The effects of transdermal rotigotine on non-motor symptoms of Parkinson's disease: a multicentre, observational, retrospective, post-marketing study.

AIM: This study evaluated the effect of ≥6 months of transdermal rotigotine on non-motor and motor symptoms of patients with advanced Parkinson's disease. MATERIALS AND METHODS: The study was conducted in Spain between September 2011 and December 2012 (ClinicalTrials.gov: NCT01504529). The primary efficacy variable was the change from baseline in non-motor symptoms, as assessed by changes in Parkinson's Disease Non-Motor Symptoms Questionnaire total scores at 6 months. Secondary endpoints included the assessment of motor symptoms by Unified Parkinson's Disease Rating Scale III scores. RESULTS: Data from 378 patients (mean age: 70.2 years; 56.9% male) with Parkinson's disease receiving rotigotine from were collected. Mean disease duration was 6.1 years, and mean rotigotine treatment duration was 45.6 months. Rotigotine reduced non-motor symptoms by 14.6% (mean change from baseline in Parkinson's Disease Non-Motor Symptoms Questionnaire: -1.5 ± 3.4; p < 0.0001). The majority of patients (58.2%) had improved non-motor symptoms at 6 months. Comparing the baseline versus study end, fewer patients experienced events in the urinary (78.6% vs. 73.3%; p = 0.0066), sleep (82.8% vs. 72.8%; p < 0.0001) and mood/cognition (77.3% vs. 66.4%; p < 0.0001) domains of the Parkinson's Disease Non-Motor Symptoms Questionnaire. Mean motor symptoms were reduced from baseline by 8.0% (mean change from baseline in Unified Parkinson's Disease Rating Scale III: -2.6 ± 8.0; p < 0.0001). CONCLUSIONS: In clinical practice in Spain, rotigotine may be an effective treatment to reduce the non-motor and motor symptoms in patients with advanced Parkinson's disease.

Assessment of late cardiomyopathy by magnetic resonance imaging in patients with acute promyelocytic leukaemia treated with all-trans retinoic acid and idarubicin.

Late cardiomyopathy CMP is regarded as a potential severe long-term complication after anthracycline-based regimens for acute promyelocitic leukaemia (APL). We assess by MRI the incidence and severity of clinical and subclinical long-term CMP in a cohort of adult APL patients in first complete remission with PETHEMA trials. Adult patients diagnosed with APL in first complete remission lasting ≥2 years underwent anamnesis and physical examination and were asked to perform a cardiac MRI. Clinical CMP was defined as radiographic and physical signs of heart failure accompanied by symptoms or by left ventricle ejection fraction (LVEF) <45% by MRI with or without symptoms. Subclinical CMP was defined as the following MRI abnormalities: LVEF 45-50% or late gadolinium enhancement or two or more of LVEF ≤55%, left ventricle end-diastolic volume index ≥98 ml/m2, left ventricle end-systolic volume index ≥38 ml/m2, right ventricle end-diastolic volume index ≥106 ml/m2 and regional wall motion abnormalities. Of the 82 patients enrolled in the study, median cumulative dose of anthracyclines (doxorubicin equivalence) was 650 mg/m2, and median time from APL diagnosis to the study was 87 months (range, 24-195). Seven out of 57 patients with available MRI (12%) had subclinical CMP (all of them showed late gadolinium enhancement in MRI), and none had clinical CMP. Among the 25 patients without MRI, none had CMP by chest X-ray and physical assessment. In summary, we found 12% of subclinical and no clinical late CMP assessed by MRI in APL patients treated with PETHEMA protocols. Due to the low number of patients, we must interpret our results cautiously.

The use of multisite left ventricular pacing via quadripolar lead improves acute haemodynamics and mechanical dyssynchrony assessed by radial strain speckle tracking: initial results.

