Long-Term Efficacy of High-Dose Imatinib in Hispanic Patients Without Access to Second-Generation Tyrosine Kinase Inhibitors Treated in LATAM Centers.

BACKGROUND: While second-generation tyrosine kinase inhibitors (TKI) revolutionized treatment for patients with chronic myeloid leukemia (CML) who developed a suboptimal response to imatinib, many patients in developing countries are fixed to the latter due to socioeconomic barriers. Despite this scenario, scarce information is available to evaluate the clinical prognosis of these patients. METHODS: We conducted a retrospective cohort analysis to compare the overall mortality of patients with CML who developed a suboptimal response to a standard dose of imatinib and were treated with either high-dose imatinib or a second-generation TKI. We created a marginal structural model with inverse probability weighting and stabilized weights. Our primary outcome was overall survival (OS) at 150 months. Our secondary outcomes were disease-free survival (DFS) at 150 months and adverse events. RESULTS: The cohort included 148 patients, of which 32 received high-dose imatinib and 116 a second-generation TKI. No difference was found in the 150-month overall survival risk (RR: 95% CI 0.91, 0.55-1.95, P-value = .77; RD: -0.04, -0.3 to 0.21, P-value = .78) and disease-free survival (RR: 1.02, 95% CI 0.53-2.71, P-value = .96; RD: 0.01, -0.26 to 0.22, P-value = .96). There was also no difference in the incidence of adverse events in either group. CONCLUSION: Ideally, patients who develop a suboptimal response to imatinib should be switched to a second-generation TKI. If impossible, however, our findings suggest that patients treated with high-dose imatinib have a similar overall survival and disease-free survival prognosis to patients receiving a second-generation TKI.

Oral N-acetylcysteine decreases IFN-γ production and ameliorates ischemia-reperfusion injury in steatotic livers.

Type 1 Natural Killer T-cells (NKT1 cells) play a critical role in mediating hepatic ischemia-reperfusion injury (IRI). Although hepatic steatosis is a major risk factor for preservation type injury, how NKT cells impact this is understudied. Given NKT1 cell activation by phospholipid ligands recognized presented by CD1d, we hypothesized that NKT1 cells are key modulators of hepatic IRI because of the increased frequency of activating ligands in the setting of hepatic steatosis. We first demonstrate that IRI is exacerbated by a high-fat diet (HFD) in experimental murine models of warm partial ischemia. This is evident in the evaluation of ALT levels and Phasor-Fluorescence Lifetime (Phasor-FLIM) Imaging for glycolytic stress. Polychromatic flow cytometry identified pronounced increases in CD45+CD3+NK1.1+NKT1 cells in HFD fed mice when compared to mice fed a normal diet (ND). This observation is further extended to IRI, measuring ex vivo cytokine expression in the HFD and ND. Much higher interferon-gamma (IFN-γ) expression is noted in the HFD mice after IRI. We further tested our hypothesis by performing a lipidomic analysis of hepatic tissue and compared this to Phasor-FLIM imaging using "long lifetime species", a byproduct of lipid oxidation. There are higher levels of triacylglycerols and phospholipids in HFD mice. Since N-acetylcysteine (NAC) is able to limit hepatic steatosis, we tested how oral NAC supplementation in HFD mice impacted IRI. Interestingly, oral NAC supplementation in HFD mice results in improved hepatic enhancement using contrast-enhanced magnetic resonance imaging (MRI) compared to HFD control mice and normalization of glycolysis demonstrated by Phasor-FLIM imaging. This correlated with improved biochemical serum levels and a decrease in IFN-γ expression at a tissue level and from CD45+CD3+CD1d+ cells. Lipidomic evaluation of tissue in the HFD+NAC mice demonstrated a drastic decrease in triacylglycerol, suggesting downregulation of the PPAR-γ pathway.

Clinical characteristics and prognosis of infections caused by OXA-48 carbapenemase-producing Enterobacteriaceae in patients treated with ceftazidime-avibactam.

