albumin and prealbumin levels and their changes during hospitalisation). Twenty-four patients developed a PCF (overall incidence 34.8%). Fistula formation was significantly higher in patients with diabetes, preoperative malnutrition (identified from low preoperative albumin and prealbumin levels). After specific nutritional evaluation and support, no patient developed a PCF. Risk factors for PCF formation are extensively treated in the literature but identification of high-risk patients is still controversial. Our study demonstrates that nutritional status of the patient, assessed by preoperative albumin, is also an important risk factor for PCF formation in addition to classical factors. Maintenance of a normal perioperative nutritional status can be helpful to avoid this complication.

Development of an Italian RM Y-STR haplotype database: Results of the 2013 GEFI collaborative exercise.

Recently introduced rapidly mutating Y-chromosomal short tandem repeat (RM Y-STR) loci, displaying a multiple-fold higher mutation rate relative to any other Y-STRs, including those conventionally used in forensic casework, have been demonstrated to improve the resolution of male lineage differentiation and to allow male relative separation usually impossible with standard Y-STRs. However, large and geographically-detailed frequency haplotype databases are required to estimate the statistical weight of RM Y-STR haplotype matches if observed in forensic casework. With this in mind, the Italian Working Group (GEFI) of the International Society for Forensic Genetics launched a collaborative exercise aimed at generating an Italian quality controlled forensic RM Y-STR haplotype database. Overall 1509 male individuals from 13 regional populations covering northern, central and southern areas of the Italian peninsula plus Sicily were collected, including both "rural" and "urban" samples classified according to population density in the sampling area. A subset of individuals was additionally genotyped for Y-STR loci included in the Yfiler and PowerPlex Y23 (PPY23) systems (75% and 62%, respectively), allowing the comparison of RM and conventional Y-STRs. Considering the whole set of 13 RM Y-STRs, 1501 unique haplotypes were observed among the 1509 sampled Italian men with a haplotype diversity of 0.999996, largely superior to Yfiler and PPY23 with 0.999914 and 0.999950, respectively. AMOVA indicated that 99.996% of the haplotype variation was within populations, confirming that genetic-geographic structure is almost undetected by RM Y-STRs. Haplotype sharing among regional Italian populations was not observed at all with the complete set of 13 RM Y-STRs. Haplotype sharing within Italian populations was very rare (0.27% non-unique haplotypes), and lower in urban (0.22%) than rural (0.29%) areas. Additionally, 422 father-son pairs were investigated, and 20.1% of them could be discriminated by the whole set of 13 RM Y-STRs, which was very close to the theoretically expected estimate of 19.5% given the mutation rates of the markers used. Results obtained from a high-coverage Italian haplotype dataset confirm on the regional scale the exceptional ability of RM Y-STRs to resolve male lineages previously observed globally, and attest the unsurpassed value of RM Y-STRs for male-relative differentiation purposes.

Aesthetic comparison between synthetic glue and subcuticular sutures in thyroid and parathyroid surgery: a single-blinded randomised clinical trial.

The aim of our study was to compare, in terms of aesthetic results, the use of synthetic glue to intradermal absorbable sutures in postthyroidectomy and parathyroidectomy wound closure in a single blinded, randomised, per protocol equivalence study. From September 2008 to May 2010, patients undergoing thyroid or parathyroid surgery (with an external approach) at the Otolaryngology Department of the University Hospital of Modena were assessed for eligibility. In total, 42 patients who had had synthetic glue application on surgical incisions (A) and 47 patients who had subcuticular sutures on their surgical incisions (B) were enrolled. The mean of the endpoint (based on the Wound Registry Scale) of group A at 10 days was 1.4, while that in group B (based on the Stony Brook Scar Evaluation Scale) was 2.9. Statistically significant (p = 0.002) and clinically significant (difference of the means = 1.5) differences in the aesthetic results were found between groups A and B at 10 days, with better results in group B. On the other hand, at 3 months, the mean of the endpoint in group A was 3.1 while that in group B was 2.8; no statistically significant (p = 0.62) or clinically significant (difference in means = 0.3) differences were found between groups A and B. In conclusion, synthetic glue differs from subcuticular suture in post-thyroidectomy or post-parathyroidectomy incision for early aesthetic results, with better outcomes for subcuticular sutures. At 3 months, there were no differences in aesthetic outcomes between groups. Moreover, sex, incision length, age, cold/hot blade and correspondence of the incision with a wrinkle in the skin did not seem to influence aesthetic outcomes with this type of incision.