AIMS: The objective of the present study was to evaluate the effect of multipoint pacing (MPP) on acute haemodynamics, cardiac contractility, and left ventricle (LV) dyssynchrony, in comparison with conventional cardiac resynchronization therapy (CRT). METHODS AND RESULTS: An open-label, non-randomized, single-centre, prospective study was designed. Twenty-seven consecutive patients were included. Evaluation of pacing configurations was performed in a random order. Transthoracic echocardiography was used to obtain haemodynamic and dyssynchrony parameters. Left ventricular ejection fraction (LVEF) was significantly superior in MPP compared with baseline (38.4 ± 1.8% vs. 26.1 ± 2.2%; P < 0.001), and in conventional pacing configuration compared with baseline (33.2 ± 1.8% vs. 26.1 ± 2.2%; P = 0.007). Cardiac index (CI) was increased by 21.8 ± 5.4% and 34.7 ± 5.1% in conventional and MPP configurations, respectively (P = 0.19). Percentage of acute responders (CI increase ≥10%) was 62.9 and 85.2% in conventional and MPP, respectively (P < 0.001). LV dyssynchrony was defined by radial strain rate parameters. Baseline anteroseptal-to-posterior wall time delay was 168 ± 21 ms. It was reduced until 70.4 ± 29 ms in conventional and -6.6 ± 11 ms in MPP (conventional vs. baseline P = 0.04; MPP vs. conventional P = 0.05). Standard deviation of the time-to-peak radial strain of the 6 LV basal segments was 101 ± 9.7, 80.3 ± 9.2, and 66 ± 8.03 ms in baseline, conventional, and MPP configurations, respectively (MPP vs. basal P = 0.012). Finally, we observed a positive correlation (r = 0.69) between reduction in dyssynchrony and CI increase (P < 0.0001). CONCLUSION: MPP showed a further reduction in LV dyssynchrony compared with conventional biventricular pacing. Moreover, MPP resulted in an additional improvement in LVEF and in CI, and this was translated into a higher number of acute responders to CRT.

Surgical treatment of acute diverticulitis. A retrospective multicentre study. / Tratamiento quirúrgico de la diverticulitis aguda. Estudio retrospectivo multicéntrico.

INTRODUCTION: To analyze short and medium-term results of different surgical techniques in the treatment of complicated acute diverticulitis (CAD). METHODS: Multicentre retrospective study including patients operated on as surgical emergency or deferred-urgency with the diagnosis of CAD. RESULTS: A series of 385 patients: 218 men and 167 women, mean age 64.4±15.6 years, operated on in 10 hospitals were included. The median (25th-75th percentile) time from symptoms to surgery was 48 (24-72) h, being peritonitis the main surgical indication in a 66% of cases. Surgical approach was usually open (95.1%), and the commonest findings, a purulent peritonitis (34.8%) or pericolonic abscess (28.6%). Hartmann procedure (HP) was the most used technique in 278 (72.2%) patients, followed by resection and primary anastomosis (RPA) in 69 (17.9%). The overall postoperative morbidity and mortality was 53.2% and 13% respectively. Age, immunosupression, presence of general risk factors and faecal peritonitis were associated with increased mortality. Laparoscopic peritoneal lavage (LPL) was associated with an increased reoperation rate frequently involving a stoma, and anastomotic leaks presented in 13.7 patients after RPA, without differences in morbimortality when compared with HP. Median postoperative length of stay was 12 days, and was correlated with age, surgical risk, ASA score, hospital and postoperative complications. CONCLUSIONS: Surgery for CAD has important morbidity and mortality and is frequently associated with an end-stoma. Moreover LPL presented high reoperation rates. It seems better to resect and anastomose in most cases, even with an associated protective stoma.

ATP synthase subunit alpha and LV mass in ischaemic human hearts.

