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Aims Functional mitral regurgitation (MR) (FMR) is common in heart failure with reduced ejection fraction and worsens morbidity and mortality, even when mild. The CARILLON (R) mitral contour system (Cardiac Dimensions, Kirkland, WA, USA), a mitral annuloplasty device delivered percutaneously to the coronary sinus, is designed to reduce the mitral annular dimension by virtue of the close anatomic relationship between the coronary sinus and the posterior mitral annulus. We performed a comprehensive individual patient data meta-analysis of all studies that used CARILLON (R) device vs. control that have measured mitral regurgitation severity, left ventricular (LV) remodelling, functional status, and heart failure-related outcomes in heart failure with reduced ejection fraction patients. Methods and results The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE were searched in July 2020. Primary outcomes of interest were measures of MR severity, LV remodelling, New York Heart Association functional class and heart failure-related outcomes [mortality and heart failure hospitalization (HFH) during follow up]. All data were received as individual patient and individual time point data-points. Mean differences and 95% confidence intervals (CIs) were calculated for continuous data using a fixed-effects model. Three studies (REDUCE FMR, TITAN and TITAN II) enrolling 209 participants were identified and included. Pooled analysis showed that, compared with control, CARILLON (R) device significantly improved both MR volume (mean difference MD -9.20, 95% C.I. -16.11 to -2.29 mL, P = 0.009) and MR grade (MD -1.12, 95% CI -1.36 to -0.88, P < 0.00001) and this was associated with a significant reduction in LA volume, MD -7.54 mL, 95% CI -14.90 to - 0.18, P = 0.04. Significant LV reverse remodelling was also seen in terms of EDV (MD -16.53, 95% CI -28.61 to -44.4 mL, P = 0.007), and a trend in ESV (MD -8.68, 95% CI -18.69 to -1.34 mL, P = 0.09) but no significant effect on LVEF (MD 0.88, 95% CI -1.52% to 2.38%, P = 0.47), due presumably to the greater residual MR in the control patients falsely elevating the LVEF. In addition, the CARILLON (R) device significantly improved New York Heart Association functional Class (MD -0.22, 95% CI -0.24 to -0.16, P < 0.00001), associated with a lower rate of HFH compared with controls (45.3% vs. 64%, respectively, P = 0.04). As a sensitivity analysis we also restricted the analyses to those patients with Class 3+/4+ MR at baseline. In this cohort, the echocardiographic results were similar, and the reduction in HFH rates was even more marked (43.9% vs. 82.9%, respectively, P = 0.04). Conclusions This comprehensive meta-analysis of individual patient data has shown that CARILLON (R) device provides statistically significant and clinically meaningful benefits on MR severity, LA and LV volumes, and remodelling and rates of subsequent heart failure hospitalization

Cardiac contractility modulation is an innovative therapy conceived for the treatment of heart failure. It is a device-based therapy, employing multiple electrodes to deliver relatively high-voltage (~7.5 V) biphasic signals to the endocardium of the right ventricular septum, in order to improve heart failure symptoms, exercise capacity and quality of life. Multiple clinical and mechanistic studies have been conducted to investigate the potential usefulness of this technology and, as of now, they suggest that it could have a place in therapy and meet a relevant medical need for a specific sub-category of underserved heart failure patients with reduced left ventricular ejection fraction. More studies are needed to further investigate its effect on outcomes such as mortality and rate of hospitalizations.

Background Chronic subdural hematoma associated with dural calcifications in previously pediatric shunted patients is a rare condition. The inner dural membrane opening can lead to progressive brain herniation into the subdural space due to brain reexpansion. Case Description A 15-year-old boy, previously shunted at birth for congenital hydrocephalus, presented with a giant chronic right hemispheric subdural hematoma. After 2 surgical procedures in which the subdural calcified neomembrane was opened and a subdural shunt was implanted, he developed a cortical brain herniation into the subdural space, resulting in brain ischemia and upper limb weakness and vomiting. The final surgical treatment consisted of an extensive wide peeling of visceral calcified membrane mutually to programmable valve placement along the subduroperitoneal shunt, in order to create a positive gradient between the subdural space and the ventricles. The patient experienced a prompt clinical improvement. Conclusions This case illustrates a rare complication of the treatment of a chronic subdural hematoma caused by insufficient opening of the calcified inner mambrane of the hematoma and encouraged by gradient pressure between the ventricular and subdural compartments. To avoid this complication, it is preferable to not open a thick, calcified, unelastic inner membrane. However, in case of lack of clinical and radiologic improvement, it may become necessary to open it: a wide opening should be attempted, in order to prevent brain strangulation.

Neuroendoscopic biopsy represents the procedure of choice for pure intraventricular lesions. Instead, in case of deep-seated paraventricular tumors, with intact ependyma, the advantage of neuroendoscopy over stereotactic biopsy is not so evident, because the lesion is not under direct vision; the tissue sample may be limited to more superficial ependymal layer, and bleeding may obscurate vision. Also, stereotactic biopsy may reserve additional problems for these lesions: inaccuracy caused by leak of cerebrospinal fluid and increased risk of severe hemorrhage due to damage of the ependymal vessels. We report two cases of young children affected by thalamic tumors that were biopsied using a modification of a recently proposed technique: endoscopic visual control, neuronavigated needle biopsy. This technique may combine the accuracy of a stereotactic needle biopsy with the advantage of visual control on site of ependymal puncture and possibility of immediate bleeding control.

Background Midbrain and surrounding areas are among the most difficult regions to surgically approach in neurosurgery. The subtemporal approach is a well-known neurosurgical approach that is rarely described in children. Objective To assess the feasibility, advantages, and disadvantages of subtemporal approach in children. Methods A total of 20 pediatric patients with intra-axial tumors involving the lateral midbrain or superior cerebellar peduncle or with extra-axial tumors in the middle incisural space/Meckel cave underwent subtemporal transtentorial approaches with the aim to remove (16 cases) or biopsy (4 cases) their lesions. These cases were retrospectively reviewed and the surgical approach described. Results Total resection was achieved in 11 patients. In the 4 patients who underwent biopsies, a diagnosis was obtained. A total of 5 patients presented non-neoplastic lesions (dermoid tumors or cavernomas). A total of 9 patients harbored low-grade tumors and 6 high-grade tumors. Patients with low-grade tumors and non-neoplastic lesions are all alive with no evidence of disease or stable residue. Four patients affected by high grade tumors died. No patient suffered permanent neurological deficits related to the surgical approach. Three patients presented temporary neurological deficits following the procedure: one case of strabismus, one case of aphasia and hemiparesis, secondary to delayed, transient thrombosis of the Labbe vein, and 1 case of trigeminal neuralgia. Conclusion The subtemporal approach represents a feasible approach for mesencephalic and perimesencephalic lesions in children. It provides an ample and direct access, with excellent outcomes and acceptable postoperative morbidity.

