Post-traumatic stress, anxiety, and depressive symptoms in caregivers of children tested for COVID-19 in the acute phase of the Italian outbreak.

BACKGROUND: The recent COVID-19 pandemic pointed out new burdens for researchers on mental health and that evidence-based (EB) studies on vulnerable populations are timely needed. The present paper aims at analysing the impact of suspicious of SARS-COV-2 infection in a cohort of parents presented at 3 major hospitals (spread between north and center of Italy) during the Italian COVID-19 pandemic phase 1. METHODS: Participants of the present cross-sectional, multicenter study were parental couples of children suspected to have COVID-19 who underwent testing with nasopharyngeal swabbing. All subjects were assessed by means of the: Impact of Event Scale-Revised (IES-R), Generalized Anxiety Disorder 7-Item (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) in order to evaluate Post-traumatic stress (PTSS), anxiety, and depressive symptoms, respectively. OUTCOMES: Results evidenced that parents whose children tested positive for COVID-19 were more prone to developing PTSS, anxiety and depressive symptoms. The same results emerged for parents who had quarantined as opposed to those who had not. Moreover, patients who suffered economic damage showed a higher prevalence of anxiety and depressive symptoms, whereas PTSS was more common among unemployed subjects and among mothers. INTERPRETATION: This study identified a mental health strain represented by parenting a child who tested positive for SARS-CoV-2 infection. Further EB research is needed to develop evidence-driven strategies to reduce adverse psychological impacts and related psychiatric symptoms in caregivers of COVID-19 infected children during the next phases of the pandemic.

Pervasive refusal syndrome or anorexia nervosa: a case report with a successful behavioural treatment.

PURPOSE: Pervasive refusal syndrome (PRS) is a rare psychiatric disease that affects children. It was first described by Lask in 1991 (Arch Dis Child 66:866-869, 1991). Recently, Otasowie and Collaborators reported a systematic review about PRS. Despite this, PRS has not yet been classified in DSM-5 and ICD-11 and the lack of evidence-based treatment makes this syndrome a real challenge for clinicians. The aim of this paper is to present our experience through the description of a case report and its treatment. METHODS AND RESULTS: The case reported is a girl aged 11 years that fits the clinical picture described in the literature of PRS. In previous reports, behavioural treatment was not used or appreciated; our case adds new knowledge regarding the PRS diagnosis and the successful behavioural treatment during hospitalization, which we describe in all its phases. CONCLUSION: PRS is a rare, life-threatening syndrome; it would be extremely important to have an official and evidence-based treatment guide. LEVEL OF EVIDENCE: Level V, case report.

Effects of rituximab therapy on B cell differentiation and depletion.

Rituximab is a human/murine chimeric anti-CD20 monoclonal antibody. It is largely used to treat B cell malignancies and has become standard in the management of B cell­mediated diseases such as rheumatoid arthritis and granulomatosis with polyangitis. The effects of rituximab need to be monitored by B cell phenotyping. Evaluate possible surface markers for monitoring B cell development in response to rituximab treatment. This review discusses the literature on the B cell surface markers analysed by flow cytometry in patients treated with rituximab. A panel of biomarkers of response to treatment to monitor by flow cytometry is also suggested. B cell phenotyping is useful to predict clinical relapses after rituximab treatment. The proposed panel of biomarkers includes CD38++CD24++IgD+/- immature B cells and IgD-CD38+/- memory B cells. In responders, Th1/Th2 balance and tolerance cells (CD4+CD25+CD127-/low Treg cells and CD19+CD24hiCD38hi Breg cells) tend to be restored after rituximab therapy. Furthermore, in responder patients, indirect depletion of CD19+/-CD27++CD38++ preplasma cells can be proposed as a predictor of response. Flow cytometric analysis of samples from patients treated with rituximab is a useful strategy to stratify patients according to response to treatment. Identification of B cell differentiation stages by means of a specific flow cytometry panel could improve monitoring of rituximab effects and enable non-responders to be distinguished from good responders.

Conservative surgery in stage I adult type granulosa cells tumors of the ovary: Results from the MITO-9 study.

