Diorganotin (IV) amino acid complexes as potential anticancer agents. Synthesis, structural characterization, and in vitro assays.

Nine new organotin (IV) derivatives from L-amino acids (l-lysine, L-ornithine, L-glutamic acid, and L-aspartic acid) were synthesized by one-pot ultrasound-assisted methodology. All compounds were characterized by ATR-FTIR (Attenuated Total Reflectance-Fourier Transform Infrared), LRMS (Low-Resolution Mass Spectrometry), and solution NMR (1H, 13C, 119Sn Nuclear Magnetic Resonance) spectroscopies. Complexes Bu2Sn(Lys) (1), Ph2Sn(Lys) (2), Bu2Sn(Orn) (3), and Ph2Sn (Glu-OMe) (6a) were crystallized, and the structures were established by single-crystal X-ray diffraction analysis. Diffraction results evidenced that complexes 1 to 3 were five-coordinated mononuclear species while the phenyl substituted derivative Ph2Sn (Glu-OMe) (6a) forms a polymeric network via Sn-O-Sn bridging whereby the tin atom is six-coordinated. In turn, 119Sn NMR results revealed that all tin complexes exist as mononuclear penta-coordinated species in solution. The tin derivatives were screened for ADME (Adsorption, Distribution, Metabolism, and Excretion) properties via the freely available tools SWISS ADME, and the results were analyzed hereafter. The antiproliferative activity of the complexes was tested against three human cancer cell lines: colorectal adenocarcinoma HT-29, breast adenocarcinoma MDA-MB-231, and chondrosarcoma SW-1353 using a non-tumoral cell line of human osteoblast as control, demonstrating selective inhibitory activities against cancer cells. Hence, these compounds could be a promising alternative to classical chemotherapy agents.

Melanoma Registry of the Spanish Academy of Dermatology and Venereology (REGESMEL): Description and Data in its First Year of Operation. / Registro de Melanoma de la Academia Española de Dermatología y Venereología (REGESMEL): descripción y datos en el primer año de funcionamiento.

INTRODUCTION: The incidence of melanoma is rising in Spain. The prognostic stages of patients with melanoma are determined by various biological factors, such as tumor thickness, ulceration, or the presence of regional or distant metastases. The Spanish Academy of Dermatology and Venereology (AEDV) has encouraged the creation of a Spanish Melanoma Registry (REGESMEL) to evaluate other individual and health system-related factors that may impact the prognosis of patients with melanoma. The aim of this article is to introduce REGESMEL and provide basic descriptive data for its first year of operation. METHODS: REGESMEL is a prospective, multicentre cohort of consecutive patients with invasive cutaneous melanoma that collects demographic and staging data as well as individual and healthcare-related baseline data. It also records the medical and surgical treatment received by patients. RESULTS: A total of 450 cases of invasive cutaneous melanoma from 19 participant centres were included, with a predominance of thin melanomas≤1mm thick (54.7%), mainly located on the posterior trunk (35.2%). Selective sentinel lymph node biopsy was performed in 40.7% of cases. Most cases of melanoma were suspected by the patient (30.4%), or his/her dermatologist (29.6%). Patients received care mainly in public health centers (85.2%), with tele-dermatology resources being used in 21.6% of the cases. CONCLUSIONS: The distribution of the pathological and demographic variables of melanoma cases is consistent with data from former studies. REGESMEL has already recruited patients from 15 Spanish provinces and given its potential representativeness, it renders the Registry as an important tool to address a wide range of research questions.

Principles for management of hip fracture for older adults taking direct oral anticoagulants: an international consensus statement.

Hip fracture is a common serious injury among older adults, yet the management of hip fractures for patients taking direct oral anticoagulants remains inconsistent worldwide. Drawing from a synthesis of available evidence and expert opinion, best practice approaches for managing patients with a hip fracture and who are taking direct oral anticoagulants pre-operatively were considered by a working group of the Fragility Fracture Network Hip Fracture Audit Special Interest Group. The literature and related clinical guidelines were reviewed and a two-round modified Delphi study was conducted with a panel of experts from 16 countries and involved seven clinical specialities. Four consensus statements were achieved: peripheral nerve blocks can reasonably be performed on presentation for patients with hip fracture who are receiving direct oral anticoagulants; hip fracture surgery can reasonably be performed for patients taking direct oral anticoagulants < 36 h from last dose; general anaesthesia could reasonably be administered for patients with hip fracture and who are taking direct oral anticoagulants < 36 h from last dose (assuming eGFR > 60 ml.min-1.1.73 m-2); and it is generally reasonable to consider recommencing direct oral anticoagulants (considering blood loss and haemoglobin) < 48 h after hip fracture surgery. No consensus was achieved regarding timing of spinal anaesthesia. The consensus statements were developed to aid clinicians in their decision-making and to reduce practice variations in the management of patients with hip fracture and who are taking direct oral anticoagulants. Each statement will need to be considered specific to each individual patient's treatment.

