Histopathological parameters reported in microinvasive oral squamous cell carcinoma: a systematic review.

BACKGROUND: Microinvasive oral squamous cell carcinoma (OSCCmi) is an incipient stage of oral cancer. Through this systematic review, we aim to assess patterns of histopathological outcomes reported in OSCCmi cases. MATERIAL AND METHODS: An online search in major databases was performed without period restriction, and 2,024 publications in English, Spanish and Portuguese were obtained. After screening and eligibility, 4 studies were selected. The risk of bias was assessed using Joanna Briggs Institute Critical Appraisal Checklist. A descriptive synthesis was conducted. RESULTS: All 4 publications included were retrospective, reporting a total of 116 OSCCmi patients, with a male predominance (1.6:1) and a mean age of 55.9 years. The main parameters considered for microinvasion were tumor thickness (TT) (range 4-10mm) and depth of invasion (DOI) (range 0,02-5mm). Definition, cut-off values, and assessment of microscopic features were not standardized. Other relevant measures such as perineural or lymphovascular invasion and pattern of invasive front were barely described, and cytological/architectural characteristics were not discussed. CONCLUSIONS: TT and DOI are currently the primary histopathological criteria used to define OSCCmi. Nonetheless, the outcomes of this systematic review showed the absence of standardized quantitative parameters to render the diagnosis of microinvasive OSCC. Therefore, additional studies aiming to standardize histopathological features to diagnose OSCCmi are paramount.

CT scan structured report for the study of abdominal wall defects: a fast, easy and practical tool at the service of both surgeons and radiologist.

PURPOSE: The advantages offered by structured reporting have already been highlighted in the literature. However, there is still no evidence on the validity of this reporting method for the study of abdominal wall defects. This study aims to show the experience of the Trentino Hernia Team (THT) multidisciplinary group in the development and use of a structured CT scan report for the study of abdominal wall defects. METHODS: A regional multidisciplinary team (THT group) used a Delphi method to identify and select the most important CT scan parameters needed to describe and stage abdominal wall defects for correct preoperative planning. Based on the selected parameters, a CT scan structured report was worked out and collectively accepted. The first 20 structured reports obtained were individually tested for compilation speed and homogeneity of the data reported by five distinct radiologists. The reports were then evaluated by five different surgeons to test the simplicity of interpretation. RESULTS: We produced a model of a structured report for the study of the abdominal wall defects and tested it in our hospital network on the first 20 reports. The average completion time was 18 min (range 12-25). There was no heterogeneity among the reported data. The reports were analysed by five distinct surgeons to evaluate completeness and simplicity of interpretation. Each surgeon used a Likert scale from 0 to 5 to evaluate each report, producing average scores of 4.8 and 4.1 for completeness and comprehensibility respectively, with a mean combined total score of 8.9 out of 10. CONCLUSIONS: Our structured report represents a fundamental tool capable of providing the surgeon with all the measurements of the parameters necessary for correct preoperative planning. At the same time, it is of crucial help for the radiologists representing an easy and fast way to report all the needed parameters using the same standards.

Multifocal lymphangioendotheliomatosis with thrombocytopenia: phenotypic variability and response to rapamycin. / Linfagioendoteliomatosis multifocal con trombopenia: variabilidad fenotípica y respuesta a rapamicina.

INTRODUCTION: Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is characterized by multiple maculopapular lesions involving the stomach and the lungs, associated with thrombocytopenia as a result of platelet entrapment. Episodes of severe digestive bleeding, which are sometimes unmanageable, are one of its most frequent presentations and a cause of mortality. Our objective was to describe the various phenotypes, as well as our treatment experience. MATERIALS AND METHODS: A retrospective analysis of patients diagnosed with MLT in our vascular abnormality unit from 2007 to 2018 was carried out. Epidemiological, clinical, and evolution data were analyzed, and a long-term follow-up was performed. RESULTS: Five patients (3 boys and 2 girls) had congenital macules and erythematous papules of various sizes. They were later associated with episodes of severe hematemesis along with thrombocytopenia, which required blood product transfusion. The most frequently involved areas were the stomach and the colon. In two patients, multiple bilateral pulmonary nodules were noted. The anatomical pathology examination showed extended vessels with a prominent, hobnail endothelium, as well as intraluminal papillary projections in the dermis. Immunohistochemical analysis was CD-31 positive and CD-34 positive in a characteristic manner. Two patients were treated with mTOR inhibitors (rapamycin), with a progressive decrease in extracutaneous involvement and platelet recovery, but with a poor response in dermal lesions. Two patients were treated with vincristine, with a reduction of digestive bleeding episodes. No deaths were reported in our series. CONCLUSION: MLT is characterized by hematological and cutaneous involvement - sometimes minimal -, with potential lesions in other internal organs. Its heterogeneous presentation, which may start with severe digestive bleeding, makes this rare pathology difficult to diagnose. mTOR inhibitors have opened up new treatment possibilities.

