Radiation Therapy in Non-Melanoma Skin Cancers: An Italian Survey on Behalf of the Italian Association of Radiotherapy and Clinical Oncology.

AIMS: The National Palliative Care and Interventional Radiotherapy Study Groups of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) carried out a survey whose aim was to obtain a "snapshot" of the real-world practice of nonmelanoma skin cancer (NMSC) treatments in Italy. MATERIALS AND METHODS: The survey was conducted on SurveyMonkey's online interface and was sent via e-mail to our society Radiation Oncologists. RESULTS: Fifty-eight Italian radiation oncologists (ROs), representing 54 centers, answered the survey. Thirteen percent of the ROs declared they treat fewer than 10 NMSC lesions annually, 36% treat between 11 and 20, and 51% treat more than 20 lesions annually. Interventional radiotherapy (IRT) was offered by 25% of the ROs, and every case was reportedly discussed by a multidisciplinary team (71%). Electrons (74%), volumetric modulated arc therapy (V-MAT) (57%), three-dimensional conformal radiotherapy (3D-CRT) (43%), and IRT (26%) were the main treatment options. With external beam radiotherapy (EBRT), 46 and 53 different RT schedules were treated for curative and palliative intent, respectively; whereas for IRT, there were 21 and 7 for curative and palliative intent, respectively. The most popular EBRT curative options were 50-70.95/22-35 fractions (fx) and 50-70 Gy/16-20fx and for EBRT palliative settings, 30Gy/10fx, and 20-35Gy/5fx. For IRT, the most popular curative options were 32-50Gy/8-10fx and 30-54Gy/3-5fx, whereas 30Gy/6fz was the palliative option. Less than 10 re-RT cases were reported in one year in 42.5%, 11-20 cases in 42.5%, and >20 cases annually in 15%. Electrons (61%), VMAT (49%), and BRT (25%) were the most widely used approaches: 20-40Gy in 10fx and 20-25Gy in 5fx were the recommended fractionations. CONCLUSION: The survey shows a variegated reality. A national registry with more detailed data could help in undercover its causes.

Doppler images of intrapulmonary arteries within atelectasis and its impact on right ventricular afterload with transesophageal echocardiography.

Video-assisted thoracoscopy (VATS) cardiac surgery requires one-lung ventilation (OLV) and transoesophageal ultrasound (TOE) monitoring. Colour and spectral Doppler make it possible to study the pattern of blood flow in the pulmonary vessels within the atelectatic lung. In this case report we describe how TOE can be used to detect blood flow within the atelectatic lung and to assess pulmonary vascular resistance (PVR) and right ventricular (RV) afterload. FINDINGS: Three anaesthetised, mechanically ventilated adults scheduled for cardiac surgery by VATS were scanned with TOE. After left OLV, the transducer was rotated away from the heart to obtain 2D colour Doppler images of blood flow within the consolidated lung parenchyma. We were able to identify the flow pattern of the intrapulmonary branches of the pulmonary artery. PVR was recorded using pulsed cardiac Doppler at baseline, after induction of general anaesthesia, 20 min after OLV and at the end of OLV, and after performing an alveolar recruitment manoeuvre (ARM) that led to complete resolution of the aforementioned consolidation. CONCLUSIONS: TOE is a semi-invasive imaging tool that can be used to diagnose and study PVR-induced atelectasis and to analyse the resulting pulmonary shunt and its possible effect on PVR.

The connection between diverticulosis and colonic superficial neoplastic lesions in patients who underwent screening colonoscopy.