Post-traumatic hydrocephalus following head injury is a well-known entity. Most cases occur in patients with severe head injuries, often following decompressive craniectomy. On the contrary, acute post-traumatic hydrocephalus, caused by aqueductal obstruction by a blood clot, following mild head injury is uncommon. Six patients aged between 6 and 15 months presented hydrocephalus secondary to a blood clot in the aqueduct. Because of intracranial hypertension at presentation, 4 patients were urgently treated with external ventricular drains (EVDs). Post-operative course was uneventful. In 2 cases, EVDs were removed without further treatments. In 2 cases, hydrocephalus recurred. These patients were successfully treated with endoscopic third ventriculostomy. The remaining two patients developed symptoms a few days after the trauma. One, that presented hydrocephalus at imaging, was managed with a ventriculo-peritoneal shunt; the other, that presented subdural hygroma, was managed with subduro-peritoneal shunt that was removed later. All patients had complete recovery. Hydrocephalus secondary to clot in the aqueduct may rarely be the result of mild head injury in young children. Usually, prompt surgical management warrants a very good outcome. Most children may be treated without a permanent shunt, by using external drains and endoscopic third ventriculostomy.

Copyright © 2021 Silvério-António, Parlato, Martins, Khmelinskii, Braz, Fonseca and Polido-Pereira. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms., A 64-year-old male presented with a 6-month history of symmetric polyarthritis involving proximal interphalangeal joints and metacarpophalangeal joints of the hands, wrists, and ankles. Associated symptoms included vomiting, progressive fatigue, and weight loss. Laboratory results showed microcytic anemia, leukocytosis, thrombocytosis, elevated C-reactive protein and erythrocyte sedimentation rate, and rheumatoid factor (RF) and anti-cyclic citrullinated protein (ACPA) antibody positivity. Joints radiographs were normal, without erosions. Upper endoscopy and gastric endoscopic ultrasonography showed a gastric adenocarcinoma with lymphatic involvement. Intraoperatively, peritoneal carcinomatosis was documented, and the patient started palliative chemotherapy. A paraneoplastic seropositive arthritis was assumed, and treatment with low-dose prednisolone and hydroxychloroquine was started. Arthritis remission was achieved and sustained up to 18 months of follow-up, although gastric cancer progression was documented. We describe a unique phenotype of paraneoplastic arthritis (PA) presenting as a seropositive (RF and ACPA positivity) rheumatoid arthritis (RA) with a good response to both low dose corticosteroids and hydroxychloroquine therapy. We also review the literature of PA, mostly the RA-like pattern, and the association between PA and ACPA positivity. This case highlights the importance of considering underlying cancer in elderly male patients, presenting with polyarthritis and systemic symptoms, even in those with ACPA-positive RA-like arthritis.

Purpose: to describe the results of preschooler hearing and language screening and the association between them. Methods: a study with 75 children enrolled in preschool. The language was screened with the Behavior Observation Guide for 0-to-6-Year-Old Children. The hearing of children up to 1 year and 11 months old was screened with meatoscopy, acoustic immittance, behavioral hearing assessment, and otoacoustic emissions, while those in the age range 2 years or older were screened with meatoscopy, acoustic immittance, and play pure-tone audiometry. The children who failed the screening were referred for diagnosis. The results of the hearing and language assessments were compared with the McNemar test. Results: of the 75 children screened, 18 (24%) failed the hearing tests and 11 (15%) failed the language test. Hearing impairment was confirmed in 12 (66%) of those referred for diagnosis, and language impairment, in 10 (90%) of them. There was no association between hearing and language impairments (p = 0.230). Conclusion: hearing and language impairments were found in preschoolers. Although they were not associated, they can impact academic performance. This result emphasizes the need for developing strategies to implement preschooler screening programs that include hearing and language. RESUMO Objetivo: descrever os resultados da triagem auditiva e de linguagem, bem como a associação entre ambos, em pré-escolares. Métodos: estudo realizado com 75 crianças matriculadas na pré-escola. A triagem de linguagem foi realizada por meio da aplicação do Roteiro de Observação do Comportamento de Crianças de 0 a 6 anos. A triagem auditiva das crianças com idade até 1 ano e 11 meses consistiu de meatoscopia, imitanciometria, avaliação auditiva comportamental e emissões otoacústicas. As crianças com idade igual ou superior a 2 anos realizaram meatoscopia, imitanciometria e audiometria tonal lúdica. As crianças que falharam na triagem foram encaminhadas para diagnóstico. A comparação entre resultado da avaliação audiológica e linguagem foi realizada por meio do teste McNemar. Resultados: das 75 crianças triadas, 18 (24%) falharam nos testes auditivos e 11 (15%) falharam no teste de linguagem. Das crianças encaminhadas para diagnóstico, 12 (66%) receberam confirmação de alteração auditiva e 10 (90%) receberam confirmação de alteração de linguagem. Não houve associação entre alteração de audição e linguagem (p=0,230). Conclusão: foram encontradas alterações de audição e linguagem em pré-escolares que, apesar de não associadas, podem impactar no desempenho acadêmico. Este resultado enfatiza a necessidade do desenvolvimento de estratégias para a implementação da triagem do pré-escolar abrangendo a audição e linguagem.

Background: Peritonitis is the leading cause of morbidity and technique failure in peritoneal dialysis (PD) patients. The International Society for Peritoneal Dialysis (ISPD) recommends each centre to monitor the peritonitis rates and the causative organisms in order to guide local empiric antibiotic protocols. The aim of this study was to report on the peritonitis rates and describe the causative microorganisms and the antibiotic susceptibility in continuous ambulatory peritoneal dialysis (CAPD) adult patients at the Universitas Academic Hospital. Methods: A single-centre, retrospective descriptive survey was conducted to determine the peritonitis rates in PD patients (January–December 2016). All CAPD patients aged ≥18 years, who presented with clinical features of PD-associated peritonitis, were included. The peritonitis episodes were studied per patient, and the causative microorganisms and the antibiotic susceptibility of the organisms were described. Results: One hundred and twenty-eight patients underwent CAPD. The peritonitis rate was 1.45 episodes per year at risk. The prevalence of CAPD patients affected by at least one episode of CAPD-associated peritonitis during 2016 was 56.3%. The majority of episodes (76.7%) ( n = 122) were mono-microbial. Gram-positive organisms accounted for 73.0% ( n = 116) of the peritonitis episodes, coagulase-negative Staphylococcus being the most common. Gram-negative organisms accounted for 15.7% ( n = 25) of the peritonitis episodes, and the common pathogens was Enterobacteriaceae. Conclusion: The peritonitis rate was alarmingly high, with 1.45 episodes per year at risk; this is three times more than the recommended 0.5 episodes per year according to the ISPD guidelines. The culture-negative rate of 8.8% is within ISPD-acceptable limits. There is a need to strengthen preventive measures with regard to peritonitis.