OBJECTIVE: About 30% of Adult type granulosa cell tumors of the ovary (AGCTs) are diagnosed in fertile age. In stage I, conservative surgery (fertility-sparing surgery, FSS), either unilateral salpingo-oophorectomy (USO) or cystectomy are possible options. The aim of this study is to compare oncological outcomes of FSS and radical surgery (RS) in apparently stage I AGCTs treated within the MITO group (Multicenter Italian Trials in Ovarian cancer). METHODS: Survival curves were calculated using the Kaplan-Meier method and compared with log-rank test. The role of clinicopathological variables as prognostic factors for survival was assessed using Cox's regression. RESULTS: Two-hundred and twenty-nine patients were included; 32.6% received FSS, 67.4% RS. In the FSS group, 62.8% underwent USO, 16.7% cystectomy, 20.5% cystectomy followed by USO. After a median follow up of 84 months, median DFS was significantly worse in the FSS-group (10 yr DFS 50% vs 74%, in FSS and RS group, p = 0.006). No significant difference was detected between RS and USO (10 yr DFS 75% vs 70%, p = 0.5).Cystectomy-group showed a significantly worse DFS compared to USO (10 yr DFS 16% vs 70%, p < 0.001). Patients receiving cystectomy and subsequent USO showed a better prognosis, even though significantly worse compared to USO (10 yr DFS 41% vs 70%, p = 0.05). Between FSS and RS, no difference in OS was detected. At multivariate analysis, FIGO stage IC and cystectomy retained significant predictive value for worse survival. CONCLUSIONS: This study supports the oncological safety of FSS in stage I AGCTs, provided that cystectomy is avoided; USO should be the preferred approach.

Design and conduct of early clinical studies of immunotherapy agent combinations: recommendations from the task force on Methodology for the Development of Innovative Cancer Therapies.

The Methodology for the Development of Innovative Cancer Therapies task force considered aspects of the design and conduct of early studies of combinations of immunotherapy agents during their 2018 meeting. The task force defined the relevant data to justify combination clinical trials, which includes a robust hypothesis for the combination, pre-clinical data with evidence of efficacy and an understanding of the pharmacodynamics effects of each agent, and ideally evidence of single agent activity. Evaluation of pharmacodynamic biomarkers is critical in early phase combination trials, and should be incorporated into trial objectives and go/no-go decisions. The task force also identified the need to develop assessment tools and end points that capture the unique patterns of tumour responses to immunotherapy, including pseudoprogression and hyperprogression. At least one additional tumour measurement before baseline and an early CT scan (at 4 weeks for example) would help define the incidence of hyperprogression, although a common definition is needed. Finally, the task force highlighted substantial redundancy and inefficiency in the combination immunotherapy space, and recommended the adoption of innovative trial designs.

[Neurodevelopment and phenocopies of attention deficit hyperactivity disorder: differential diagnosis]. / Neurodesarrollo y fenocopias del trastorno por deficit de atencion/hiperactividad: diagnostico diferencial.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders. Other neurodevelopmental disorders may appear as a comorbidity or mimicking ADHD itself. DEVELOPMENT: This study reviews the high prevalence of other neurodevelopmental disorders (specific learning difficulties, communication disorders, etc.) in patients with ADHD. Moreover, the possible differential diagnoses include the same neurodevelopmental disorders that can occur as a comorbidity. Based on the literature, the study evaluates the role of clinical evaluation and neuropsychology in distinguishing between comorbidity and mimicry. CONCLUSIONS: The clinical evaluation could be insufficient for the comorbid diagnosis of neurodevelopmental disorders. In these cases, a neuropsychological evaluation is generally required, since it can also offer alternative diagnostic hypotheses about the symptoms observed and may therefore be a valuable aid for the differential diagnosis.

