Periprocedural Direct Oral Anticoagulant Management: The RA-ACOD Prospective, Multicenter Real-World Registry.

Introduction There is scarce real-world experience regarding direct oral anticoagulants (DOACs) perioperative management. No study before has linked bridging therapy or DOAC-free time (pre-plus postoperative time without DOAC) with outcome. The aim of this study was to investigate real-world management and outcomes. Methods RA-ACOD is a prospective, observational, multicenter registry of adult patients on DOAC treatment requiring surgery. Primary outcomes were thrombotic and hemorrhagic complications. Follow-up was immediate postoperative (24-48 hours) and 30 days. Statistics were performed using a univariate and multivariate analysis. Data are presented as odds ratios (ORs [95% confidence interval]). Results From 26 Spanish hospitals, 901 patients were analyzed (53.5% major surgeries): 322 on apixaban, 304 on rivaroxaban, 267 on dabigatran, 8 on edoxaban. Fourteen (1.6%) patients suffered a thrombotic event, related to preoperative DOAC withdrawal (OR: 1.57 [1.03-2.4]) and DOAC-free time longer than 6 days (OR: 5.42 [1.18-26]). Minor bleeding events were described in 76 (8.4%) patients, with higher incidence for dabigatran (12.7%) versus other DOACs (6.6%). Major bleeding events occurred in 17 (1.9%) patients. Bridging therapy was used in 315 (35%) patients. It was associated with minor (OR: 2.57 [1.3-5.07]) and major (OR: 4.2 [1.4-12.3]) bleeding events, without decreasing thrombotic events. Conclusion This study offers real-world data on perioperative DOAC management and outcomes in a large prospective sample size to date with a high percentage of major surgery. Short-term preprocedural DOAC interruption depending on the drug, hemorrhagic risk, and renal function, without bridging therapy and a reduced DOAC-free time, seems the safest practice.

Optical coherence tomography analysis of filtering blebs after long-term, functioning trabeculectomy and XEN® stent implant.

PURPOSE: The purpose of this study was to use Triton® SweptSource OCT to evaluate the morphology of blebs formed when eyes are treated with XEN® implants and to compare these with the blebs in successfully functioning eyes after trabeculectomy (TB) and with eyes of healthy controls. METHODS: A cross-sectional, observational study. We analyzed 25 eyes, 15 after TB and 10 with XEN® implants, comparing them with 23 healthy eyes (controls). We evaluated the conjunctival morphology of the eyes using AS-OCT. The main parameters evaluated were bleb height, sub-epithelial fibrosis, epithelial thickness, and changes in intraocular pressure (IOP). RESULTS: We found that the filtering blebs formed in eyes in which a XEN® stent was implanted were significantly flatter (bleb height 417 ± 183 µm) than the blebs formed in TB eyes (bleb height 618 ± 256 µm, p < 0.05). Moreover, sub-epithelial fibrosis did not develop in any of the blebs produced by the XEN stent, whereas some fibrosis was evident in 40% of the blebs that formed after TB (p < 0.05). The epithelium was thicker when the XEN implant was used (65 ± 18.5 µm) than when eyes underwent TB (60 ± 17.7 µm), and it was thicker than in control eyes (51 ± 9.7 µm, p < 0.05). Moreover, the decrease in the IOP induced by the XEN® stent (- 8.5 ± 5.3 mmHg) was similar to that produced by TB (- 8.8 ± 5.2 mmHg, p > 0.05). CONCLUSIONS: Filtering blebs obtained after the introduction of a XEN® stent were morphologically distinct to those produced by TB, and they are more similar to the healthy conjunctiva.

Outcomes of Trabeculectomy and Phacotrabeculectomy With Collagen Matrix Implant (Ologen) and Low-dose Mitomycin C: 2-Year Follow-up.

