Changes in admissions, and hospitalization outcomes of IBD patients in an Italian tertiary referral center over a 13-year period.

OBJECTIVE: The management of Inflammatory Bowel Disease (IBD) has changed significantly in recent years, mainly due to the introduction of biologic medications, however, other factors may also have a role. The aim of this study was to evaluate the evolution of IBD admissions, including trends, modality of admission and rates of surgical intervention, in a tertiary care center. PATIENTS AND METHODS: Hospitalization of patients with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) were identified between 2000 and 2013, using ICD-9-CM codes for IBD, from our hospital database. The following parameters were evaluated for each admission: type of admission (ordinary vs. day care service), mode of admission (elective vs. emergency care, for ordinary admissions only), admission code, surgical procedures and complication rates. Comparison between pre- and post-biologic therapy introduction years was also performed. RESULTS: Between 2000 and 2013 a total of 8834 IBD-related admissions were recorded. Hospitalizations increased linearly reaching a peak in 2006, with a downward trend in the following years. The downward trend was especially marked for patients younger than 40 years. No significant differences in hospitalization trends between CD and UC were recorded. Disease flare represented the cause of hospitalization in approximately 50% of cases. Overall, 10.8% of patients underwent surgery with no difference between the two conditions. Complications occurred in 28.7% of admissions. CONCLUSIONS: Hospitalizations for IBD patients have decreased in recent years, especially in younger patients. However, a significant proportion of patients are still admitted to complete diagnostic workup, indicating the need to better implement outpatient services. A clear reduction in surgery occurrence over time could not be observed in our study.

Web-mediated counseling to counteract the emotional impact of COVID-19 for women with interstitial cystitis/bladder pain syndrome.

OBJECTIVE: Interstitial Cystitis (IC) is a chronic and rare disease, more frequent in women. Symptoms of continuous pain can produce psychological disorders, such as anxiety and depression. The spread of COVID-19 pandemic added to distress experienced by patients with IC emotions, such as fear, sadness, boredom, frustration and anger. MATERIALS AND METHODS: A research on very recent literature outlines the necessity for patients facing the complexity of IC during the COVID-19 outbreak to prevent the temporary crisis, to broaden perspectives, to deal with confusion, to support in struggling with unpleasant and unexpected events. CONCLUSIONS: People affected by IC have a psychological vulnerability that needs tailored support interventions, particularly in the COVID era. A multidisciplinary approach offers a personalized treatment through a web-mediated counseling intervention for patients and their caregivers: a space for continuous discussion and reflection can favour a relationship-based process of change aimed at an improvement in quality of life.

Mental health and counseling intervention for hereditary hemorrhagic telangiectasia (HHT) during the COVID-19 pandemic: perspectives from Italy.

OBJECTIVE: Hereditary hemorrhagic telangiectasia (HHT) is an inherited disorder of fibrovascular tissue, transmitted as an autosomal dominant trait. This rare disease can involve one or more organs and clinical manifestations interest several medical specialties. MATERIALS AND METHODS: A review of recent literature and our clinical experience shows that COVID-19 pandemic greatly influences the autonomy and psychic sphere of patients with HHT, causing them further distress. RESULTS: Often patients affected by HHT experience a sense of loneliness due to the rarity of this pathology and COVID-19 pandemic adds a burden for them and their caregivers who have to face emotional experiences that interfere with personal, social and working functioning. CONCLUSIONS: Multidisciplinary approach and web-mediated counseling intervention could offer a valid and personalized support for patients affected by HHT and their caregivers during quarantine due to COVID-19 pandemic.

Nutrition and IBD: Malnutrition and/or Sarcopenia? A Practical Guide.

Malnutrition is a major complication of inflammatory bowel disease (IBD). This mini review is focusing on main determinants of malnutrition in IBD, the most important components of malnutrition, including lean mass loss and sarcopenia, as an emerging problem. Each one of these components needs to be well considered in a correct nutritional evaluation of an IBD patient in order to build a correct multidisciplinary approach. The review is then focusing on possible instrumental and clinical armamentarium for the nutritional evaluation.

Helicobacter pylori infection is associated with high methane production during lactulose breath test.