Mitochondrial dysfunction plays a critical role in the development of ischaemic cardiomyopathy (ICM). In this study, the mitochondrial proteome in the cardiac tissue of ICM patients was analysed by quantitative differential electrophoresis (2D-DIGE) and mass spectrometry (MS) for the first time to provide new insights into cardiac dysfunction in this cardiomyopathy. We isolated mitochondria from LV samples of explanted hearts of ICM patients (n = 8) and control donors (n = 8) and used a proteomic approach to investigate the variations in mitochondrial protein expression. We found that most of the altered proteins were involved in cardiac energy metabolism (82%). We focused on ATPA, which is involved in energy production, and dihydrolipoyl dehydrogenase, implicated in substrate utilization, and observed that these molecules were overexpressed and that the changes detected in the processes mediated by these proteins were closely related. Notably, we found that ATPA overexpression was associated with reduction in LV mass (r = -0.74, P < 0.01). We also found a substantial increase in the expression of elongation factor Tu, a molecule implicated in protein synthesis, and PRDX3, involved in the stress response. All of these changes were validated using classical techniques and by using novel and precise selected reaction monitoring analysis and an RNA sequencing approach, with the total heart samples being increased to 24. This study provides key insights that enhance our understanding of the cellular mechanisms related to the pathophysiology of ICM and could lead to the development of aetiology-specific heart failure therapies. ATPA could serve as a molecular target suitable for new therapeutic interventions.

Initial Experience with a New Image Integration Module Designed for Reducing Radiation Exposure During Electrophysiological Ablation Procedures.

INTRODUCTION: Reduction of radiation exposure during cardiac arrhythmia ablation procedures is desirable. We sought to evaluate the utility of a new image integration module (CARTOUNIVU(TM) ) in reducing fluoroscopy times and dosages during left atrial arrhythmia (LAA) and ventricular tachycardia (VT) ablation procedures. METHODS AND RESULTS: Consecutive patients undergoing LAA (n = 28)/VT (n = 13) ablation using the CARTOUNIVU(TM) module were included. Total fluoroscopy time, radiation dose (total dose area product [tDAP], effective dose [ED]), and procedure duration were evaluated. A retrospective cohort of patients who underwent LAA (n = 16)/VT(n = 8) ablation without the new image integration module served as a control group. The use of the new image integration module significantly reduced mean fluoroscopy time (5.2 minutes [IQR 1.9;6.8] in the LAA ablation UNIVU group vs. 28.2 minutes [IQR 15.3;37.8] in the control group, P<0.001; 9.8 minutes [IQR 4.5;13.1] vs. 25.5 minutes [IQR 14.1;30.9] for VT ablation, P = 0.013), tDAP (2,088 cGy*cm(2) [IQR 664;2911] vs. 5,893 cGy*cm(2) [IQR 3088;8483], P< 0.001 for LAA ablation; 3,917 cGy*cm(2) [IQR 948;4217] vs. 12,377 cGy*cm(2) (IQR 3385;23157) for VT ablation patients, P = 0.025) and ED (4.1 mSv [IQR 1;5.8] vs. 11.8 mSv [IQR 6.2;16.9] for LAA ablation patients, P< 0.001; 7.8 mSv [IQR 1.9;8.4] vs. 24.7 mSv [IQR 6.8;46.3] for VT ablation patients, P = 0.025). Procedure duration did not significantly change (174 ± 45 minutes vs. 197 ± 36 minutes for LAA ablation, P = 0.083; 201 ± 51 minutes vs. 201 ± 63 minutes for VT ablation, P = 0.860). No serious adverse events related to the use of the CARTOUNIVU(TM) module occurred. CONCLUSIONS: The new image integration module significantly reduced total fluoroscopy time and mean radiation dose without influence in procedure duration during ablation of complex atrial and ventricular arrhythmias.

Systematic Implantation of Pacemaker/ICDs under Active Oral Anticoagulation Irrespective of Patient's Individual Preoperative Thromboembolic Risk.

