Advanced endoscopic imaging methods for colon neoplasia

The main goal of lumenal endoscopic visualization of the colon is to detect mucosal pathologies, which when removed will result in cure or palliation of a disease process. Whereas traditionally endoscopic imaging was performed with fiber-optic technology, currently there are many new methods that improve our visual acuity when evaluating the colon mucosa. Most of these methods are collectively called 'advanced colonic imaging'. The 2 main aims of standard (white light) and advanced colonic imaging are to enhance the superficial mucosal detail (i.e. 'pit pattern') and allow a detailed view of the submucosal capillary pattern, thus potentially improving the detection characterization of pathological lesions. However, the current literature dealing with most methods used for advanced endoscopic imaging of the colon is fraught with many controversial findings which have resulted in opposing views regarding its utility. Whereas some investigators vehemently support the use of most of these methods in routine clinical practice, most experts and practicing endoscopists still refuse to accept that these methods aid in the clinical routine. For now, white light video-colonoscopy and high-definition white light video-colonoscopy will remain the standard endoscopic methods for investigating the colon mucosa until new methods convincingly and clearly prove their superiority over white light endoscopy.     

Nasogastric or nasointestinal feeding in severe acute pancreatitis

AIM:To assess the rate of spontaneous tube migration and to compare the effects of naso-gastric and nasointestinal(NI)(beyond the ligament of Treitz) feeding in severe acute pancreatitis(SAP).METHODS:After bedside intragastric insertion,tube position was assessed,and enteral nutrition(EN) started at day 4,irrespective of tube localization.Patients were monitored daily and clinical and laboratory parameters evaluated to compare the outcome of patients with nasogastric(NG) or NI tube.RESULTS:Spontaneous tube ...     

HCV carriers with normal alanine aminotransferase levels: Healthy persons or severely ill patients?: Dealing with an everyday clinical problem

Approximately 30% of patients with chronic HCV infection show persistently normal ALT levels. Although formerly referred to as ‘healthy’ or ‘asymptomatic’ HCV carriers, and thus historically excluded from antiviral treatment, it has now become clear that the majority of these patients have some degree of histological liver damage that may be significant in up to 20% of patients and might progress toward a more severe degree of liver fibrosis. A significant proportion of patients (≥ 20%) experience periods of increased serum ALT (flare) associated with enhanced disease progression. However, controversies still exist in clinical practice regarding the definition of ‘persistent’ ALT normality, the virological and histological features of these subjects, the need for liver biopsy, the role of non invasive tools for the assessment of liver fibrosis (transient hepatic elastography, fibroscan), and the natural history and optimal management of chronic hepatitis C with normal ALT. The advent of new therapeutic options (pegylated interferons plus ribavirin) has shifted treatment targets toward eradication of underlying infection, with therapy decision based on age, severity of disease and likelihood of response rather than on aminotransferase levels. This review does approach the main unresolved issues on this topic in the form of a dialog between a hepatologist and a patient with HCV infection but normal alanine aminotransferase levels, trying to give evidence-based answers to the more frequently asked questions from patients and their physicians.     

Deoxygenation affects tyrosine phosphoproteome of red cell membrane from patients with sickle cell disease

Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder related to the production of a defective form of hemoglobin, hemoglobin S (HbS). One of the hallmarks of SCD is the presence of dense, dehydrate highly adhesive sickle red blood cells (RBCs) that result from persistent membrane damage associated with HbS polymerization, abnormal activation of membrane cation transports and generation of distorted and rigid red cells with membrane perturbation and cytoskeleton dysfunction. Although modulation of phosphorylation state of the proteins from membrane and cytoskeleton networks has been proposed to participate in red cell homeostasis, much still remains to be investigated in normal and diseased red cells. Here, we report that tyrosine (Tyr-) phosphoproteome of sickle red cells was different from normal controls and was affected by deoxygenation. We found proteins, p55 and band 4.1, from the junctional complex, differently Tyr-phosphorylated in SCD RBCs compared to normal RBCs under normoxia and modulated by deoxygenation, while band 4.2 was similarly Tyr-phosphorylated in both conditions. In SCD RBCs we identified the phosphopeptides for protein 4.1R located in the protein FERM domain (Tyr-13) and for α-spectrin located near or in a linker region (Tyr-422 and Tyr-1498) involving protein areas crucial for their functions in the context of red cell membrane properties, suggesting that Tyr-phosphorylation may be part of the events involved in maintaining membrane mechanical stability in SCD red cells.     