PURPOSE: If could be a potential pathophysiological connection between colonic diverticula and colonic superficial neoplastic lesions, beyond the shared risk factors, has been a subject of debate in the last years. This study tries to evaluate the association between diverticulosis and colonic neoplastic lesions. METHODS: This is a cross-sectional study including asymptomatic patients who underwent a screening colonoscopy (patients with a positive fecal occult blood test under the regional program of colorectal cancer (CRC) screening), surveillance after polypectomy resection, or familiarity (first-degree relatives) between 2020 and 2021 to evaluate the association between diverticula and colonic polyps. A multivariate analysis with multiple logistic regression and odds ratio (OR) to study the independent association between adenomas and adenocarcinomas was performed. RESULTS: One thousand five hundred one patients were included. A statistically significant association between adenomas or CRC alone and colonic diverticula was found (p = 0.045). On a multivariate analysis of demographic (age, gender) and clinical parameters (familiarity for diverticula and adenoma/CRC), only age was significantly associated with the development of colorectal adenomas or cancer (OR 1.05, 95% CI 1.03-1.07, p < 0.0001). CONCLUSIONS: This study showed a statistically significant association between diverticula and colonic adenomas. However, it is impossible to establish a cause-effect relationship due to the intrinsic characteristics of this study design. A study with a prospective design including both patients with diverticulosis and without colonic diverticula aimed at establishing the incidence of adenoma and CRC could help to answer this relevant clinical question, since a potential association could indicate the need for closer endoscopic surveillance.

MRI-derived radiomics to guide post-operative management of glioblastoma: Implication for personalized radiation treatment volume delineation.

Background: The glioblastoma's bad prognosis is primarily due to intra-tumor heterogeneity, demonstrated from several studies that collected molecular biology, cytogenetic data and more recently radiomic features for a better prognostic stratification. The GLIFA project (GLIoblastoma Feature Analysis) is a multicentric project planned to investigate the role of radiomic analysis in GB management, to verify if radiomic features in the tissue around the resection cavity may guide the radiation target volume delineation. Materials and methods: We retrospectively analyze from three centers radiomic features extracted from 90 patients with total or near total resection, who completed the standard adjuvant treatment and for whom we had post-operative images available for features extraction. The Manual segmentation was performed on post gadolinium T1w MRI sequence by 2 radiation oncologists and reviewed by a neuroradiologist, both with at least 10 years of experience. The Regions of interest (ROI) considered for the analysis were: the surgical cavity ± post-surgical residual mass (CTV_cavity); the CTV a margin of 1.5 cm added to CTV_cavity and the volume resulting from subtracting the CTV_cavity from the CTV was defined as CTV_Ring. Radiomic analysis and modeling were conducted in RStudio. Z-score normalization was applied to each radiomic feature. A radiomic model was generated using features extracted from the Ring to perform a binary classification and predict the PFS at 6 months. A 3-fold cross-validation repeated five times was implemented for internal validation of the model. Results: Two-hundred and seventy ROIs were contoured. The proposed radiomic model was given by the best fitting logistic regression model, and included the following 3 features: F_cm_merged.contrast, F_cm_merged.info.corr.2, F_rlm_merged.rlnu. A good agreement between model predicted probabilities and observed outcome probabilities was obtained (p-value of 0.49 by Hosmer and Lemeshow statistical test). The ROC curve of the model reported an AUC of 0.78 (95% CI: 0.68-0.88). Conclusion: This is the first hypothesis-generating study which applies a radiomic analysis focusing on healthy tissue ring around the surgical cavity on post-operative MRI. This study provides a preliminary model for a decision support tool for a customization of the radiation target volume in GB patients in order to achieve a margin reduction strategy.

IMproved MAnagement (IM-MA study) in cancer-related pain: the value of a joint approach by an integrated team of radiotherapist and anesthetist.

PURPOSE: Purpose of this study was to retrospectively review our experience of multidisciplinary clinic providing a joint approach by radiation oncologist and anesthetist for patients with cancer pain to evaluate the adequacy and the IMprovement in MAnagement (IM-MA study) of this symptom. METHODS: A Team for Pain Management (TPM) represented by radiation oncologist and anesthetist weekly provided consultations to patient presenting cancer pain. TPM prospectively reported epidemiologic, symptomatic, and pharmacological data. TPM modified pain therapy and indicated antalgic radiotherapy. Patients were evaluated at baseline and after 4 weeks after intervention. RESULTS: From November 2015 to April 2016, 65 patients were evaluated by TPM. At the baseline, 18 patients (27.7%) were undertreated (i.e., receiving inadequate pain management); furthermore, 27 patients (41.5%) despite receiving strong opioids had uncontrolled pain. After 4 weeks from intervention, undertreated patients were reduced to 1.53%. For those patients undergone to radiotherapy, response at 34 weeks was scored as follows: complete response 28.8%, partial response 46.7%, pain progression 0.95%, indeterminate response 23.8%. CONCLUSIONS: A multidisciplinary Team for Pain Management improved the clinical management, optimizing pain control and increasing adequacy of pharmacological management. The TPM intervention seems particularly worth for patients presenting specific features including BTcP, neuropathic pain, severe pain due to bone metastases, and any potential candidate to radiotherapy. Larger series and QoL questionnaires are required to confirm these results.

