Variant alleles in factor V, prothrombin, plasminogen activator inhibitor-1, methylenetetrahydrofolate reductase and risk of thromboembolism in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab.

Single-nucleotide polymorphisms (SNPs) related to hereditary thrombophilia were investigated as risk factors for thromboembolism in cancer patients. Their effect in metastatic colorectal cancer (mCRC) has never been explored so far. Our aim was to analyse the effect of coagulation factor V (FVL G1691A), prothrombin (PT G20210A), methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and plasminogen activator inhibitor type 1 (PAI-1 5G/4G) allelic variants in this setting. Fifty-two patients treated with first-line chemotherapy plus bevacizumab who developed a thromboembolic event in their lifetime were initially genotyped. A contemporary cohort of 127 patients who did not experience any thromboembolic event was also analysed. DNA was extracted from peripheral blood and genotypes were determined by real-time PCR, using LightSNiP (TIB MOLBIOL) on LightCcler 480 (Roche). The association between thromboembolism and SNPs was investigated by univariable and multivariable analyses. All SNPs were in Hardy-Weinberg equilibrium (χ2 test P>0.20). FVL G1691A and PT G20210A were present only in heterozygosis in 4 (2.2%) and 7 (3.9%) patients, respectively; MTHFR C677T in homozygosis in 29 (16.2%), MTHFR A1298C in homozygosis in 13 (7.3%); PAI-1 5G/4G in 98 (54.7%) and 4G/4G in 41 (23%) patients. At univariable analysis, treatment duration was significantly associated with thromboembolism (P<0.001), whereas gender, age, obesity, platelets count and chemotherapy backbone were not. Similarly, FVL G1691A and PT G20210A as well as MTHFR C677T and PAI-1 4G allele were significantly associated, whereas MTHFR A1298C was not. At multivariable model including PT G20210A, MTHFR C677T and PAI-1 4G (age, obesity, treatment duration and chemotherapy backbone were included as adjustment factors), the three SNPs were significantlty associated with higher risk of thromboembolism (P=0.025, <0.0001 and P=0.033, respectively). Further validation studies are warranted in order to design a prospective trial of thromboprophylaxis in mCRC patients with high-risk genotypes.

Clinical prognostic factors in advanced epithelioid haemangioendothelioma: a retrospective case series analysis within the Italian Rare Cancers Network.

BACKGROUND: This multicentric, retrospective study conducted within the Italian Rare Cancer Network describes clinical features and explores their possible prognostic relevance in patients with advanced epithelioid haemangioendothelioma (EHE) started on surveillance. PATIENTS AND METHODS: We collected data on adult patients with molecularly confirmed, advanced EHE consecutively referred at five sarcoma reference centres between January 2010 and June 2018, with no evidence of progressive disease (PD) and started on surveillance. Overall survival (OS) and progression-free survival (PFS) univariable and multivariable Cox analyses were performed. In the latter, due to the low number of cases and events, penalized likelihood was applied, and variable selection was performed using a random forest model. RESULTS: Sixty-seven patients were included. With a median follow-up of 50.2 months, 51 (76%) patients developed PD and 16 (24%) remained stable. PD at treatment start did not meet RECIST version 1.1 in 15/51 (29%) patients. The 3-year PFS and OS were 25.4% and 71.1%, respectively, in the whole population. Tumour-related pain (TRP) was the most common baseline symptom (32.8%), followed by temperature (20.9%), fatigue (17.9%), and weight loss (16.4%). Baseline TRP (P = 0.0002), development of TRP during follow-up (P = 0.005), baseline temperature (P = 0.002), and development of fatigue during follow-up (P = 0.007) were associated with a significantly worst PFS. An association between baseline TRP (P < 0.0001), development of TRP during follow-up (P = 0.0009), evidence of baseline serosal effusion (P = 0.121), and OS was recorded. CONCLUSION: Because of the poor outcome observed in EHE patients presenting with serosal effusion, TRP, temperature, or serosal effusion, upfront treatment in this subgroup could be considered.

Surface reactions of a plasma-sprayed CaO-P2O5-SiO2-based glass with albumin, fibroblasts and granulocytes studied by XPS, fluorescence and chemiluminescence.

X-ray photoelectron spectroscopy (XPS) was used to define the chemical composition of the outermost surface layer and the surface modification of a plasma-coated phospho-silicate glass (identified as BVA) when immersed in K-phosphate buffer or in phosphate buffered human albumin solution. Its behavior was compared with that of a soda-lime-based glass (identified as BVH) treated in the same way. The surface % composition of plasma-sprayed glass was consistent with bulk composition. After incubation with buffer, a Ca-P-rich layer developed only on the surface of BVA glass. Human serum albumin was bound reversibly to both glasses maintaining its native state. However, the protein completely covered the BVA glass surface within 24 h, with the formation of a mixed albumin-Ca-P layer, while 4 days incubation was necessary for complete coverage of BVH glass surface. Murine fibroblasts seeded on plasma-coated BVA glass showed a proliferation pattern similar to that of control cells grown on Petri dish, while cells seeded on BVH had more restricted growth. A limited response was induced in polymorphonuclear granulocytes by both bulk glasses powder. In conclusion, the glass identified as BVA has the suitable characteristics of its surface layers to be considered biologically active from both a chemical and a cellular point of view.