INTRODUCCION: La linfangioendoteliomatosis multifocal con trombopenia (LMT) es una anomalía, caracterizada por múltiples lesiones maculo-papulosas con afectación visceral gástrica y pulmonar, asociado a trombopenia por atrapamiento plaquetar. Una de sus presentaciones más frecuentes es en forma de episodios de hemorragia digestiva severa, en ocasiones inmanejable, y que es la responsable de su mortalidad. Nuestro objetivo es describir los diferentes fenotipos, así como nuestra experiencia en su tratamiento. MATERIAL Y METODOS: Hemos realizado un análisis retrospectivo de los pacientes diagnósticos de LMT según las características histológicas típicas entre 2007 y 2018 en nuestra unidad de anomalías vasculares. Se analizaron datos epidemiológicos, clínicos y de evolución, así como seguimiento a largo plazo. RESULTADOS: Cinco pacientes (3 hombres y 2 mujeres) presentaron al nacimiento máculas y pápulas eritematosas de diferentes tamaños a los que más adelante se les asoció episodios de hematemesis graves junto a trombopenia, que llegaron a requerir transfusión de hemoderivados. Las regiones más afectadas fueron el estómago seguido del colon. En dos pacientes se detectaron múltiples nódulos pulmonares bilaterales. La anatomía patológica describió vasos alargados con endotelio prominente y en tachuela junto a proyecciones papilares intraluminales en dermis. La inmunohistoquímica fue positiva de forma característica para CD-31 y CD-34. Dos pacientes fueron tratados con inhibidores de mTOR (rapamicina) con disminución progresiva de la afectación extracutánea y recuperación plaquetar, pero con una pobre respuesta de las lesiones dérmicas. Dos pacientes fueron tratados con vincristina con reducción de los episodios de sangrado digestivo. No se registró ningún fallecimiento en nuestra serie. CONCLUSION: La LMT se caracteriza por una afectación cutánea, a veces mínima, y hematológica que puede asociar lesiones en otros órganos internos. La presentación heterogénea, pudiendo debutar con hemorragias digestivas severas, hacen de esta entidad una patología de difícil diagnóstico. Los inhibidores de mTOR han abierto una nueva vía que arroja cierta esperanza para el tratamiento de esta patología tan poco frecuente.

Thoracic outlet syndrome in adolescents: a case series. / Síndrome del opérculo torácico en adolescentes: serie de casos.

OBJECTIVE: Thoracic Outlet Syndrome (TOS) is caused by a compression of the brachial plexus and the subclavian vessels in their passage to the upper limb. It mostly occurs in women aged 20-50, so it is infrequent in children. We present our results in the diagnosis and management of pediatric TOS. MATERIAL AND METHODS: Retrospective study of patients diagnosed with TOS between December 2017 and June 2018. Clinical, radiological, surgical, and evolution variables were assessed. RESULTS: Five TOS were diagnosed in 4 patients - one TOS was bilateral. Mean age at diagnosis was 12.5 years (7-15), and there was a delay in diagnosis of 153 days (10-36). TOS was either venous (3) or neurogenic (2). Patients presented with pain (5/5), edema (4/5), hypoesthesia (3/5), decreased strength (3/5), and cervical pain (2/5). One patient presented with sport-related pain. Neurophysiological study was normal in three cases. Two patients presented bone anomalies at CT-scan. Three surgeries were performed in two patients using the supraclavicular approach with resection of the anomalous first rib and scalenectomy. One patient refused surgery, and another patient remained expectant without reappearance of symptoms. Postoperative follow-up was 9 months (6-12), with progressive improvement of symptoms. CONCLUSIONS: TOS may occur in adolescents in the form of upper limb pain and edema. Imaging tests are recommended to detect abnormal anatomical structures. The supraclavicular approach represents a safe and effective technique in decompressing the thoracic outlet.

OBJETIVO: El síndrome del opérculo torácico (SOT) está causado por una compresión del plexo braquial y vasos subclavios en su paso hacia la extremidad superior. Patología típica de mujeres entre 20 y 50 años, que es infrecuente diagnosticar en niños. Presentamos nuestros resultados en el diagnóstico y tratamiento del SOT pediátrico. MATERIAL Y METODOS: Estudio retrospectivo de pacientes diagnosticados de SOT entre diciembre 2017 y junio 2018. Se analizaron variables clínicas, radiológicas, quirúrgicas y de evolución. RESULTADOS: Cinco SOT fueron diagnosticados en cuatro pacientes, uno de ellos bilateral. La edad media al diagnóstico fue de 12,5 años (7-15) y hubo una demora en el diagnóstico de 153 días (10-360). SOT venoso (3) y neurológico (2). Presentaron dolor (5/5), edema (4/5), hipoestesia (3/5), disminución de fuerza (3/5) y dolor cervical (2/5). Una paciente presentaba dolor asociado al deporte. El estudio neurofisiológico fue normal en tres casos. Dos pacientes presentaron anomalías óseas por TAC. Se realizaron tres intervenciones quirúrgicas en dos pacientes por abordaje supraclavicular realizando resección de la primera costilla anómala y escalenectomía. Una paciente rechazo la intervención y en otra se mantuvo en una actitud expectante sin reaparición de los síntomas. Seguimiento posoperatorio de 9 meses (6-12) con mejoría progresivas de los síntomas. CONCLUSION: El SOT puede darse en adolescentes siendo el dolor y edema de la extremidad superior lo más específico. Se recomienda la realización de pruebas de imagen para detectar estructuras anatómicas anómalas. El abordaje supraclavicular se presenta como una técnica segura y eficaz en la descompresión del desfiladero torácico.

