Vincenzo Graziano

Limiting the access to direct-acting antivirals against HCV: an ethical dilemma

ABSTRACT Introduction: Hepatitis C virus (HCV) infection affects about 200 million people worldwide and represents a leading cause of liver-related mortality. Eradication of HCV infection, achieved mainly through direct-acting antivirals (DAA), results in a decrease of mortality and an improvement of quality of life. These drugs have a maximal efficacy and an optimal tolerability. However, their high cost precludes a universal access even in wealthy countries. Areas covered: This article deals with the policies adopted for the use of the new anti-HCV drugs, especially in Europe and most of all in Italy, supposedly the developed country with the highest HCV prevalence. The literature search was performed using Pubmed and Web of Science. Moreover, national regulatory institutional websites were consulted. Expert commentary: The current policy of limitation to the access of the DAA presents a series of ethical issues that makes it non-applicable. A ‘treat-all’ strategy should resolve all ethical dilemmas, by virtue of the wide benefits of anti-HCV treatment not only for the advanced stage of infection, but also for the initial stages. A reduction in price of the drugs is the actual condition to achieve such a change.

Early Medical Skull Surgery for Treatment of Post-Traumatic Osteomyelitis 5,000 Years Ago

Here we describe the findings of a unique example of the early techniques adopted in neurosurgery around 5000 years ago, consisting in a double well healed skull trephination associated with a post-cranial traumatic event occurring intra vitam to a young male from the Early Chalcolithic cemetery of Pontecagnano (South Italy, ca. 4,900 - 4,500 cal BP). Morphological, X-ray and 3D-CT scan skull-cap evaluation revealed that the main orifice was produced by scraping, obtained by clockwise rotary motion of a right-handed surgeon facing the patient, while the partial trephination was carried out by using a stone point as a drilling tool. In both cases, bone regrowth is indicative of the individuals prolonged postoperative survival and his near-complete recovery. The right femur shows a poorly healed mid-shaft fracture presumably induced by a high energy injury, and a resulting chronic osteomyelitis, affecting both femurs by hematogenous spread of the infection. Our observations on the visual and radiological features of skull and femur lesions, along with evidence on the timing of experimental bone regrowth vs. healing of lower limb fractures associated to long-term bone infections now suggest that this young man underwent a double skull trephination in order to alleviate his extremely painful condition induced by chronic osteomyelitis, which is thought to have been the cause of death.

Delay in diagnosis affects the clinical outcome in a cohort of cvid patients with marked reduction of iga serum levels

Common variable immunodeficiency disorders (CVID) represent a collection of diseases leading to an absent or strongly impaired antibody production. CVID presents a wide range of immunological abnormalities and clinical manifestations, including infections, inflammatory and autoimmune diseases, and malignancies. The aim of this observational study was to analyze the epidemiological and clinical features of a cohort of 75 Italian CVID patients, and evaluate the correlation with comorbidity and mortality. Clinical data were retrospectively collected: the cohort was followed-up for a maximum of 30years (mean time of 10.24years, median of 9years). An higher age at the diagnosis of CVID and an higher age at onset of symptoms were significantly associated with a reduction of patients survival if stratified per median of IgA (less than or >8.00mg/dl). Thus IgA levels at diagnosis are correlated with patients survival contributing to identify a subset with a worse prognostic outcome.

Iatrogenic splenic injury: review of the literature and medico-legal issues

Abstract Introduction Iatrogenic splenic injury is a recognized complication in abdominal surgery. The aim of this paper is to understand the medico-legal issues of iatrogenic splenic injuries. We performed a literature review on PubMed and Scopus using iatrogenic splenic or spleen injury and iatrogenic splenic rupture as keywords. Iatrogenic splenic injury cases were identified. Most cases were related to colonoscopy, but we also identified cases related to upper gastrointestinal procedures, colonic surgery, ERCP, left nephrectomy and/or adrenalectomy, percutaneous nephrolithotomy, vascular operations involving the abdominal aorta, gynecological operation, left lung biopsy, chest drain, very rarely spinal surgery and even cardiopulmonary resuscitation. There are several surgical procedures that can lead to a splenic injury. However, from a medico-legal point of view, it is important to assess whether the cause can be attributed to a technical error of the operator rather than being an unpredictable and unpreventable complication. It is important for the medico-legal expert to have great knowledge on iatrogenic splenic injuries because it is important to evaluate every step of the first procedure performed, how a splenic injury is produced, and whether the correct treatment for the splenic injury was administered in a judgment.

Cosmetic surgery: Medicolegal considerations

Abstract Cosmetic surgery is one of the two branches of plastic surgery. The characteristic of non-necessity of this surgical speciality implies an increased severity in the evaluation of the risk-benefit balance. Therefore, great care must be taken in providing all the information necessary in order to obtain valid consent to the intervention. We analyzed judgments concerning cosmetic surgery found in national legal databases. A document of National Bioethics Committee (CNB) was also analyzed. Conclusion: The receipt of valid, informed consent is of absolute importance not only to legitimise the medical-surgical act, but it also represents the key element in the question concerning the existence of an obligation to achieve certain results/use of certain methods in the cosmetic surgery.