Sepsis and non-septic systemic inflammatory response syndrome (SIRS) are the same syndromes, differing by their cause, sepsis being secondary to microbial infection. Microbiological tests are not enough to detect infection early. While more than 50 biomarkers have been proposed to detect infection, none have been repeatedly validated. To assess the accuracy of circulating biomarkers to discriminate between sepsis and non-septic SIRS. The CAPTAIN study was a prospective observational multicenter cohort of 279 ICU patients with hypo- or hyperthermia and criteria of SIRS, included at the time the attending physician considered antimicrobial therapy. Investigators collected blood at inclusion to measure 29 plasma compounds and ten whole blood RNAs, and—for those patients included within working hours—14 leukocyte surface markers. Patients were classified as having sepsis or non-septic SIRS blindly to the biomarkers results. We used the LASSO method as the technique of multivariate analysis, because of the large number of biomarkers. During the study period, 363 patients with SIRS were screened, 84 having exclusion criteria. Ninety-one patients were classified as having non-septic SIRS and 188 as having sepsis. Eight biomarkers had an area under the receiver operating curve (ROC-AUC) over 0.6 with a 95% confidence interval over 0.5. LASSO regression identified CRP and HLA-DRA mRNA as being repeatedly associated with sepsis, and no model performed better than CRP alone (ROC-AUC 0.76 [0.68–0.84]). The circulating biomarkers tested were found to discriminate poorly between sepsis and non-septic SIRS, and no combination performed better than CRP alone.

Purpose: The aim of this study was to evaluate the clinical, neuroradiological, and neuropathological outcomes of patients treated with equine collagen foil (TissuDura®) as a dura mater substitute during cranial and spinal neurosurgical procedures. Materials and Methods: All patients treated at the Department of Neurosurgery of the Second University of Naples with TissuDura between 2005 and 2009 were included. Dural reconstruction was performed using TissuDura, overlaid 1 cm over the dural defect with additional fixation using fibrin glue. No surgical sutures were used. Patients underwent postoperative contrast-enhanced magnetic resonance scans at 1 week, 1 month, and 1 year after surgery to detect any cerebrospinal fluid (CSF) leaks, infections, inflammations, or CSF circulation in the surgical region. Results: Dural reconstruction was performed in 74 patients, including 50 patients with tumors, two with C2 neurinoma, two with acoustic neurinoma, six with Chiari I malformation, two with severe head injury, and 12 requiring spinal surgery. Clinical and neuroradiological findings were normal and no signs of graft rejection or CSF leaks at postoperative follow-up were observed. In two cases of atypical meningioma, re-operation of the dural reconstruction was performed after 1 year. No adherences between brain and neodura were detected, and histopathological investigations demonstrated dural regeneration. Conclusions: Following dural reconstructions with TissuDura without surgical sutures, no local toxicity or complications were observed for up to 1 year. TissuDura demonstrated elasticity, non-reactivity, and good adaptability. The overlay technique using fibrin glue was simple and fast. Future studies and longer follow-up are needed to confirm the efficacy of TissuDura. © 2010 Springer-Verlag.

Cancer and cardiovascular diseases are globally the leading causes of mortality and morbidity. These conditions are closely related, beyond that of sharing many risk factors. The term bidirectional relationship indicates that cardiovascular diseases increase the likelihood of getting cancer and vice versa. The biological and biochemical pathways underlying this close relationship will be analyzed. In this new overlapping scenario, physical activity and exercise are proven protective behaviors against both cardiovascular diseases and cancer. Many observational studies link an increase in physical activity to a reduction in either the development or progression of cancer, as well as to a reduction in risk in cardiovascular diseases, a non-negligible cause of death for long-term cancer survivors. Exercise is an effective tool for improving cardio-respiratory fitness, quality of life, psychological wellbeing, reducing fatigue, anxiety and depression. Finally, it can counteract the toxic effects of cancer therapy. The protection obtained from physical activity and exercise will be discussed in the various stages of the cancer continuum, from diagnosis, to adjuvant therapy, and from the metastatic phase to long-term effects. Particular attention will be paid to the shelter against chemotherapy, radiotherapy, cardiovascular risk factors or new onset cardiovascular diseases. Cardio-Oncology Rehabilitation is an exercise-based multi-component intervention, starting from the model of Cardiac Rehabilitation, with few modifications, to improve care and the prognosis of a patient’s cancer. The network of professionals dedicated to Cardiac Rehabilitation is a ready-to-use resource, for implementing Cardio-Oncology Rehabilitation.

Emergency department assessment is a critical opportunity to identify elder abuse and violence against women, which represent a growing problem, requiring the attention of health care systems. Elder abuse is most frequently perpetrated by family members because of the higher levels of stress, burnout, and financial problems affecting the caregivers that can even lead to deadly consequences. Intimate partner violence is defined as physical, sexual, or psychological harm caused to another by a current or former partner or spouse, and can range from a single acute hit to chronic battering, varying in frequency and severity. Radiologists have a critical role in detecting those injury findings suggestive of abuse and violence. When appropriate, additional information about the social circumstances in which an injury took place, linked with imaging findings, may also be helpful in diagnosing abuse. The purpose of this article is to highlight the role of diagnostic imaging in the detection of lesions compatible with domestic abuse in elderly patients and women, and to allow the recognition of the alterations most frequently associated with this type of violence. (C) 2018 Published by Elsevier Inc.

This study was aimed at assessing the anti-HBs persistence and immune memory 18–19 y after vaccination against hepatitis B in healthy individuals primed as infants or adolescents. We enrolled 405 teenagers (Group A) vaccinated as infants, and 409 young adults (Group B) vaccinated as adolescents. All vaccinees were tested for anti-HBs and anti-HBc antibodies; those found anti-HBc positive were further tested for HBsAg and HBV DNA. Eight individuals belonging to Group B were positive for anti-HBc alone, and were excluded from analysis. Individuals with anti-HBs concentration ≥ 10 mIU/ml were considered protected while those with anti-HBs concentration

ObjectiveMedication reconciliation (MedRec) is a relevant safety procedure in medication management at transitions of care. The aim of this study was to evaluate the impact of MedRec, including abest possible medication history(BPMH) compared with a standard medication history in patients admitted to an internal medicine ward.DesignProspective interventional study. Data were analysed using descriptive statistics followed by univariate and multivariate Poisson regression models and a zero-inflated Poisson regression model.SettingInternal medicine ward in a secondary care hospital in Southern Switzerland.ParticipantsThe first 100 consecutive patients admitted in an internal medicine ward.Primary and secondary outcome measuresMedication discrepancies between the medication list obtained by the physician and that obtained by a pharmacist according to a systematic approach (BPMH) were collected, quantified and assessed by an expert panel that assigned a severity score. The same procedure was applied to discrepancies regarding allergies. Predicting factors for medication discrepancies were identified.ResultsThe median of medications per patient was 8 after standard medication history and 11 after BPMH. Total admission discrepancies were 524 (5.24 discrepancies per patient) with at least 1 discrepancy per patient. For 47 patients, at least one discrepancy was classified as clinically relevant. Discrepancies were classified as significant and serious in 19% and 2% of cases, respectively. Furthermore, 67% of the discrepancies were detected during the interview conducted by the pharmacist with the patients and/or their caregivers. The number of drugs used and the autonomous management of home therapy were associated with an increased number of clinically relevant discrepancies in a multivariable Poisson regression model.ConclusionEven in an advanced healthcare system, a standardised MedRec process including a BPMH represents an important strategy that may contribute to avoid a notable number of clinically relevant discrepancies and potential adverse drug events.