Intracardiac tromboembolism during liver transplantation. / Tromboembolismo intracardíaco durante trasplante hepático.

We describe a case of intraoperative cardiac trombosis during orthotopic liver transplant surgery that resulted in intraoperative death. By using transesophageal echocardiography, the cause of the descompensation of the patient could be determined and the mechanism of trombus migration from thrombi from the venous circulation to the left heart was accurately observed.

Phylogenomic analysis of a rapid radiation of misfit fishes (Syngnathiformes) using ultraconserved elements.

Phylogenetics is undergoing a revolution as large-scale molecular datasets reveal unexpected but repeatable rearrangements of clades that were previously thought to be disparate lineages. One of the most unusual clades of fishes that has been found using large-scale molecular datasets is an expanded Syngnathiformes including traditional long-snouted syngnathiform lineages (Aulostomidae, Centriscidae, Fistulariidae, Solenostomidae, Syngnathidae), as well as a diverse set of largely benthic-associated fishes (Callionymoidei, Dactylopteridae, Mullidae, Pegasidae) that were previously dispersed across three orders. The monophyly of this surprising clade of fishes has been upheld by recent studies utilizing both nuclear and mitogenomic data, but the relationships among major lineages within Syngnathiformes remain ambiguous; previous analyses have inconsistent topologies and are plagued by low support at deep divergences between the major lineages. In this study, we use a dataset of ultraconserved elements (UCEs) to conduct the first phylogenomic study of Syngnathiformes. UCEs have been effective markers for resolving deep phylogenetic relationships in fishes and, combined with increased taxon sampling, we expected UCEs to resolve problematic syngnathiform relationships. Overall, UCEs were effective at resolving relationships within Syngnathiformes at a range of evolutionary timescales. We find consistent support for the monophyly of traditional long-snouted syngnathiform lineages (Aulostomidae, Centriscidae, Fistulariidae, Solenostomidae, Syngnathidae), which better agrees with morphological hypotheses than previously published topologies from molecular data. This result was supported by all Bayesian and maximum likelihood analyses, was robust to differences in matrix completeness and potential sources of bias, and was highly supported in coalescent-based analyses in ASTRAL when matrices were filtered to contain the most phylogenetically informative loci. While Bayesian and maximum likelihood analyses found support for a benthic-associated clade (Callionymidae, Dactylopteridae, Mullidae, and Pegasidae) as sister to the long-snouted clade, this result was not replicated in the ASTRAL analyses. The base of our phylogeny is characterized by short internodes separating major syngnathiform lineages and is consistent with the hypothesis of an ancient rapid radiation at the base of Syngnathiformes. Syngnathiformes therefore present an exciting opportunity to study patterns of morphological variation and functional innovation arising from rapid but ancient radiation.

McConnell's sign in intra-operative acute right ventricle ischaemia: An under-recognized aetiology. / Signo de McConnell en isquemia aguda de ventrículo derecho intraoperatoria: una etiología poco reconocida.

Transoesophageal echocardiography (TEE) has become a fundamental tool in modern cardiothoracic anaesthesia. It has an indisputable role in coronary valve surgery and revascularisations with severe impairment of ventricle function. It helps in making diagnoses that can optimise the surgical strategy and to minimal invasively dynamically monitor volaemia and cardiac function during the post-operative period, detecting complications unobservable by other methods. The McConnell sign, visualised using TEE as an akinesis of the right ventricular free wall, with a normal apex motility and enlargement of the right cavities, is characteristic of right ventricular (RV) dysfunction. This sign has a 77% sensitivity and 94% specificity for the diagnosis of acute pulmonary embolism (APE). The case is presented of a 53-year-old man scheduled for aortic valve and ascending aorta replacement surgery, with a history of severe valve aortic stenosis, aortic root and arch aneurysm, and with normal coronary arteries. Post-cardiopulmonary bypass (CBP), the patient presented with haemodynamic instability, with the TEE showing a typical image of the McConnell sign, with no pulmonary hypertension. This enabled making an early diagnosis of acute RV ischaemia, that led to a change in the surgical plan, the performing of coronary revascularisation surgery. As a result, the McConnell sign, which describes the characteristics of RV dysfunction, led to making a differential diagnosis between APE, RV infarction and acute myocardial ischaemia.