The 2011 GeFI collaborative exercise. Concordance study, proficiency testing and Italian population data on the new ENFSI/EDNAP loci D1S1656, D2S441, D10S1248, D12S391, D22S1045.

The 2011 collaborative exercise of the ISFG Italian Working Group GeFI was aimed at validating the five ENFSI/EDNAP miniSTR loci D1S1656, D2S441, D10S1248, D12S391 and D22S1045. The protocol required to type at least 50 multilocus profiles from locally resident individuals and two blind bloodstains in duplicate (i.e., using at least two different commercial kits), and to send the electropherograms to the Organizing Committee. Nineteen laboratories distributed across Italy participated, collecting a total of 960 samples. Full concordance was found for the five new miniSTRs as observed from the comparison of 13,150 alleles. The inspection of the electropherograms allowed the identification of a very limited number of mistypings in the miniSTR genotypes thus contributing to the establishment of an high quality Italian database of frequencies.

Bronchial selective ventilation in a wide tracheocutaneous fistula.

We present the treatment and management of a wide tracheocutaneous fistula after tracheotomy correlated with excessive cuff pressure in a 36-year-old woman with cerebral palsy since infancy in which persistent type II respiratory failure required continuous ventilatory support. We discuss the surgical treatment adopted for the management of this particularly wide lesion. At the end of surgery, mechanical ventilation through a tracheal cannula was hindered by the reduced length of the residual trachea below the tracheotomy. The need to guarantee mechanical ventilation to the patient led to the implementation of a cuff securing system in the two main bronchi. We describe the approach that may be attempted under extreme conditions, when traditional ventilation methods cannot be applied for anatomical reasons.

DAMPening inflammation by modulating TLR signalling.

Damage-associated molecular patterns (DAMPs) include endogenous intracellular molecules released by activated or necrotic cells and extracellular matrix (ECM) molecules that are upregulated upon injury or degraded following tissue damage. DAMPs are vital danger signals that alert our immune system to tissue damage upon both infectious and sterile insult. DAMP activation of Toll-like receptors (TLRs) induces inflammatory gene expression to mediate tissue repair. However, DAMPs have also been implicated in diseases where excessive inflammation plays a key role in pathogenesis, including rheumatoid arthritis (RA), cancer, and atherosclerosis. TLR activation by DAMPs may initiate positive feedback loops where increasing tissue damage perpetuates pro-inflammatory responses leading to chronic inflammation. Here we explore the current knowledge about distinct signalling cascades resulting from self TLR activation. We also discuss the involvement of endogenous TLR activators in disease and highlight how specifically targeting DAMPs may yield therapies that do not globally suppress the immune system.

Targeting Toll-like receptors in autoimmunity.

In the past few years there has been an increasing appreciation of the importance of Toll-like receptors (TLRs), not just in immunity, but also in autoimmune diseases. TLRs were first identified as sensors of viral and bacterial pathogens that form an integral part of the innate immune response. It was later discovered that these receptors can also respond to endogenous ligands that are produced as a result of tissue damage. This lead to the hypothesis that TLRs may be key contributors to the pathogenesis of chronic inflammatory conditions. A large body of data supporting the role of TLRs in autoimmunity has emerged from animal models and more data is increasingly being generated from human studies as further tools to examine these receptors have become available. Developing strategies to manipulate TLR function is of great interest in autoimmunity, as well as other diseases that include allergy and cancer. This review explores the evidence that points to a role for TLRs in autoimmunity and highlights some of the potential ways in which modulation of their action may yield clinical benefits.

Developing chemokine mutants with improved proteoglycan affinity and knocked-out GPCR activity as anti-inflammatory recombinant drugs.