TITLE: Neurodesarrollo y fenocopias del trastorno por deficit de atencion/hiperactividad: diagnostico diferencial.Introduccion. El trastorno por deficit de atencion/hiperactividad (TDAH) es uno de los trastornos del neurodesarrollo mas prevalentes. Otros trastornos del neurodesarrollo pueden aparecer de forma comorbida o mimetizar el propio TDAH. Desarrollo. Se revisa la elevada prevalencia de otros trastornos del neurodesarrollo (trastornos especificos del aprendizaje, trastornos de la comunicacion...) en los pacientes con TDAH. Por otro lado, entre los posibles diagnosticos diferenciales se situan los mismos trastornos del neurodesarrollo que pueden aparecer de forma comorbida. Se valorara, de acuerdo a la bibliografia, el papel de la valoracion clinica y la neuropsicologia en la distincion entre comorbilidad y mimetismo. Conclusiones. La valoracion clinica podria ser insuficiente para el diagnostico comorbido de los trastornos del neurodesarrollo. En estos casos, la valoracion neuropsicologica es generalmente necesaria; esta puede igualmente ofrecer hipotesis diagnosticas alternativas de la sintomatologia observada y, por tanto, ser util para el diagnostico diferencial.

Laparoscopic surgery in the treatment of stage I adult granulosa cells tumors of the ovary: Results from the MITO-9 study.

OBJECTIVE: Surgery represents the mainstay of treatment of stage I adult type granulosa cell tumors of the ovary (AGCTs). Because of the rarity and indolent course of the disease, no prospective trials are available. Open surgery has long been considered the traditional approach; oncological safety of laparoscopy is only supported by small series or case reports. The aim of this study was to compare the oncological outcomes between laparoscopic and open surgery in stage I AGCTs treated within the MITO (Multicenter Italian Trials in Ovarian cancer) Group. METHODS: Data from patients with stage I AGCTs were retrospectively collected. Clinicopathological features were evaluated for association with relapse and death. Survival curves were calculated using the Kaplan-Meier method and compared with the log-rank test. The role of clinicopathological variables as prognostic factors for survival was evaluated using Cox's regression model. RESULTS: 223 patients were identified. Stage 1A, 1B and 1C were 61.5%, 1.3% and 29.6% respectively. 7.6% were apparently stage I. Surgical approach was laparoscopic for 93 patients (41.7%) and open for 130 (58.3%). 5-years DFS was 84% and 82%, 10-years DFS was 68% and 64% for the laparoscopic and open-group (p = 0.6).5-years OS was 100% and 99%, 10 years OS was 98% and 97% for the laparoscopic and open-surgery group (p = 0.8). At multivariate analyses stage IC, incomplete staging, site of primary surgery retained significant prognostic value. CONCLUSION: The present study suggests that surgical route does not affect the oncological safety of patients with stage I AGCTs, with comparable outcomes between laparoscopic and open approach.

[An update on the pharmacological treatment of attention deficit hyperactivity disorder: lisdexamphetamine and extended-release guanfacine]. / Actualizacion en el tratamiento farmacologico del trastorno por deficit de atencion/hiperactividad: lisdexanfetamina y guanfacina de liberacion retardada.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is one of the most frequent neurodevelopmental disorders in the child population. Its treatment is complex and must include psychoeducational, environmental and pharmacological measures. In recent years, the main novelties as regards its pharmacological treatment have been the appearance of lisdexamphetamine and extended-release guanfacine. AIMS: The increase in the number of drugs available for the treatment of ADHD makes it possible to treat and cover a very wide range of different clinical situations. The purpose of this review is to perform an analysis of the literature on the two drugs. DEVELOPMENT: The study determines the strong points of both treatments, with special attention given to their mechanism of action, their tolerability and their efficacy. CONCLUSIONS: Extended-release guanfacine enables the professional to treat situations that are poorly covered by stimulants, such as children with irritability and tics, with a significant profile characterised by moderate efficacy and good tolerability and safety. The appearance of lisdexamphetamine has brought about a very important change because, according to the literature, it is a drug that, from the clinical point of view, is both complete and effective in improving the symptoms of ADHD. Moreover, it has a good safety profile.