Background/Aims: Over the years a rise in the incidence of congenital hypothyroidism (CH) has been described worldwide. The aim of our study was to investigate trends in the incidence of CH in Italy over the period 1987-2008, and to investigate which factors may have influenced the CH incidence in our country. Methods: Data were derived from the Italian National Registry of Infants with Congenital Hypothyroidism. Since 1998 the laboratory procedures related to neonatal screening for CH have changed drastically. Accordingly, we estimated the CH incidence during the period 1987-1998 (period 1) and the period 1999-2008 (period 2). Results: The incidence of CH confirmed at birth (including transient hypothyroidism) has increased from 1:3,000 liveborn infants in period 1 to 1:1,940 in period 2 (+54%), whereas the incidence of purely permanent CH increased from 1:3,200 to 1:2,320 (+38%). Lowering of the TSH cutoff was the most important factor contributing to the increase of CH incidence in Italy. Moreover, an increment of 58% of preterm babies with permanent CH was found in period 2 compared with period 1. Conclusion: Our results suggest that more than one cause is responsible for the rise in the increasing CH incidence, with lowering of the screening TSH cutoff and an increased survival rate of a growing number of preterm babies both playing an important role.

The incidence of fractures of the humerus has increased exponentially in recent years. The most used classifications for humerus fracture are morphological (Neer), biological (AO/ASIF) and descriptive (Hertel). The types of surgical treatment for humerus fracture include prosthetic replacement and synthesis using different devices, including the Tension Guide Fixator (TGF), Gex-Fix. External fixation for displaced proximal humeral fractures avoids dissection and soft tissue stripping and has been reported by some authors to be associated with higher union rates, a lower incidence of avascular necrosis, less scarring of the scapulohumeral interface, and faster rehabilitation compared with open reduction and internal fixation. Other authors have reported that external fixation does not ensure acceptable reduction and fracture stability, particularly in patients with osteoporosis. The external fixation technique involves the introduction of Steinmann's pin to keep manual reduction, the introduction of two K-wires in the humeral head, the removal of the Steinmann's pin, and the introduction of two fiches on the humeral shaft. Hub connectors are mounted on the wires and on the chips to connect the outer bar and tensioning system. A total of 84 patients aged 42–84 years with proximal end humeral fractures (66% had two-part fractures) were treated with Fixator TGF in this study from December 2007 to June 2012. The postoperative recovery was earlier and the active-assisted motion was less painful than has been reported with other surgical techniques. The TGF was removed without anaesthesia at the outpatient clinic at a mean of 7 weeks (range 5–8 weeks) after surgery, and there was no loss of reduction or secondary displacement after removal. These results, after five years of experience, confirm that the best indication for this fixator is two- or three-part fractures because the device enables early active mobilisation. The limitations of this fixator are evident in fractures in which closed reduction is not possible and in three-part fractures with varus displacement because the TGF has less stability than other systems, such as the plate or cage. The short learning curve, reduced surgical time and risk, and low cost encourage the use of this technique.

Glioblastoma (GBM) is the most common brain cancer in adults. It is also, unfortunately, the most aggressive type and the least responsive to therapy. Overexpression of EGFR and/or EGFRvIII is frequently found in GBM and is frequently associated with the more malignant phenotype of the disease and a poor clinical outcome. EGFR-targeted therapy represents a promising anti-GBM therapy. Two EGFR kinase inhibitors, gefitinib and erlotinib have been tested in clinical trials for malignant gliomas. However, the clinical efficacy of EGFR-targeted therapy has been only modest in GBM patients. AREAS COVERED: The authors provide an evaluation of erlotinib as a potential therapy for GBM. The authors highlight experiences drawn from clinical trials and discuss the challenges, which include the insufficient penetration through the blood-brain barrier (BBB) and chemoresistance. EXPERT OPINION: Malignant brain tumours have a very complex signalling network that is not only driven by EGFR. This complexity dictates tumour sensitivity to EGFR-targeted therapies. Alternative kinase signalling pathways may be involved in parallel with the inhibited target, so that a single target's inactivation is not sufficient to block downstream oncogenic signalling. The use of nanocarriers offers many opportunities, such as the release of the drug to specific cells or tissues, together with the ability to overcome different biological barriers, like the BBB.

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The study of writing impairment in brain-damaged adult patients has usually been considered as a secondary aspect of their communication disorders. Writing rehabilitation has suffered from the same kind of limitations, its practice being considered only a tool contributing to the recovery of speech or the patient's occupation in everyday life. In 1967 Pizzamiglio and Roberts presented data concerning the ability of aphasic patients to learn written verbal material through a machine-aided technique. This machine, controlled by a punch tape, provided a typed sentence with the final word missing. The patient had to write the word by means of an external keyboard. The patient's reading abilities were extensively studied during a period of 15 months, two sessions a week. The main results of the study, reported by Carlomagno et al., allowed us to classify his reading impairment as surface dyslexia syndrome. The patient demonstrated a clear use of the learned strategy when he attempted to read this kind of written material.

The immaturity of born to preterm infants may predispose to sucking difficulties. This research aimed to evaluate if pacifier use is associated with preterm birth and influenced in type of infant feeding. This comparative cross-sectional study was conducted in Belo Horizonte, Brazil and evaluated 250 children aged 3 to 5 years. As a sample, two groups were established: the normal term children group (n=125) was selected at a day-care centre and the group of preterm children (125) was identified at a public university hospital with a preterm care project from birth to seven years of age. To collect data, a pre-tested questionnaire regarding information on gestational age, infant development, infant feeding and non-nutritive sucking habits was used for both groups. Bivariate and multivariate Poisson regression was used for the statistical analysis. Pacifier use was more prevalent in the preterm group (PR=1.20, 95% CI=1.02-1.42) who used the bottle (PR=1.38, 95% CI=1.15-1.64) and were breastfed for less than six months (PR=1.19, 95% CI=1.01-1.41). The majority of breastfed infants were of normal term birth (PR=1.14, 95% CI=1.04-1.20) and had monthly family income greater than USD 450.28 (RP= 1.10, 95% CI=1.01-1.20). In this study, pacifier use was more prevalent among preterm infants and associated with less than six months of breastfeeding and used of bottle. Monthly family income was associated with a prevalence of breastfeeding.

