Low Golimumab Trough Levels at Week 6 Are Associated With Poor Clinical, Endoscopic and Histological Outcomes in Ulcerative Colitis Patients: Pharmacokinetic and Pharmacodynamic Sub-analysis of the Evolution Study.

BACKGROUND AND AIMS: Golimumab has an established exposure-response relationship in patients with ulcerative colitis [UC]. However, the association of serum golimumab trough levels [TL] with objective markers of disease activity, such as endoscopic and histological activity scores and concentrations of biomarkers, remains less understood. This report describes the relationship of serum golimumab TL at the end of the induction period [Week 6] with clinical, endoscopic, histological, and biomarker parameters. METHODS: This was an open-label, uncontrolled, prospective and interventional study. Moderate to severely active UC patients naïve to biologic therapy were treated with golimumab. Serum golimumab TL and faecal calprotectin levels were measured at baseline [Week 0 of induction] and Week 6. RESULTS: A total of 34 patients completed the induction phase [Week 6] and were included in this analysis. Overall, 47.1% and 14.7% of patients achieved clinical response and remission with significantly higher serum golimumab TL in patients with early response or remission [3.7 µg/mL vs 1.3 µg/mL, p = 0.0013; and 3.1 µg/mL vs 1.7 µg/mL, p = 0.0164, respectively]. In addition, golimumab TL were significantly higher in patients achieving histological remission [4.2 µg/mL vs 1.7 µg/mL, p = 0.0049]. Week 6 golimumab TL were inversely correlated with the total Mayo score [rs = -0.546; p = 0.0008], the Mayo endoscopic subscore [rs = -0.381; p = 0.0262], the Geboes histological activity score [rs = -0.464; p = 0.0057], and faecal calprotectin levels [rs = -0.497; p = 0.0044]. CONCLUSIONS: A higher early exposure to golimumab is associated with a better objective response in active UC patients and appears to drive the outcome at Week 6.

Estimating the prevalence of inflammatory bowel disease in Portugal using a pharmaco-epidemiological approach.

PURPOSE: To estimate inflammatory bowel disease (IBD) prevalence in Portugal from 2003 to 2007, and to obtain disease, sex and age specific estimates. METHODS: A pharmaco-epidemiological approach based on intestinal anti-inflammatory (IAI) drugs consumption was used. Proportion of patients taking IAI drugs and mean prescribed daily dose (PDD) were estimated from a sample of 513 IBD patients. Assumptions were made about unknown parameters and sensitivity analysis performed: drug compliance (80% in base case; range 70-85%) and proportion of sulphasalazine used in IBD (52%; range 40-80%). Sex and age specific estimates were based on a proposed methodological extension and results from a nationwide (n = 5893) cross-sectional study. RESULTS: IBD prevalence increased from 86 patients per 100 000 in 2003 to 146 in 2007. Regions more affected were Lisboa and Porto (173 and 163 per 100 000 in 2007, respectively). Prevalence increased from 42 and 43 per 100 000 in 2003 to 71 and 73 in 2007, respectively for ulcerative colitis (UC) and Crohn's disease (CD). In 2007, prevalence was higher in the 40-64 age stratum for UC (99 per 100 000) and in the 17-39 stratum for CD (121). Prevalence was consistently higher in females. CONCLUSIONS: Portugal is half way between countries with the highest and lowest IBD prevalence, but is steeply making the road to the highest-level group. Despite limitations of the proposed methods, assumptions were reasonable and estimates seem to be valid. Feasibility and comparability of this methodology makes it an interesting tool for future studies on IBD epidemiology.

Inflammatory bowel disease: a patient's and caregiver's perspective.

The purpose of this study was to conduct a survey examining the impact of inflammatory bowel disease (IBD) on patients' and their caregivers' daily activities. Questionnaires were distributed to patients registered in the APDI (Portuguese Association for IBD) database and their respective caregivers in 2007. Of 422 patient respondents, 251 had Crohn's disease (CD) and 171 had ulcerative colitis (UC), with the majority of patients being women (58.1%) and aged over 40 years (37.4%). The number of disease flares experienced by IBD patients was slightly higher for patients with CD than for patients with UC (2.64 vs. 2.34), and surgery was more often required in CD patients as compared to UC patients (42.4 vs. 7%). Sixty percent (60%) of patients reported having no problems with mobility, daily activities, or personal hygiene; however, over half of all patients experienced some pain and anxiety. Adult patients and children and adolescents respectively experienced time off work or school due to their disease but caregivers were not affected in this regard. The caregivers life (N=324) was affected by anxiety, with the major concern reported as the risk of the patient developing cancer. Both IBD patients and caregivers thought that the provision of information on new drugs and contact time with a doctor would have the biggest impact on improving care. The symptoms and complications of IBD have a considerable impact on the lives of patients and their caregivers, and several actions could be taken to improve their care.