Evening chronotype, disordered eating behavior, and poor dietary habits in bipolar disorder.

OBJECTIVE: Our aim was to evaluate the relationship between evening chronotype, a proxy marker of circadian system dysfunction, and disordered eating behavior and poor dietary habits in individuals with bipolar disorder (BD). METHODS: In this cross-sectional study, we evaluated 783 adults with BD. Chronotype was determined using item 5 from the reduced Morningness-Eveningness Questionnaire. The Eating Disorder Diagnostic Scale (EDDS) and the Rapid Eating Assessment for Participants-Shortened Version (REAP-S) were used to assess disordered eating behavior and dietary habits respectively. General linear models and logistic regression models were utilized to evaluate differences between chronotype groups. RESULTS: Two hundred and eight (27%) BD participants self-identified as having evening chronotypes. Compared to non-evening types, evening types were younger (P < 0.01) and, after controlling for age, had higher mean EDDS composite z-scores (P < 0.01); higher rates of binge-eating (BE) behavior (P = 0.04), bulimia nervosa (P < 0.01), and nocturnal eating binges (P < 0.01); and a higher body mass index (P = 0.04). Compared to non-evening types, evening chronotypes had a lower REAP-S overall score (P < 0.01) and scored lower on the 'healthy foods' and 'avoidance of unhealthy food' factors. Evening types also skipped breakfast more often (P < 0.01), ate less fruit (P = 0.02) and vegetables (P = 0.04), and consumed more fried foods (P < 0.01), unhealthy snacks (P = 0.02), and soft drinks (P = 0.01). CONCLUSIONS: Our findings suggest that the circadian system plays a role in the disordered eating and unhealthy dietary behaviors observed in BD patients. The circadian system may therefore represent a therapeutic target in BD-associated morbidity that warrants further investigation.

[Arterial sinus pericranii. First case report]. / Sinus pericranii arterial. Una entidad desconocida.

INTRODUCTION: Sinus pericranii (SP) is a rare vascular anomaly consisting in an abnormal intradiploic communication between intra and extra cranial venous systems. It usually presents as a congenital soft mass in the cranial midline with progressive growth, which enlarges significantly with Valsalva maneuver. A similar congenital vascular anomaly involving intra and extra cranial arterial systems has not been previously described in the medical literature. CLINICAL CASE: A 6-year-old boy with suspected midline capillary malformation of the frontal bone was referred to our Vascular Anomalies Unit for progressive increase in size. A conclusive ultrasound of high flow malformation was performed. Angio-TAC confirmed the arterial nature of the lesion and its communication with the middle meningeal artery. Embolization of the distal portion of the middle meningeal artery was performed prior to surgery. Previous to exeresis of the malformation, skin expanders were placed to cover the subsequent defect. The histopathological result was an arteriovenous malformation. Currently the patient is 10 years old and is asymptomatic, with no recurrence of the lesion. CONCLUSIONS: Since its first description, SP has been classified and described in the literature as a venous malformation. Although morphologically may resemble a SP, histologically and immunohistochemically it corresponds to an arteriovenous malformation with intracranial arterial connection. It is especially important to know how to diagnose this type of cranial malformations because their long-term evolution will depend on correct management and initial follow-up.

INTRODUCCION: El sinus pericranii (SP) es una malformación vascular rara en la que existe una conexión intradiploica entre el sistema venoso intra y extracraneal. Se presenta como una masa blanda en línea media del cráneo con crecimiento progresivo, que aumenta de tamaño con maniobras de Valsalva. Una conexión similar entre los sistemas arteriales intra y extracraneales no ha sido descrita previamente. CASO CLINICO: Niño de 6 años con sospecha de malformación capilar en línea media del hueso frontal fue derivado a nuestra Unidad de Anomalías Vasculares por aumento progresivo de tamaño. Se realizó una ecografía concluyente de malformación de alto flujo. La angio-TAC confirmó la naturaleza arterial de la lesión y su comunicación con la arteria meníngea media. Se realizó una embolización de la porción distal de la arteria meníngea media previa a la cirugía. Previo a la exeresis de la malformación se procedió a colocar expansores cutáneos para poder cubrir el defecto posterior. El resultado histopatológico fue de una malformación arteriovenosa. Actualmente el paciente tiene 10 años y se encuentra asintomático, sin recidiva de la lesión. CONCLUSION: Desde su primera descripción, el SP se ha clasificado y descrito en la literatura como una malformación venosa. Aunque morfológicamente aparentase de un SP, histológica e inmunohistoquimicamente corresponde una malformación arteriovenosa con conexión arterial intracraneal. Es de especial importancia saber diagnosticar este tipo de malformaciones craneales porque su evolución a largo plazo dependerá de un correcto manejo y seguimiento inicial.

