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Summary: Background: Each high-risk HPV genotype has different oncogenic potential, and the risk of CIN3+ varies according to genotype. We evaluated the performance of different strategies of HPV-positivity triage combining cytology, p16/ki67 dual staining (DS), and extended genotyping. Methods: Samples from 3180 consecutive women from the NTCC2 study (NCT01837693) positive for HPV DNA at primary screening, were retrospectively analyzed by the BD Onclarity HPV Assay, which allows extended genotyping. Genotypes were divided into three groups based on the risk of CIN3+. HPV DNA-positive women were followed up for 24 months or to clearance. Findings: Combining the three groups of genotypes with cytology or DS results we identify a group of women who need immediate colposcopy (PPV for CIN3+ from 7.8 to 20.1%), a group that can be referred to 1-year HPV retesting (PPV in those HPV-positive at retesting from 2.2 to 3.8), and a group with a very low 24-month CIN3+ risk, i.e. 0.4%, composed by women cytology or DS negative and positive for HPV 56/59/66 or 35/39/68 or negative with the Onclarity test, who can be referred to 3-year retesting. Interpretation: Among the baseline HPV DNA positive/cytology or DS negative women, the extended genotyping allows to stratify for risk of CIN3+, and to identify a group of women with a risk of CIN3+ so low in the next 24 months that they could be referred to a new screening round after 3 years. Funding: Italian Ministry of Health (grant number RF-2009-1536040). Hologic-Genprobe, Roche Diagnostics, and Becton & Dickinson provided financial and non-financial support.

IntroductionThrombotic events in neonates and children represent a rare although severe occurrence in view of the associated risk of mortality and sequelae. Quality evidence is limited in this field, and registry studies provide an essential base for research. The aim of this paper is to present the new Italian Registry of Infantile Thrombosis (RITI), set it into the scene of international thrombosis and stroke registries, and provide some insight on the challenges associated with registry management.MethodsWe present the detailed structure and content of the new RITI registry, a brief overview of its main data, and a reflection on its features, pitfalls and the main challenges related to its management.ResultsThe RITI, initially started in 2007 and officially re-launched in 2017 after structural modifications, is a non-interventional retrospective and prospective registry study collecting data on neonatal and pediatric patients (0–18 years) who experienced a systemic or cerebral thrombotic event in Italy. The RITI is managed by a multidisciplinary team with expertise in pediatric thrombosis, and participation is open to all Italian physicians, on a voluntary basis. The overall aim of the registry is to acquire new evidence to better characterize the population of children with thrombotic events and improve their management and outcome. 48 Italian pediatric and intensive care units are actively involved in the RITI, including 85 medical doctors from 16 Italian regions. A total of 1,001 neonates and children affected by cerebral or systemic thrombosis have been enrolled.DiscussionThe RITI is one of the largest available European registries of neonatal and pediatric thrombosis. National registries like the RITI represent a model for the study of rare conditions based on multidisciplinary and multicenter collaboration, aimed at overcoming the limitations due to small populations of patients, and creating a network of experts for patient referral and continuous education. Moreover, registry studies have a pivotal role in the research on pediatric thrombosis, due to the limited feasibility of high-quality studies. In our experience, the main critical stages, pitfalls and challenges in registry management include adequate registry designing, diffusion, data completeness and quality control.

The aim of this study was to investigate the involvement of the mesencephalic superior colliculus (SC) in the pathogenetic mechanism of SIDS, a syndrome frequently ascribed to arousal failure from sleep. We analyzed the brains of 44 infants who died suddenly within the first 7 months of life, among which were 26 infants with SIDS and 18 controls. In-depth neuropathological investigations of serial sections of the midbrain showed the SC layered cytoarchitectural organization already well known in animals, as made up of seven distinct layers, but so far never highlighted in humans, albeit with some differences. In 69% of SIDS cases but never in the controls, we observed alterations of the laminar arrangement of the SC deep layers (precisely, an increased number of polygonal cells invading the superficial layers and an increased presence of intensely stained myelinated fibers). Since it has been demonstrated in experimental studies that the deep layers of the SC exert motor control including that of the head, their developmental disorder could lead to the failure of newborns who are in a prone position to resume regular breathing by moving their heads in the sleep-arousal phase. The SC anomalies highlighted here represent a new step in understanding the pathogenetic process that leads to SIDS.