BACKGROUND: A wide variability in the perioperative management of oral anticoagulation (OAC) has been documented in patients receiving cardiac rhythm management devices (CRMDs). We sought to evaluate the safety and feasibility of a new perioperative strategy consisting in systematically continuing OAC in all patients irrespective of their individual thromboembolic (TE) risk. METHODS: A total of 278 consecutive patients on chronic OAC receiving CRMDs were prospectively included. Patients were classified in high and low TE risk according to current guidelines for the perioperative management of antithrombotic therapy, but underwent implantation under active OAC (international normalized ratio 2-4) irrespective of their preoperative TE risk. Bleeding and TE complications were evaluated as well as other procedure-related complications, hospital stays, and the feasibility of outpatient implantations. RESULTS: A total of 117 patients were considered at high TE risk and 161 at low TE risk. Overall, the incidence of pocket hematoma was 2.9% with only three patients requiring pocket revision. Low TE risk patients had a very low incidence of pocket hematoma (1.9%) without needing pocket revision. The mean hospital stay was 1.17 ± 1.8 days and 169 patients (61%) received their CRMD in an outpatient basis, including 77 patients who were implanted with an implantable cardioverter defibrillator. No TE events were detected during the 30-day postimplant observation period in any patient. No other significant complications related with the implant (pneumothorax, hemothorax, cardiac tamponade) were registered. CONCLUSIONS: Systematic continuation of OAC in all patients undergoing implantation of CRMDs is safe and feasible, thus simplifying and standardizing the perioperative management in this setting.

Metabolic syndrome in heart transplantation: impact on survival and renal function.

The aim of our study was to analyze the early presence of metabolic syndrome (MS) in heart transplant (HTx) patients, and to assess its long-term impact on survival and renal function. From January 2000 to October 2011, 253 consecutive HTx patients who survived more than 90 days were included. MS was diagnosed if patients met revised NCEP-ATP III criteria at HTx or within 3 months post-HTx. The prevalence of MS was 41.9%. Patients with MS had greater overall mortality after a mean follow-up of 1700 ± 979 days (log-rank test, P = 0.020). In the multivariate analysis, and subject to a minimum survival of 90 days, the only independent predictor variables of long-term mortality were the presence of MS (OR, odds ratio 2.087, P = 0.032), and rejection episodes (OR 1.833, P = 0.001). Patients with MS had worse renal function at baseline both in plasma creatinine (1.19 ± 0.44 vs. 1.03 ± 0.29 mg/dl, P = 0.002) and glomerular filtration rate estimated by modified diet in renal disease (73.60 ± 26.76 vs. 87.30 ± 43.55 ml/min/1.73 m(2) , P = 0.005), whereas progressive impairment of renal function was of equal magnitude in both groups. The presence of MS prior to transplant or its development within the first 3 months identified a subgroup at greater risk of mortality and long-term renal dysfunction.

A new mixed reality tool for training in minimally invasive robotic-assisted surgery.

Robotic-assisted surgery (RAS) is developing an increasing role in surgical practice. Therefore, it is of the utmost importance to introduce this paradigm into surgical training programs. However, the steep learning curve of RAS remains a problem that hinders the development and widespread use of this surgical paradigm. For this reason, it is important to be able to train surgeons in the use of RAS procedures. RAS involves distinctive features that makes its learning different to other minimally invasive surgical procedures. One of these features is that the surgeons operate using a stereoscopic console. Therefore, it is necessary to perform RAS training stereoscopically. This article presents a mixed-reality (MR) tool for the stereoscopic visualization, annotation and collaborative display of RAS surgical procedures. The tool is an MR application because it can display real stereoscopic content and augment it with virtual elements (annotations) properly registered in 3D and tracked over time. This new tool allows the registration of surgical procedures, teachers (experts) and students (trainees), so that the teacher can share a set of videos with their students, annotate them with virtual information and use a shared virtual pointer with the students. The students can visualize the videos within a web environment using their personal mobile phones or a desktop stereo system. The use of the tool has been assessed by a group of 15 surgeons during a robotic-surgery master's course. The results show that surgeons consider that this tool can be very useful in RAS training.

