Do concomitant diseases and therapies affect the persistence of ulcer symptoms in the elderly?

Risk factors of slow healing were previously researched in a large sample of duodenal (DU) and gastric ulcer (GU) patients over 65 years of age; persistence of ulcer symptoms was proven the most reliable factor in predicting nonhealing ulcer, while ulcer size was of importance only for DU. We aimed to complete the analysis, with a more careful evaluation of concomitant diseases and therapies. Ranitidine 300 mg daily was given for four to eight weeks to 310 GU and 699 DU patients. Ninety-three patients dropped out of the study: 79/294 gastric ulcers and 138/635 duodenal ulcers were unhealed after four weeks. Cardiovascular, gastrointestinal, and pulmonary disorders were the most frequent concomitant diseases; NSAIDs, cardiovascular drugs, and antihypertensives were the most frequent concomitant therapies. Esophagitis was diagnosed in 15.5% of patients. Ulcer healing was the major determinant of persistence of ulcer symptoms; esophagitis emerged as an important adjunctive and independent factor. Use of hypoglycemic agents in the whole sample and smoking habit (in GU) may have also a role. With persistence of ulcer symptoms removed from the analysis, ulcer size was the most constant factor affecting ulcer healing. NSAID use, cardiovascular disorders, esophagitis (in GU), and concomitant therapy with cardiovascular drugs (in DU) also play a role. In conclusion, persistence of ulcer symptoms, the major indicator of slow ulcer healing in the elderly, is independently affected also by the presence of esophagitis. Use of hypoglycemic agents and smoking habit may also have a role in persistence of ulcer symptoms. NSAIDs, cardiovascular disorders, cardiovascular drugs, and esophagitis affect ulcer healing, for which the most constant indicators remained persistence of ulcer symptoms and ulcer size.This study was performed under the auspices of the R. Farini Foundation for Gastrointestinal Research.     

"Ultrasound comet-tail images": a marker of pulmonary edema: a comparative study with wedge pressure and extravascular lung water

BACKGROUND: Echographic examination of the lung surface may reveal multiple "comet-tail images" originating from water-thickened interlobular septa. These images could be useful for noninvasive assessment of interstitial pulmonary edema. STUDY OBJECTIVE: The purpose of this study was to assess the diagnostic accuracy of lung comet-tail images compared with chest radiography, wedge pressure, and extravascular lung water (EVLW) quantified by the indicator dilution method (PiCCO System, version 4.1; Pulsion Medical Systems; Munich, Germany). METHODS AND PATIENTS: We enrolled 20 patients (mean age, 62.6 +/- 11.5 years [+/- SD]). Patients were studied before, immediately after, and 24 h following cardiac surgery with chest ultrasound, chest radiography, pulmonary artery catheterization, and the PiCCO system. Performing echo scanning (right and left hemithorax, from second to fourth intercostal space, from parasternal to midaxillary line), an individual patient comet score was obtained by summing the number of comets in each scanned space. RESULTS: A total of 60 comparisons were obtained. Significant positive linear correlations were found between comet score and EVLW determined by the PiCCO System (r = 0.42, p = 0.001), between comet score and wedge pressure (r = 0.48, p = 0.01), and between comet score and radiologic lung water score (r = 0.60, p = 0.0001). CONCLUSIONS: The presence and the number of comet-tail images provide reliable information on interstitial pulmonary edema. Therefore, ultrasonography represent an attractive, easy-to-use, bedside diagnostic tool for assessing cardiac function and pulmonary congestion.     