OBJECTIVE: Despite a growing interest toward the interplay between H. pylori and gastric microbiota, few data are available about this correlation. The aim of this study was to explore the relationship between H. pylori infection and gas production during lactulose breath test. MATERIALS AND METHODS: Data of patients undergoing both 13C-urea breath test (UBT) and lactulose breath test (LBT) under standard conditions in our GI unit were retrospectively analyzed. GI symptoms, such as dyspepsia, bloating, abdominal pain/discomfort, and epigastric pain on an eleven-point scale were also analyzed and correlate with the results of those tests. H2 and CH4 were calculated using the trapezoidal rule; a considerable CH4 production was defined by AUCCH4 ≥1200 ppm*4h. Statistical analyses were performed with Fisher's exact test and independent samples Mann-Whitney test. RESULTS: Data of 136 patients during a period of time of 3 months were analyzed. 36 patients (26.5%) showed a positive UBT. We do not find any difference as regards age, sex, symptom complaints, and small intestinal bacterial overgrowth between HP negative and positive patients. A greater methane production was observed in infected rather than non-infected patients (47.2% vs. 26% respectively, p=0.02). Furthermore, 25% infected and 10% non-infected produced greater amounts of CH4 compared to H2, resulting in a AUCCH4/AUCH2 ratio >1 (p=0.046). CONCLUSIONS: This study shows for the first time, a significant association between H. pylori infection and methane production, suggesting that H. pylori might influence gut microbiota composition. Further studies are needed to clarify mechanisms underlying this phenomenon.

Sonic hedgehog gene therapy increases the ability of the dystrophic skeletal muscle to regenerate after injury.

The Hedgehog (Hh) pathway is a crucial regulator of muscle development during embryogenesis. We have previously demonstrated that Sonic hedgehog (Shh) regulates postnatal myogenesis in the adult skeletal muscle both directly, by acting on muscle satellite cells, and indirectly, by promoting the production of growth factors from interstitial fibroblasts. Here, we show that in mdx mice, the murine equivalent of Duchenne muscular dystrophy in humans, progression of the dystrophic pathology corresponds to progressive inhibition of the Hh signaling pathway in the skeletal muscle. We also show that the upregulation of the Hh pathway in response to injury and during regeneration is significantly impaired in mdx muscle. Shh treatment increases the proliferative potential of satellite cells isolated from the muscles of mdx mice. This treatment also increases the production of proregenerative factors, such as insulin-like growth factor-1 and vascular endothelial growth factor, from fibroblasts isolated from the muscle of mdx mice. In vivo, overexpression of the Hh pathway using a plasmid encoding the human Shh gene promotes successful regeneration after injury in terms of increased number of proliferating myogenic cells and newly formed myofibers, as well as enhanced vascularization and decreased fibrosis.

Intestinal gas production and gastrointestinal symptoms: from pathogenesis to clinical implication.

Intestinal gases are the expression of metabolic activity of gut microbiota in the gut, particularly carbohydrates in the case of H2, CH4. Alterations in composition of gases and air handling, directly or upon challenge with food are relevant for GI and extra-GI diseases. Assessing gas composition in breath can be a very useful tool for clinic, but technical issues are crucial (breath sampling, storing and analyzing). Aim of the present review is to summarize the understanding of the importance of intestinal gases in gastro-intestinal physiology and patho-physiology. Practical considerations on how to collect samples and instruments available for the clinic have also been provided.

Tricks for interpreting and making a good report on hydrogen and 13C breath tests.

Breath tests (BT) represent a valid and non-invasive diagnostic tool in many gastroenterological disorders. Their wide diffusion is due to the low cost, simplicity and reproducibility and their common indications include diagnosis of carbohydrate malabsorption, Helicobacter pylori infection, small bowel bacterial overgrowth, gastric emptying time and orocaecal transit time. The review deals with key points on methodology, which would influence the correct interpretation of the test and on a correct report. While a clear guideline is available for lactose and glucose breath tests, no gold standard is available for Sorbitol, Fructose or other H2 BTs. Orocaecal transit time (OCTT) defined as time between assumption of 10 g lactulose and a peak > 10 ppm over the baseline value, is a well-defined breath test. The possible value of lactulose as a diagnostic test for the diagnosis of small bowel bacterial overgrowth is still under debate. Among (13)C breath test, the best and well characterized is represented by the urea breath test. Well-defined protocols are available also for other (13)C tests, although a reimbursement for these tests is still not available. Critical points in breath testing include the patient preparation for test, type of substrate utilized, reading machines, time between when the test is performed and when the test is processed. Another crucial point involves clinical conclusions coming from each test. For example, even if lactulose could be utilized for diagnosing small bowel bacterial overgrowth, this indication should be only secondary to orocaecal transit time, and added into notes, as clinical guidelines are still uncertain.