We describe a rare case of giant intracranial chordoma, emphasizing the patient's long survival and his excellent response to radiotherapy that led to a progressive regression of neurological symptomatology up to disappearance, in the absence of cerebral white matter damages.

A total of 58 patients consecutively underwent surgical treatment for lumbar intervertebral foraminal stenosis. We performed a microsurgical combined transarticular lateral and medial procedure with partial facetectomy in all patients to decompress the affected nerve root. All patients underwent assessment of depressive symptoms by means of the Zung Self Depression Scale (SDS). Subjective pain was self-evaluated by the Visual Analogue Scale (VAS). Both the tools were administered preoperatively, at 3 and 12 months' follow-up 0. The difference between the three SDS scores was significant (Friedman ANOVA, χ2 = 53.171, p < 0.00001). The Wilcoxon rank test showed significant difference between preoperative SDS scores as compared with three months follow-up (Z = -6.393, p < 0.0001) and the last, in turn, as compared with twelve months follow- up (Z = -3.720, p = 0.0002). The comparison between preoperative and 12 months' follow-up also reached significance (Z = -3.285, p = 0.001). About VAS, the difference between the three VAS scores was significant (Friedman ANOVA, χ2 = 69.932, p < 0.00001). The Wilcoxon rank test showed significant difference between preoperative VAS scores as compared with 3 months' follow-up (Z = -6.567, p < 0.0001) and the last, in turn, as compared with 12 months' follow-up (Z = -3.153, p < 0.002). The comparison between preoperative and 12 months' follow-up was also significance (Z = -5.520, p < 0.0001). Our results would alert clinicians to accurately consider the real need to treat and to include a careful psychiatric and psychological evaluation of these patients in the diagnosis and follow-up 0.

The aim of this study was to analyse mammographic and ultrasound (US) features of fibroadenoma and phyllodes tumour and assess the diagnostic accuracy of mammography, US and US-guided core needle biopsy (CNB) in the differential diagnosis of these two lesions.The results of the pathological analysis of excision biopsy of 83 lesions (67 fibroadenomas and 16 phyllodes tumours) were correlated with the findings of mammography, US and US-guided CNB performed on 83 women with a mean age of 45.4 years (range 18-75 years).Sensitivity, specificity and positive predictive values compared with histology were 45%, 50% and 79% for mammography, 34%, 69% and 82% for US and 81%, 97% and 87% for US-guided CNB (p=0.001).The almost complete overlap between mammographic and US parameters of fibroadenomas and phyllodes tumours and the absence of pathognomonic features preclude the differential diagnosis between the two histological types. US-guided CNB is a valuable tool in the differential diagnosis between fibroadenoma and phyllodes tumour.

PURPOSE: Although a nation-wide salt iodization program on voluntary basis was implemented in 2005, many areas in our country are still characterized by mild iodine deficiency. Differently from the rest of Italy, an efficient program of iodine prophylaxis was implemented in 1981 in the Autonomous Province of Bolzano. The aim of this study was to investigate whether an adequate iodine intake in the population may affect the incidence of permanent congenital hypothyroidism (CH). METHODS: The incidence trends of permanent CH between 1987 and 2006 in Bolzano Province and in the rest of Italy were estimated. RESULTS: Over the years, the CH incidence has remained steadily lower in Bolzano than in the rest of the country. CONCLUSIONS: Primary prevention of permanent CH may be possible by assuring an adequate nutritional iodine intake in the population. However, the time needed to observe a decrease in the incidence of CH is about a decade under conditions of iodine sufficiency.

The prognosis of patients affected by glioblastoma (GBM) is grim albeit the integrated therapeutic approaches now available. Standard surgery followed by chemoradiation median overall survival (OS) reaches 15 months in clinical trials. Despite primary treatment, recurrence is the rule in patients with GBM and for them OS ranges from 6 to 9 months. In recent years, the therapeutic scenario has been profoundly changed in view of the promising results obtained by bevacizumab (Avastin* *Avastin is a registered trade name of Bevacizumab, F. Hoffmann-La Roche Ltd, Basel, Switzerland.), the most promising anti-angiogenesis agent, in two clinical trials. The results of both trials were presented at the last ASCO meeting in Chicago. Progression free survival was significantly improved with an acceptable safety and tolerability profile but surprisingly quality of life was preserved only in the AVAGlio trial. However, both studies showed that overall survival was not improved adding bevacizumab to temozolomide and radiotherapy. © 2014 Informa UK Ltd. The prognosis of patients affected by glioblastoma (GBM) is grim albeit the integrated therapeutic approaches now available. Standard surgery followed by chemoradiation median overall survival (OS) reaches 15 months in clinical trials. Despite primary treatment, recurrence is the rule in patients with GBM and for them OS ranges from 6 to 9 months. In recent years, the therapeutic scenario has been profoundly changed in view of the promising results obtained by bevacizumab (Avastin*), the most promising anti-angiogenesis agent, in two clinical trials. The results of both trials were presented at the last ASCO meeting in Chicago. Progression free survival was significantly improved with an acceptable safety and tolerability profile but surprisingly quality of life was preserved only in the AVAGlio trial. However, both studies showed that overall survival was not improved adding bevacizumab to temozolomide and radiotherapy.

Background Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage ≥3 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage ≥3 CKD in a large cohort of patients affected by T1DM. Methods A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage ≥3 CKD (eGFR 30% from baseline was evaluated. Results The mean estimated GFR was 98 ± 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions Albuminuria and eGFR reduction represent independent risk factors for incident stage ≥3 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening. Electronic supplementary material The online version of this article (10.1186/s12882-018-1136-6) contains supplementary material, which is available to authorized users.