[Diagnostic accuracy of Epworth sleepiness scale in the acute phase of myocardial infarction]. / Intérêt du score d'Epworth à la phase aiguë d'infarctus du myocarde.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is underdiagnosed in cardiologist daily practice, especially in patients with acute coronary syndrome. Its diagnosis is based on a polysomnography study. The Epworth Sleepiness Scale (ESS) stands as a simple and rapid means to select patients for the sleep investigation. AIM: The aim of this study was to determine the diagnostic accuracy of the ESS for screening OSAS in patients with ST elevation myocardial infarction. METHODS: We conducted a prospective study of 120 consecutive patients admitted for acute myocardial infarction, from April 2011 to March 2012. Daytime sleepiness was evaluated using the ESS, when patients were in the intensive care unit. All patients have undergone an overnight sleep study using a portable diagnostic device, in the 15 days following the acute coronary syndrome. The diagnostic of OSA was considered as apnea-hypopnea index (AHI) of ≥5 events/hour, severe OSA was defined as AHI of ≥30. RESULTS: The study included 120 patients comprising 102 men and 18 women. The mean age was 58 ± 12 years. Smoking was the major cardiovascular risk factor with 72% of all patients; prevalence of diabetes was 40% and hypertension was found in 44% of the population. The prevalence of OSA was 79%. Severe OSA was diagnosed in 16% of all patients and mean AHI was 15.76 ± 14.93. Mean ESS was 2.2 ± 1.84 in the global population while it was 5.2 ± 1.2 in patients with severe OSAS. Multivariate analysis showed that ESS score ≥ 4 was an independent predictive factor for severe OSA (OR=28; 95% IC: 8-101; P<0.001). CONCLUSION: The prevalence of OSA in patients with acute myocardial infarction was very high. ESS score ≥ 4 was an independent predictive factor for severe OSA. Despite its subjective feature, the ESS seems to be an interesting score for screening patients to undergo polysomnography.

Different subsets of circulating angiogenic cells do not predict bronchopulmonary dysplasia or other diseases of prematurity in preterm infants.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease occurring in very and extremely preterm infants undergoing mechanical ventilation. Given the altered lung vascular growth characterizing BPD, circulating angiogenic cells could be useful biomarkers to predict the risk. The objective of the study was to determine whether the percentages of circulating angiogenic cells (CD34+VEGFR-2+, CD34+CD133+VEGFR-2+, and CD45-CD34+CD133+VEGFR-2+ cells), assessed in the peripheral blood at birth by flow cytometry, could be used as markers for the risk of BPD. In one-hundred and forty-two preterm neonates (gestational age less than 32 weeks and/or birth weight less than 1500 g) admitted to our tertiary care Neonatal Intensive Care Unit between 2006 and 2009, we evaluated the percentages of circulating angiogenic cells at birth, at 7 days, and, in a subset of infants (n=40), at 28 days of life. The main outcome was the correlation between cell counts at birth and the subsequent risk of developing BPD. In our study, all the three cell populations failed to predict the development of BPD or other diseases of prematurity. We suggest that these cells cannot be used as biomarkers in preterm infants, and that research is needed to find other early predictors of BPD.

Development of an oncolytic herpes simplex virus using a tumor-specific HIF-responsive promoter.