Prenatal BACs-on-Beads™ : a new technology for rapid detection of aneuploidies and microdeletions in prenatal diagnosis.

OBJECTIVE: Molecular cytogenetic techniques on uncultured prenatal samples are the sole tests applied in some countries in cases with advanced maternal age (AMA) or increased risk after prenatal screening. Moreover, there is a trend to perform invasive prenatal diagnosis (PD) during the first trimester before ultrasound manifestations, so new rapid and reliable assays are necessary to investigate microdeletions not detectable with the conventional karyotype. We report the validation study of the prenatal bacterial artificial chromosomes-on-Beads™ (BoBs™ ; CE-IVD), a bead-based multiplex assay detecting chromosomes 13, 18, 21, X/Y aneuploidies and nine microdeletion regions having an overall detection rate of 1/1700. METHOD: We retrospectively studied 408 selected samples and prospectively tested 212 consecutive samples ascertained for conventional karyotyping. RESULTS: We did not find false-positive results. Triploidies were not detected. Maternal cell contamination of male samples up to 90% was unmasked inspecting gonosome profiles. Mosaic conditions at 20 to 30% were revealed. Failures were due to low amount of DNA. CONCLUSION: Prenatal BoBs™ is a robust technology for the investigation of fetuses with normal karyotype with or without sonographic abnormalities. Running in parallel with the karyotype analysis, it can be proposed instead of rapid FISH or QF-PCR providing rapid results on common aneuploidies and additional information regarding the microdeletion syndromes.

Pro-inflammatory genetic profiles in subjects with peripheral arterial occlusive disease and critical limb ischemia.

OBJECTIVES: Single nucleotide polymorphisms in genes encoding inflammatory molecules may determine genetic profiles associated with increased risk of development and progression of cardiovascular diseases. In this study, we evaluated distribution and reciprocal interaction of a set of functionally important polymorphisms of genes encoding prototypical inflammatory molecules in subjects with peripheral arterial occlusive disease (PAOD) and critical limb ischemia (CLI). We also investigated whether synergistic interactions between these pro-inflammatory gene polymorphisms influence the risk of PAOD and CLI. DESIGN, SUBJECTS AND METHODS: In a genetic association study that included 157 PAOD patients and 206 controls, the following gene polymorphisms were analysed: C-reactive protein (CRP) 1059 G/C, interleukin-6 (IL-6)-174 G/C, macrophage migration inhibitory factor (MIF)-173 G/C, monocyte chemoattractant protein (MCP-1) - 2518 A/G, E-selectin (E-Sel) Ser128Arg, intercellular adhesion molecule-1 (ICAM-1) 469 E/K, matrix metalloproteinase (MMP)-1 -1607 1G/2G, MMP-3-1171 5A/6A and MMP-9-1563 C/T. RESULTS: We found that IL-6, E-sel, ICAM-1, MCP-1, MMP-1 and MMP-3 gene polymorphisms were significantly and independently associated with PAOD. We also found that these pro-inflammatory polymorphisms determine genetic profiles that are associated with different levels of risk for PAOD and CLI, depending on the number of high-risk genotypes concomitantly carried by a given individual. CONCLUSIONS: Pro-inflammatory genetic profiles are significantly more common in subjects with PAOD. Synergistic effects between pro-inflammatory genotypes might be potential markers for the presence and severity of atherosclerotic disorders.

Coagulation factor XIII Val34Leu gene polymorphism and Alzheimer's disease.