PURPOSE: The purpose of this article is to analyze the results achieved in lowering intraocular pressure (IOP) after trabeculectomy or combined surgery (phacotrabeculectomy) with low-dose mitomycin C (MMC) using the Ologen Collagen Matrix (Ologen CM) implant. MATERIALS AND METHODS: This retrospective study included 58 eyes from 47 consecutive patients with glaucoma who underwent filtering surgery alone or combined with cataract surgery. The study group included 29 eyes that underwent trabeculectomy (14 eyes) or phacotrabeculectomy (15 eyes) with low-dose MMC (0.1 mg/mL×1 min) and subconjunctival Ologen CM implant at the end of surgery. The control group included 29 eyes, 12 that underwent trabeculectomy and 17 that underwent phacotrabeculectomy, with the same MMC dose but without the collagen matrix implant. All surgical procedures were performed by the same surgeon. The follow-up period for the patients was 2 years. RESULTS: We found statistically significant differences between the 2 groups in the age of the patients (P=0.02). We found no statistically significant differences in the baseline IOP (P=0.37) or preoperative IOP (P=0.5), nor in the visual field damage measured with mean deviation (P=0.2). The number of hypotensive medications used preoperatively was higher in the study group (P=0.0001). At 1 and 2 years after surgery, we only found statistically significant differences in favor of the study group in patients who underwent phacotrabeculectomy (P=0.0008 and 0.02, respectivily). CONCLUSION: The Ologen CM implant can be considered as an adjunct to MMC in patients undergoing filtering surgery combined with phacoemulsification to improve postoperative IOP results over the long term.

Chemoprevention, chemotherapy, and chemoresistance in colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death in industrialized countries. Chemoprevention is a promising approach, but studies demonstrating their usefulness in large populations are still needed. Among several compounds with chemopreventive ability, cyclooxygenase inhibitors have received particular attention. However, these agents are not without side effects, which must be weighed against their beneficial actions. Early diagnosis is critical in the management of CRC patients, because, in early stages, surgery is curative in >90% of cases. If diagnosis occurs at stages II and III, which is often the case, neoadjuvant chemotherapy and radiotherapy before surgery are, in a few cases, recommended. Because of the high risk of recurrence in advanced cancers, chemotherapy is maintained after tumor resection. Chemotherapy is also indicated when the patient has metastases and in advanced cancer located in the rectum. In the last decade, the use of anticancer drugs in monotherapy or in combined regimens has markedly increased the survival of patients with CRC at stages III and IV. Although the rate of success is higher than in other gastrointestinal tumors, adverse effects and development of chemoresistance are important limitations to pharmacological therapy. Genetic profiling regarding mechanisms of chemoresistance are needed to carry out individualized prediction of the lack of effectiveness of pharmacological regimens. This would minimize side effects and prevent the selection of aggressive, cross-resistant clones, as well as avoiding undesirable delays in the use of the most efficient therapeutic approaches to treat these patients.

Eating disorders in patients with traumatic brain injury: a report of four cases.

BACKGROUND: Traumatic brain injury (TBI) can lead to changes in eating behavior patterns with significant clinical manifestations. METHODS: Medical records of four patients with severe TBI and eating disorders attending the neurorehabilitation program of our brain injury unit were reviewed. CONCLUSIONS: Several eating disorders observed among the four cases, may be present from early phases and remain years after the lesion. Symptoms do not adhere to the typical forms of anorexia and bulimia. Factors influencing the weight changes experienced by patients with brain injury included reduction in physical activity, metabolic disorders and treatment with psychotropic drugs.

Role of vitamin C transporters and biliverdin reductase in the dual pro-oxidant and anti-oxidant effect of biliary compounds on the placental-fetal unit in cholestasis during pregnancy.

Maternal cholestasis causes oxidative damage to the placental-fetal unit that may challenge the outcome of pregnancy. This has been associated with the accumulation of biliary compounds able to induce oxidative stress. However, other cholephilic compounds such as ursodeoxycholic acid (UDCA) and bilirubin have direct anti-oxidant properties. In the present study we investigated whether these compounds exert a protective effect on cholestasis-induced oxidative stress in placenta as compared to maternal and fetal livers, and whether this is due in part to the activation of anti-oxidant mechanisms involving vitamin C uptake and biliverdin/bilirubin recycling. In human placenta (JAr) and liver (HepG2) cells, deoxycholic acid (DCA) similar rates of free radical generation. In JAr (not HepG2), the mitochondrial membrane potential and cell viability were impaired by low DCA concentrations; this was partly prevented by bilirubin and UDCA. In HepG2, taurocholic acid (TCA) and UDCA up-regulated biliverdin-IX alpha reductase (BVR alpha) and the vitamin C transporter SVCT2 (not SVCT1), whereas bilirubin up-regulated both SVCT1 and SVCT2. In JAr, TCA and UDCA up-regulated BVR alpha, SVCT1 and SVCT2, whereas bilirubin up-regulated only SVCT2. A differential response to these compounds of nuclear receptor expression (SXR, CAR, FXR and SHP) was found in both cell types. When cholestasis was induced in pregnant rats, BVR alpha, SVCT1 and SVCT2 expression in maternal and fetal livers was stimulated, and this was further enhanced by UDCA treatment. In placenta, only BVR alpha was up-regulated. In conclusion, bilirubin accumulation and UDCA administration may directly and indirectly protect the placental-fetal unit from maternal cholestasis-induced oxidative stress.