Emergence in Brazil of methicillin-resistant Staphylococcus aureus isolates carrying SCCmecIV that are related genetically to the USA800 clone.

An increasing incidence of nosocomial infections caused by non-multiresistant methicillin-resistant Staphylococcus aureus (nMMRSA) has been reported worldwide. The present study genotyped nMMRSA isolates obtained from hospitals in two cities in Brazil. The hospital isolates displayed pulsed-field gel electrophoresis (PFGE) patterns that were similar to those of the USA100 (ST5-SCCmecII) and USA 800 (ST5-SCCmecIV) strains, which are related to the New York/Japan and paediatric clones, respectively. Carriage of SCCmecIV and the classification by multilocus sequence typing (MLST) of a representative of this PFGE pattern in clonal complex 5 (CC5) confirmed the genetic relationship of the Brazilian isolates with USA800. The USA800-related Brazilian isolates were responsible for severe nosocomial infections in compromised adults and elderly patients in Brazil. A higher growth rate, an ability to form biofilm on inert polystyrene surfaces and the presence of the egc locus may have contributed, at least in part, to the fitness of these organisms as global nosocomial pathogens.

Endosonographic Doppler-guided manometry of esophageal varices: experimental validation and clinical feasibility.

BACKGROUND AND STUDY AIMS: The risk of variceal bleeding cannot be accurately predicted using endoscopy alone. Although variceal pressure has been demonstrated to be a major determinant for the rupture of esophageal varices, direct determination by needle puncture is unsuitable for routine clinical use. Due to their operator-dependency, current noninvasive endoscopic methods for determination of variceal pressure have not gained wide acceptance. We have developed a new method of measuring variceal pressure, using endoscopic power Doppler imaging to monitor the manometry of esophageal varices. The aims of this study were to test in vitro the accuracy of Doppler-guided manometry and to assess the clinical feasibility of this method. MATERIALS AND METHODS: Experimental validation of this technique was performed using an in vitro model of artificial varices of different sizes. A linear-array endosonography (EUS) probe with power Doppler capability was used to assess flow in the varices and a balloon for manometry of esophageal varices was attached to the tip of the probe. Pressure readings were made at the time of disappearance of the Doppler signal during variceal compression by the balloon. Linear regression analysis was used to compare the results of Doppler-guided and direct intraluminal pressure measurement in the artificial varices. Variceal pressure was then measured with this technique in 28 patients with portal hypertension and esophageal varices without previous bleeding, and the results were compared with portal pressure assessed according to the hepatic vein pressure gradient (HVPG). RESULTS: In vitro studies demonstrated a good correlation between the pressure measured with Doppler monitoring and the actual intravariceal pressure (r > or = 0.922; P < 0.001). The determination of variceal pressure with this method was technically successful in 26/28 patients (93 %). The intraoperator variance was 9.3 +/- 8.6 %. Overall, the mean variceal pressure was significantly lower than the mean HVPG (21.2 +/- 5.3 mmHg vs. 24.3 +/- 7.8 mmHg; P < 0.01). Variceal pressure and portal pressure (as assessed by the HVPG) correlated significantly (r = 0.64; P < 0.001). CONCLUSIONS: Our preliminary results indicate that EUS Doppler-guided manometry of esophageal varices is feasible and accurate. This technique may become a more reliable method for noninvasive measurement of variceal pressure and warrants further investigation.

Cerebral protection: the surgeon's view.

The cardiothoracic team has to be ready with a strategy that corners the preoperative to postoperative period, but the cardiothoracic surgeon has to be prepared to perform the optimal procedure by concentrating on the procedure and avoiding circulatory arrest. If it is not possible to avoid circulatory arrest the surgeon should choose the ideal cerebroprotective technique for each patient, which is not always the same technique, change the method during the procedure if necessary, and remember that cerebral protection is not the same as cerebral metabolic preservation.

Octreotide in acute bleeding esophageal varices: a prospective randomized study.