Blood coagulation factor XIII (FXIII) plays a role in inflammatory processes and a pathogenetic role of inflammation in neurodegenerative disorders has been proposed. FXIIIa subunit was immunohistochemically detected in a subpopulation of reactive microglia in Alzheimer's disease (AD). Aim of the present study is to evaluate whether a common polymorphism of the FXIII gene is associated with sporadic AD. We examined 90 patients affected by sporadic AD and 139 age- and sex-matched controls to assess the distribution of V/L alleles and genotypes of the FXIIIa-subunit gene. The LL genotype showed a significantly higher frequency in AD patients (p<0.05) with a significantly increased risk of AD in the presence of LL genotype at the logistic regression analysis [odds ratio: 3.6 (1.36-9.44), p<0.01]. This study shows for the first time an association between FXIII Val34Leu polymorphism and AD.

Interleukin-6 gene polymorphism and risk of osteoarthritis of the hip: a case-control study.

OBJECTIVES: Osteoarthritis (OA) is considered a polygenic disease controlled by the expression of genetic factors. Genes encoding for cytokines have been associated with susceptibility for joint OA and interleukin (IL)-6 gene is also supposed to be involved in the cartilage degradation process. In this case-control study, we evaluated for the first time whether the risk of hip OA might be influenced by the -174 IL-6 gene polymorphism. METHODS: The distribution of IL-6 genotypes was evaluated in 75 patients affected by hip OA and in 107 age- and sex-matched controls. RESULTS: The distribution of IL-6 genotypes in (1) patients with hip OA: 33 GG, 30 GC, 12 CC and (2) control subjects: 34 GG, 40 GC, 33 CC. The frequency of the CC genotype was significantly higher in control patients (P=0.02). Logistic regression analysis indicated that the presence of the CC genotype is independently associated with a decreased risk of OA (odds ratio 0.4 [95% confidence interval 0.1-0.9], P=0.04). CONCLUSIONS: Primary OA of the hip has an important genetic component and variations of genes encoding for inflammatory cytokines, such as IL-6, may play an important role in the series of events responsible for the pathophysiology of OA.

Prevalence of the K469E polymorphism of intercellular adhesion molecule 1 gene in Italian patients with inflammatory bowel disease.

BACKGROUND: Intercellular adhesion molecule 1 plays an important role in the recruitment of leucocytes at sites of inflammation and is up-regulated in intestinal mucosa of inflammatory bowel disease. Intercellular adhesion molecule 1 gene lies on chromosome 19p13, implicated in determining susceptibility to inflammatory bowel disease. Recently, the polymorphism K469E of intercellular adhesion molecule 1 gene has been identified. AIM: To assess the potential association of this polymorphism with inflammatory bowel disease. PATIENTS: A total of 165 inflammatory bowel disease patients, 75 with Crohn's disease and 90 with ulcerative colitis, and 187 controls were studied. METHODS: The K469E polymorphism was detected by polymerase chain reaction and restriction enzyme analysis. Statistical analysis was performed by chi2-test. RESULTS: In inflammatory bowel disease, the distribution of intercellular adhesion molecule 1 genotypes was 24.9% E/E, 44.2% E/K and 30.9% K/K. In controls, 11.8% showed E/E genotype, 55.6% E/K and 32.6% K/K. The frequency of the E/E genotype was significantly higher in inflammatory bowel disease (Crohn's disease and ulcerative colitis) patients than in controls. Subgroup analysis showed that the frequency of the E469 allele was significantly increased only in Crohn's disease patients with ileocolonic location of disease and penetrating behaviour compared with controls. CONCLUSIONS: We found an association of inflammatory bowel disease with the E/E genotype of intercellular adhesion molecule 1 gene, while allele E469 was associated with a subgroup of Crohn's disease patients with more extensive location of disease and penetrating behaviour. However, further studies are needed to confirm our findings.

Comparative analysis of the in vivo angiogenic properties of stable prostacyclin analogs: a possible role for peroxisome proliferator-activated receptors.