Morphometric investigations of the mitochondrial damage in ceroid lipopigment accumulation due to vitamin E deficiency

Numeric (Nv) and volume (Vv) densities, as well as the average size (skeleton: Sk) of synaptic mitochondria from adult, normally fed and adult, vitamin E deficient animals (11 months of age) were semiautomatically measured by computer-assisted morphometry in the cerebellar granular layer. Nv, Vv and the average mitochondrial volume (V) were measured on perikaryal Purkinje cell organelles preferentially stained for succinic dehydrogenase (SDH) activity. Adult vitamin E deficient animals showed a significant decrease of Nv, a significant increase of Sk and an unchanged value of Vv. While in adult normally fed animals the mitochondria of increased size (Sk>5 microm) were 5.3%, in the adult vitamin E deficient rats this fraction accounted for 25.5%. In Purkinje cell perikarya, vitamin E deficiency resulted in a significant decrease of Vv, Nv and V, as well as a steeper reduction of the percentage of SDH-positive mitochondria of larger size. Taken together, these findings document that vitamin E deficiency is responsible of mitochondrial morphometric alterations in adult rats. Structurally deteriorated mitochondria are reported to play a role in producing increased amounts of free radicals, which can facilitate the accumulation of ceroid pigment.     

Surface markers: An identity card of endothelial cells

All endothelial cells have the common characteristic that they line the vessels of the blood circulatory system. However, endothelial cells display a large degree of heterogeneity in the function of their location in the vascular tree. In this article, we have summarized the expression patterns of a number of well‐accepted endothelial surface markers present in normal microvascular endothelial cells, arterial and venous endothelial cells, lymphatic endothelial cells, tumor endothelial cells, and endothelial precursor cells.     

Tumor necrosis factor receptor-associated periodic syndrome as a model linking autophagy and inflammation in protein aggregation diseases

Autophagy prevents cellular damage by eliminating insoluble aggregates of mutant misfolded proteins, which accumulate under different pathological conditions. Downregulation of autophagy enhances the inflammatory response and thus represents a possible common pathogenic event underlying a number of autoinflammatory syndromes, such as tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS). The pathogenesis of other monogenic or complex disorders that display symptoms of excessive inflammation also involve the autophagy pathway. Studies have shown that TRAPS-associated TNFRSF1A mutations induce cytoplasmic retention of the TNFR1 receptor, defective TNF-induced apoptosis, and production of reactive oxygen species (ROS). Furthermore, autophagy impairment may account for the pathogenic effects of TNFRSF1A mutations, thus inducing inflammation in TRAPS. In this review, we summarize the molecular interactions and functional links between autophagy with regard to nuclear factor-kappa B activation, ROS production, and apoptosis. Furthermore, we propose a complex interplay of these pathways as a model to explain the relationship between mutant protein misfolding and inflammation in genetically determined and aggregation-prone diseases. Accordingly, autophagy function should be investigated in all diseases showing an inflammatory component, and for which the molecular pathogenesis is still unclear.     

Balanced and unbalanced solutions modulate the release of Matrix Metalloproteinase-9 (MMP-9) from neutrophils in response to inflammatory stimuli: an in vitro study

Objectives and design

We investigated the effect of balanced (BS) and unbalanced (UBS) solutions in the absence or presence of hydroxyethyl starch (HES) on neutrophil functionality, evaluating the release of matrix metalloproteinase (MMP)-9, myeloperoxidase (MPO), and MMP-8.

Materials and methods

Neutrophils were isolated by gradient centrifugation and dextran sedimentation and incubated in BS or UBS without or with HES, in the absence or presence of Interleukin-8 (IL-8) or Lipopolysaccharide (LPS). MMP-9, MPO, and MMP-8 were assayed by commercially available ELISA kits.

Results

There was not any influence of volume replacement solutions on the release of the enzymes from resting neutrophils. After IL-8 stimulation, the release of MMP-9 was higher in BS than in UBS or RPMI-1640, whereas HES enhanced its release regardless of the composition. After LPS stimulation, the release of MMP-9 was higher in both UBS and BS than RPMI-1640, but HES brought its release back to physiological conditions. No difference was found in the release of MPO and MMP-8 after stimulation with IL-8 or LPS.