Preparation of Volborthite by a Facile Synthetic Chemical Solvent Extraction Method.

In this work, the extraction of vanadium (V) ions from an alkaline solution using a commercial quaternary ammonium salt and the production of metal vanadates through precipitation stripping were carried out. The crystallization of copper vanadates from the extracts was performed using a solution containing a copper(II) source in concentrated chloride media as a stripping agent. In an attempt to control growth, a stabilizing polymer (polyvinylpyrrolidone, PVP) was added to the stripping solution. The structural characteristics of the crystallized products, mainly copper pyrovanadate (volborthite, Cu3V2O7(OH)2·(H2O)2) nanoflakes and nanoflowers and the experimental parameter influencing the efficiency of the stripping process were studied. From the results, the synthesis of nanostructured vanadates is a simple and versatile method for the fabrication of valuable three-dimensional structures providing abundant active zones for energy and catalytic applications.

Influence of heart failure on nucleolar organization and protein expression in human hearts.

We investigate for the first time the influence of heart failure (HF) on nucleolar organization and proteins in patients with ischemic (ICM) or dilated cardiomyopathy (DCM). A total of 71 human hearts from ICM (n=38) and DCM (n=27) patients, undergoing heart transplantation and control donors (n=6), were analysed by western-blotting, RT-PCR and cell biology methods. When we compared protein levels according to HF etiology, nucleolin was increased in both ICM (117%, p<0.05) and DCM (141%, p<0.01). Moreover, mRNA expression were also upregulated in ICM (1.46-fold, p<0.05) and DCM (1.70-fold, p<0.05. Immunofluorescence studies showed that the highest intensity of nucleolin was into nucleolus (p<0.0001), and it was increased in pathological hearts (p<0.0001). Ultrastructure analysis by electron microscopy showed an increase in the nucleus and nucleolus size in ICM (17%, p<0.05 and 131%, p<0.001) and DCM (56%, p<0.01 and 69%, p<0.01). Nucleolar organization was influenced by HF irrespective of etiology, increasing fibrillar centers (p<0.001), perinucleolar chromatin (p<0.01) and dense fibrillar components (p<0.01). Finally, left ventricular function parameters were related with nucleolin levels in ischemic hearts (p<0.0001). The present study demonstrates that HF influences on morphology and organization of nucleolar components, revealing changes in the expression and in the levels of nucleolin protein.

Myocardial G protein receptor-coupled kinase expression correlates with functional parameters and clinical severity in advanced heart failure.

BACKGROUND: In heart failure (HF), sympathetic hyperactivation induces deleterious effects in myocardial ß-adrenergic signaling, with receptor down-regulation and desensitization mediated by G protein receptor-coupled kinases (GRKs). We hypothesised that changes in GRK isoforms may be associated with clinical status in advanced HF, using the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) scale. METHODS: We included 31 patients with advanced HF undergoing transplantation. According to INTERMACS profiles, mRNA and protein levels of GRK isoforms in left ventricular (LV) myocardium were analyzed and compared with nonfailing LV samples. RESULTS: In failing LV myocardium, GRK2 and GRK5 (but not GRK3) protein was up-regulated compared with control samples. Among HF patients, an increase in GRK2 and GRK5 mRNA and protein abundance was observed in ß-agonist-treated patients (vs ß-blockers: P < .05) and in higher-risk INTERMACS status (profiles 2 and 3 vs 4 and 5: P < .05). A significant negative correlation of GRK2 expression with LV stroke volume supported these findings. CONCLUSIONS: Increased GRK2 correlates with clinical severity using the INTERMACS scale and LV stroke volume, supporting it as a potential target in advanced HF. These changes are paralleled by GRK5 expression in the failing myocardium, suggesting a relevant role in human HF.