BACKGROUND/AIMS: To assess the value of octreotide in the control of acute bleeding esophageal varices, in a prospective randomized study. METHODOLOGY: One hundred and ninety-seven patients admitted for variceal bleeding confirmed at endoscopy were recruited and divided into two groups: group I (n = 111) with endoscopic stigmata of recent bleeding; and group II (n = 86) with active bleeding at emergency endoscopy. Patients in group I were randomized to receive a continuous infusion of octreotide (n = 58) or emergency sclerotherapy (n = 53). Patients in group II were assigned to sclerotherapy (n = 42) or to sclerotherapy plus octreotide (n = 44). At the end of the period of study (48 hours), patients were submitted to sclerotherapy or band ligation until variceal obliteration was achieved. RESULTS: In group I, octreotide was found to be as effective as sclerotherapy regarding hemostasis at 48 hours and on day 7 after the index bleeding episode. Transfusion needs were not significantly different for the two treatment modalities. In group II, the association of octreotide with sclerotherapy was significantly better than sclerotherapy alone either in controlling acute active bleeding (P < 0.001) or in achieving hemostasis at 48 hours (P < 0.01). Transfusion needs were significantly fewer in patients treated with this therapeutic association as compared to sclerotherapy alone. CONCLUSIONS: These results suggest that octreotide infusion is effective in the treatment of variceal bleeding. In patients with recent bleeding, octreotide infusion is as effective as emergency sclerotherapy. In active variceal bleeding, it is a valuable adjuvant treatment in association with emergency sclerotherapy.

Endoscopic injection therapy vs. multipolar electrocoagulation vs. laser vs. injection + octreotide vs. injection + omeprazole in the treatment of bleeding peptic ulcers. A prospective randomized study.

BACKGROUND/AIMS: A prospective randomized study was performed to assess the effectiveness and safety of 5 different methods of hemostasis in selected patients with high-risk bleeding peptic ulcers. METHODOLOGY: Two hundred and eight patients (n = 208; mean age: 61.6 yrs) with endoscopic stigmata of active hemorrhage, non-bleeding vessel or adherent fresh clot were randomized during emergency endoscopy to receive one of the following modalities of endoscopic therapy (with or without pharmacological therapy): I) injection of absolute alcohol (n = 44); II) multipolar electrocoagulation (BICAP; n = 42); III) Nd-YAG laser (n = 40); IV) injection of absolute ethanol + octreotide (n = 42); V) injection of absolute ethanol + omeprazole (n = 40). RESULTS: The 5 treatment groups were clinically and endoscopically comparable. The initial hemostatic success was > 90% in every group. No significant differences between groups were found in any of the following parameters assessed during hospitalization: incidence of rebleeding (I = 14.8% vs. II = 19.0% vs. III = 16.6% vs. IV = 18.1% vs. V = 20.0%; P > 0.05 mean = 17.7%); incidence of definitive hemostasis (I = 89.3% vs. II = 85.7% vs. III = 86.6% vs. IV = 84.0% vs. V = 86.6%; P > 0.05; mean = 86.5%); incidence of emergency surgery (I = 8.5% vs. II = 11.9% vs. III = 10.0% vs. IV = 6.8% vs. V = 11.1%; P > 0.05; mean = 9.6%); mortality rate (I = 4.2% vs. II = 4.7% vs. III = 3.3% vs. IV = 13.6% vs. V = 4.4%; P > 0.05; mean = 6.2%). Mean age of deceased patients was significantly higher than living patients (71.2 +/- 13.4 vs. 60.9 +/- 14.4; P < 0.05). Approximately 2/3 of the fatal cases were strongly weakened by coexistent medical diseases. The duration of hospital stay was similar for all groups. The BICAP group required less units of blood transfusion (1.9 +/- 1.8 vs. I = 3.0 +/- 2.6; III = 3.5 +/- 3.6; IV = 2.8 +/- 2.3; V = 3.1 +/- 2.5; P < 0.05), perhaps due to the higher mean value of hemoglobin of these patients at hospital admission, compared to all other groups. No significant complications were reported. CONCLUSIONS: This study provides good evidence that injection of absolute ethanol, multipolar electrocoagulation (BICAP) and Nd-YAG laser are equally safe and effective in the endoscopic therapy of acute bleeding peptic ulcers. In contrast, no additional hemostatic benefits arose from the association of pharmacological agents (octreotide or omeprazole) to sclerosis injection.

[Total arterial myocardial revascularization with both mammary arteries without extracorporeal circulation]. / Revascularización miocárdica arterial completa con ambas arterias mamarias sin circulación extracorpórea.