TITLE: Actualizacion en el tratamiento farmacologico del trastorno por deficit de atencion/hiperactividad: lisdexanfetamina y guanfacina de liberacion retardada.Introduccion. El trastorno por deficit de atencion/hiperactividad (TDAH) es uno de los trastornos del neurodesarrollo mas frecuentes en la poblacion infantil. Su tratamiento es complejo y debe incluir medidas psicoeducativas, ambientales y farmacologicas. En los ultimos años, las principales novedades respecto a su tratamiento farmacologico son la aparicion de la lisdexanfetamina y la guanfacina de liberacion retardada. Objetivo. El aumento del numero de farmacos disponibles para el tratamiento del TDAH permite tratar y cubrir situaciones clinicas muy diversas. El proposito de la presente revision es realizar un analisis de la bibliografia sobre ambos farmacos. Desarrollo. Se establecen los puntos fuertes de ambos tratamientos, atendiendo especialmente a su mecanismo de accion, a su tolerabilidad y a su eficacia. Conclusiones. La guanfacina de liberacion retardada permite tratar situaciones escasamente cubiertas con los estimulantes, tales como los niños con irritabilidad y tics, con un perfil significativo de moderada eficacia y una buena tolerabilidad y seguridad. La aparicion de la lisdexanfetamina ha supuesto un cambio muy importante porque, segun la bibliografia, se trataria de un farmaco completo y efectivo, desde el punto de vista clinico, para mejorar los sintomas del TDAH. Ademas, posee un buen perfil de seguridad.

[Attention deficit hyperactivity disorder: from a neurodevelopmental perspective]. / Trastorno por deficit de atencion/hiperactividad: perspectiva desde el neurodesarrollo.

INTRODUCTION: Neurodevelopmental disorders cover a heterogeneous group of disorders such as intellectual disability, autism spectrum disorders or specific learning difficulties, among others. The neurobiological and clinical variables seem to clearly justify the recent inclusion of attention deficit hyperactivity disorder (ADHD) as a neurodevelopmental disorder in the international classifications. DEVELOPMENT: Neurodevelopmental disorders are characterised by their dimensional nature and the distribution of the different symptoms in the population. These aspects are reviewed, specifically from the perspective of the clinical features and the neuropsychology of ADHD. The dimensional symptomatic nature of ADHD contrasts with the diagnostic criteria of this disorder according to different classifications or clinical guidelines. It also contrasts with the data collected by means of different complementary examinations (scales, tests, etc.). CONCLUSIONS: It is essential to understand the clinical continuum within each neurodevelopmental disorder (including ADHD), among the different neurodevelopmental disorders, and among the neurodevelopmental disorders and normality for their research, diagnosis and management. The development of instruments that provide support for this dimensional component is equally significant.

TITLE: Trastorno por deficit de atencion/hiperactividad: perspectiva desde el neurodesarrollo.Introduccion. Los trastornos del neurodesarrollo engloban a un grupo heterogeneo de trastornos como la discapacidad intelectual, el trastorno del espectro autista o los trastornos especificos del aprendizaje, entre otros. La reciente inclusion en las clasificaciones internacionales del trastorno por deficit de atencion/hiperactividad (TDAH) dentro de los trastornos del neurodesarrollo parece claramente justificada atendiendo a variables neurobiologicas y clinicas. Desarrollo. El caracter dimensional y la distribucion de diferentes sintomas en la poblacion caracterizan a la mayoria de los trastornos del neurodesarrollo. Se revisan estos aspectos, particularmente desde la sintomatologia y neuropsicologia en el TDAH. El caracter sintomatico dimensional del TDAH contrasta con los criterios diagnosticos de este trastorno de acuerdo a diferentes clasificaciones o guias clinicas. Contrasta igualmente con los datos recogidos a traves de diferentes exploraciones complementarias (escalas, tests...). Conclusiones. El entendimiento del continuo clinico dentro de cada trastorno del neurodesarrollo (incluido el TDAH), entre los diferentes trastornos del neurodesarrollo, y entre los trastornos del neurodesarrollo y la normalidad, es esencial para la investigacion, el diagnostico y el abordaje de todos ellos. El desarrollo de instrumentos que avalen este componente dimensional es igualmente trascendental.

Kikuchi-Fujimoto Disease in an Old Italian Woman: Case Report and Review of the Literature.