Offering HCV treatment to prisoners is an important opportunity: key principles based on policy and practice assessment in Europe.

BACKGROUND: Prisoners have a high prevalence of hepatitis C virus (HCV) infection but may find it difficult to access healthcare services. This may be related to risk behaviour including history of injecting drugs and marginalisation related to problem drug use/ opioid use disorder (OUD). Direct-acting antiviral products with superior efficacy and safety compared to interferon-based regimens offer HCV cure. Many citizens in Europe have been treated, although few received therapy in prisons. METHODS: Analysis of prisoner HCV treatment need and policy determinants of clinical practice was completed for 5 EU countries. Evidence was collected from national statistical sources and peer-reviewed publications to describe prison populations and HCV prevalence, to map national prison/ HCV health policy or guidance. A consensus of important principles for prisoner HCV care was developed. RESULTS: Data from published sources describing prisoner HCV prevalence is limited. Prisoner population requiring HCV treatment is not known; estimated numbers based on analysis of evidence: England and Wales, 9000, France, 8000, Spain, 6000, Italy, 6000, Germany, 6000. Treatment access: national law defines right to equivalent care in all countries implying access to HCV therapy in prison similar to community; useful prisoner HCV guidance facilitating treatment decisions present in: 4 of 5 national/ regional HCV policy documents, 4 of 5 national prison healthcare policies. Four of five had practical prison HCV clinical guidelines. Despite existence of policy, implementation of guidance, and so HCV treatment, is suboptimal in many locations. CONCLUSIONS: Prison is an important location to detect, address and treat HCV infection in people who may be underserved for healthcare and find it difficult to navigate community treatment pathways. This is often related to problems with OUD and resulting social inequity. HCV management in prisons must be improved. Policy and clinical practice guidance must be set to promote treatment, and practical steps to make treatment easy should be followed including education to promote engagement, set-up of optimal screening and work up processes with modern tools to reduce time needed/ achieve efficiency; programs to make it easier to get specialists' input include remote working and nurse-led services.

[Slipping rib syndrome in paediatrics: report of 4 cases]. / Síndrome de la costilla deslizante. Serie de 4 casos clínicos.

AIM OF THE STUDY: The slipping rib syndrome (SRS) is an unknown pathology for the pediatric surgeon due to its low incidence in children. The weakness of the costal ligaments allowing an area of rib hypermobility has been postulated recently as the main etiology. It produces an intermittent pain in the lower thorax or upper abdomen that can affect to the daily activities and can be the origin of unspecific chronic pain. METHODS: A retrospective review of patients diagnosed with SRS between october 2012 and march 2017 was performed. Data of demographics, symptoms, imaging studies, surgical findings and long-term follow-up were collected. RESULTS: During this period, 4 patients were diagnosed with SRS. Median age at diagnosis was 13 years (12-15 years) with a mean duration of symptoms of 13 months (12-36 months). In 2 patients the SRS was associated with Costal Dysmorphia (CD). The initial diagnosis was clinical with posterior ultrasound confirmation. Resection of the affected cartilages was performed in 3 patients and after a follow-up of 6 months (3-30 months), they all are painless and refer a good cosmetic result. One patient refused the intervention. CONCLUSIONS: The SRS is an infrequent cause of thoracic pain with an etiology not well understood. The awareness of this disease and its typical presentation can avoid unnecessary studies. The resection of the affected cartilages is a safe and effective treatment.

INTRODUCCION: El síndrome de costilla deslizante (SCD) es una entidad poco frecuente en niños. Se cree que su causa es una debilidad en los ligamentos costales que permite una hipermovilidad de las costillas. Genera un dolor intermitente en la región baja del tórax o alta del abdomen que puede afectar a las actividades de la vida diaria o generar un dolor crónico. MATERIAL Y METODOS: Revisión retrospectiva de SCD entre octubre de 2012 y diciembre de 2017. Se recogió información acerca de los datos demográficos, síntomas, estudios de imagen, hallazgos intraoperatorios, material fotográfico y seguimiento a largo plazo. RESULTADOS: Durante este periodo, 4 pacientes fueron diagnosticados de SCD. La mediana de edad al diagnóstico fue de 13 años (12-15 años) con una duración previa de los síntomas de 13 meses (12-36 meses). En 2 pacientes se asoció una dismorfia costal (DC). El diagnóstico fue clínico con confirmación ecográfica. Se realizó resección de los cartílagos afectos en 3 pacientes con un seguimiento posterior de 6 meses (3-30 meses). Actualmente se encuentran sin dolor y con un resultado estético satisfactorio. Un paciente rechazó la intervención. CONCLUSIONES: El SCD aparece en pacientes preadolescentes que en algunos casos asocian DC. Una exploración física y ecografía enfocada son las claves para un diagnóstico certero. La resección de cartílagos es efectiva a largo plazo.

Oral mucositis in paediatric acute lymphoblastic leukemia patients receiving methotrexate-based chemotherapy: case series.