BACKGROUND: Ceftazidime-avibactam has in vitro activity against Gram-negative bacilli that produce Class A, C and some D ß-lactamases, and has been successfully used in the treatment of infections caused by cephalosporin and carbapenem-resistant Enterobacteriaceae. However, actual experience in the treatment of OXA-48 carbapenemase-producing Enterobacteriaceae (CPE) is limited. OBJECTIVE: To review the characteristics and prognosis of OXA-48 CPE infections treated with ceftazidime-avibactam since introduction of the drug to the current centre during the period October 2014 to December 2016. METHODS: Retrospective assessment of episodes of infection caused by OXA-48 CPE treated with ceftazidime-avibactam, analysing data collected from infection diagnosis until 90 days after the end of treatment. RESULTS: Twenty-four episodes were analysed. Ceftazidime-avibactam was given as the initial definitive treatment in 15 (62.5%) and as salvage therapy in nine (37.5%). Intraabdominal (seven, 29%), urinary (six, 25%) and respiratory (five, 21%) were the most common sources. The 30-day and 90-day mortality rates were 8.3% and 20.8%, respectively. Clinical cure at 30 days was achieved in 62.5% of episodes. Four (16.7%) patients had adverse events, two of them were related to impaired renal function. Among patients who finished the treatment with ceftazidime-avibactam, seven (35%) were diagnosed with infection recurrence within 90 days of the end of treatment. CONCLUSIONS: From experience, ceftazidime-avibactam is an effective drug for treating infections due to OXA-48 CPE. From these results a better safety profile than the current best available therapy could be expected.

Comparative analysis of iron status and other hematological parameters in preeclampsia.

OBJECTIVE: To compare serum ferritin (SF) concentrations and other hematological parameters between patients with preeclampsia (PE) and normal pregnant women of the same gestational period who received supplemental iron during pregnancy. METHODS: Prospective, comparative, observational pilot study that included 31 women with PE and 30 healthy pregnant women, at 20 weeks' of gestation. Ferritin, iron and complete blood cell count were compared between groups. RESULTS: In comparison with controls, preeclamptic patients had a higher weight, body mass index, and arterial pressure. Serum ferritin and serum iron were higher in patients with PE (median: 36.5 µg/l vs. 20.9 µg/l and 103.9 µg/dl vs. 90.8 µg/dl) with a significant difference (P = 0.019 and P = 0.345). SF values >40 µg/l correlated with PE (r = 0.281; P = 0.032). A platelet count less than 100 × 109/l was higher in the PE group than in the control group (13% vs. 3%, P = 0.354). CONCLUSION: Higher SF levels, despite being within normal range, were associated with PE. The incidence of thrombocytopenia was higher in preeclamptic women, however, the remaining hematological parameters were similar in both groups.

The p53 tumor suppressor protein protects against chemotherapeutic stress and apoptosis in human medulloblastoma cells.

Medulloblastoma (MB), a primitive neuroectodermal tumor, is the most common malignant childhood brain tumor and remains incurable in about a third of patients. Currently, survivors carry a significant burden of late treatment effects. The p53 tumor suppressor protein plays a crucial role in influencing cell survival in response to cellular stress and while the p53 pathway is considered a key determinant of anti-tumor responses in many tumors, its role in cell survival in MB is much less well defined. Herein, we report that the experimental drug VMY-1-103 acts through induction of a partial DNA damage-like response as well induction of non-survival autophagy. Surprisingly, the genetic or chemical silencing of p53 significantly enhanced the cytotoxic effects of both VMY and the DNA damaging drug, doxorubicin. The inhibition of p53 in the presence of VMY revealed increased late stage apoptosis, increased DNA fragmentation and increased expression of genes involved in apoptosis, including CAPN12 and TRPM8, p63, p73, BIK, EndoG, CIDEB, P27Kip1 and P21cip1. These data provide the groundwork for additional studies on VMY as a therapeutic drug and support further investigations into the intriguing possibility that targeting p53 function may be an effective means of enhancing clinical outcomes in MB.

La historia clínica estomatológica como herramienta en el método clínico y documento médico-legal / The clinical dental history as a tool in the clinical method and as medical-legal document

La historia clínica desempeña un papel fundamental en la calidad de la atención médica-estomatológica, es vital en la interrelación entre los diferentes niveles de atención. Los problemas en su confección, son atribuibles al desconocimiento de funciones, tipos, beneficios o perjuicios derivados de un contenido incompleto. El propósito del artículo es valorar la importancia de la calidad de la historia clínica estomatológica, por su valor en el diagnóstico preciso, como herramienta del método clínico y como documento médico legal. La historia clínica ideal es la que refleja de forma fidedigna todas las características clínicas del paciente y su evolución periódica. Los estomatólogos deben de reflejar todo el pensamiento médico durante el tratamiento del paciente, a fin de lograr mayor calidad en la historia clínica(AU)