In the present study we investigated the feasibility and effectiveness of a new biweekly schedule of fotemustine (FTM) in patients with recurrent glioblastoma, after at least one previous treatment. The primary endpoint was progression-free survival at 6 months; secondary objectives were clinical response, overall survival, disease-free survival, and toxicity. Forty patients (median age 52.8 years; median Karnofsky Performance Status at progression 90) underwent second-line chemotherapy with FTM. Selected patients were previously treated with a standard radiotherapy course with concomitant temozolomide (TMZ). After tumor relapse or progression proven by magnetic resonance imaging (MRI), all patients underwent chemotherapy with FTM, given intravenously at dose of 80 mg/m2 every 2 weeks for five consecutive administrations (induction phase), and then every 3 weeks at 100 mg/m2 as maintenance. A total of 329 infusions were administered; the median number of cycles administered was 8. All patients completed the induction phase, and 29 patients received at least one maintenance infusion. Response to treatment was assessed using MacDonald criteria. One complete response [2.5%, 95% confidence interval (CI): 0-10%], 9 partial responses (22.5%, 95% CI: 15-37%), and 16 stable diseases (40%, 95% CI: 32-51%) were observed. Median time to progression was 6.7 months (95% CI: 3.9-9.1 months). Progression-free survival at 6 months was 61%. Median survival from beginning of FTM chemotherapy was 11.1 months. The schedule was generally well tolerated; the main toxicities were hematologic (grade 3 thrombocytopenia in two cases). To the best of our knowledge, this is the first report specifically dealing with the use of a biweekly induction schedule of FTM. The study demonstrates that FTM has therapeutic efficacy as single-drug second-line chemotherapy with a favorable safety profile. © 2010 The Author(s). In the present study we investigated the feasibility and effectiveness of a new biweekly schedule of fotemustine (FTM) in patients with recurrent glioblastoma, after at least one previous treatment. The primary endpoint was progression-free survival at 6 months; secondary objectives were clinical response, overall survival, disease-free survival, and toxicity. Forty patients (median age 52.8 years; median Karnofsky Performance Status at progression 90) underwent second-line chemotherapy with FTM. Selected patients were previously treated with a standard radiotherapy course with concomitant temozolomide (TMZ). After tumor relapse or progression proven by magnetic resonance imaging (MRI), all patients underwent chemotherapy with FTM, given intravenously at dose of 80 mg/m2 every 2 weeks for five consecutive administrations (induction phase), and then every 3 weeks at 100 mg/m2 as maintenance. A total of 329 infusions were administered; the median number of cycles administered was 8. All patients completed the induction phase, and 29 patients received at least one maintenance infusion. Response to treatment was assessed using MacDonald criteria. One complete response [2.5%, 95% confidence interval (CI): 0-10%], 9 partial responses (22.5%, 95% CI: 15-37%), and 16 stable diseases (40%, 95% CI: 32-51%) were observed. Median time to progression was 6.7 months (95% CI: 3.9-9.1 months). Progression-free survival at 6 months was 61%. Median survival from beginning of FTM chemotherapy was 11.1 months. The schedule was generally well tolerated; the main toxicities were hematologic (grade 3 thrombocytopenia in two cases). To the best of our knowledge, this is the first report specifically dealing with the use of a biweekly induction schedule of FTM. The study demonstrates that FTM has therapeutic efficacy as single-drug second-line chemotherapy with a favorable safety profile. © 2010 The Author(s).

International audience; The putative induction of adult β-cell regeneration represents a promising approach for the treatment of type 1 diabetes. Toward this ultimate goal, it is essential to develop an inducible model mimicking the long-lasting disease progression. In the current study, we have established a novel β-cell ablation mouse model, in which the β-cell mass progressively declines, as seen in type 1 diabetes. The model is based on the β-cell specific genetic ablation of the transcription initiation factor 1A, TIF-IA, essential for RNA Polymerase I activity (TIF-IA(Δ/Δ)). Using this approach, we induced a slow apoptotic response that eventually leads to a protracted β-cell death. In this model, we observed β-cell regeneration that resulted in a complete recovery of the β-cell mass and normoglycemia. In addition, we showed that adaptive proliferation of remaining β-cells is the prominent mechanism acting to compensate for the massive β-cell loss in young but also aged mice. Interestingly, at any age, we also detected β-like cells expressing the glucagon hormone, suggesting a transition between α- and β-cell identities or vice versa. Taken together, the TIF-IA(Δ/Δ) mouse model can be used to investigate the potential therapeutic approaches for type 1 diabetes targeting β-cell regeneration.

We assessed the persistence of hepatitis B surface antigen antibody (anti-HBs) and immune memory in a cohort of 571 teenagers vaccinated against hepatitis B as infants, 17 years earlier. Vaccinees were followed-up in 2003 and in 2010 (i.e. 10 years and 17 years after primary vaccination, respectively). When tested in 2003, 199 vaccinees (group A) had anti-HBs

Aim of this study is to analyze data reported in literature concerning the efficacy of using wound low-vacuum suction drainages in orthopedic surgery after total hip arthroplasty. We analyzed studies concerning the use of drainages in prosthetic hip replacement surgery, performing our research through Pubmed, Cochrane database and Google Scholar, and selecting the ones evaluating the following parameters: bleeding, the need for blood transfusions, number or reinforcement of post-operative medications, length of hospitalization, functional results, periprosthetic and surgical wound infection, post-operative hematoma. Our review did not show any demonstrated advantage from the use of wound drainages in total hip arthroplasty. Moreover, some studies enlighted a possible complication related to their employment, represented by the greater need for blood transfusions. Despite the absence of a statistically demonstrated positive influence on wound outcome using suction drains after total hip replacement, many orthopedic surgeons still recommend using drainages, just because there is no certified proof of a negative effect.

Context: Over the years lower TSH cutoffs have been adopted in some screening programs for congenital hypothyroidism (CH) worldwide. This has resulted in a progressive increase in detecting additional mild forms of the disease, essentially with normally located and shaped thyroid. However, the question of whether such additional mild CH cases can benefit from detection by newborn screening and early thyroid hormone treatment is still open. Objective: The aim of this study was to estimate the frequency of cases with mild increase of TSH at screening in the Italian population of babies with permanent CH and to characterize these babies in terms of diagnosis classification and neonatal features. Methods: Data recorded in the Italian National Registry of infants with CH were analyzed. Results: Between 2000 and 2006, 17 of the 25 Italian screening centers adopted a TSH cutoff at screening of < 15.0 mu U/mL. It was found that 21.6% of babies with permanent CH had TSH at screening of 15.0 mu U/mL or less, whereas this percentage was 54% in infants with transient hypothyroidism. Among the babies with permanent CH and mild increase of TSH at screening (

The forkhead transcription factor FOXE1 is mutated in patients with Bamforth-Lazarus syndrome that exhibit hair follicle defects, suggesting a possible role for Foxe1 in hair follicle morphogenesis. Here, we report that Foxe1 is specifically expressed in the lower undifferentiated compartment of the hair follicle, at a time and site that parallel activation of the Shh signaling pathway. The Foxe1 protein is also expressed in human and mouse basal cell carcinoma in which hedgehog signaling is constitutively activated, whereas it is undetectable in normal epidermis and squamous cell carcinoma. Moreover, expression of a dominant-negative form of Gli2 in skin results in complete suppression of Foxe1 expression in the hair follicle, whereas transcriptionally active Gli2 stimulates activity of the Foxe1 promoter. Foxe1-null skin displays aberrant hair formation with the production of thinner and curly pelage hairs. Although the hair follicle internal structure is conserved and several lineage markers are properly expressed, the orderly downgrowth of follicles is strikingly disrupted, causing disorientation, misalignment and aberrantly shaped of hair follicles. Our findings provide a strong indication that the defect in Bamforth-Lazarus syndrome is due to altered FOXE1 function in the hair follicle, and is independent of systemic defects present in affected individuals. In addition, we establish Foxe1 as a downstream target of the Shh/Gli pathway in hair follicle morphogenesis, and as a crucial player for correct hair follicle orientation into the dermis and subcutis.