Abstract Background Worldwide approximately 2.6 million are stillborn, mostly occurring in developing countries. In the great part these deaths are inexplicable. The evenness and standardisation of the diagnostic criteria are prerequisites to understand their pathogenesis. The core goal of this article is to propose new evidence based investigative post-mortem guidelines that should be adopted in all the Institutions especially when a fetal death, after a routine autopsy procedure, is diagnosed as “unexplained”. The proposed protocol is mainly focused on the anatomopathological examination of the autonomic nervous system and in particular of the brainstem where the main centers that control vital functions are located. Methods Updated investigative guidelines for the examination of unexplained stillbirths, prevalently focused on the histological examination of the brainstem, where the main centers that are involved in monitoring the vital functions are located, are here presented. A section of this protocol concerns the Immunohistochemical evaluation of specific functional markers such as the neuronal nuclear antigen, nicotinic acetylcholine receptors, serotonin, orexin, apoptosis and gliosis. The important role of risk factors, having regard in particular to maternal smoking and air pollution is also contemplated in these guidelines. Results Specific morphological and/or functional alterations of vital brainstem structures have been found with high incidence in over 100 cases of unexplained fetal death sent to the “Lino Rossi Research Center” of the Milan University according to the Italian law. These alterations were rarely detected in a group of control cases. Conclusions We hope this protocol can be adopted in all the Institutions notably for the examination of unexplained fetal deaths, in order to make uniform investigations. This will lead to identify a plausible explanation of the pathogenetic mechanism behind the unexplained fetal deaths and to design preventive strategies to decrease the incidence of these very distressing events for both parents and clinicians. Trial registration not applicable for this study.

El manejo inadecuado de antimicrobianos (ATM), tiene como consecuencia el aumento de la resistencia de los gérmenes, problema actual en salud pública. El objetivo de este trabajo fue identificar el uso y la prescripción de ATM utilizados en la clínica de animales de compañía, en la ciudad de Córdoba, Argentina. Se realizó un estudio observacional, mediante un cuestionario compuesto por 18 preguntas. El 98% (149/152) de los profesionales encuestados, utilizó ATM en forma empírica, siendo los más empleados penicilina y sus derivados (74%). Frente a síndromes de piel y urinario, se observó una mayor probabilidad estadística de prescripción empírica (2,08 y 3,22 veces respectivamente). Debido a la alta frecuencia observada en el uso de ATM y siendo algunos de ellos clasificados como de importancia crítica en medicina humana, es necesario contar con datos epidemiológicos locales, para orientar los tratamientos empíricos iniciales y crear planes de vigilancia y control para su uso.

Abstract Background Empathy is a key element of “Patient and Family Centered Care”, a clinical approach recommended by the American Academy of Pediatrics. However, there is a lack of validated tools to evaluate paediatrician empathy. This study aimed to validate the Visual CARE Measure, a patient rated questionnaire measuring physician empathy, in the setting of a Pediatric Emergency Department (ED). Methods The empathy of physicians working in the Pediatric ED of the University Hospital of Udine, Italy, was assessed using an Italian translation of the Visual Care Measure. This test has three versions suited to different age groups: the 5Q questionnaire was administered to children aged 7–11, the 10Q version to those older than 11, and the 10Q–Parent questionnaire to parents of children younger than 7. The internal reliability, homogeneity and construct validity of the 5Q and 10Q/10Q–Parent versions of the Visual Care Measure, were separately assessed. The influence of family background on the rating of physician empathy and satisfaction with the clinical encounter was also evaluated. Results Seven physicians and 416 children and their parents were included in the study. Internal consistency measured by Cronbach’s alpha was 0.95 for the 10Q/10Q–Parent versions and 0.88 for the 5Q version. The item-total correlation was > 0.75 for each item. An exploratory factor analysis showed that all the items load onto the first factor. Physicians’ empathy scores correlated with patients’ satisfaction for both the 10Q and 10Q–Parent questionnaires (Spearman’s rho = 0.7189; p