The medical history plays a fundamental role in the quality of dentistry care, and it is vital in the interrelation among the various levels of care. The problems encountered in its preparation are attributable to the lack of knowledge about its functions, types, benefits or possible damages caused by the incomplete contents of the document. The objective of this article was to assess the significance of the quality of a dental history for accurate diagnosing, for the clinical method in dentistry and as a medical legal instrument. The ¿ideal¿ clinical history is the one that shows in a reliable way all the clinical characteristics of a patient and his/her systematic progress. It is important that the dentist expresses his/her medical thinking in the history during the treatment of a patient in order to raise the quality of the medical history(AU)

La historia clínica estomatológica como herramienta en el método clínico y documento médico-legal / The clinical dental history as a tool in the clinical method and as medical-legal document

La historia clínica desempeña un papel fundamental en la calidad de la atención médica-estomatológica, es vital en la interrelación entre los diferentes niveles de atención. Los problemas en su confección, son atribuibles al desconocimiento de funciones, tipos, beneficios o perjuicios derivados de un contenido incompleto. El propósito del artículo es valorar la importancia de la calidad de la historia clínica estomatológica, por su valor en el diagnóstico preciso, como herramienta del método clínico y como documento médico legal. La historia clínica "ideal" es la que refleja de forma fidedigna todas las características clínicas del paciente y su evolución periódica. Los estomatólogos deben de reflejar todo el pensamiento médico durante el tratamiento del paciente, a fin de lograr mayor calidad en la historia clínica.

The medical history plays a fundamental role in the quality of dentistry care, and it is vital in the interrelation among the various levels of care. The problems encountered in its preparation are attributable to the lack of knowledge about its functions, types, benefits or possible damages caused by the incomplete contents of the document. The objective of this article was to assess the significance of the quality of a dental history for accurate diagnosing, for the clinical method in dentistry and as a medical legal instrument. The ¨ideal¨ clinical history is the one that shows in a reliable way all the clinical characteristics of a patient and his/her systematic progress. It is important that the dentist expresses his/her medical thinking in the history during the treatment of a patient in order to raise the quality of the medical history.

Oral supplementation with glycine reduces oxidative stress in patients with metabolic syndrome, improving their systolic blood pressure.

Reactive oxygen species derived from abdominal fat and uncontrolled glucose metabolism are contributing factors to both oxidative stress and the development of metabolic syndrome (MetS). This study was designed to evaluate the effects of daily administration of an oral glycine supplement on antioxidant enzymes and lipid peroxidation in MetS patients. The study included 60 volunteers: 30 individuals that were supplemented with glycine (15 g/day) and 30 that were given a placebo for 3 months. We analysed thiobarbituric acid reactive substances (TBARS) and S-nitrosohemoglobin (SNO-Hb) in plasma; the enzymatic activities of glucose-6-phosphate dehydrogenase (G6PD), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) in erythrocytes; and the expression of CAT, GPX, and SOD2 in leukocytes. Individuals treated with glycine showed a 25% decrease in TBARS compared with the placebo-treated group. Furthermore, there was a 20% reduction in SOD-specific activity in the glycine-treated group, which correlated with SOD2 expression. G6PD activity and SNO-Hb levels increased in the glycine-treated male group. Systolic blood pressure (SBP) also showed a significant decrease in the glycine-treated men (p = 0.043). Glycine plays an important role in balancing the redox reactions in the human body, thus protecting against oxidative damage in MetS patients.

Patterns of iodine intake and urinary iodine concentrations during pregnancy and blood thyroid-stimulating hormone concentrations in the newborn progeny.