We exploited the differential activation of hypoxia-inducible factor (HIF)-dependent gene expression in tumors versus normal tissue for the design of a targeted oncolytic herpes simplex virus type-1 (HSV-1). A gene that is essential for viral replication, infected cell polypeptide 4 (ICP4), was placed under the regulation of an HIF-responsive promoter and then introduced into the thymidine kinase locus (U(L)23) of HSV d120, which contains partial deletions in the two endogenous ICP4 genes. Recombinant HIF-HSV was isolated and their derivation from d120 was verified by expression of a truncated, non-functional form of ICP4 protein. Disruption of the U(L)23 locus was confirmed by loss of thymidine kinase expression and resistance to acyclovir. Unexpectedly, HIF-HSV expressed ICP4 and induced tumor cell lysis at similar levels under normoxia and hypoxia. The lack of HIF-dependent ICP4 transgene expression by HIF-HSV was due to two factors that have not previously been reported-reversion of the ICP4 gene region to its wild-type configuration and increased HIF-transcriptional activity under normoxia when cells were infected with any strain of HSV-1. The findings that an oncolytic HSV-1 is genetically unstable and can activate a tumor-related promoter in a non-specific manner have important implications for any proposed use of this virus in cancer therapy.

Second-generation HIF-activated oncolytic adenoviruses with improved replication, oncolytic, and antitumor efficacy.

There is a need to develop more potent oncolytic adenoviruses (Ads) that show increased antitumor activity in patients. The HYPR-Ads are targeted oncolytic Ads that specifically kill tumor cells, which express active hypoxia-inducible factor (HIF). While therapeutically efficacious, the HYPR-Ads showed attenuated replication and oncolytic activity. To overcome these deficiencies and improve antitumor efficacy, we created new HIF-activated oncolytic Ads, HIF-Ad and HIF-Ad-IL4, which have two key changes: (i) a modified HIF-responsive promoter to regulate the E1A replication gene and (ii) insertion of the E3 gene region. The HIF-Ads showed conditional activation of E1A expression under hypoxia. Importantly, the HIF-Ads show hypoxia-dependent replication, oncolytic and cellular release activities, and potent antitumor efficacy, all of which are significantly greater than that of the HYPR-Ads. Notably, HIF-Ad-IL4 treatment led to regressions in tumor size by 70% and extensive tumor infiltration by leukocytes resulting in an antitumor efficacy that is up to six-fold greater than that of the HYPR-Ads, HIF-Ad and wild-type Ad treatment. These studies show that treatment with an HIF-activated oncolytic Ad leads to a measurable therapeutic response. The novel design of the HIF-Ads represents a significant improvement compared with first-generation oncolytic Ads and has great potential to increase the efficacy of this cancer therapy.

Lichens on asbestos-cement roofs: bioweathering and biocovering effects.

Asbestos-cement roofs, the most widespread sources of airborne, toxic and carcinogenic asbestos fibres, are often colonized by lichens. Since these latter are physical and chemical weathering agents, they have been often considered as significant responsible of disaggregation processes increasing fibre dispersion. Consequently, official guidelines for the management of asbestos often suggest their removal. Weathering and/or covering effects of lichens on asbestos-cement, however, have never been deeply investigated and available procedures to evaluate asbestos-cement aging do not take the biological colonization into account. In this study we show that a 25% lichen cover modifies physical and chemical properties of asbestos-cement sheets containing chrysotile and crocidolite fibres. By innovatively coupling pull up tests and image analysis of linear structures, we show that fibre loss is significantly lower ( approximately 30%) where lichens develop and offer a physical barrier to the fibre detachment. Below the most covering lichens (Acarospora cervina, Candelariella ssp.), chrysotile and crocidolite undergo a partial incongruent dissolution, which in laboratory assays generally determined a reduction of their surface reactivity. Because of their biocovering and bioweathering effects, lichens on asbestos-cement play a role which differs from the current public opinion and the assumptions of some official regulations, acting as effective spontaneous bioattenuation agents.

[Conductive disorders following open-heart valvular surgery. Concerning 230 operated patients]. / Les troubles conductifs après chirurgie cardiaque valvulaire sous circulation extracorporelle. A propos de 230 malades opérés.