Kikuchi-Fujimoto disease (KFD) is a rare, benign, generally self-limiting disease that has higher prevalence in Asian people with a few cases reported in European countries. It generally affects young subjects under 40 years of age and is characterized by regional lymphadenopathy. Here, we present a case of a 66-year-old Italian woman who was extensively examined for right unilateral laterocervical lymph nodes associated with fever, night sweats, fatigue, and weight loss. She was diagnosed as having the KFD only after an excision biopsy of the largest laterocervical lymph node and was then managed symptomatically with NSAIDs. We also made a review of the literature for better awareness of the disease among physicians especially in those countries, like Italy, where the disease is not prevalent and may be frequently misdiagnosed. In fact, to our best knowledge, only seven Italian cases of KFD have been published in the last 15 years with patients being younger than 40 years. We finally highlight that it is noteworthy to consider KFD as differential diagnosis of lymphadenopathy even in old patients, and, since a misdiagnosis of lymphoma is actually feasible, an early biopsy has to be taken into account for confirming diagnosis and helping in the timely and appropriate management.

Role of Whole-Body MR with DWIBS in child's Bartonellosis.

Cat-scratch disease (CSD) is a zoonosis in children, result of infection by Bartonella henselae, a gram-negative bacillus. Infection is generally characterized by regional and self-limited lymphadenopathy after exposure to a scratch or bite from a cat. Rarely, B. henselae is cause of fever of unknown origin (FUO), with dissemination to various organs, most often involving the reticuloendothelial system (liver, spleen, bone marrow), mimicking an inflammatory rather than a lymphoproliferative disease. Whole-body Magnetic Resonance Imaging (WBMRI), in association with diffusion-weighted imaging (DWIBS), allows a comprehensive evaluation of pediatric patients, without the risks inherent to ionizing radiation. It is a rapid and sensitive method for detecting and monitoring multifocal lesions such as proliferative or inflammatory and infectious processes. We report a case of systemic CDS in an immunocompetent young boy with fever of unknown origin, without history of cat contact, investigated by WBMRI.

Pomological Traits, Sensory Profile and Nutraceutical Properties of Nine Cultivars of Loquat (Eriobotrya japonica Lindl.) Fruits Grown in Mediterranean Area.

In this paper the diversity of fruit quality within nine loquat cultivars, including five international affirmed cultivars (Algerie, Golden Nugget, Peluche, Bueno, El Buenet) and four local cultivars (Sanfilippara, Nespolone di Trabia, BRT20 and Claudia), were investigated in order to discriminate the variation in pomological characteristics, sensory profile, and antioxidant properties. Finally, to evaluate potential bioactivity, antiproliferative activity of hydrophilic extracts from loquat fruits was assessed, at dietary relevant concentrations, against three human epithelial cell lines. Even though the international cultivars confirmed an appropriate level of commercial qualities in association to high levels in antioxidant compounds, the local cultivars revealed the best performances in a wide range of chemical-physical and sensory characteristics. Concerning bioactivity, our results indicate that hydrophilic extracts from all tested cultivars showed concentration-dependent antiproliferative activity with a significant variability of effects between different cell lines and between different cultivars. HeLa cells, the most sensitive and hydrophilic extracts from Peluche, showed the highest inhibitory effect followed by Nespolone di Trabia and Claudia. The results of this trial provide useful information on the pomological traits and the not yet known specific nutritional and functional properties of loquat fruits. Our data, besides helping to promote specific local cultivars, could serve to establish a database that will permit to improve the utilization of specific genetic resources in breeding programs.

[The neuroanatomy of attention deficit hyperactivity disorder: neuropsychological and clinical correlates]. / Neuroanatomia del trastorno por deficit de atencion/hiperactividad: correlatos neuropsicologicos y clinicos.