AIM: Oral mucositis (OM) is a painful and inflammatory ulcerative lesion occurring as an adverse effect during chemotherapy in children with acute lymphoblastic leukemia (ALL). This condition may cause significant systemic anomalies such as malnutrition, opportunistic infections, and delay in the chemotherapy course. This report aims to describe a case series of 11 ALL patients treated with methotrexate as chemotherapy agent. CASE SERIES: Each patient was carefully followed-up and orally examined for 14 days after their chemotherapy session. OM occurred in all children. Then, the Multinational Association of Supportive Care in Cancer and the International Society of Oral Oncology (MASCC/ISOO) management protocol for OM was applied to them. The mean time of the lesion total resolution was 3.7 days. CONCLUSIONS: It is necessary to emphasise the importance of early detection of OM through a close clinical oral examination of children and adolescents with ALL undergoing methotrexate chemotherapy. Pain/infection control and the maintenance of good levels of oral hygiene are fundamental during the management of OM. Therefore, paediatric dentists need to be part of the oncology care team, and thus contributing and helping with ALL treatment.

Oral management of children with Henoch-Schönlein Purpura and associated Glomerulonephritis: a scoping review.

AIM: To perform a scoping review of the existing literature in order to gather the most relevant information in the paediatric dentistry field related to the oral management of children affected by Henoch-Schönlein Purpura and associated Glomerulonephritis (HSPG). MATERIALS AND METHODS: Using scoping review methodology for the screening and selection of valid articles, the steps of this review were the following: first, to pose a research question; second, to identify relevant studies; third, to select and retrieve the studies; fourth, to chart the critical data, and finally, to collate, summarise, and report the results from the included articles. Relevant articles published over a 25-year period, up to July 31, 2017, were identified and retrieved from four Internet databases: PubMed; EMBASE/Ovid; Ebsco/Dentistry & Oral Science Source, and the Cochrane Collaboration Library. RESULTS: By title and abstract screening and after removing duplicates, four articles were finally included in the scoping review. According to the extracted data, the following are the most important clinical issues to be considered: (1) the disease can appear as a consequence of a dental treatment, such as those indicated for oral infectious processes; (2) children with HSPG are highly susceptible to dental caries and apical periodontitis, and (3) in affected children, oral infectious foci must be exhaustively eradicated in order to avoid the dissemination of the infection. CONCLUSIONS: Paediatric Dentists should be aware of HSPG, because the disease can be triggered or worsen subsequent to dental treatment. Adequate treatment of oral active infectious processes, together with an exhaustive oral preventive programme and long-term patient screening, are the best management approaches for children with HSPG.

Epidemiological profile of smoking and nicotine addiction among asthmatic adolescents.

OBJECTIVE: Despite the harmful effects of cigarette smoking, this habit in asthmatic adolescents continues to be a health problem worldwide. Our objectives were to determine the epidemiological profile of smoking and the degree of nicotine dependence among asthmatic adolescents. STUDY DESIGN: Through a cross-sectional investigation, 3383 adolescents (13-19 years of age) were studied. METHODS: Information was collected using a previously validated questionnaire. Two study groups of adolescent smokers were formed: one composed of asthmatic adolescents and the other of healthy youths. RESULTS: Asthmatic adolescents were found to be more likely to smoke (21.6% vs 11.8%) and to have some degree of nicotine dependence compared with healthy adolescents (51.6% vs 48.8%). The most important characteristic of smoking in asthmatic adolescents was found to be an onset before 11 years of age due to curiosity about cigarettes. Asthmatic youths continue smoking because this habit decreases their anxiety and stress. Adolescents know that smoking is addictive and often smoke on waking up in the morning or when they are sick. Yet, these adolescents do not consider smoking to be a problem. CONCLUSION: In this study, curiosity about cigarettes was the primary reason why asthmatic adolescents smoked for the first time and developed a greater dependence to nicotine compared with healthy adolescents. Moreover, the findings show that many of the factors that favour the development of smoking are preventable, given that they are present in the family and social environment.

Kidney Transplantation in HIV-Infected Recipients: Therapeutic Strategy and Outcomes in Monocentric Experience.

BACKGROUND: In Human immunodeficiency virus (HIV)-positive patients undergoing kidney transplantation, outcomes and immunosuppression (IS) protocol are not yet established due to infectious and neoplastic risks as well as to pharmacokinetic interactions with antiretroviral therapy (TARV). METHODS: We report a retrospective, 1-center study on 18 HIV+ patients undergoing, between October 2007 and September 2015, kidney transplantation (13 cases) or combined kidney-liver transplant (5 cases). Inclusion criteria for transplant were based on the Italian National Transplant Center protocol. IS regimen was based on quick tapering of steroids and the use of mTOR inhibitors (mTORi) with low dose of calcineurin inhibitors (CNI). In the early post-transplant period, TARV was based on enfuvirtide, raltegravir, plus 1 or more nucleoside analogues. RESULTS: In a mean follow-up of 3.1 years, patient survival rate at 1 and 3 years was, respectively, 86.6% and 84.6%, whereas graft survival was 81.2% and 78.6%. Cumulative rejection rate was 20.0% and 26.6% (1- and 3-year results). Median eGFR (MDRD) was 58.8 mL/min and 51.9 mL/min at 1 and 3 years. We had 9 cases of clinically relevant infections (2 Pneumocystis jirovecii pneumonia, 1 pulmonary aspergillosis, 2 severe sepsis, and 4 HCV reactivation) as well as 1 case (5.5%) of HIV reactivation. CONCLUSIONS: IS therapy based on mTORi and low CNI dose ensures good graft survival, low rate of acute rejection, limited drug toxicity, and control of HIV disease. TARV has no significant interaction with IS therapy.