Mitral valve reserve in double-orifice technique: an exercise echocardiographic study

BACKGROUND AND AIM OF THE STUDY: The edge-to-edge technique is used to restore valvular competence in mitral insufficiency. The efficacy of the method is under debate due to the potential for creating functional mitral stenosis. An exercise echocardiographic study was carried out to investigate valve function and hemodynamics in patients who had undergone double-orifice mitral valve repair. METHODS: Thirty patients (mean age 49.1 +/- 12.7 years) with previous double-orifice mitral valve repair underwent exercise echocardiography (10 W/min). An annular prosthesis was present in 28 patients (93%). The mean and maximum mitral valve gradient, planimetric valve area, stroke volume, systolic pulmonary artery pressure, heart rate and systolic blood pressure were measured at baseline and at peak stress. RESULTS: At peak stress, heart rate (77.7 +/- 12.2 versus 118.6 +/- 26.0 beats/min, p < 0.00001), systolic blood pressure (124.1 +/- 10.9 versus 146.6 +/- 22.8 mmHg, p < 0.00001) and stroke volume (78.0 +/- 10.2 versus 97.0 +/- 15.1 ml, p < 0.00001) were significantly increased, showing a physiological behavior of the mitral valve. The mean mitral valve gradient (2.8 +/- 1.3 versus 4.6 +/- 1.9 mmHg, p < 0.00001), maximum mitral valve gradient (6.4 +/- 2.8 versus 10.5 +/- 4.6 mmHg, p < 0.00002) and systolic pulmonary artery pressure (22.8 +/- 6.1 versus 28.2 +/- 9.9 mmHg, p < 0.001) were increased, but not to pathologic levels. Planimetric valve area increased significantly (3.2 +/- 0.6 versus 4.3 +/- 0.7 cm2, p < 0.00001). A significant negative linear correlation was found between the relative change in mitral valve area and planimetric valve area at rest (r = -0.51, p < 0.05). CONCLUSION: The double-orifice repair, even with concomitant ring annuloplasty, does not cause mitral valve obstruction, either at baseline or during physical exercise, and does not affect valve hemodynamic and valve reserve.     

<Emphasis Type="Italic">In vitro</Emphasis> evaluation of antibiotics' combinations for empirical therapy of suspected methicillin resistant <Emphasis Type="Italic">Staphylococcus aureus</Emphasis>severe respiratory infections

Background  

Methicillin resistant Staphylococcus aureus (MRSA) is an increasingly common cause of nosocomial infections, causing severe morbidity and mortality worldwide, and accounting in some hospitals for more than 50% of all S. aureus diseases. Treatment of infections caused by resistant bacterial pathogens mainly relies on two therapeutic modalities: development of new antimicrobials and use of combinations of available antibiotics.     

Methotrexate-induced mucositis in acute leukemia patients is not associated with the MTHFR 677T allele in Mexico