Contour scanning for penumbra improvement in pencil beam scanned proton therapy.

Proton therapy, especially in the form of pencil beam scanning (PBS), allows for the delivery of highly conformal dose distributions for complex tumor geometries. However, due to scattering of protons inside the patient, lateral dose gradients cannot be arbitrarily steep, which is of importance in cases with organs at risk (OARs) in close proximity to, or overlapping with, planning target volumes (PTVs). In the PBS approach, physical pencil beams are planned using a regular grid orthogonal to the beam direction. In this work, we propose an alternative to this commonly used approach where pencil beams are placed on an irregular grid along concentric paths based on the target contour. Contour driven pencil beam placement is expected to improve dose confirmation by allowing the optimizer to best enhance the penumbra of irregularly shaped targets using edge enhancement. Its effectiveness has been shown to improve dose confirmation to the target volume and reduce doses to OARs in head-and-neck planning studies. Furthermore, the deliverability of such plans, as well as the dosimetric improvements over conventional grid-based plans, have been confirmed in first phantom based verifications.

A comprehensive and efficient daily quality assurance for PBS proton therapy.

There are several general recommendations for quality assurance (QA) measures, which have to be performed at proton therapy centres. However, almost each centre uses a different therapy system. In particular, there is no standard procedure for centres employing pencil beam scanning and each centre applies a specific QA program. Gantry 2 is an operating therapy system which was developed at PSI and relies on the most advanced technological innovations. We developed a comprehensive daily QA program in order to verify the main beam characteristics to assure the functionality of the therapy delivery system and the patient safety system. The daily QA program entails new hardware and software solutions for a highly efficient clinical operation. In this paper, we describe a dosimetric phantom used for verifying the most critical beam parameters and the software architecture developed for a fully automated QA procedure. The connection between our QA software and the database allows us to store the data collected on a daily basis and use it for trend analysis over longer periods of time. All the data presented here have been collected during a time span of over two years, since the beginning of the Gantry 2 clinical operation in 2013. Our procedure operates in a stable way and delivers the expected beam quality. The daily QA program takes only 20 min. At the same time, the comprehensive approach allows us to avoid most of the weekly and monthly QA checks and increases the clinical beam availability.

Improving Radiation Awareness and Feeling of Personal Security of Non-Radiological Medical Staff by Implementing a Traffic Light System in Computed Tomography.

PURPOSE: Non-radiological medical professionals often need to remain in the scanning room during computed tomography (CT) examinations to supervise patients in critical condition. Independent of protective devices, their position significantly influences the radiation dose they receive. The purpose of this study was to assess if a traffic light system indicating areas of different radiation exposure improves non-radiological medical staff's radiation awareness and feeling of personal security. MATERIAL AND METHODS: Phantom measurements were performed to define areas of different dose rates and colored stickers were applied on the floor according to a traffic light system: green = lowest, orange = intermediate, and red = highest possible radiation exposure. Non-radiological medical professionals with different years of working experience evaluated the system using a structured questionnaire. Kruskal-Wallis and Spearman's correlation test were applied for statistical analysis. RESULTS: Fifty-six subjects (30 physicians, 26 nursing staff) took part in this prospective study. Overall rating of the system was very good, and almost all professionals tried to stand in the green stickers during the scan. The system significantly increased radiation awareness and feeling of personal protection particularly in staff with ≤ 5 years of working experience (p < 0.05). The majority of non-radiological medical professionals stated that staying in the green stickers and patient care would be compatible. Knowledge of radiation protection was poor in all groups, especially among entry-level employees (p < 0.05). CONCLUSION: A traffic light system in the CT scanning room indicating areas with lowest, intermediate, and highest possible radiation exposure is much appreciated. It increases radiation awareness, improves the sense of personal radiation protection, and may support endeavors to lower occupational radiation exposure, although the best radiation protection always is to re-main outside the CT room during the scan. KEY POINTS: • A traffic light system indicating areas with different radiation exposure within the computed tomography scanner room is much appreciated by non-radiological medical staff. • The traffic light system increases non-radiological medical staff's radiation awareness and feeling of personal protection. • Knowledge on radiation protection was poor in non-radiological medical staff, especially in those with few working experience.