Interstitial Lung Disease After Kidney Transplantation and the Role of Everolimus.

BACKGROUND: Kidney transplant recipients are at higher risk of developing pulmonary complications related to immunosuppression, and inhibitor of the mammalian target of rapamycin (mTORi) has been reported as a potential cause. METHODS: Five hundred kidney-transplanted patients were retrospectively analyzed for pulmonary complications on the basis of clinical and instrumental data (chest radiography, high-resolution computed tomography, broncho-alveolar lavage, oximetry). RESULTS: We found 26 interstitial lung diseases (ILD) (16%): 12 cases (46.2%) were from infections (42.8% by Pneumocystis jirovecii) and 14 cases of ILD (53.8%) resulted as drug-induced ILD (DI-ILD). According to anti-rejection protocols, DI-ILD occurred in 8 patients (57%) while on triple regimen including steroids, everolimus (EVL), and cyclosporine (CyA) and in 6 patients on double regimen with steroids and mTORi: EVL or sirolimus (43%). In ILD+ patients, everolimus trough-concentration (EVL(TLC)) and cyclosporine (2nd-hour concentration: CyA(C2)) levels were higher than in patients in the same regimen but with ILD- (EVL(TLC) [ng/mL] 9.84 versus 6.85; CyA(C2) [ng/mL] 303.97 versus 298.56). The formula that used the combined blood levels of both drugs (EVL(TLC) + CyA(C2)/100) resulted in a significant difference between groups of patients (12.88 ± 1.61 versus 9.83 ± 1.91). Applying receiver operator characteristic curve (ROC) analysis to detect risk of developing ILD when on combined protocol with EVL and CyA, we obtained an area under the curve of 0.8622 (P = .0081) and 0.9082 (P = .0028), respectively, when using EVL(TLC) or the combination formula with both drugs. CONCLUSIONS: In renal transplant patients, we obtained a relationship of ILD to specific drug concentration. On the basis of ROC analysis, patients on EVL and CyA combined protocol are at risk of ILD when EVL(TLC) is >9.03 ng/mL or >11.41 when a formula with summation of EVL(TLC) and CyA(C2) is used.

HIV treatment and care among Italian inmates: a one-month point survey.

BACKGROUND: HIV infection, with an estimated prevalence be between 2 and 50 times those of the general adult population is a major health challenge for prison authorities worldwide. Since no nationwide surveillance system is present in Italy, data on HIV prevalence and treatment in prisons are limited to only a few and small observational studies. We aimed to estimate HIV prevalence and obtain an overview on diagnostic and therapeutic activities concerning HIV infection in the Italian penitentiary system. METHODS: We piloted a multi-centre cross-sectional study investigating the prevalence of HIV infection and assessing HIV-related medical activities in Italian correctional institutions. RESULTS: A total of 15,675 prisoners from 25 institutions, accounting for approximately one-fourth of the prison inmates in Italy, were included in the study, of whom, 97.7 % were males, 37.1 % foreigners and 27 % had a history of intravenous drug addiction. HIV-tests were available in 42.3 % of the total population, with a known HIV Infection proportion of 5.1 %. In the month prior to the study, 604 of the 1,764 subjects who entered prison were tested for HIV, with a HIV-positive prevalence of 3.3 %. Among the 338 HIV-positive prisoners, 81.4 % were under antiretroviral treatment and 73.5 % showed undetectable HIV-RNA. In 23/338 (6.8 %) a coinfection with HBV and in 189/338 (55.9 %) with HCV was also present. Among the 67 (19.8 %) inmates with HIV who did not receive HIV treatment, 13 (19.5 %) had T-CD4+ count <350 cells/mm(3) and 9 (69.2 %) of these had refused the treatment. The majority of the inmates with HIV-infection were on a PI-based (62.5 %) or on NNRTIs-based (24.4 %) regimen. Only a minority of patients received once daily regimens (17.2 %). CONCLUSIONS: Although clinical and therapeutic management of HIV infection remains difficult in Italian prisons, diagnostics, treatment and care were offered to the majority of HIV-infected inmates. Specific programs should be directed towards the prison population and strict cooperation between prison and health institutions is needed to increase HIV treatment.

The INTERPRET-DD study of diabetes and depression: a protocol.