This report describes a case of sudden collapse of a 20-hour-old newborn, while he was placed close to their mother according to skin-to-skin care, attributed to developmental alterations of brainstem nuclei involved in regulation of the vital functions. The infant, after a normal pregnancy, appeared well developed at birth, with no evidence of malformations or trauma, but showing severe asphyxia. The routine autopsy did not reveal a possible cause of death. Only the in-depth anatomopathological examination of the autonomic nervous system, according to the protocol developed by the “Lino Rossi” Research Center of Milan University, provided an explanation of the pathogenetic mechanism of this early death. The sudden death, a few hours after birth, was the unavoidable outcome of a complex of abnormalities of brainstem nuclei, particularly of the Kölliker-Fuse nucleus, an essential structure for eupneic breathing at birth, exacerbated by the prone position implied by the skin-to-skin contact.

An updated neuropathological protocol for the examination of the nervous system in case of unexplained stillbirth has been elaborated and presented in this review. It is focused on the examination of the nervous centers located in the brainstem, which are involved in monitoring the vital functions. Only through a deep analysis of the brainstem it is possible to highlight developmental alterations of these essential centers, and then provide a plausible explanation of the pathogenetic mechanism behind the death. The guidelines, drawn up on the basis of numerous researches performed by the authors, include a histopathological protocol, with an indication of standardized samples, and an immunohistochemical protocol for the study of biological markers, frequently involved in these deaths. The main risk factors that can be related to the neuronal alterations are also reported, together with the indications for the toxicological examination, which should be possibly applied. The authors hope that this protocol will be soon adopted in all the institutions where a fetal death, after a routine autopsy procedure, is diagnosed as “unexplained”, in order to make standardized investigations on stillbirth. Nowadays, preventive strategies to decrease the incidence of these very distressing events for both parents and clinicians are necessary.

We report a case of a baby, who, after pregnancy complicated by maternal Addison's disease and Hashimoto's thyroiditis and natural delivery, unexpectedly presented a cardiorespiratory collapse and died 1 hour after birth without responding to prolonged neonatal resuscitation maneuvers. The cause of death was reliably established by carrying out a forensic postmortem examination. More specifically, the histological examination of the lungs showed the presence of abundant endoalveolar and endobronchial cornea scales caused by absorption of amniotic fluid. The neuropathological examination of the brainstem highlighted severe hypodevelopment of the retrotrapezoid/parafacial respiratory group, which is a complex of neurons located in the caudal pons that is involved in respiratory rhythm coordination, especially expiration, in conditions of enhanced respiratory drive, as well as in chemoreception. This neuropathological finding shed new light on the mechanisms underlying the massive amniotic fluid aspiration which led to this early death.

Fragmento El próximo mes de abril de 2018, en Cartagena de Indias, Colombia, a orillas del mar Caribe, tendremos la oportunidad de celebrar un nuevo Congreso Latinoamericano de Endocrinología. Imaginar un mejor lugar en Latinoamérica como sede para realizar este COLAEN 2018 es muy difícil, sumando a ello el aporte que hace la Asociación Colombiana de Endocrinología, ACE, que con su magnífica organización y experiencia, garantiza uno de los mejores congresos que podamos disfrutar. Así mismo, unido a COLAEN 2018, la ACE también llevará a cabo la séptima versión del Curso Internacional de Endocrinología, Diabetes y Metabolismo. El programa científico ha sido elaborado por reconocidos líderes en las distintas y principales temáticas que comprende la endocrinología. Ellos conformaron un programa de muy alto nivel científico, que seguramente colmará el interés de la amplia asistencia latinoamericana de profesionales endocrinos. Temas como diabetes, tiroides, obesidad, osteoporosis, andrología, hipófisis, pediatría, suprarrenales, disruptores y ginecología serán desarrollados por prestigiosos conferencistas internacionales de Latinoamérica, Estados Unidos y Europa. Se dará prioridad a la calidad científica en cada temática de manera que los asistentes puedan incorporar las últimas novedades endocrinas a través de conferencias magistrales, discusiones con el experto y simposios. Además, podrán presentar sus trabajos científicos a través de presentaciones orales y posters en espacios preparados para ello.