Methylenetetrahydrofolate reductase (MTHFR) has two common variants with reduced activity due to polymorphisms at nucleotides 677 and 1298. Both affect folate metabolism and thus remethylation of homocysteine, but are also thought to affect nucleotide synthesis and DNA methylation. Methotrexate (MTX), which interrupts folate metabolism, is used in the treatment of a variety of diseases including acute lymphoblastic leukemia (ALL), but exerts in some patients toxic effects on fast dividing tissues such as mucosal epithelia. The enhanced toxicity may be due to cooperative effects between MTX and MTHFR variants. Accordingly, it has been reported that carrying the 677T allele of the MTHFR is a risk factor for MTX-associated mucositis. As in the Mexican population, which is characterized by a high prevalence of the 677T MTHFR variant, several of its commonly associated defects have not been observed, we investigated the relationship between MTX toxicity and the 677T allele. Out of 28 patients with ALL (CC: 2, CT: 10, TT: 16), 16 had episodes of MTX-associated mucositis (CC: 0, CT: 6, TT: 10). Neither at the gene level nor at the genotype level was a significant association with mucositis found. It may be postulated that the risk of higher MTX toxicity in patients with decreased MTHFR activity could be neutralized by the normally folate rich diet in Mexico.     

A risk score for the management of pregnant women with increased risk of venous thromboembolism: a multicentre prospective study

Patients with thrombophilia and/or a history of venous thromboembolism (VTE) exhibit a high risk of thrombosis during pregnancy. The present multicentre study prospectively assessed a prophylaxis strategy, based on a risk score, in pregnancies with increased risk of VTE. Among 286 patients included in the study, 183 had a personal history of VTE (63·98%) and 191 patients (66·8%) had a thrombophilia marker. Eighty nine (46·6%) thrombophilic women had a personal history of VTE. Patients were assigned to one of three prophylaxis strategies according to the risk scoring system. In postpartum, all patients received low molecular weight heparin (LMWH) prophylaxis for at least 6 weeks. In antepartum, LMWH prophylaxis was prescribed to 61·8% of patients with high risk of VTE. Among them, 37·7% were treated in the third trimester only and 24·1% were treated throughout pregnancy. In this cohort, one antepartum-related VTE (0·35%) and two postpartum-related VTE (0·7%) occurred. No case of pulmonary embolism was observed during the study period. The rate of serious bleeding was 0·35%. There was no evidence of heparin-induced thrombocytopenia or osteoporosis. The use of a risk score may provide a rational decision process to implement safe and effective antepartum thromboprophylaxis in pregnant women at high risk of VTE.     

Detection of Neuroendocrine Tumors of the Small Bowel by Double Balloon Enteroscopy

Background Neuroendocrine tumors (NET) account for one-third of all small bowel neoplasms. The search for the primary tumor in NET is important, even though it is difficult to localize, as its surgical excision leads to a better prognosis, even in metastasized stages of the disease. The objective of this study was to evaluate the use of double balloon enteroscopy (DBE) for the detection of the primary tumor in patients with NET. Methods Twelve consecutive patients (eight women, four men) with suspected carcinoid syndrome, either metastatic to the liver (n = 5), symptoms of a neuroendocrine tumor with elevated tumor markers (n = 5), or obscure gastrointestinal bleeding (n = 2) underwent DBE for the search of the primary tumor or the source of bleeding. All patients underwent abdominal sonography and a computed tomography (CT) scan, esophagogastroduodenoscopy (EGD), ileocolonoscopy, and octreotide scintigraphy prior to DBE. Capsule endoscopy was performed in four patients. Results A total of 17 DBE were performed in the 12 patients. The CT scan and sonography of the abdomen as well as EGD and ileocolonoscopy were unable to detect the primary tumor in any patient. A submucosal tumor of the ileum or the jejunum could be detected by DBE was detected in seven patients (58%) (anal route, n = 4; oral route, n = 3). In four of these patients (33%) this finding could be confirmed by the surgical resection of a NET. In two patients (17%) with a submucosal ileum protrusion suspicious for NET, laparotomy and intraoperative endoscopy did not confirm the tumor. Conclusions In this study, the diagnostic yield of DBE for primary tumor search in patients with metastatic or suspected NET was 33%. Although endoscopic small bowel investigation by DBE seems to enrich the diagnostic possibilities for the diagnosis of small bowel-NET, at the present time DBE should only be performed in selected cases, possibly based on a positive previous work-up. Michael Bellutti and Lucia C. Fry contributed equally to this paper.