AIMS: Conductive disorders following open-heart valvular surgery represent serious complications that may require definitive pacemaker implantation. The natural history of these troubles is not well established thus, controversy persist concerning the timing of pacemaker implantation. In this study we identify the predictive factors of permanent conductive disorders in order to assess the optimal time of pacing. METHODS AND RESULTS: Two hundred thirty valvular replacements were done between 1993 and 2003. The mean age of our patients was 42 +/- 13.4 years. Rheumatic valvulopathies accounted for 76% of cases, with 54% of multiple valvulopathies. Twenty-two patients (9,5%) had an early postoperative conductive disorder, 9 of them (4%) were definitively implanted after a mean delay of 31.8 days. Preoperative bifascicular bloc and early installation of postoperative high-grade conduction disturbances and its persistence for more than 48 hours are significantly associated with permanent postoperative conductive disorders (respectively P = 0.04 and = 0.03). Aortic valve surgery and infective endocarditis were more frequent in the implanted group but the difference was not significant. CONCLUSION: After open-heart valvular surgery; predictive factors of definitive conductive troubles justify an earlier pacemaker implantation. This attitude may accelerate the hospital discharge and decrease the disease cost effectiveness.

BRCA1 mutations and polymorphisms in a hospital-based consecutive series of breast cancer patients from Apulia, Italy.

INTRODUCTION: Hereditary breast cancer has been partly attributed to germline mutations in the BRCA1 gene that are deleterious for BRCA1 protein activity. This paper analyzes the incidence and characteristics of detectable BRCA1 mutations and polymorphisms in a hospital-based consecutive series of breast cancer patients from southern Italy to investigate the incidence and the association of these molecular alterations with breast cancer biology and family history. METHODS: One hundred cases with familial characteristics were selected from a consecutive series of 511 patients with a first diagnosis of breast cancer. DNA from peripheral blood was screened for whole BRCA1 gene mutations utilizing dHPLC as a pre-screening analysis and automatic DNA sequencing for the identification of specific alterations. RESULTS: In the overall series of 511 patients, 100 had a family history of breast cancer and were investigated for BRCA1 mutations. Two types of BRCA1 mutations were identified, 5382insC in six cases and 4566delA in one case. The 5382insC mutation was present in two out of six cases with ovarian cancer while 4566delA in one case of male cancer. The most frequent missense polymorphisms were E1038G, P871L, K1183R in exon 11, S1613G, M1652I in exon 16 and D1778G in exon 22. Confirming what found in previous studies, patients in whom pathological BRCA1 mutations were detected had early-onset breast cancer (p=0.05), positive nodal status (p=0.05), lower ER (p=0.02) and PgR (p=0.01) content. Interestingly, the K1183R polymorphism and, less strongly, S1613G polymorphism were associated to mutational risk (K1183R: OR 0.1 p=0.03; S1613G: OR 2.7 p=0.08). CONCLUSION: Mutations in the BRCA1 gene are frequent also in our consecutive series of patients from southern Italy. An association between two detected single nucleotide polymorphisms (SNPs) and BRCA1 mutational risk was ascertained. Finally, we confirm the fact that peculiar clinical-pathological features seem to characterize patients with a family history of breast cancer and BRCA1 alterations.

Central venous catheter-related complications in children with oncological/hematological diseases: an observational study of 418 devices.

BACKGROUND: The use of indwelling central venous catheters (CVCs) has become commonplace in the management of children undergoing anticancer treatment. Several types of CVC are available, while information on complications observed in children is scarce. We describe the experience of two tertiary care centers in Italy that prospectively followed up three types of CVC used at both institutions over a 30-month period. PATIENTS AND METHODS: Between January 2000 and May 2002, double-lumen (DL) or single-lumen (SL) Hickman-Broviac (HB) catheters, and single-lumen pressure-activated safety valve (PASV) catheters were used and prospectively evaluated. Four types of possible complication were defined a priori: mechanical, thrombotic, malfunctioning and infectious. RESULTS: Four hundred and eighteen CVCs (180 SL-HB, 162 DL-HB and 76 PASV) were inserted in 368 children, for a total of 107 012 catheter days at risk of complication. At least one complication occurred while using 169 of the devices (40%): 46% of the DL-HB, 46% of the PASV and 33% of the SL-HB (P=0.02) catheters. Subjects with hematological malignancies or non-malignant diseases had significantly more complications than those with solid tumors (P <0.0001). Overall, 234 complications were documented: 93 infectious [complication rate per 1000 catheter days at risk (CR)=0.87], 84 malfunctioning (CR=0.78), 48 mechanical (CR=0.45) and nine thrombotic (CR=0.08). SL-HB had statistically fewer infectious complications, while PASV had more mechanical complications. In a multivariate regression model, the most significant risk factors for having a CVC complication were hematological disease [relative risk (RR)=3.0; 95% confidence interval (CI) 1.8-4.8] and age <6 years at CVC insertion (RR=2.5; 95% CI 1.5-4.1). As for the type of CVC, compared with SL-HB, the DL-HB catheter had a statistically significant two-fold increased risk of any complication (RR=2.1; 95% CI 1.2-3.6), while the PASV catheter had a borderline RR of 1.8 (95% CI 1.0-3.6). Analysis by tumor type showed a higher risk of any kind of complication in patients with solid malignancies who had received a DL-HB catheter as compared with an SL-HB catheter (RR=7.2; 95% CI 2.8-18.7). CONCLUSIONS: CVCs may cause complications in up to 40% of patients, with type of CVC, underlying disease and patient age being the three main factors that affect the incidence of CVC-related complications. SL-HB catheters have the best performance.