Morbidity associated with three different antiplatelet regimens in patients undergoing implantation of cardiac rhythm management devices.

AIMS: Perioperative management of antiplatelet (AP) therapy in patients undergoing implantation of cardiac rhythm management devices (CRMD) remains an issue of concern that has not been prospectively evaluated in a large series. We sought to describe the morbidity associated with three different AP regimens in this setting. METHODS AND RESULTS: We conducted a prospective observational study including 849 consecutive patients who were classified in three groups according to the presence of any AP treatment: Group 1 (n= 220): single AP therapy; Group 2 (n= 60): dual AP therapy; and Group 3 (n= 40): oral anticoagulant (OAC) + enoxaparin 'bridging' + AP therapy. Two other groups served as controls: Group 4 (n= 375): no AP or OAC therapy; and Group 5 (n= 154): OAC + enoxaparin 'bridging'. The incidence of pocket haematoma, pocket revisions, hospital stays duration, and unscheduled follow-up visits due to pocket-related complications were compared. Patients on Groups 2, 3 and 5 had significantly higher incidences of pocket haematoma (13.3, 15, and 14.9%, respectively) when compared with Groups 1 and 4 (3.2 and 2.4%, respectively), as well as longer hospital stays and more unscheduled follow-up visits. Of note, only patients on enoxaparin 'bridging' required surgical revision of the pocket. Dual AP therapy (P< 0.001), enoxaparin 'bridging' (P< 0.001) and renal insufficiency (P= 0.02) were independent predictors of pocket haematoma in multivariate analysis. CONCLUSION: Dual AP therapy and OAC + AP therapy is strongly associated with a significant risk of pocket haematoma, longer hospital stays, and unscheduled follow-up visits. Importantly, surgical revision of the pocket was associated with enoxaparin 'bridging' strategy but was never necessary in patients taking exclusively antiaggregant agents.

Cardiac magnetic resonance imaging at 1.5 T in patients with cardiac rhythm devices.

AIMS: Recent studies suggest that non-cardiac magnetic resonance imaging (MRI) scanning can be performed safely in selected cardiac rhythm device patients. However, little is known about the safety of performing specific cardiac MRI in this setting. We sought to determine the feasibility of cardiac MRI in patients with pacemakers (PMs) or implantable cardioverter-defibrillators (ICDs). METHODS AND RESULTS: Thirty-eight patients underwent a total of 39 (8 ICDs and 31 PM) cardiac MRI examinations at 1.5 T using usual protocols without specific absorption rate (SAR) restrictions. Nine PM-dependent patients were included. All devices were interrogated before and immediately after MRI. During the scan, pacing mode was programmed to asynchronous for PM-dependent patients whereas ICDs were programmed to a monitor-only mode. All devices were functioning appropriately after cardiac MRI. Comparison of device parameters obtained before and immediately after MRI revealed no significant changes in pacing threshold, lead impedance, battery status, or sensing signal amplitude. Neither clinical events nor patient complaints were reported. Significant imaging artefacts were present on 11 of 39 scans (28.2%). These artefacts were significantly more frequent in ICDs (8 of 8, 100%) vs. PMs (3 of 31, 9.7%) (P < 0.001). Diagnostic questions were answered in 92.3% of the cases, with just three pronounced artefacts preventing an adequate diagnosis in three ICD patients. CONCLUSIONS: Our results suggest that cardiac MRI may be performed safely in appropriately selected patients with close monitoring during the scan without limitation of peak SAR level using several precautionary measures. Image artefacts were more frequent in ICD patients.

Failure of the active-fixation mechanism during removal of active-fixation pacing leads.