OBJETIVO: verificar se as crianças na faixa etária entre quatro e cinco meses reconhecem o próprio nome. MÉTODO: estudo transversal, realizado com 16 bebês com idade entre quatro e cinco meses, avaliados pelo programa Estadual de Triagem Auditiva Neonatal Universal (TANU) no Ambulatório de Fonoaudiologia do Hospital das Clínicas da Universidade Federal de Minas Gerais (HC-UFMG). Foram realizadas avaliações auditiva e de linguagem, além do teste de reconhecimento do próprio nome. Realizou-se análise descritiva das variáveis utilizadas no estudo e análise estatística. As variáveis contínuas foram comparadas por meio do teste T pareado e considerou-se nível de significância de 5% e coeficiente de confiança de 95%. RESULTADOS: verificou-se predominância das respostas dos bebês à evocação do próprio nome, na maioria dos bebês avaliados. CONCLUSÕES: com base nos critérios utilizados neste estudo, entre quatro e cinco meses as crianças já são capazes de reconhecer seu próprio nome. PURPOSE: to verify that children aged between four and five months recognize their own names. METHOD: it is a cross-sectional study with 16 infants aged between four and five months, assessed by the Newborn Hearing Screening State Program (NHSP) in the Speech and Language Therapy Clinic of Hospital das Clínicas of Universidade Federal de Minas Gerais (HC - UFMG). In addition to the recognition test of the name, it was realized hearing and language assessment. A descriptive analysis of the variables of the study was held and the statistical analysis. Continuous variables were compared using the paired T test and it was considered a significance level of 5% and confidence coefficient of 95%. RESULTS: it was verified a predominance of responses to recall the name itself, in most infants evaluated. CONCLUSIONS: on the basis of the criteria set out in this study, infants aged between four and five months are capable of recognize their own names.

We report on one case of variant origin of right ophthalmic artery (OA) from C4 choroidal segment of the right supraclinoid internal carotid artery. A 41-year-old woman affected by bitemporal hemianopsia performed Magnetic Resonance Imaging with gadolinium showing tuberculum sellae meningioma. During angiography we observed this variant of origin of OA. At surgical dissection, we observed this variant in carotid cistern.

"In Italy, the nationwide newborn screening programme for congenital hypothyroidism (CH) represents an integrated approach to the disease including screening tests, diagnosis, treatment, follow up and nation-wide surveillance of the disease. The latter is performed by the Italian National Registry of Infants with Congenital Hypothyroidism (INRICH). The INRICH is a population-based Registry, this implies that results obtained in the analyses conducted on the data collected in the INRICH are highly representative, can be easily used to improve the health of CH children, and provide information critical to understanding the etiology of the disease. Over the years, the INRICH has contributed: i) to improve procedures for diagnosis, treatment and follow-up of affected babies, by identifying critical points in screening program procedures; ii) to estimate the incidence of CH and the prevalence of the different forms of the disease (thyroid dysgenesis, normally located and shaped thyroid) in our country; iii) to provide a unique opportunity for research into this condition given the large amount and the high quality of information collected in this registry."

QUESTIONS UNDER STUDY: Hypokalaemia in inpatients is common, and is associated with morbidity and mortality. Its management is risky and not always effective. We launched an educational programme with the aim of increasing the rate of potassium normalisation during hospital stay, and of reducing unmonitored cases. METHODS: The project consisted of three phases: (I) retrospective analysis on 26 471 patients hospitalised in 2012 in five acute care hospitals of southern Switzerland (Ente Ospedaliero Cantonale, EOC) with identification of improvement goals on a sample survey (588 cases of hypokalaemia); (II) revision of internal guidelines, and implementation of educational activities in one of the five hospitals (Ospedale Regionale di Locarno, ODL); (III) follow-up analysis on the 26 726 patients hospitalised in 2014 and second sampling to complete the evaluation of the efficacy of the intervention. RESULTS: Phase I, ODL vs EOC: prevalence of hypokalaemia, 21.7 vs 23.2% (p

Neuroendocrine chromaffin cells exist in both intra- and extra-adrenal locations; the organ of Zuckerkandl (OZ) constitutes the largest accumulation of extra-adrenal chromaffin tissue in mammals. The OZ disappears postnatally by modes that are still enigmatic but can be maintained by treatment with glucocorticoids (GC). Whether the response to GC reflects a pharmacological or a physiological role of GC has not been clarified. Using mice with a conditional deletion of the GC-receptor (GR) gene restricted to cells expressing the dopamine β-hydroxylase (DBH) gene [GR(fl/fl) ; DBHCre abbreviated (GR(DBHCre) )], we now present the first evidence for a physiological role of GC signalling in the postnatal maintenance of the OZ: postnatal losses of OZ chromaffin cells in GR(DBHCre) mice are doubled compared to wild-type littermates. We find that postnatal cell loss in the OZ starts at birth and is accompanied by autophagy. Electron microscopy reveals autophagic vacuoles and autophagolysosomes in chromaffin cells. Autophagy in OZ extra-adrenal chromaffin cells is confirmed by showing accumulation of p62 protein, which occurs, when autophagy is blocked by deleting the Atg5 gene (Atg5(DBHCre) mice). Cathepsin-D, a lysosomal marker, is expressed in cells that surround chromaffin cells and are positive for the macrophage marker BM8. Macrophages are relatively more abundant in mice lacking the GR, indicating more robust elimination of degenerating chromaffin cells in GR(DBHCre) mice than in wild-type littermates. In summary, our results indicate that extra-adrenal chromaffin cells in the OZ show signs of autophagy, which accompany their postnatal numerical decline, a process that is controlled by GR signalling.

Repeated exposure to opiates leads to cellular and molecular changes and behavioral alterations reflecting a state of dependence. In noradrenergic neurons, cyclic AMP (cAMP)-dependent pathways are activated during opiate withdrawal, but their contribution to the activity of locus coeruleus noradrenergic neurons and behavioral manifestations remains controversial. Here, we test whether the cAMP-dependent transcription factors cAMP responsive element binding protein (CREB) and cAMP-responsive element modulator (CREM) in noradrenergic neurons control the cellular markers and the physical signs of morphine withdrawal in mice. Using the Cre/loxP system we ablated the Creb1 gene in noradrenergic neurons. To avoid adaptive effects because of compensatory up-regulation of CREM, we crossed the conditional Creb1 mutant mice with a Crem-/- line. We found that the enhanced expression of tyrosine hydroxylase normally observed during withdrawal was attenuated in CREB/CREM mutants. Moreover, the withdrawal-associated cellular hyperactivity and c-fos expression was blunted. In contrast, naloxone-precipitated withdrawal signs, such as jumping, paw tremor, tremor and mastication were preserved. We conclude by a specific genetic approach that the withdrawal-associated hyperexcitability of noradrenergic neurons depends on CREB/CREM activity in these neurons, but does not mediate several behavioral signs of morphine withdrawal.