Clinical and prognostic value of autoantibodies in puerto Ricans with systemic lupus erythematosus.

The aim of this study was to determine the association between lupus autoantibodies and the clinical manifestations and outcome in a cohort of Puerto Ricans patients with systemic lupus erythematosus (SLE). All patients fulfilled the American College of Rheumatology classification criteria for SLE. Demographic parameters, clinical manifestations over time and damage accrual were obtained at the last study visit. Disease damage was assessed with the Systemic Lupus International Collaborating Clinics Damage Index (SDI). ANA, ANA pattern, and anti-dsDNA, anti-Smith, anti-Ro (SSA), anti-La (SSB) and anti-snRNP antibodies were measured at the time of SLE diagnosis. Chi-square test, Fisher exact test, ANOVA, logistic regression and general lineal model analyses were used to evaluate these associations. Ninety-six percent of patients were females. The cohort had a mean age of 40.2 +/- 12.0 years and mean disease duration of 9.6 +/- 7.0 years. Patients with elevated anti-dsDNA antibodies were more likely to have vasculitis, pericardial effusion, renal involvement, anaemia, leukopenia, lymphopenia and thrombocytopenia. Anti-Smith antibodies were positively associated with skin ulcerations, elevated liver enzymes, renal involvement and thrombocytopenia. Anti-Ro antibodies were related with the presence of discoid lupus, serositis, pneumonitis, elevated liver enzymes, hemolytic anaemia, leukopenia and lymphopenia. No positive associations were found for anti-snRNP or anti-La antibodies. The presence of anti-dsDNA, anti-Smith and anti-Ro antibodies was associated with higher SDI scores. In conclusion, anti-dsDNA, anti-Smith and anti-Ro antibodies are associated with several clinical manifestations and more damage accrual in Puerto Ricans with SLE. These findings provide valuable clinical and prognostic information for this ethnic population.

Differences between patients with non-Hodgkin's lymphomas in a cohort of HIV/AIDS patients in Puerto Rico.

The close association between AIDS and non-Hodgkin's lymphoma (NHL) is well known. Few studies are available that evaluate the profile of NHL in a cohort of HIV-infected patients who reside in Puerto Rico. The present study was performed in a cohort of 2,843 HIV-infected patients followed in the Retrovirus Research Center at Bayamón, Puerto Rico, evaluated between January 1992 until December 2000. NHL prevalence was determined and differences between AIDS defining and non-AIDS defining NHL were evaluated with the Fisher and ANOVA test. NHL prevalence was 0.9%. Nine (33%) were AIDS-defining (AIDS-d) NHL and 18 (67%) were non-AIDS-d NHL. Both groups were similar in gender distribution and mean diagnosis age. The median CD4+ T cell count at diagnosis was below 150/mm3 in both groups. Injecting drug use was higher in AIDS-d NHL patients and Homo-Bisexual contact was higher in non-AIDS-d NHL patients. Death rate in the first year after the NHL was 67% in the AIDS-d group and 56% in the non-AIDS-d group. AIDS-d NHL incidence decreased after the implementation of combined antiretroviral therapy in the cohort, a finding not seen in the non-AIDS-d NHL. In summary the study detected low NHL prevalence, with high degree of immunological damage at the time of the lymphoma diagnosis. Conversely dissimilar response to the antiretroviral therapies was also perceived in the incidence of the two NHL groups.

A prospective randomized controlled study of the efficacy of ketamine for postoperative pain relief in children after adenotonsillectomy.

BACKGROUND: Adenotonsillectomy is commonly needed by children with obstructive sleep apnoea syndrome. This population is at high risk of life threatening airway obstruction in the postoperative period. METHODS: Fifty children were studied to test the efficacy of an alternative analgesic to the use of opioids in providing analgesia in the immediate postoperative period. Patients were randomized to receive either 0.1 mg.kg-1 morphine or 0.5 mg.kg-1 ketamine at induction. RESULTS: Ketamine was as effective as morphine with no additional side-effects. CONCLUSIONS: Ketamine is a safe and effective alternative to morphine to provide analgesia in the immediate postoperative period after tonsillectomy.