BACKGROUND: Active-fixation pacing leads are being widely employed due to their theoretical advantages when compared with traditional passive-fixation leads: easy fixation and reposition, possible deployment in alternative pacing sites, lower rates of dislodgment, and chronic removability. However, the behavior of the active-fixation mechanism during lead removal has not been yet systematically studied and may have important clinical implications. OBJECTIVE: To evaluate if the active-fixation mechanism was still working properly in pacing leads that were removed due to different causes. METHODS: Thirty-one consecutive patients undergoing active-fixation lead removal (40 leads) were studied. Before lead removal, the helix was retracted using the appropriate tool, and fluoroscopy signs were evaluated. After removal, the helix status was examined, and the active-fixation mechanism was once again retested when possible. RESULTS: In nine of 40 leads (22.5%), the helix remained extended after lead removal in spite of having applied the number of rotations recommended by the manufacturer with the clip-on tool. There was no linear relationship between lead longevity and the presence of an extended helix after lead removal. However, failure of the active-fixation mechanism was more frequent among leads implanted <1 year before versus >1 year before (OR 6.8, 95% CI 1.1-42.7, P = 0.043). In 38% of patients with failure of the active-fixation mechanism, a previous lead reposition had been attempted before lead removal due to significant pacing threshold rise. CONCLUSIONS: In our series, the active-fixation mechanism failed in up to 22.5% of explanted leads. This may have important clinical implications during active-fixation lead removal and reposition.

[Selective intestinal preparation in a multimodal rehabilitation program. Influence on preoperative comfort and the results after colorectal surgery]. / Preparación intestinal selectiva en un programa de rehabilitación multimodal. Influencia en el confort preoperatorio y resultados tras cirugía colorrectal.

INTRODUCTION: Despite there being no evidence of the advantages of its use, mechanical bowel preparation (MBP) continues to be routine in colorectal surgery. Our objective is to analyse the impact of its selective use, as regards patient comfort and results, comparing a perioperative multimodal rehabilitation program (MMRH) with conventional care (CC). MATERIAL AND METHODS: A prospective study of 108 patients proposed for elective surgery, assigned consecutively 2:1 to an MMRH protocol which only included MBP in rectal surgery with low anastomosis, or to CC in whom MBP was used except in right colon surgery. We also studied two Groups (A and B) with and without the use of MBP. Their tolerance, results and postoperative recovery variables were analysed. RESULTS: Thirty-nine patients were included in Group A, and 69 in Group B. A MMRH protocol was used in another 69 patients. The Group A patients had more abdominal pain, anal discomfort, nausea and thirst, but there were no differences as regards, death, overall or local complications, whilst there was less complications, suture failures and death in the MMRH when compared with CC Group (P<.05). There were no advantages observed in the use of MBP as regards the start of bowel movements, tolerance to diet or hospital stay, but these parameters were favourable to the MMRH when compared with CC Group. CONCLUSIONS: The restriction of MBP is safe, and associated with an MMRH program, contributes to a faster and more comfortable recovery, without increasing complications.

Influence of Genetic Polymorphisms on Response to Biologics in Moderate-to-Severe Psoriasis.

Psoriasis is a chronic inflammatory skin pathology of autoimmune origin and unknown etiology. There are various therapies for treating it, including a wide range of biopharmaceuticals indicated in moderate-to-severe psoriasis. Depending on their therapeutic target, they are classified as tumor necrosis factor inhibitors (anti-TNF) or cytokine inhibitors (interleukin-12, 23, and 17 antagonists). Although they have proved effective and safe, in clinical practice, many patients show a short- and long-term suboptimal response and even varying degrees of toxicity. This variability in response may be influenced by genetic factors, such as polymorphisms in the genes involved in the pathological environment, metabolism or mechanism of action of the drug that could affect the effectiveness and toxicity of biological therapies. This review assesses pharmacogenetic studies of the impact of genetic factors on response to biopharmaceuticals and toxicity in patients diagnosed with moderate-to-severe psoriasis. The results suggest that polymorphisms detected in the HLA genes, in genes that encode cytokines (TNF, IL genes, TNFAIP3), transporters (PDE3A-SLCO1C1, SLC12A8), receptors (TNFRSF1B, CD84, FCGR2A and FCGR3A, IL17RA, IL23R, TLR genes, PGLYRP4) and associated proteins (TNFAIP3, LY96, TIRAP, FBXL19), as well as other genes implicated in the pathogenesis of psoriasis (CDKAL1, CARD14, PTTG1, MAP3K1, ZNF816A, GBP6, CTNNA2, HTR2A, CTLA4, TAP1) can be used in the future as predictive markers of treatment response and/or toxicity with biological therapies in patients diagnosed with moderate-to-severe psoriasis, tailoring treatment to the individual patient.