BACKGROUND: Appropriate maternal intake of iodine during pregnancy is essential for maternal thyroxine production and thyroid status of the fetus. It should be possible to enhance iodine intake during pregnancy by using iodine fortified salt or taking iodine supplements. In the present report we determined the status of iodine nutrition in pregnant women who were stratified on the basis of their history of taking or not taking iodized salt or iodine supplements. The study was performed in Toledo (Spain), a region in which prior studies have noted borderline iodine sufficiency. Iodine nutrition was assessed by measuring urinary iodine concentration (UIC) and neonatal thyrotropin (TSH). METHODS: UIC was measured in 525 pregnant women. They were grouped according to their history of iodine intake. Diet Group 1 patients (n = 69) did not take iodized salt or iodine supplements during pregnancy. Diet Group 2 patients (n = 75) took iodized salt but not iodine supplements during pregnancy. Diet Group 3 patients (n = 381) took iodine supplements during pregnancy. Plasma determinations included TSH, free thyroxine, thyroid peroxidase antibody, and thyroglobulin antibody. UIC was measured in a single urine sample from all the pregnant women. Neonatal TSH was measured in capillary spot blood from all the neonates as part of a screening for congenital metabolic abnormalities. RESULTS: The median UIC in all subjects was 164 µg/L (interquartile range [IR]: 116-245). The median UICs in Diet Groups 1, 2, and 3 were 134.5 (IR: 90-196), 146 (IR: 103-205), and 183 (IR: 124-261) µg/L, respectively (p = not significant [NS] for Diet Group 1 vs. 2; p < 0.01 for Diet Group 2 vs. 3; all other comparisons NS). The median (IR) TSH of the neonates in all Diet Groups was 1.0 (IR: 0.7-1.6) µU/mL. Only 2 neonates had blood TSH concentrations >5 mU/L. Neonatal blood TSH concentrations were similar in all Diet Groups. CONCLUSIONS: In a region with a history of borderline iodine deficiency the UICs were below 150 µg/L in a substantial percentage of pregnant women who did not take iodine supplements, regardless of whether or not they took iodized salt. Our results support the use of iodine supplements from the start of the pregnancy, or even before pregnancy in women who live in regions with a history of even small degrees of iodine deficiency. In addition, neonate TSH screening is not the best tool to assess whether the iodine status in populations is ideal.

Dietary n-3 polyunsaturated fatty acids fail to reduce prostate tumorigenesis in the PB-ErbB-2 x Pten(+/-) preclinical mouse model.

Diet and obesity, and their associated metabolic alterations, are some of the fastest-growing causes of disease and death in America. Findings from epidemiological studies correlating obesity, the sources of dietary fat and prostate cancer (PCa) are conflicting. We have previously shown that 15% of PB-ErbB-2 x pten(+/-) mice developed PCa and exhibited increased phosphorylated 4E-BP1, but not the key PI3-kinase intermediary phospho-protein, mTOR, when maintained on unrefined mouse chow. We report herein that 100% of animals fed refined, westernized AIN-93-based diets containing corn oil developed PCa by 12 months of age. Increases in visceral fat and mTO R activation in the tumors were also observed. Furthermore, nuclear cyclin E levels were significantly induced by the AIN-93-corn oil-based diets versus chow. Replacing 50% of the corn oil with menhaden oil, with 21% of its triglycerides being n-3 PUFA's, had no effect on tumorigenesis, fat deposition, cyclin E or mTOR. Phosphorylated BAD levels were similar in the tumors of mice in all three diets. Our data demonstrated that in the context of our preclinical model, components of crude chow, but not dietary n-3 PUFAs, protect against PCa progression. In addition, these data establish phosphorylated mTOR, nuclear cyclin E and visceral fat deposits as possible biomarkers of increased dietary risk for PCa.

Empleo de la tintura de propóleo al 5 en la cura de heridas sépticas faciales / Use of propolis tincture 5 to cure septic facial wounds

Debido a las propiedades que se le atribuyen a la tintura de propóleo empleamos esta sustancia para curar heridas sépticas faciales en un grupo de 10 pacientes, con el objetivo de comprobar su efectividad, si tenemos en cuenta además la situación económica de nuestro país. Queda demostrada la efectividad de este producto apícola como medicina alternativa, ya que el 90 de los pácientes presentó una total mejoría en los primeros 7 días de tratamiento y sólo 1 paciente necesitó 13 días para la cura total de la herida, por lo que se demuestra su gran efectividad en esta afección y se recomienda su uso (AU)

Empleo de la tintura de propóleo al 5 en la cura de heridas sépticas faciales / Use of propolis tincture 5 to cure septic facial wounds

Debido a las propiedades que se le atribuyen a la tintura de propóleo empleamos esta sustancia para curar heridas sépticas faciales en un grupo de 10 pacientes, con el objetivo de comprobar su efectividad, si tenemos en cuenta además la situación económica de nuestro país. Queda demostrada la efectividad de este producto apícola como medicina alternativa, ya que el 90 de los pácientes presentó una total mejoría en los primeros 7 días de tratamiento y sólo 1 paciente necesitó 13 días para la cura total de la herida, por lo que se demuestra su gran efectividad en esta afección y se recomienda su uso