Mariano Paternoster

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.

Confocal laser endomicroscopy in breast surgery: a pilot study

BackgroundBreast neoplasms include different histopathological entities, varying from benign tumors to highly aggressive cancers. Despite the key role of imaging, traditional histology is still required for a definitive diagnosis. Confocal Laser Endomicroscopy (CLE) is a new technique, which enables to obtain histopathological images in vivo, currently used in the diagnosis of gastrointestinal diseases. This is a single-center pilot feasibility study; the main aim is to describe the basic morphological patterns of Confocal Laser Endomicroscopy in normal breast tissue besides benign and malignant lesions.MethodsThirteen female patients (mean age 52.7, range from 22 to 86) who underwent surgical resection for a palpable breast nodule were enrolled. CLE was performed soon after resection with the Cellvizio® Endomicroscopy System (Mauna Kea Technologies, Paris, France), by using a Coloflex UHD-type probe; intravenous fluorescein was used as contrast-enhancing agent. The surgical specimen was cut along the main axis; dynamic images were obtained and recorded using a hand-held probe directly applied both to the internal part of the lesion and to several areas of surrounding normal tissue. Each specimen was then sent for definitive histologic examination.ResultsHistopathology revealed a benign lesion in six patients (46%), while a breast cancer was diagnosed in seven women (54%). Confocal laser endomicroscopy showed some peculiar morphological patterns. Normal breast tissue was characterized by a honeycomb appearance with regular, dark, round or hexagonal glandular lobules on a bright stroma background; tubular structures, representing ducts or blood vessels, were also visible in some frames. Benign lesions were characterized by a well-demarcated “slit-like” structure or by lobular structures in abundant bright stroma. Finally, breast cancer was characterized by a complete architectural subversion: ductal carcinoma was characterized by ill-defined structures, with dark borders and irregular ductal shape, formingribbons, tubules or nests; mucinous carcinoma showed smaller cells organized in clusters, floating in an amorphous extracellular matrix.ConclusionsThis is the first pilot study to investigate the potential role of confocal laser imaging as a diagnostic tool in breast diseases. Further studies are required to validate these results and establish the clinical impact of this technique.

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.

Donation of the body for scientific purposes in Italy: ethical and medico-legal considerations.

Abstract In recent years in Italy (and in the other European Countries) a new debated topic involves anatomists and the scientific world: donation of the body after death for scientific purposes. The aim of our analysis is to analyze the issue of voluntary body donation in Italy focusing first of all, on key principles of the disciplines of donation. Considering the rise of exhibitions and events in which death is spectacularized, the debate is focus on will, on respect and overall on the purpose for which the body is donated. Anatomical dissection is considered necessary in the direct learning of the human body, of surgical practices and new scientific techniques but the scarcity of programmes and regulations regarding the donation of bodies for study and research make it an uncommon practice. After discussing what are the constitutional principles underlying the issue we want to emphasize the need of a more effective and updated regulation to set limits and methods of a practice still essential for scientific progress.

Complications after orthognathic surgery: our experience on 423 cases

IntroductionOrthognathic surgery is widely used to correct dentofacial discrepancies. However, this procedure presents numerous possible complications. The aim of our study is to review intraoperative and postoperative complications related to orthognathic surgery based upon a 10-year period in the Maxillofacial Surgery Department of Federico II University of Naples.Materials and methodsMedical records of 423 patients who undergone orthognathic surgery in a 10-year period were retrospectively analyzed and complications was noted. Statistical analysis was conduced in order to understand if the type of surgical procedure influenced complications rate.ResultsOne hundred eighty-five complications in 143 (33.8%) of the 423 treated patients were reported. Complications detected were nerve injury (49 cases, 11.9%), infections (10 cases, 2.4%), complications related to fixation plates or screws (30 cases, 7.1%), bad split osteotomy (8 cases, 1.9%), secondary temporo-mandibular joint disorders (36 cases, 8.5%), dental injuries (21 cases, 5%), condilar resorption (2 cases, 0.5%), and necessity of a second-time surgery (24 cases, 5.7%).ConclusionsSerious complications seem to be quite rare in orthognathic surgery. Some of the surgical complications found are related to the surgeon experience and not strictly to the risks of the operation itself. Understanding potential complications allows the surgeon to guarantee safe care through early intervention and correctly inform the patient in the preoperative colloquy.

Diagnosis of placental abruption: a legal issue for physicians

Obstetrician–gynecologists are frequently exposed to malpractice claims. One of the most frequently seen type of medical malpractice involves cases of misdiagnosis, or the failure to promptly diagnose placental abruption. Nevertheless, despite heightened awareness, placental abruption still remains unpredictable and unpreventable. The diagnosis is usually made clinically and confirmed by gross or histologic examination of the placenta, however, it may be occult and may go undiagnosed until after delivery. Most cases of placental abruption occur before the onset of labor in low-risk pregnancies and are not predictable with regard to maternal reproductive risk factors. Current antepartum methods of detecting utero-placental problems, including Doppler ultrasonography, are not effective in prenatal prediction of placental abruption. Using clinical criteria and ultrasound evaluation the diagnosis is made prior to delivery in only 62% of cases so that430% may go undiagnosed until examination of placenta after delivery. Placenta abruption (also known as abruption placentae), defined as a premature separation of a normally implanted placenta, is one of the more serious problems that can occur during pregnancy, labor and delivery [1]. This is an obstetric emergency, with an overall prevalence rate of 1%, in which the placenta separates from the lining of the uterus, depriving the fetus of oxygen and nutrients, and potentially causing severe hemorrhage into the decidua basalis with higher risk of maternal and fetal morbidity and mortality [1,2]. Obstetrician–gynecologists are frequently exposed to malpractice claims [3,4]. Approximately 77% of the ob/gyns surveyed by the American College of Obstetricians and Gynecologists (ACOG) in 2012 said they had been named in a malpractice suit during their careers [5]. One of the most frequently seen type of medical malpractice involves cases of misdiagnosis, or the failure to promptly diagnose placental abruption, with a very high number of cases of placental abruption management errors and high average monetary settlement for each cases [5]. The diagnosis of placental abruption is clinical, while ultrasound scan and conventional electronic fetal heart monitoring (i.e. cardiotocography) are tools with limited use.

Genetic risk in insurance field

Abstract The risk-delimiting tools available to insurance companies are therefore substantial and it is also possible to argue that a margin of uncertainty is a natural component of the insurance contract. Despite this, businesses look at the potential of predictive medicine, and in particular the growing understanding of genetic mechanisms that support many common diseases. In particular, the rapid development of genetics has led many insurance companies to glimpse in the predictive diagnosis of disease by genetic testing the possibility of extending the calculation of the individual risk of developing a particular disease to appropriate premiums or even denying insurance coverage.

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.