Tumor Fas (APO-1/CD95) up-regulation results in increased apoptosis and survival times for rats with intracranial malignant gliomas.

OBJECTIVE: The cellular "death" receptor Fas has been proposed to be a potential specific target for anti-glioma therapy. However, little is known regarding the effects of Fas expression on glioma viability in vivo. The goal of this study was to clarify the relationships among Fas expression, apoptosis, and survival rates for high-grade astrocytomas. METHODS: Fas expression was measured in several human glioblastoma multiforme cell lines and a malignant rat glioma cell line (36B10), before and after Fas up-regulation by gene transfer. Expression was correlated with the degree of Fas-mediated cytotoxicity and apoptosis induced after Fas activation. Subsequently, rats underwent intracranial implantation of either wild-type or genetically altered 36B10 cell lines, for study of the effects of Fas up-regulation on survival rates. RESULTS: Low levels of cell surface Fas expression in glioblastomas multiforme were correlated with their limited susceptibility to Fas-mediated cytotoxicity. Through Fas receptor up-regulation, relationships among increased Fas expression, Fas-mediated cytotoxicity, and apoptosis were demonstrated. The percentage of cells undergoing apoptosis after exposure to a Fas ligand-producing cell line increased from 4% in the sham-transfected line (36B10-) to 27% in the Fas-transfected line (36B10-Fas). After intracranial implantation of these tumors into rats, the median survival time increased significantly from 14 days (36B10 and 36B10-) to 24.5 days (36B10-Fas), which represents a 75% increase in the survival time for the greater Fas-expressing group (P = 0.0005). CONCLUSION: It seems that the overall low rate of apoptosis in high-grade astrocytomas is related to low levels of cell surface Fas expression. With increases in cellular Fas expression, rates of Fas-mediated apoptosis and survival rates were increased.

Nosocomial infections in pediatric cardiac surgery, Italy.

OBJECTIVE: To evaluate the incidence of nosocomial infection (NI) in pediatric patients who received cardiothoracic surgery and to identify possible associated risk factors. DESIGN: Prospective observational study. SETTING: The cardiac surgery and cardiac intensive care units at the Regina Margherita Children's Hospital, Turin, Italy. PATIENTS: All patients who underwent surgery from July 20, 1998, to July 19, 1999, were enrolled, except patients with operative catheterization only. METHODS: Clinical data were collected daily from July 20, 1998, to July 19, 1999. NIs were diagnosed according to US Centers for Disease Control and Prevention criteria. RESULTS: 104 patients were included in the present study, 80 (76.9%) of whom underwent extracorporeal circulation. The NI ratio was 48.1% (50/104); the percentage of patients with NI was 30.8% (32/104): 23.1% developed one infection, 7.7% two or more. The rate of NI was 2.17 per 100 days of hospitalization (50/2,304). The most common pathogen was Pseudomonas aeruginosa. Important risk factors were length of preoperative admission >5 days, total length of admission >10 days, open chest during postoperative phase, and cyanotic heart disease. There was a significant association between sepsis and central venous catheterization for 3 days or more. Rate of sepsis was 19 per 1,000 catheter days (16/852). CONCLUSION: NIs represent a frequent complication for children who undergo heart surgery. Based on our data, we suggest decreasing the preoperative stay as much as possible. The higher NI incidence in patients with an open chest postoperatively suggests that an alternative antibiotic strategy should be considered for these patients.