Skin and lung toxicity in synchronous bilateral breast cancer treated with volumetric-modulated arc radiotherapy: a mono-institutional experience.

PURPOSE: To evaluate acute and late skin/subcutaneous toxicities and radiation-induced lung fibrosis (RILF) in patients treated with adjuvant radiotherapy (RT) for synchronous bilateral breast cancers (SBBC), after conservative surgery. METHODS/PATIENTS: Twenty-five patients were treated with volumetric-modulated arc therapy (VMAT/RapidArc®) on both breasts, and checked clinically for detecting RT toxicities during and after treatment. A high-resolution computed tomography (HRCT) was performed, for detecting RILF during follow-up. RESULTS: We registered acute Grade-1 skin toxicity in 18 patients (72%), while six patients (24%) experienced Grade-2 toxicity. No breath symptoms were reported during and after RT. Late Grade-1 subcutaneous toxicity and late Grade-2 skin toxicity were registered in four patients (16%) and one patient (4%), respectively, at a mean follow-up of 36 months. Grade-1 RILF was detected in six patients (30%). The median volume of fibrosis area was 6.5 cc (range 1.3-21.5 cc). The partial volumes receiving a specified dose (V20, V30, V40, and V50) in patients who developed lung fibrosis were significantly bigger than who did not (p < 0.01). We showed that the mean volume of the tumour boost of patients who developed fibrosis (77.7 cc) was not significantly different from the other patients (90.8 cc) (p = 0.5). CONCLUSION: The clinical impact of this technique is favourable, and this is the first clinical study showing RILF by HRCT in a setting of SBBC. Further study with larger accrual is mandatory.

[Visitation policy, design and comfort in Spanish intensive care units]. / Política de visitas, diseño y confortabilidad en las unidades de cuidados intensivos españolas.

OBJECTIVE: To determine the design and comfort in the Intensive Care Units (ICUs), by analysing visiting hours, information, and family participation in patient care. DESIGN: Descriptive, multicentre study. SETTING: Spanish ICUs. METHODS: A questionnaire e-mailed to members of the Spanish Society of Intensive Care Medicine, Critical and Coronary Units (SEMICYUC), subscribers of the Electronic Journal Intensive Care Medicine, and disseminated through the blog Proyecto HU-CI. RESULTS: A total of 135 questionnaires from 131 hospitals were analysed. Visiting hours: 3.8% open 24h, 9.8% open daytime, and 67.7% have 2 visits a day. Information: given only by the doctor in 75.2% of the cases, doctor and nurse together in 4.5%, with a frequency of once a day in 79.7%. During weekends, information is given in 95.5% of the cases. Information given over the phone 74.4%. Family participation in patient care: hygiene 11%, feeding 80.5%, physiotherapy 17%. Personal objects allowed: mobile phone 41%, computer 55%, sound system 77%, and television 30%. Architecture and comfort: all individual cubicles 60.2%, natural light 54.9%, television 7.5%, ambient music 12%, clock in the cubicle 15.8%, environmental noise meter 3.8%, and a waiting room near the ICU 68.4%. CONCLUSIONS: Visiting policy is restrictive, with a closed ICU being the predominating culture. On average, technological communication devices are not allowed. Family participation in patient care is low. The ICU design does not guarantee privacy or provide a desirable level of comfort.

General issues on microbial translocation in HIV-infected patients.

The lumen of the gastrointestinal tract is home to an enormous quantity of different bacterial species that thrive in an often symbiotic relationship with the host. It is the principal source of microbial products because of its massive bacterial load. Injury to the immune component of the gastrointestinal mucosal surface, along with damage to the intestinal epithelial microenvironment with its antimicrobial functions, may affect systemic immune activation during the chronic phase of HIV infection through the increased translocation of luminal microbial products. Moreover, microbial translocation, which is defined as "the passage of both viable and nonviable microbes and microbial products such as endotoxin across anatomically intact intestinal barrier", may be a fundamental mechanism through which HIV accelerates progression of chronic viral hepatitis. Improvements in the tools available to microbiota research, and especially advancement of our knowledge in this area may help us in controlling the evolution of HIV disease, although population complexity and diversity between individuals make this challenging.