Pseudotumor cerebri is a condition characterized by raised intracranial pressure, normal CSF contents, and normal brain with normal or small ventricles on imaging studies. It affects predominantly obese women of childbearing age; however, its incidence seems to be increasing among adolescent and children. While among older children the clinical picture is similar to that of adults, younger children present demographic and clinical peculiarities. Different diagnostic criteria for adults and pre-pubertal children have been proposed. Etiology and pathogenesis are still unclear, particular concerning the role of obstruction to venous outflow.An extensive literature review concerning all the aspects of pseudotumor cerebri has been performed, both among adults and pre-pubertal children.Pseudotumor cerebri is an avoidable cause of visual loss, both in adults and children. Few diagnostic measures are usually sufficient to determine the correct diagnosis. Since pseudotumor cerebri is a diagnosis of exclusion, the differential diagnosis work out is of special importance. Modern neuroimaging techniques, especially magnetic resonance imaging and magnetic resonance venography may clarify the role of obstruction to venous outflow in each case. Various therapeutic options are available: medical, surgical, and endovascular procedures may be used to prevent irreversible visual loss. Treatment is usually effective, and most patients will experience complete resolution of symptoms without persistent deficits.

The transcription factor Gata3 is essential for the development of sympathetic neurons and adrenal chromaffin cells. As Gata3 expression is maintained up to the adult stage, we addressed its function in differentiated sympathoadrenal cells at embryonic and adult stages by conditional Gata3 elimination. Inactivation of Gata3 in embryonicDBH-expressing neurons elicits a strong reduction in neuron numbers due to apoptotic cell death and reduced proliferation. No selective effect on noradrenergic gene expression (THandDBH) was observed. Interestingly, Gata3 elimination inDBH-expressing neurons of adult animals also results in a virtually complete loss of sympathetic neurons. In the Gata3-deficient population, the expression of anti-apoptotic genes (Bcl-2,Bcl-xL, andNFκB) is diminished, whereas the expression of pro-apoptotic genes (Bik,Bok, andBmf) was increased. The expression of noradrenergic genes (THandDBH) is not affected. These results demonstrate that Gata3 is continuously required for maintaining survival but not differentiation in the sympathetic neuron lineage up to mature neurons of adult animals.

Background: Healthcare professionals play a key role in tobacco use prevention because they are considered as model by patients. This multicenter study was aimed to evaluate smoking prevalence, knowledge and attitudes towards tobacco among Italian hospital professionals. Methods: A crosssectional study was carried out using a questionnaire administered to healthcare professionals in seven Italian hospitals, to investigate personal and occupational data, knowledge, attitudes, job setting, clinical activities, smoking habits and pattern for current smokers. Potential predictors of current smoking habits were evaluated using multiple logistic regressions. Results: Sample population was comprised of 1082 health professionals (51.4% females; mean age was 37.3 years: 25.3% were nurses, 24.5% medical doctors, 17.1% students and 33.1% other healthcare workers). Smoking prevalence was 44%. Among responders, 67.7% considered healthcare professional as a model for citizens, 90.5% declared to see colleagues smoking cigarettes inside the hospital (47.4% in the dependents’ toilets, 33.4% in the department kitchens and 4.7% in the patient room). Multivariate analysis showed that healthcare professionals working in Naples had a higher risk to be smokers in comparison to Rome [odds ratio (OR) = 2.29; 95% confidence interval (CI) 1.40–3.73]. Compared to medical doctors, post-graduate students (OR = 3.42; 95% CI: 1.81–6.44), nurses (OR = 2.48; 95% CI 1.51–4.08), nursing students (OR = 1.91; 95% CI 1.08–3.38) and auxiliary personnel (OR = 2.72; 95% CI 1.51–4.88), showed a higher likelihood of smoking. Conclusions: Among Italian hospital personnel there is a paradoxically large prevalence of smokers, higher than in the general population. Interventions aimed for the development of an adequate culture of health promotion, among these professionals, are urgently needed.

Cigarette smoking (CS) is the main risk factor for bladder cancer development. There are more than 100 carcinogens present in cigarette smoke. Among the potential mediators of CS-induced alterations is nuclear factor-kappa (NF-κB), which is responsible for the transcription of genes related to cell transformation, tumor promotion, angiogenesis, invasion and metastasis. Curcumin is a polyphenol compound derived from Curcuma longa that suppress cellular transformation, proliferation, invasion, angiogenesis, and metastasis by down regulating NF-κB and its regulated genes. The aim of our study was to assess the effects of curcumin in bladder urothelial carcinoma. We studied the effects of curcumin in vitro and in vivo using the orthotropic syngeneic bladder tumor animal model MB49. Curcumin promotes apoptosis of bladder tumor cells in vitro. In vivo tumors of animals treated with curcumin were significantly smaller as compared to controls. Using immunohistochemistry, we demonstrated a decrease in the expression of Cox-2 by 8% and Cyclin D1 by 13% in the animals treated with curcumin; both genes regulated by NF-κB and related to cell proliferation. In this study, we showed that curcumin acts in bladder urothelial cancer, possibly dowregulating NF-κB-related genes, and could be an option in the treatment of urothelial neoplasms. The results of our study suggest that further research is warranted to confirm our findings.

Background Hepatitis B vaccination has proven to be very safe and highly effective. This study assessed the proportion of successfully vaccinated individuals among cases with acute hepatitis B, the proportion of preventable cases if individuals were vaccinated as recommended, and the reasons for failures. Methods We analyzed data reported to the Italian Surveillance System for Acute Viral Hepatitis from 1993 to 2014. Results A total of 362 of 11 311 (3.2%) cases with acute hepatitis B were vaccinated. Of the 277 cases for whom immunization data were available, 50 (18%) received a complete vaccination course according to the correct schedule and before exposure to hepatitis B virus. Molecular characterization of 17 of these cases showed that 6 were infected with S-gene mutants. Among the 10 949 unvaccinated cases, 213 (1.9%) escaped mandatory vaccination and 2821 (25.8%) were not vaccinated despite being at increased risk of infection. Among the latter, the most common risk factors were cohabitation with hepatitis B surface antigen (HBsAg) carriers, intravenous drug use, and homosexual/bisexual practices. Thirty-seven percent of the unvaccinated households with HBsAg carriers were aware of their risk. Lack of trust in the vaccination, negative attitude, and inaccurate beliefs followed by lack of or poor communication and low perceived severity of the disease were the most frequent reasons for vaccine hesitancy. Conclusions Development of acute disease in successfully vaccinated individuals is a rare event. Further efforts are needed to enhance the vaccine coverage rate in individuals at increased risk of infection.