Radiosensitization by derivatives of isoindole-4,7-dione.

New derivatives of isoindole -4,7-dione have been synthesized and their radiation sensitization and chemical behavior have been studied. One-electron reduction potentials have been determined by pulse radiolysis and found to be in the range of -0.45 to -0.36 V vs NHE . Radiosensitization effects were tested in vivo using soft tissue sarcoma transplanted in mice. All the isoindole -4,7-diones tested were found to exert considerable radiosensitization, approaching that of misonidazole tested under comparable conditions. The derivatives which contain a carbethoxy group on the pyrrolic ring were found to have more positive reduction potentials and to act as more efficient sensitizers. Further development of this class of radiosensitizers is underway.

[The use of guacetisal in chronic obstructive bronchopneumopathy. Controlled clinical study]. / L'impiego del guacetisal nella broncopneumopatia cronica ostruttiva. Studio clinico controllato.

A single-blind, between-patients trial was run to compare the fluidifying, expectorant, antitussive, antipyretic and anti-inflammatory activity, and the local and systemic tolerance of guacetisal, an active principle obtained by the esterification of acetylsalicylic acid and guaiacol, and oxolamine phosphate, in which the suspension formulation for adults was administered to 30 presenile and senile patients of both sexes with chronic obstructive bronchopathy. A higher activity on the part of guacetisal was noted. The results obtained are illustrated and discussed.

Hepatocellular Carcinoma Metastasis to the Orbit in a Coinfected HIV+ HBV+ Patient Previously Treated with Orthotopic Liver Transplantation: A Case Report.

Hepatocellular carcinoma rarely metastasizes to the orbit. We report a 45-year-old male, HBV+, HIV+, with a past history of a liver transplant for ELSD (end-stage liver disease) with hepatocellular carcinoma and recurrent HCC, who presented with proptosis and diplopia of the left eye. CT scans of the head revealed a large, irregular mass in the left orbit causing superior and lateral destruction of the orbital bone. Biopsy specimens of the orbital tumor showed features of metastatic foci of hepatocellular carcinoma. Only 16 other cases of HCC metastasis to the orbit have been described in literature, and this is the first case in a previously transplanted HIV+, HBV+ patient.

M-H loop tracer based on digital signal processing for low frequency characterization of extremely thin magnetic wires.

A high-sensitivity ac hysteresis loop tracer has been developed to measure the low frequency hysteresis loop of soft magnetic materials. It has been applied successfully to characterize straight pieces of amorphous glass-covered microwires with metallic nucleus down to 1.5 microm thick. Based on the electromagnetic induction law, the proposed design is extremely simple and exploits the capabilities of commercially available data acquisition cards together with digital signal processing in order to achieve high-sensitivity without the need of expensive analog equipment.

Current problems in treating tuberculosis in Italian HIV-infected patients.

31 Italian HIV-infected patients with newly diagnosed tuberculosis (TB) were reviewed to verify the effectiveness of the most common antituberculosis drugs. The patients were mostly intravenous drug addicts (90%), and 14 (45%) had recently been in prison. 5 patients (16%) had pulmonary TB, 15 (48%) had both pulmonary and extrapulmonary involvement, and 11 (30%) had extrapulmonary disease alone. 6 patients received the association of HRZ, and a 4-drug association including ethambutol was given to an additional 7 patients. The remaining 18 patients were administered the association of HRE. Response to therapy was good in 13 patients (42%), and lacking or delayed in 18 patients (58%). Treatment failure was partly related to the increased occurrence in our area of Mycobacterium tuberculosis strains resistant to the first-line anti-tuberculosis drugs. These observations, along with the need of a faster response to therapy than that currently obtained for TB in AIDS and in view of epidemiological effects, should prompt the definition of alternative therapeutic and prophylactic regimens.

Albumin-containing sol-gel glasses: chemical and biological study.

Glasses incorporating increasing amounts of bovine serum albumin were prepared by sol-gel techniques from a tetra methoxy silane precursor. The surface of the glass samples was studied by X-ray photoelectron spectroscopy, revealing that the protein is present also in the superficial layer of the silica network. Moreover, the protein is distributed in a dose-dependent way, since the N/Si atomic ratio increases linearly with the albumin concentration in the reaction mixture. Angle-dependent measurements show that the protein distribution occurs homogeneously and is the same at different sampling depths. Protein incorporation in the bulk SiO2 network, with a uniform protein distribution between bulk and surface, is confirmed by infrared spectroscopy measurements, performed both in reflectance and transmittance mode. The reaction with a specific antibody and the adhesivity assay of osteoblastic cells show that embedded albumin present on the glass surface is able to interact with other proteins.