Conclusion

Volume replacement solutions might have an impact on the release of MMP-9 depending on the inflammatory milieu, suggesting that the use of balanced or unbalanced solutions is not a neutral choice.     

Clustering of genomic breakpoints at the MLL locus in therapy‐related acute leukemia with t(4;11)(q21;q23)

Genomic characterization of translocation breakpoints is relevant to identify possible mechanisms underlying their origin. The consistent association of anthracylines (e.g., epirubicin and idarubicin) in inducing therapy‐related acute leukemias (t‐AL) with mixed lineage leukemia (MLL) gene rearrangement suggests that MLL translocations are causative events for t‐AL. Using asymmetric multiplex PCR strategy followed by direct DNA sequencing, we characterized the genomic breakpoints of the MLL and AFF1 genes in two patients who developed t‐AL with t(4;11)(q21;q23). Chemotherapeutic treatment of the primary disease in both patients included topoisomerase II (topo II) targeting agents. In one case, the MLL breakpoint was located in intron 9 at nucleotide position chr11:118354284 while the AFF1 breakpoint was in intron 3 at nucleotide position chr4:87992070. The breakpoint junction sequences revealed an insertion of two nucleotides at the MLL‐AFF1 junction. In the other patient, the MLL breakpoint was located in intron 11 at nucleotide position chr11:118359130‐32 and the AFF1 break was in intron 3 at nucleotide position chr4:87996215‐17. The MLL breakpoint found in the latter patient was identical to that of two previously reported cases, strongly suggesting the presence of a preferential site of DNA cleavage in the presence of topo II inhibitor. In addition, microhomologies at the breakpoint junctions were indicative of DNA repair by the non‐homologous end joining (NHEJ) pathway. This study further supports the evidence that MLL breakpoints in therapy‐related acute leukemia with MLL‐AFF1 are clustered in the telomeric half of the breakpoint cluster region that contains topo II recognition sites. © 2013 Wiley Periodicals, Inc.     

Acute alcoholic hepatitis,end stage alcoholic liver disease and liver transplantation: An Italian position statement

Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the “6-mo rule”. Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The “Group of Italian Regions” suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups.     

Granulo-monocyto apheresis is more effective in mild ulcerative colitis than in moderate to severe disease

AIM:To evaluate whether the effectiveness of Granulomonocyto apheresis(GMA),a technique that consists of the extracorporeal removal of granulocytes and monocytes from the peripheral blood,might vary according to the severity of ulcerative colitis(UC)in patients with mild to moderate-severe disease UC activity.METHODS:We retrospectively reviewed prospectively collected data of patients undergoing GMA at our inflammatory bowel disease centre who had at least a 6 mo of follow-up.The demographics,clinical and laboratory data were extracted from the patients’charts and electronic records.The severity of UC was scored according to the Modified Truelove Witts Severity Index(MTWSI).A clinical response was defined as a decrease from baseline of≥2 points or a value of MTWSI≤2 points.RESULTS:A total of 41(24 males/17 females;meanage 47 years)patients were included in the study.After GMA cycle completion,21/28(75%)of mild UC patients showed a clinical response compared with 7/13(54%)of patients with moderate to severe disease(P=0.27).At 6-mo,14/28(50%)of the mild UC patients maintained a clinical response compared with 2/13(15%)of the patients with moderate to severe disease(P=0.04).After the GMA cycle completion and during the 6-mo follow up period,13/16(81%)and 9/16(56%)of mild UC patients with intolerance,resistance and contraindications to immunosuppressants and/or biologics showed a clinical response compared with 2/6(33%)and 0/6(0%)of patients with moderate to severe disease activity with these characteristics(P=0.05and P=0.04,respectively).CONCLUSION:Patients with mild UC benefit from GMA more than patients with moderate to severe disease in the short-term period.GMA should be considered a valid therapeutic option in cases of contraindications to immunosuppressants,corticosteroids and/or biologics.