INTRODUCTION: Tector has described the off-pump total arterial revascularization technique, using multiple anastomosis with both internal thoracic arteries. To reduce surgical morbid-mortality, we have proposed the use of this technique without extracorporeal circulation. PATIENTS AND METHODS: From April, 1998 the off-pump <> technique was performed in 92 patients, 74 male (80%) and 18 female (20%), with a mean age of 64.9+/-8.1 years (42-78). Preoperative angiography demonstrated triple-vessel disease in 58 (63%) patients, and left main disease was present in 19 (20.5%) patients. Forty patients (43.5%) showed unstable angina, 24 patients (26%) significant peripheral vascular disease, and 26 (28%) diabetes mellitus. Both internal thoracic arteries were harvested using the skeletonization technique and were used like a <> graft. The flow in the graft was measured using a flowmeter, and in 24 (26%) patients by angiographic study. RESULTS: A total of 274 distal anastomoses were performed, 122 (44.6%) in the lateral or inferior wall, and 69 (25.2%) were sequential, with an average of 2.98 bypass/patient. In 59.8% of the patients a triple bypass was performed, 22% double bypass, 17% cuadruple bypass and 1 patient a quintuple bypass. During the initial six hours 64.9% of patients were extubated. Only one patient (1.1%) needed intraaortic ballon pumping and 3 (3.2%) inotropics during the postoperative course. Hospital mortality was 3 (3.2%) patients. Reoperation for bleeding was needed in just one patient (1.1%), and 78.3% of patients were not transfused. Mediastinitis occurred in 3 patients (3.2%). Postoperative stroke was not observed. At 7.7+/-2.8 months of mean follow-up all patients were free of symptoms and the global patency rate of 94%. CONCLUSIONS: Off-pump Tector technique appears to be safe, offering a complete arterial revascularization and showing a reduction of surgical morbidity.

Absence of enteroviral RNA in hearts explanted from patients with dilated cardiomyopathy.

BACKGROUND: The role of enterovirus infection in the pathogenesis of dilated cardiomyopathy (DCM) remains unclear. The objective of this study was to determine the prevalence of enterovirus in hearts explanted from patients with DCM and to compare it with enterovirus prevalence in hearts explanted from patients with other etiologies and in healthy donor hearts. METHODS: A total of 138 cardiac samples were analyzed, 70 from heart donors and 68 from transplant recipients (22 with DCM). A highly sensitive enterovirus-specific nested RT-PCR was used to test for enterovirus. RESULTS: All tests were negative except for one positive result that was attributed to carryover because sequencing of the amplification product showed it to be identical to the positive control. CONCLUSIONS: In this study the sample of explanted hearts nested RT-PCR showed no evidence of the presence of enteroviral RNA. This suggests that if enterovirus had a role in the genesis of DCM, it does not require or lead to the persistence of the virus in myocardial tissue.

A simple technique to perform combined ultrafiltration.

To combine the advantages of conventional and modified ultrafiltration while keeping cardiopulmonary bypass technique simple, we have developed a simplified circuit of combined ultrafiltration, which is presently used in our pediatric patients. In addition to the benefits of combined ultrafiltration, this circuit allows the rewarming and prevention of heat loss in small children and neonates.

Endosonography in the diagnosis of "blue rubber bleb nevus syndrome": an uncommon cause of gastrointestinal tract bleeding.

Blue rubber bleb nevus syndrome is a rare condition characterized by the presence of multiple angiomatic lesions of the skin. These are associated with similar lesions in other organs, namely in the gastrointestinal tract, causing anemia through chronic bleeding. We describe the case of a 72-year-old woman with microcytic anemia. A barium study revealed irregular lacunae in the distal esophagus. A subsequent endoscopy showed blue nodular lesions similar to angiomas of the esophagus and stomach fundus. Endosonography confirmed its angiomatic nature. Exploration of other organs, using magnetic resonance and cranial computed tomography, did not reveal the presence of this type of lesion. In physical examination, two angiomatic lesions were observed on the face and lips, respectively. These were blue in color and compressible, leaving an empty wrinkled sac that rapidly refilled, typical of angiomas.

[Combined perioperative ultrafiltration in pediatric cardiac surgery. The preliminary results]. / Ultrafiltración combinada perioperatoria en cirugía cardíaca pediátrica. Resultados preliminares.