INTRODUCTION: The development of structural magnetic resonance scanning and new methods of analysis has made it possible to explore, in a hitherto unknown way, the neuroanatomical bases of attention deficit hyperactivity disorder (ADHD). Yet, little is known about the relation between the clinical symptoms and the neuropsychological dysfunctions characterising ADHD and the neuroanatomical alterations that are observed. AIM: To explore the relation between neuroanatomy, clinical features and neuropsychology in ADHD. DEVELOPMENT: At group level, there are a number of marked differences between the brain of children, adolescents and adults with ADHD and the brain of subjects with a typical development. These differences are observed cross-sectionally and longitudinally in all the measurements, both in the grey matter and in the white matter. Although still scarce, there is an increasing body of evidence showing that these differences are related with the core symptoms of the disorder and with the degree of clinical dysfunction. They also appear to be associated with cognitive functioning (mainly attention and inhibitory control). CONCLUSIONS: The relation among the different levels of analysis in the study of ADHD bring research closer to the clinical features and allows a better understanding and management of the disorder. Although progress is undoubtedly being made in this field, there are still many questions that need exploring in greater depth. There is a need for a better understanding of the association between the neuroanatomical measurements and each dimension of the symptoms, and their relationship with other neuropsychological processes that are also involved in the disorder.

TITLE: Neuroanatomia del trastorno por deficit de atencion/hiperactividad: correlatos neuropsicologicos y clinicos.Introduccion. El desarrollo de la resonancia magnetica estructural y de nuevos metodos de analisis ha permitido examinar, como nunca antes, las bases neuroanatomicas del trastorno por deficit de atencion/hiperactividad (TDAH). No obstante, poco se sabe todavia sobre la relacion de los sintomas clinicos y las disfunciones neuropsicologicas caracteristicas del TDAH con las alteraciones neuroanatomicas observadas. Objetivo. Explorar la relacion entre neuroanatomia, clinica y neuropsicologia en el TDAH. Desarrollo. A nivel de grupo, existen diferencias marcadas entre el cerebro de niños adolescentes y adultos con TDAH y el cerebro de personas con desarrollo tipico. Estas diferencias se observan transversal y longitudinalmente en todas las medidas, tanto de la sustancia gris como de la sustancia blanca. Aunque todavia escasa, cada vez existe mayor evidencia que señala que estas diferencias se relacionan con los sintomas nucleares del trastorno y con el grado de disfuncion clinica. Tambien parecen asociarse con el funcionamiento cognitivo (principalmente, atencion y control inhibitorio). Conclusiones. La relacion entre los distintos niveles de analisis de estudio del TDAH acerca la investigacion a la clinica y permite comprender y tratar mejor el trastorno. Aunque el avance en este campo es innegable, todavia son muchas las cuestiones que hay que explorar y profundizar en mayor detalle. Se requiere comprender mejor la asociacion entre las medidas neuroanatomicas y cada dimension sintomatologica, y la relacion con otros procesos neuropsicologicos tambien implicados en el trastorno.

Radical hysterectomy after chemoradiation in FIGO stage III cervical cancer patients versus chemoradiation and brachytherapy: Complications and 3-years survival.

BACKGROUND: To compare patterns and rates of early and late complications, and survival outcome in FIGO stage III cervical cancer patients underwent to radical hysterectomy after chemo-radiation (CT-RT) vs. chemo-radiation alone. METHODS: Between May 1996 and April 2013 150 FIGO stage III cervical cancer patients were treated. We divide patients according to type of treatment: 77 were submitted to standard treatment (Group A), and 73 to completion hysterectomy after chemo-radiation (Group B). RESULTS: The baseline characteristics of the 2 groups were superimposable. We observed lower intra-operative and treatment-related early urinary and gastro-intestinal complications in Group B with respect to Group A (p < 0.001). Vascular complications were registered only in Group B (p < 0.001). We found a significantly higher rate of local recurrences in the Group A than in the Group B (p < 0.002). We registered 29 deaths in the Group A and 22 in the Group B (p = 0.021). The 3-years disease-free survival rate in the Group A and in the Group B was 62.9% and 68.3%, respectively (p = 0.686), and the 3-years overall survival rate in the Group A and in the Group B was 63.2% and 67.7%, respectively (p = 0.675). CONCLUSIONS: This study confirms that radical hysterectomy after CT-RT is an effective therapeutic approach for advanced cervical cancer. Further prospective and randomized studies should be performed in order to solve the question about the standard approach, and how the different pattern of complication could impact on the quality of life.