AIM: People with diabetes are at an increased risk of developing depression and other psychological disorders. However, little is known about the prevalence, correlates or care pathways in countries other than the UK and the USA. A new study, the International Prevalence and Treatment of Diabetes and Depression Study (INTERPRET-DD) aims to address this dearth of knowledge and identify optimal pathways to care across the globe. METHOD: INTERPRET-DD is a 2-year longitudinal study, taking place in 16 countries' diabetes outpatients' facilities, investigating the recognition and management of depressive disorders in people with Type 2 diabetes. Clinical interviews are used to diagnose depression, with clinical and other data obtained from medical records and through patient interviews. Pathways to care and the impact of treatment for previously unrecognized (undocumented) depression on clinical outcomes and emotional well-being are being investigated. RESULTS: Initial evidence indicates that a range of pathways to care exist, with few of them based on available recommendations for treatment. Pilot data indicates that the instruments we are using to measure both the symptoms and clinical diagnosis of depression are acceptable in our study population and easy to use. CONCLUSIONS: Our study will increase the understanding of the impact of comorbid diabetes and depression and identify the most appropriate (country-specific) pathways via which patients receive their care. It addresses an important public health problem and leads to recommendations for best practice relevant to the different participating centres with regard to the identification and treatment of people with comorbid diabetes and depression.

Everolimus, cyclosporine, and thrombotic microangiopathy: clinical role and preventive tools in renal transplantation.

INTRODUCTION: Thrombotic microangiopathy (TMA) is characterized by endothelial cell injury and formation of fibrin thrombi within capillary and arterioles. In renal allograft recipients, TMA mainly presents as hemolytic uremic syndrome. Its occurrence is rare, and diagnosis requires a high degree of suspicion. Drug toxicity, in particular from calcineurin inhibitors (CNIs) and mTOR inhibitors (mTORi), is the most common cause posttransplant and has recently been emphasized in the setting of lung transplantation. OBJECTIVE: The goal of this study was to investigate the role of mTORi as an added risk factor in the development of TMA to propose strategies for modulation of immunosuppressive (IS) therapy. PATIENTS AND METHODS: From a database of 496 renal graft recipients, we analyzed 350 renal graft biopsy specimens gathered at our center from 1998 to 2012. In patients undergoing combined therapy with mTORi and CNI, we compared drugs levels in TMA-affected and TMA-free groups, using mTORi and CNI TLC and the summation of [everolimus TLC+(cyclosporine C2/100)] (Σ) as a surrogate marker of combined exposition to 2 drugs. Receiver-operating characteristic analysis of association of EVL TLC+(C2/100) was performed for patients exposed to mTORi. RESULTS: Histologic features of TMA were found in 36 patients (prevalence of 7.3%). The caseload was divided into 2 groups: not drug-related TMA (n=19) and drug-related TMA (n=17). Despite the prevalence of TMA in patients exposed to mTORi being greater (8 of 153; prevalence, 5.3%) compared with therapies without mTORi (9 of 324; prevalence, 2.8%), statistical difference was not reached. Patients treated with mTORi who developed de novo drug-related TMA had higher blood levels of IS drugs compared with those who did not develop TMA. Receiver-operating characteristic analysis found a significant threshold of 12.5 ng/mL (area under the curve, 0.803; P=.006). CONCLUSIONS: Results confirm the pivotal role of IS drugs in the onset of de novo TMA. On the basis of literature, we could speculate a sequence of endothelial damage by CNI, on which everolimus fits hindering the repair of endothelial injury. Therefore, high blood levels of CNI and mTORi seem to predispose patients to posttransplant TMA. Combined monitoring of these 2 drugs might be used to prevent the complication. Σ [everolimus TLC + (cyclosporine C2/100)]>12.5 ng/mL should be avoided as a surrogate risk factor for adverse effects.

Contribution of V/Q SPECT to planar scintigraphy in the diagnosis of pulmonary embolism.

AIM: To evaluate the feasibility of V/Q SPECT and analyze its contribution to planar V/Q lung scintigraphy in the diagnosis of pulmonary embolism (PE). MATERIAL AND METHODS: A total of 109 patients with suspected PE showing Wells score>2 and elevated D-dimer were studied. The V/Q could not be completed in 7 patients, so they were excluded. Ventilation and perfusion scans were done using Technegas and (99m)Tc-MAA. Planar study included 8 projections on a 256×256 matrix and 128 projections on a 128×128 matrix were acquired for the SPECT study, applying an iterative method. Planar images were interpreted according to modified PIOPED criteria, and SPECT by the guidelines of the EANMMI. The results with both techniques were compared. RESULTS: V/Q planar scintigraphy and SPECT could be performed in 102 patients. V/Q planar scintigraphy was considered "diagnostic" in 39 of the 102 patients, and "non-diagnostic" in 63. Of the 39 "diagnostic" studies, 31 were reported as high probability of PE and 8 as normal. Of the 63 "non-diagnostic", 26 corresponded to intermediate, 29 to low, and 8 to very low probability. The SPECT study was "diagnostic" in 97 and indeterminate in only 5. All patients with a high probability planar scintigraphy had a positive SPECT. In the 8 patients with a normal planar scintigraphy SPECT was negative in 5 and positive in 3. In the 63 patients with a "non-diagnostic" planar scintigraphy SPECT was "diagnostic" in 58 of them, positive in 17 and negative in 41. CONCLUSION: V/Q SPECT is a feasible technique as it was performed in 102 of the 109 patients who were enrolled in the study (94%). The addition of V/Q SPECT to planar V/Q decreases the number of "non-diagnostic" reports from 62% in planar scintigraphy to 4.9% in SPECT. Therefore, V/Q SPECT should be included in the diagnosis approach of PE due to its high diagnostic yield.