INTRODUCTION AND OBJECTIVES: Recently, ultrafiltration techniques are used more and more as a treatment for the inflammatory response of cardiopulmonary bypass. It also provides fine control of fluids. The purpose of this study is to present a technique which combines conventional and modified ultrafiltration and to analyze the obtained results. PATIENTS AND METHODS: 22 patients (mean weight 13.1 +/- 8.4 kg) operated on cardiopulmonary bypass. Combined ultrafiltration was performed during cardiopulmonary bypass (conventional) and after pump (modified ultrafiltration). We analyzed cardiopulmonary bypass variables, the first 24-hour hemodynamics, biological variables (arterial blood gases, cell counts, IL-6, adhesion molecules ICAM-1 and VCAM-1, and coagulation profiles). RESULTS: A total amount of 1,399 +/- 680 ml/m2 of mean combined ultrafiltrate volume was obtained (657 +/- 386 ml/m2 during cardiopulmonary bypass and 845 +/- 358 ml/m2 post-cardiopulmonary bypass). After modified ultrafiltration, hematocrit rose from 23 +/- 2.3 to 32 +/- 4.1, arterial systolic blood pressure rose from 74 +/- 13 to 98 +/- 20 mmHg, heart rate decreased from 133 +/- 22 to 126 +/- 23 bpm, and central versus pressure did not change. A statistically significant relationship (multivariable), was shown between modified ultrafiltration time and VCAM-1 post-ultrafiltration levels. Platelet count was lower and diuresis rose related to cardiopulmonary bypass ultrafiltration volume and diuresis increased. CONCLUSIONS: Perioperative combined ultrafiltration is feasible without undue morbidity and provides adequate hemoconcentration and excellent postoperative hemodynamic results. More studies with control groups are necessary to better define the therapeutic influence in antiinflammatory properties of this technique.

Is the femoral cannulation for minimally invasive aortic valve replacement necessary?

INTRODUCTION: Minimally invasive cardiac surgery through a small transverse sternotomy is a new promising technique that can be considered an alternative in most cases to aortic valve replacement thus reducing surgical trauma and subsequent time of hospitalization. The need to avoid the risks associated with femoro-femoral bypass has lead to the interest in aortic valve replacement (AVR) operations without femoral vessels cannulation. We want to emphasize a few important points of our technique, which differs somewhat from the one applied by Cosgrove and associates. OBJECTIVE: This study details the approach to the minimally invasive AVR as first described by. Cosgrove et al. without standard femoral cannulation and points out our preliminary clinical experience. PATIENTS AND METHODS: From October 1996 to May 1997 we have operated on 25 patients using minimally invasive AVR (MI-AVR) In 23 cases, access through transverse sternotomy as described by Cosgrove et al., was performed. In two additional cases the chest is opened via a mini-median sternotomy with an 'L'-shape extending from the sternal notch to the superior edge of the third interspace. Twenty-three patients underwent AVR through transverse sternotomy. The male/female ratio was 13:10. The mean age was 67 years (range 45-78 years). Seventy-four percent of the patients were over 65. Predominantly, in 43% of cases aortic valve stenosis and in 25% of cases aortic valve regurgitation isolated is presented. In 19 cases, a 10-cm transverse incision is performed over the second interspace. Likewise, in four cases over the third interspace according to the thorax morphology and length of the ascending aorta assessed by chest X-ray films. By convention, cannulation of the ascending aorta and right atrial appendage was performed as usual. In contrast, in one patient (5.5%), cannulation was placed in the superior vena cava and right common femoral vein into the inferior vena cava. In the present series, 15 mechanical prostheses and eight bioprostheses whose used sizes were 19, 21,23, and 25 mm in diameter were placed in four, nine, nine, and one of the cases, respectively. All patients underwent AVR electively and a transesophageal echocardiography probe is made. RESULTS: During surgery, conversion to median sternotomy was not required in any patient. Mean aortic cross-clamp time was 68 min (range 38-90 min). Mean total bypass time was 87 min (range 50-120 min). Mean postoperative bleeding was 434 ml. (range 200-850 ml). Perioperative blood transfusion was required in 17% of the patients. Mean mechanical ventilation time was 7.3 h (range 3-24 h), with a mean ICU stay of 18 h. Mean postoperative hospital stay was 4.5 days (range 3-10 days). In all cases, transthoracic and transesophageal echocardiography were performed postoperatively Prosthetic valve dysfunction was not observed. On the other hand, just one patient (4%) died 5 days after operation due to sudden cardiac death. Further, in two patients (8%), during follow-up, pericardial effusion is detected. In one case, cardiac tamponade with hemodynamic instability required a pericardial window procedure. In addition, in two patients (8%), non-infectious sternal dehiscence required reinforced sternal closure. CONCLUSIONS: Minimally invasive AVR surgery without femoral vessel cannulation is a safe procedure with less surgical aggression. After a learning curve, benefits on fast-track programs will be accomplished.

Chylous ascites following heart transplantation.

We report a case of chylous ascites in a 52-year-old woman after an orthotopic heart transplantation. The patient was successfully managed with conservative treatment including dietetic measures and repeated paracentesis. The potential aetiopathological factors involved and other implications for cardiac transplant patients are discussed.