Dolor de la articulación sacroilíaca. Anatomía, diagnóstico y tratamiento / Sacroiliac joint pain. Anatomy, diagnosis and treatment

El dolor de la articulación sacroilíaca es una causa frecuente de dolor bajo de espalda, sin embargo el diagnóstico de artralgia sacroilíaca no es fácil de confirmar y la exploración física de la articulación es controvertido. Además este diagnóstico a menudo pasa inadvertido para el médico, por lo que la falta de consideración de esta posible causa de lumbalgia da lugar a tratamientos inapropiados e inadecuados. La articulaciones sacroilíacas, sinoviales del tipo anfiartrosico irregular, monoaxiales, en la cual se articulan las carillas articulares del sacro al ilion, Su innervación es cuestión de debate, pero las más recientes investigaciones refieren que deriva de L2-S2, L4-S2, L5-S2. La prevalencia del dolor de la articulación sacroilíaca no esta bien estudiado, hay numerosas etiologías para el dolor de articulación sacroilíaca, estas causas se pueden dividir en intraarticulares y extraarticulares. Para la exploración física se cuenta con una serie de 12 pruebas las cuales fueron emitidas por un comité de expertos y se concluye que encontrar 3 o más pruebas positivas es muy sugestivo de dolor de dicha. El tratamiento se puede dividir en conservador, intervencionista donde se puede utilizar desde la infiltración con anestésico local y esteroide hasta radiofrecuencia y por ultimo quirúrgico para casos seleccionados (AU)

The pain of the sacroiliac joint is a frequent cause of low back pain, however the diagnose of sacroiliac artralgia it is not easy to confirm and the physical exploration of the joint is controversial. Also this I often diagnose it happens inadvertent for the physician, for what the lack of consideration of this possible low back pain cause gives place to inappropriate and inadequate treatments. The sacroiliac joint is synovial of the type irregular anphiarthrosic, monoaxial, in which the sides joint are articulated from the sacrum one to the Ilion, Their innervation is debate question, but those but recent investigations refer that it derives of L2-S2, L4-S2, L5-S2. The prevalence of the pain of the sacroiliac joint not this well studied one, there is numerous etiology for the sacroiliac joint pain, these causes can be divided in intraarticular and extraarticular. For the physical exploration it is had a series of 12 tests which were emitted by a committee of experts and you concludes that to find 3 or but positive tests are very suggestive of pain of happiness. The treatment you can divide in conservative, interventionist where you can use from the infiltration with local anesthetic and steroid until radiofrequency and for finish surgical for selected cases (AU)

Rotación de morfina a metadona en domicilio. Descripción de 4 Casos / Ambulatory morphine rotation to metadone description of 4 clinical cases

Introducción: La metadona es un opioide eficaz para el control del dolor por cáncer, posee características que lo hacen indispensable en la terapia opioide como su potencia, vida media larga, efecto NMDA, bajo costo, aunque es un fármaco de segunda línea en el manejo del dolor oncológico debido a su larga e imprevisible vida media, situación que la hace susceptible de acumulación en dosis repetidas, por tal motivo su rotación se realiza en el medio hospitalario. Describimos cuatro casos en los que se roto de morfina a metadona en el domicilio. Presentación de Casos: Describimos la rotación de morfina a metadona en cuatro pacientes oncológicos que presentaban dolor por actividad tumoral y en los cuales se llevo a cabo la rotación debido a que presentaban efectos adversos intensos. Dicha rotación se llevo a cabo en el domicilio del paciente previo consentimiento informado del paciente y familiares y dando capacitación a los familiares para detectar efectos adversos graves como somnolencia, bradipnea además de un seguimiento estrecho, en todos los pacientes la rotación fue exitosa y no se presentaron efectos adversos graves. Discusión: En todos los pacientes se logro realizar la rotación de morfina a metadona con un adecuado control el dolor y de los efectos adversos, además de que no se presentaron efectos adversos por el uso de metadona en forma domiciliaria con lo que hubo una mejoría en la calidad de vida y muerte. Conclusión: Estos casos nos permiten proponer esta forma de rotación en pacientes seleccionados e iniciar estudios de seguridad para la rotación morfina a metadona domiciliaria (AU)

Introduction: The methadone is an effective opioid for the control of cáncer pain, it possesses characteristic that make it indispensable in the therapy opioid like its potency, long half life, effect NMDA, low cost. although it is a drug of second line in the handling of the cáncer pain due to their long and unforeseeable half life, situation that makes it susceptible of accumulation in repeated dose, for such a reason their rotation is carried out in the hospital. We describe four cases in those that you rotation of morphine to methadone in the home. Presentation of Cases: We describe the rotation of morphine to methadone in four oncological patients that presented pain for activity tumoral and in which you carries out the rotation because they presented intense adverse effects. This rotation you carry out in the home of the patient's patient previous informed consent and family and giving training to the relatives to detect serious adverse effects as drowsiness, bradypnea besides a narrow pursuit, in all the patients the rotation was successful and serious adverse effects were not presented. Discussion: In all the patients you achievement to carry out the rotation of morphine to methadone with an appropriate control the pain and of the adverse effects besides that adverse effects were not presented by the methadone use in domiciliary form with what there was an improvement in the quality of life and death. Conclusion: These cases allow to intend this rotation form in selected patients and to begin studies of security for the rotation morphine to domiciliary methadone (AU)