Advanced systemic amyloidosis secondary to metastatic renal cell carcinoma.

Secondary amyloidosis is a rare complex complication related to chronic inflammatory disease. This complication is sparsely associated to malignant neoplasms. Renal cell carcinoma (RCC) is the most common solid organ malignancy related with this paraneoplastic syndrome. Some case reports have described stabilisation or even remission of amyloidosis with cytoreductive nephrectomy. Majority of those reports were based on locally advanced RCC. We report the first case of early aggressive systemic secondary amyloidosis in high-volume metastatic RCC. The subject was diagnosed with metastatic RCC within 6 months of secondary amyloidosis; on month 5 of initiation of targeted therapy (pazopanib) developed nephrotic syndrome with a heavy proteinuria (>18 g/day), severe hypoalbuminaemia (1.53 g/dL), intense and progressive oedema, severe pancolitis and mild dyspnoea with hypotension. A colon biopsy and the immunohistochemistry confirmed the histological diagnosis of a secondary amyloidosis. The multidisciplinary tumour board decided to perform cytoreductive nephrectomy in order to reduce the pro-inflammatory status. Pathology report showed a complete resection of clear cell RCC plus renal amyloid deposits. The patient died within 4 days of surgery due to multiorgan failure.

Hypertension and sleep apnea-hypopnea syndrome: changes in echocardiographic abnormalities depending on the presence of hypertension and treatment with CPAP.

INTRODUCTION: Sleep apnea-hypopnea syndrome (SAHS) is an emerging disease with high prevalence. There is controversy as to whether cardiac abnormalities are due to the disease itself or to the arterial hypertension frequently associated with this disease. OBJECTIVES: To analyze echocardiographic abnormalities in a population of SAHS patients depending on the presence or absence of hypertension at the time of diagnosis and after six months of treatment with continuous positive airway pressure (CPAP). METHODS: We studied 85 consecutive patients diagnosed with SAHS who required treatment with CPAP (Hypertensive: 43, nonhypertensive: 42). We performed a baseline echocardiogram after six months of treatment. We analyzed morphological (wall thickness, diameters, ejection fraction) and functional (peak E- and A-wave velocities, deceleration time, Tei index) parameters of the left and right ventricles. RESULTS: Hypertensive patients were older and had higher blood pressure values, but there were no differences between groups in other clinical parameters. The hypertensive group had greater septal thickness (hypertensive: 12.1+/-2.3; nonhypertensive: 10.8+/-2.1mm; p=0.01). There were also differences in impairment of left (hypertensiveHT: 92.9%, nonhypertensive: 65%, p=0.002) and right (hypertensive: 74.4%, nonhypertensive: 42.1%, p=0.006) ventricular filling. After six months of treatment, an improvement of the myocardial performance index was noted in nonhypertensive patients (baseline Tei: 0.55+/-0.1 vs. 6-month Tei: 0.49+/-0.1; p=0.01), whereas no significant change was observed in hypertensive patients. CONCLUSIONS: Cardiac abnormalities in SAHS patients are increased in the presence of associated hypertension. Treatment with CPAP for six months improves cardiac abnormalities in nonhypertensive patients but not in hypertensive patients.