Comparison of 99mTc-sestamibi and 11C-methionine PET/CT in the localization of parathyroid adenomas in primary hyperparathyroidism.

AIM: To evaluate the usefulness of (11)C-methionine PET/CT (MET) in the localization of the parathyroid adenomas and to compare the results with those obtained with the conventional technique in double-phase (99m)Tc-sestamibi scintigraphy (MIBI). We evaluated the optimal timing to acquire MET images. MATERIAL AND METHODS: A prospective study that included 14 patients (mean age: 65.5 ± 9.7 years) with primary hyperparathyroidism (PH) who underwent surgery was performed. Mean serum iPTH was 215.8 ± 108 pg/mL and serum calcium 10.8 ± 0.9 mg/dL. MIBI (planar and SPECT) was obtained 10 min and 2-3h after injection of 740 MBq (20 mCi) of (99m)Tc-sestamibi. MET was obtained 10 min and 40 min after injection of 740 MBq (20 mCi) of (11)C-methionine. MIBI and MET images were visually evaluated and compared. A score for 10 min and 40 min MET images from 0 (no abnormal uptake) to 3 (intense uptake) was assigned. RESULTS: MIBI and MET were positive and concordant in 11/14 patients and in 10 of them the parathyroid adenoma was correctly localized. In 3/14 MIBI was positive and MET negative (MIBI correctly localized the parathyroid adenoma in 2 of them). According to the timing of MET imaging acquisition, the 10 min and 40 min acquisition showed the same score in 10 patients, it was higher at 10 min acquisition in 3 and in 1 the parathyroid adenoma was only detected at 40 min acquisition. CONCLUSION: MIBI remains the technique of choice for the localization of parathyroid adenomas in patients with PH. MET may play a complementary role in selected patients. Delayed acquisition should be included in the MET protocol when the early acquisition is negative.

Comparison of early (60 min) and delayed (180 min) acquisition of 18F-FDG PET/CT in large vessel vasculitis.

PURPOSE: To compare the contribution of the (18)F-FDG-PET/CT acquisition at 180 min and at 60 min in suspicion of large vessel vasculitis (LVV). MATERIAL AND METHODS: A prospective study including 23 patients was performed. PET/CT was acquired at 60 and 180 min (early and delayed scan) after (18)F-FDG injection. A visual analysis was performed at the supra-aortic trunks (SAT), thoracic aorta (TA), abdominal aorta (AA), iliac arteries (IA) and femoral/tibioperoneal arteries (FTA). Intensity (0-3) and uptake pattern (diffuse/linear) were assessed in the 115 vascular regions. RESULTS: There was no FDG uptake in the early and delayed acquisition in 20/115 vascular regions (17.4%). Of the 95 regions (82.6%) showing FDG uptake at the early, delayed or both acquisitions, intensity did not change in the delayed acquisition in 46 and changed in 49. Of the 49 regions in which the intensity changed, it decreased in 36 and increased in 13 (TA:8, SAT:5). AA, IA and FTA intensity did not increase in any of the cases. Uptake pattern at the TA in the early acquisition was diffuse in 16 patients. In 7, it changed to linear and in 9 the uptake disappeared. The early pattern was linear in 7 patients and 6 of them showed increased intensity in the delayed acquisition and in 1 remained the same. CONCLUSION: The 180 min delayed FDG-PET/CT acquisition provides a more detailed visualized of the vessel wall, showing the washout of the blood pool activity. Therefore, it may contribute to a more accurate diagnosis of LVV.

Pituitary volume in schizophrenia spectrum disorders.

INTRODUCTION: There is converging evidence supporting hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in schizophrenia spectrum disorders (SSD), such as schizotypal personality disorder (SPD), first-episode schizophrenia (FESZ) and chronic schizophrenia (CHSZ). Such an aberrant HPA activity might have volumetric consequences on the pituitary gland. However, previous magnetic resonance imaging (MRI) studies assessing pituitary volume (PV) in SSD are conflicting. The main objective of this study was to examine further PV in SSD. METHODS: PV were manually traced on structural MRIs in 137 subjects, including subjects with SPD (n = 40), FESZ (n = 15), CHSZ (n = 15), and HC (n = 67). We used an ANCOVA to test PV between groups and gender while controlling for inter-subject variability in age, years of education, socioeconomic status, and whole brain volume. RESULTS: Overall, women had larger PV than men, and within the male sample all SSD subjects had smaller PV than HC, statistically significant only for the SPD group. In addition, dose of medication, illness duration and age of onset were not associated with PV. CONCLUSION: Chronic untreated HPA hyperactivity might account for smaller PV in SPD subjects, whereas the absence of PV changes in FESZ and CHSZ patients might be related to the normalizing effects of antipsychotics on PV. SPD studies offer a way to examine HPA related alterations in SSD without the potential confounds of medication effects.