In this study, the authors propose a complete framework based on a hierarchical activity model to understand and recognise activities of daily living in unstructured scenes. At each particular time of a long‐time video, the framework extracts a set of space‐time trajectory features describing the global position of an observed person and the motion of his/her body parts. Human motion information is gathered in a new feature that the authors call perceptual feature chunks (PFCs). The set of PFCs is used to learn, in an unsupervised way, particular regions of the scene (topology) where the important activities occur. Using topologies and PFCs, the video is broken into a set of small events (‘primitive events’) that have a semantic meaning. The sequences of ‘primitive events’ and topologies are used to construct hierarchical models for activities. The proposed approach has been tested with the medical field application to monitor patients suffering from Alzheimer's and dementia. The authors have compared their approach to their previous study and a rule‐based approach. Experimental results show that the framework achieves better performance than existing works and has the potential to be used as a monitoring tool in medical field applications.

Nicotinic acetylcholine receptors (nAChRs) are cationic channels of the neuronal cell membrane, differentially expressed in the central nervous system which, when activated by endogenous acetylcholine or exogenous nicotine, are able to enhance cholinergic transmission. The aim of this study was to investigate in human perinatal age the immunohistochemical expression of the α7-nAChR subtype, given its involvement in neuronal differentiation and its significant vulnerability to the toxic effects of nicotine. Thirty fetuses (with a gestational age between 25 and 40 weeks) and 35 infants (1–6 months old), suddenly died of known (controls) and unknown causes (unexplained deaths), with smoking and nonsmoking mothers, were included in this study. A negative or low immunoexpression of α7-nAChRs, indicative of their inactivation, was observed in the granular layers of the cerebellar cortex in 66% of the sudden unexplained perinatal deaths and 11% of the controls. A high correlation was also observed between these findings and maternal smoking. Apart from the well-known adverse effects of nicotine exposure during pregnancy, it may also cause significant alterations in cerebellar cholinergic transmission in areas of the brain involved in vital functions. These events may give us insights into the pathogenetic mechanisms leading to sudden unexplained fetal and infant death.

Abstract: Several reports have demonstrated difficulties and lack of agreement in the histopathological diagnosis of particular melanocytic lesions, with problems in their management. A histogenetic approach to the study of these lesions originated the following classification: 1. superficial atypical proliferation significance; 2. melanocytic tumor of uncertain potential; 3. pigmented epithelioid melanocitoma of uncertain potential; 4. microinvasive radial growth phase of uncertain potential. The terminology remains controversial, reflecting the uncertainty of the diagnosis and the biological potential of these atypical melanocytic lesions.

The aim of this study was to investigate the involvement of the mesencephalic superior colliculus (SC) in the pathogenetic mechanism of SIDS, a syndrome frequently ascribed to arousal failure from sleep. We analyzed the brains of 44 infants who died suddenly within the first 7 months of life, among which were 26 infants with SIDS and 18 controls. In-depth neuropathological investigations of serial sections of the midbrain showed the SC layered cytoarchitectural organization already well known in animals, as made up of seven distinct layers, but so far never highlighted in humans, albeit with some differences. In 69% of SIDS cases but never in the controls, we observed alterations of the laminar arrangement of the SC deep layers (precisely, an increased number of polygonal cells invading the superficial layers and an increased presence of intensely stained myelinated fibers). Since it has been demonstrated in experimental studies that the deep layers of the SC exert motor control including that of the head, their developmental disorder could lead to the failure of newborns who are in a prone position to resume regular breathing by moving their heads in the sleep-arousal phase. The SC anomalies highlighted here represent a new step in understanding the pathogenetic process that leads to SIDS. [ABSTRACT FROM AUTHOR]