Iliac arteriovenous fistula secondary to iliac aneurysm rupture associated with pulmonary embolism and anuria.

We present a case of iliac aneurysm rupture that started with high-output cardiac failure and anuria and later presented as a pulmonary embolism that needed a preoperatory filter for the cava vein.

Analgesic requirements for appendicectomy: the differences between adults and children.

AIM: The analgesia provided for children is often less than for adults with the same underlying pathology. This paper attempts to quantify the postoperative analgesic requirements of patients undergoing appendicectomy. METHODS: Patients between 6 and 30 years of age who underwent an unscheduled appendicectomy were prospectively recruited. Regular non-opiate analgesia, calculated according to weight, was administered. Hourly visual analogue pain scores and morphine patient controlled analgesia (mPCA) usage were recorded for 24 h following surgery. RESULTS: 19 children (6-16 years) and 23 adults (17-30 years) were recruited. There was no significant difference in the pain scores following appendicectomy between the two groups. Significantly more mPCA was demanded (t = 2.02, P < 0.02) and morphine received (t = 2.02, P < 0.005) by adults than children following appendicectomy. CONCLUSION: Children appear to require and do demand less analgesia than adults following appendicectomy to maintain similar postoperative pain scores. Acceptable pain scores may be achieved by the administration of regular analgesia to these patients.

Association of sunlight exposure and photoprotection measures with clinical outcome in systemic lupus erythematosus.

This study was designed to explore the relationship of sunlight exposure and ultraviolet (UV) light protection measures with clinical outcome in systemic lupus erythematosus (SLE). A structured questionnaire was administered to sixty Puerto Rican SLE patients, to assess their attitudes and behavior regarding sunlight exposure and photoprotection measures. Medical records were reviewed to evaluate the clinical outcome measures that included: clinical manifestations, number of SLE-related hospitalizations, number of exacerbations and pharmacologic treatment. Almost all (98.3%) patients were well acquainted of sunlight effects on disease activity. Two thirds were exposed to direct sunlight for an average of less than one hour per day and 33.3% for one hour or more. Thirty patients (50%) reported use of sunscreen, with sun protective factor of 15 or greater, when exposed to sunlight. Less than 40% of patients regularly wore hat or long-sleeves clothes to protect from sunlight. Although there were some clinical differences between the groups with different sunlight exposure times, none reached statistical significance. Also, no significant differences were found between the groups in regards to sunlight protective clothes. However, patients that regularly used sunscreen had significantly lower renal involvement (13.3 vs 43.3%), thrombocytopenia (13.3 vs 40%), hospitalizations (26.7 vs. 76.7%), and requirement of cyclophosphamide treatment (6.7 vs. 30%) than patients that did not used it (P < 0.05). We conclude that use of sunscreen photoprotection was associated with a better clinical outcome in our SLE patients. These findings further support the importance and benefits of photoprotective measures in patients with SLE.

[Recombinant hepatitis B vaccine in health personnel. Immunogenicity of a rapid vaccination schedule]. / Vacuna recombinante de la hepatitis B en personal sanitario. Inmunogenicidad de una pauta rápida de vacunación.

The immunogenic effect of a recombinant hepatitis B vaccine, administered in a dosage of 20 micrograms intramuscularly in the deltoid muscle on the months 0, 1 and 2, was evaluated in 185 employers of a general hospital. The influence of sex, age, overweight and smoking habit on the antibody response induced by the vaccine was also assessed. The seroconversion rate 40-60 days after the third dose in the 160 health professionals who completed the vaccination schedule was 88% (83% in males and 90% in females). It was 97% in individuals less than 30 years of age, 89% in those between 30 and 50 years, and 69% in those over 50 years. It was 97% in non obese and 66% in obese individuals (p less than 0.0001). No differences in seroconversion rate were found between nonsmokers, moderate smokers and heavy smokers. Untoward reactions were minimal. The rate of vaccinated individuals developing anti-HBs titers higher than 10 mIU/ml was 68%. This rate was lower than that found in most studies after vaccination in the months 0, 1 and 6, the difference being probably due to the use of a rapid schedule with a short interval between the second and third doses. Nevertheless, this schedule facilitates the vaccination programs in health staff and reduces the failure rate due to poor compliance.