The interaction of chemokines and GAGs (glycosaminoglycans) on endothelial surfaces is a crucial step for establishing a chemotactic gradient which leads to the functional presentation of chemokines to their GPCRs (G-protein-coupled receptors) and thus to activation of approaching leucocytes. Based on molecular modelling, biophysical investigations, cell-based and in vivo experiments, we have developed a novel concept for therapeutically interfering with chemokine-GAG interactions, namely dominant-negative chemokine mutants with improved GAG binding affinity and knocked-out GPCR activity. These recombinant proteins displace their wild-type chemokine counterparts from the natural proteoglycan co-receptors without being able to activate leucocytes via GPCRs. Our mutant chemokines therefore represent the first protein-based GAG antagonists with high therapeutic potential in inflammatory diseases.

International collaboration in mass disasters involving foreign nationals within the EU: medico-legal investigation of Finnish victims of the Milan Linate airport SAS SK 686 aircraft accident on 8 October 2001.

Identification of and investigation into the cause of death of foreign nationals in mass disasters are generally conducted according to the jurisdiction of the country in which the disaster occurs. However, such identification can be achieved only through co-operation with the authorities of the victims' countries of residence. On October 8th 2001 at Linate airport in Milan, Italy, an MD87 SAS airplane with 110 crew members and passengers on board collided on the ground with a Cessna Citation II jet with 2 pilots and 2 passengers. The plane then caught fire after having crashed into an airport baggage hangar causing the death of 4 other victims among the groundstaff. The accident claimed a total of 118 victims of 9 nationalities. Based on our experience from investigation of the Finnish victims, we explore how current national legislations of the EU member states and varying compliance with existing recommendations may influence the medico-legal investigation of a mass disaster. Legislative measures and further harmonisation of medico-legal procedures in connection with mass disasters within the EU are needed.

Molecular diagnosis in a child with sudden infant death syndrome.

Although sudden infant death syndrome (SIDS) has been associated with long QT syndrome-a genetic disorder that causes arrhythmia-a causal link has not been shown. We screened genomic DNA from a child who died of SIDS and identified a de-novo mutation in KVLQT1, the gene most frequently associated with long QT syndrome. This mutation (C350T) had already been identified in an unrelated family that was affected by long QT syndrome. These results confirm the hypothesis that some deaths from SIDS are caused by long QT syndrome and support implementation of neonatal electrocardiographic screening.

Y-chromosome haplotypes in Italy: the GEFI collaborative database.

A sample of 1176 males from 10 Italian regions have been typed for DYS19, DYS389-I, DYS389-II, DYS390, DYS391, DYS392, DYS393, and DYS385. Individual haplotype data are available on line. A low degree of variation is present among regions. Use of this database is specifically recommended for forensic applications in Italy.

Comparison of serum and liver hepatitis C virus quasispecies in HCV-related hepatocellular carcinoma.

BACKGROUND/AIMS: The hepatitis C virus (HCV) genome consists of quasispecies populations of heterogeneous variants, especially in the hypervariable region. To assess the profiles of viral quasispecies in HCV-related hepatocellular carcinoma, we studied the viral population patterns in serum and liver tissues of 13 HCV-positive patients with hepatocellular carcinoma developed on cirrhotic and non-cirrhotic livers (5 and 8 cases, respectively). METHODS: HCV genome heterogeneity was analyzed by polymerase chain reaction-mediated single-strand conformation polymorphism analysis, which showed multiple DNA bands representing different hypervariable region sequences. RESULTS: The HCV populations were different between tumorous and nontumorous tissues in 3/5 hepatocellular carcinomas with cirrhosis and in 6/8 without cirrhosis. At least one or more than one common band was detected in both compartments in all but one case. No significant differences in the complexity of HCV quasispecies were found in hepatocellular carcinoma with or without underlying cirrhosis. Comparison of the HCV quasispecies profiles in serum and liver tissues showed a different distribution of HCV variants between these two compartments in 6/7 patients. In four cases, both common and compartmentalized sequences were detected, whereas in two cases, both without cirrhosis, the HCV population in serum was completely different from that found in the liver. CONCLUSIONS: These results suggest that the complexity of HCV populations is influenced by the presence of hepatocellular carcinoma rather than by the severity of the underlying chronic liver disease. The different quasispecies patterns found in serum and liver may reflect different biological properties of circulating and intrahepatic HCV particles or the existence of extrahepatic sites of replication.