Genetic testing: ethical aspects

Abstract The aim of this article is to provide an analysis of the main issues related to the application of predictive medicine by analysing the most significant ethical implications. Genetic medicine is indeed a multidisciplinary matter that covers broad contexts, sometimes transversely. Its extreme complexity, coupled with possible perceived repercussions on an individual’s life, involves important issues in the ethical, deontological and legal medical field. The aspects related to the execution of genetic testing have to be addressed at different levels, starting with the correct information about the “cognitive” meaning they intend (by forcefully disassociating it from the strange “preventive aspect”) to the legal medical issues that can be aroused in the field of forensic pathology, medical responsibility and insurance. There is no doubt that in recent years, from the decoding of the human genome, genetic research has exponentially expanded with an equally exponential increase in its use in clinical practice and the ethical and social evolution of it.

Some inconsistencies in Demirjian’s method

Nowadays, given the massive migration movements toward and across EU countries, age assessment can be highly useful for estimating the real age of asylum seekers or in medico-legal assessments of age-disputed children charged with criminal acts. Demirjian et al.s dental maturity score is currently a dental scoring system universally adopted for age assessment of unidentified children. Here we explore the biological compatibility of Demirjians scores with respect to the estimation of certain chronological ages of forensic interest through an algorithm based on the theory of constrained graphs integrated with combinatory analysis. Rather than simply respect Demirjians indications (direct method) on a sample of children, we followed a reverse procedure (indirect method) as follows: i. chronological age selection and identification of the corresponding maturity score (MS); ii. determination of all the possible combinations of dental maturity stages whose sum of the scores is equal to the MS under consideration; iii. checking for all such possible combinations the biological congruity of the state of maturity of each tooth compared to the chronological age initially chosen. By evidencing dental development inconsistencies, our mathematical approach explains why Demirjians method typically overestimates age. Therefore, even if the method in question remains the recommended way to assess individual dental maturity, it should definitely be considered unsuitable for application in certain forensic scenarios, particularly as regards the most disputed age range 14-16 years.

Clinical Influence of Micromorphological Structure of Dental Implant Bone Drills

Background Considerations about heat generation, wear, and corrosion due to some macrostructural bur components (e.g., cutting lips, rake angle, flute, and helix angle) have been widely reported. However, little is known about how the microstructural components of the implant drill surface can influence the implant drill lifetime and clinical performance. Aim To investigate accurately the surface morphology of surgical bone drill, by means of multivariate and multidimensional statistical analysis, in order to assess roughness parameters able to predict the evolution of tribological phenomena linked to heat development, wear, and corrosion occurring in clinical use. Materials and Methods The surfaces of implant drills approximately 2.0mm in diameter made by five manufacturers were examined by means of confocal microscope with white light laser interferometry, obtaining several surface roughness parameters. Statistical multivariate analysis based on discriminant analysis showed, for each cut-off, the parameters which discriminate the manufacturers. Results The microstructural parameters used by discriminant analysis evidenced several differences in terms of drill surface roughness between the five manufacturers. Conclusions The observed surface roughness difference of drills is able to predict a different durability and clinical performance especially in heat generation and wear onset.

To kill or be killed: the coup de grâce for a warrior after multiple sword wounds

Finding traumatic lesions on ancient skeletal remains offers a unique opportunity to investigate the circumstances surrounding the time of death. Here we present the unique find of a late 17th, early 18th century young male from Southern Italy with eight traumatic skull lesions. A detailed anthropological examination using X-ray and 3D CT scanning techniques was conducted in order to evaluate traumatic extent, direction and degree of severity of each skull injury. The nature, number and timing of repair of the traumata suggest that they were intentional blows inflicted in battle. Gross and radiographic evidence shows that the individual survived long after one of these traumata, most likely suffered in a previous battle. Shape, size and location, as well as different orientation and implied trajectory of the multiple wounds, suggest that they were produced by a heavy, sharp cutting weapon. The perimortem aspect of most of the traumata revealed them to be contemporary injuries, suffered in a final assault by a heavy sword during a face-to-face combat. The largest and deepest fracture penetrating the skull cavity possibly resulting in traumatic brain injury was here suggested as the fatal one, even if the victim may have survived for several days prior to death.

Otolaryngological features in a cohort of patients affected with 22q11.2 deletion syndrome: A monocentric survey

Otorhinolaryngologic manifestations are common in 22q11.2 deletion syndrome (22q11.2DS), but poorly described. This study aimed to better define the ear‐nose‐throat (ENT) phenotype of 22q11.2DS patients, in the attempt to best detect subjects requiring subspecialist intervention. We enrolled 25 patients affected with 22q11.2DS. Anatomic and functional ENT findings were investigated using clinical, laboratory, and instrumental data. Immunophenotype and frequency of infections were evaluated. Univariate and multivariate analyses were performed. ENT anomalies were found in 88% of patients, and in 20% congenital palate defects required surgery. Adenoid or palatine tonsil hypertrophy was noted in 80% and 48%. Forty‐eight percent of subjects had rhinolalia/phonia, severe in half of these. We also found nasal regurgitation or laryngeal penetration/aspiration in 20% and 16%, respectively. Instrumental exams revealed a mild conductive hearing loss in 32% (bilateral in most cases), tympanometric anomalies in 28%, and swallowing abnormalities in 16%. Statistical univariate analysis showed a direct association between rhinolalia/phonia and episodes of laryngeal aspiration (p = .016) and between tympanometric anomalies and increased adenoid volume (p = .044). No association between episodes of food aspiration and palatal anomalies was found. Moreover, no statistically significant association was observed between the number of airway infections and the ENT findings. This study contributes to better define the ENT phenotype in patients with 22q11.2DS, helpful to prevent potential complications. Furthermore, the identification of a subcategory of patients may allow the early adoption of specific speech therapy programs to improve the clinical outcome of 22q11.2DS patients.