Comparison of peginterferon pharmacokinetic and pharmacodynamic profiles.

The pharmacokinetics and in dosing regimens of the currently available pegylated interferon (peginterferon) alfa molecules differ greatly, depending on the size and nature of their polyethylene glycol (PEG) moiety. Peginterferon alfa-2a has a branched 40 kDa PEG chain covalently attached to lysine residues and circulates as an intact molecule. On the other hand, peginterferon alfa-2b has a linear 12 kDa PEG chain covalently attached to interferon-a-2b via an unstable urethane bond that is hydrolysed after injection, releasing native interferon alfa-2b. The difference in pegylation between the two peginterferons has a significant impact on their pharmacokinetic properties. Data from comparative and non-comparative studies indicate that peginterferon alfa-2b has a shorter half-life in serum than peginterferon alfa-2a, and a significant proportion of patients receiving peginterferon alfa-2b may have trough concentrations below the limit of detection during the latter part of the 7-day dosing schedule. However, the pharmacodynamic parameters of the two drugs appear to be similar.

Usefulness of 124I PET/CT imaging to predict absorbed doses in patients affected by metastatic thyroid cancer and treated with 131I.

AIM: The aim of this work was the evaluation of the usefulness of 124I PET/CT sequential scans to predict absorbed doses to metastatic thyroid cancer in patients undergoing 131I therapy. METHODS: From July 2011 until April 2012 8 patients affected by metastatic thyroid cancer were enrolled. Each patient underwent 4 PET/CT scans at 4, 24, 48, 72 h after the administration of about 74 MBq of 124I. Blood samples and whole body exposure measurements were obtained to calculate blood and red marrow doses. Activity concentrations and lesion volumes obtained from PET/CT images were used to evaluate tumour doses with MIRD formalism and spheres model. The average administered 131I therapeutic activity was 6475 MBq (range: 3700-9250 MBq). RESULTS: 124I PET/CT images showed, with a very good resolution, all 131I avid lesions detected by post therapy whole body scans. The average dose rates for blood, red marrow and lesions were respectively: 6.58E-02 ± 1.64E-02 mGy/MBq, 5.73E-02 ± 1.57E-02 mGy/MBq, 2.22E+01 ± 1.62E+01 mGy/MBq. Three out of eight patients did not show any uptake of 124I in all PET/CT scans, despite high level of TSH and CT detectable lesions. Post-therapy 131I whole body scan confirmed the absence of focal iodine uptake. CONCLUSION: Negative 124I PET/CT images probably could be used as predictive of real absence of iodine avidity, avoiding all toxicity from useless 131I therapy. A higher number of patients is necessary to validate these preliminary results and a project is ongoing to compare MIRD results to voxel dosimetry based on Monte Carlo simulation.

Sulfated K5 Escherichia coli polysaccharide derivatives inhibit human immunodeficiency type-1 (HIV-1) infection: candidate microbicides to prevent sexual HIV transmission.

The ideal microbicide must fulfill a number of criteria including a broad and potent activity against transmission of HIV and other sexually transmitted agents in the absence of toxicity and inflammation. We have described that derivatives of K5 polysaccharide from Escherichia coli inhibit HIV entry in target cells. K5 derivatives have a structure that resembles that of heparin, but they are devoid of the anticoagulant activity typical of heparin. Moreover, in contrast to heparin, they inhibit a broad spectrum of HIV-1 laboratory-adapted and primary isolates that use either CCR5 or CXCR4 or both coreceptors in terms of their infection and replication in primary CD4+ lymphocytes and monocytes-derived macrophages (MDM). Therefore, these compounds could be developed as candidate microbicides for preventing sexual HIV transmission, a predominant modality of HIV spreading in both the developed and underdeveloped world.