Multiple protective effects of melatonin against maternal cholestasis-induced oxidative stress and apoptosis in the rat fetal liver-placenta-maternal liver trio.

Maternal cholestasis is usually a benign condition for the mother but induces profound placental damage and may be lethal for the fetus. The aim of this study was to investigate the protective effects in rat maternal and fetal livers as also the placenta of melatonin or silymarin against the oxidative stress and apoptosis induced by maternal obstructive cholestasis during the last third of pregnancy (OCP). Melatonin or silymarin administration (i.e. 5 mg/100 g bw/day after ligation of the maternal common bile duct on day 14 of pregnancy) reduced OCP-induced lipid peroxidation, and prevented decreases in total glutathione levels. However, the protective effect on OCP-induced impairment in the GSH/GSSG ratio was mild in the placenta and fetal liver, while absent in maternal liver. Melatonin or silymarin also reduced OCP-induced signs of apoptosis (increased caspase-3 activity and Bax-alpha upregulation) in all the organs assayed. Moreover, melatonin (but not silymarin) upregulated several proteins involved in the cellular protection against the oxidative stress in rats with OCP. These included, biliverdin-IX alpha reductase and the sodium-dependent vitamin C transport proteins SVCT1 and SVCT2, whose expression levels were enhanced in maternal and fetal liver by melatonin treatment. In contrast, in placenta only biliverdin-IX alpha reductase and SVCT2 were upregulated. These results indicate that whereas the treatment of cholestatic pregnant rats with melatonin or silymarin affords a direct protective antioxidant activity, only melatonin has dual beneficial effects against OCP-induced oxidative challenge in that it stimulates the expression of some components of the endogenous cellular antioxidant defense.

Transtornos psiquiátricos en un Hospital de Neurorrehabilitación / Psychiatric disorders among inpatients of a Neurorehabilitation Hospital

Objetivo: Estabelecer la prevalencia de transtornos psiquiátricos en pacientes con lesiones de sistema nervioso central e identificar grupos de riesgo. Materiales y Métodos: Estudio de prevalencia con pacientes ingresados en un Hospital de Neurorrehabilitación valorados mediante entrevista clínica. Pacientes: La población estaba conformada por 90 pacientes; 61 con lesión medular, 22 con lesión cerebral y 7 con lesión tanto medular como cerebral. Resultados: La mayoría de los pacientes estaban entre el tercer al sexto mes de evolución de la lesión. En nuestro estudio la patología diagnosticada con mayor frecuencia fue la depresión con una prevalencia del 36,1 por cento. Conclusiones: la depresión y los transtornos adaptativos fueron los diagnósticos psiquiátricos más frecuentes en nuestra población. El factor de riesgo para dichas patologías fue un tiempo de evolución prolongado a partir de la lesión neurológica

Effect of artemisinin/artesunate as inhibitors of hepatitis B virus production in an "in vitro" replicative system.

The antiviral effect against hepatitis B virus (HBV) of artemisinin, its derivative artesunate and other compounds highly purified from traditional Chinese medicine remedies, were investigated. HBV production by permanently transfected HepG2 2.2.15 cells was determined by measuring the release of surface protein (HBsAg) and HBV-DNA after drug exposure (0.01-100 microM) for 21 days. The forms of HBV-DNA released were investigated by Southern-blotting. Neutral Red retention test was used to evaluate drug-induced toxicity on host cells. The compounds were classified according to their potential interest as follows: (i) none: they had no effect on viral production (daidzein, daidzin, isonardosinon, nardofuran, nardosinon, tetrahydronardosinon and quercetin); (ii) low: they were able to markedly reduce viral production, but also induced toxicity on host cells (berberine and tannic acid) or they had no toxic effect on host cells but only had a moderate ability to reduce viral production (curcumin, baicalein, baicalin, bufalin, diallyl disulphide, glycyrrhizic acid and puerarin); (iii) high: they induced strong inhibition of viral production at concentrations at which host cell viability was not affected (artemisinin and artesunate). Moreover, artesunate in conjunction with lamivudine had synergic anti-HBV effects, which warrants further evaluation of artemisinin/artesunate as antiviral agents against HBV infection.