OBJECTIVE: Until recently, prostacyclin (PGI2) biological activities were thought to be exclusively mediated by cell surface receptors named IP. Recent studies have instead identified a novel pathway of PGI2 signaling, occurring through activation of peroxisome proliferator-activated receptors (PPARs) located in the nucleus. The availability of stable PGI2 analogs with different affinity for IP receptors and PPARs provides the possibility to test the importance and function of this dual pathway in vitro and in vivo. In this study, the in vivo angiogenic properties of different PGI2 analogs and the potential relationship between PPAR-mediated pathways, vascular endothelial growth factor (VEGF), and angiogenesis were investigated. METHODS AND RESULTS: By using the murine corneal model of angiogenesis, we found that PGI2 analogs able to act on nuclear PPARs, such as iloprost and carbaprostacyclin (cPGI), induce angiogenesis in vivo. In contrast, cicaprost, a PGI2 analog that only acts on IP receptors, has no in vivo angiogenic activity. Interestingly, angiogenesis induced by iloprost and cPGI does not differ in extent and morphology from that induced by VEGF and is associated with local increment of VEGF mRNA expression and protein levels. Finally, iloprost-induced angiogenesis is significantly decreased by systemic inhibition of VEGF activity, obtained by gene transfer of a soluble form of the VEGF receptor Flt-1. CONCLUSIONS: These data demonstrate that stable PGI2 analogs may have angiogenic properties in vivo, depending on their ability to act on PPARs. The resulting angiogenic process appears to be mediated by VEGF. These findings indicate that important physiological activities in the cardiovascular system, such as angiogenesis and VEGF induction, may be modulated by PGI2 through specific activation of the PPAR signaling pathway in vivo, with potentially important fundamental and clinical implications.

The -174 G/C polymorphism of the interleukin-6 gene promoter and essential hypertension in an elderly Italian population.

Several studies have proposed a relationship between blood pressure and inflammation. Interleukin-6 (IL-6) is a multifunctional cytokine involved in inflammation and tissue injury and potentially influencing blood pressure. Recently, a common polymorphism of the IL-6 gene, associated with differences in the transcription rate of the protein, has been described. The aim of this study was to investigate a possible association between genetic variations of the -174GC polymorphism of the IL-6 gene promoter and hypertension in humans. IL-6 gene promoter polymorphism was evaluated by polymerase chain reaction followed by restriction enzyme analysis in 210 elderly Italian patients affected by essential hypertension (EH) and 177 age- and sex-matched controls. The distribution of IL-6 genotypes was 85 GG, 88 GC, 37 CC in the hypertensive patients and 65 GG, 73 GC, 39 CC in the control subjects. In this elderly cohort, no statistically significant association was found between the two groups (P = 0.45 for GG homozygous, P = 0.89 for GC heterozygous and P = 0.27 for CC homozygous). In conclusion the -174 GC polymorphism of the IL-6 gene promoter is not a marker for EH in this sample of elderly Italians.

The -174 G/C polymorphism of the interleukin-6 gene promoter is associated with peripheral artery occlusive disease.

OBJECTIVE AND DESIGN: high plasma levels of Interleukin-6 (IL-6) are found in patients with atherosclerotic disorders. Recently, a common polymorphism of the IL-6 gene promoter, influencing the transcription rate of the gene, has been described and associated with atherosclerosis of carotid and coronary arteries. The objective of this study was to test whether IL-6 gene promoter polymorphism is associated with peripheral artery occlusive disease (PAOD) in a case-control study. METHODS: IL-6 gene promoter polymorphism was evaluated by polymerase chain reaction followed by restriction enzyme analysis in 84 patients affected by PAOD and 183 controls. RESULTS: the distribution of IL-6 genotypes was: patients with PAOD: 44 GG, 30 GC, 10 CC; control subjects: 53 GG, 80 GC, 50 CC. The GG genotype was significantly more common in the PAOD group (p<0.0001), while the CC genotype was significantly more common in control patients (p=0.005). CONCLUSIONS: this study indicates a strong association between IL-6 gene polymorphism and PAOD and support the hypothesis that IL-6 and IL-6 gene polymorphism are important in the pathophysiology and evolution of ischaemic diseases of the lower limbs.

The K469E polymorphism of the ICAM-1 gene is a risk factor for peripheral arterial occlusive disease.

Intercellular adhesion molecule-1 (ICAM-1) plays a crucial role in lymphocyte migration and activation, and is considered important in the pathogenesis of atherosclerosis. K469E is a common polymorphism of the ICAM-1 gene with potential functional significance. The aim of the present case-control study was to evaluate the association between this polymorphism and peripheral arterial occlusive disease (PAOD). ICAM-1 gene polymorphism was examined by polymerase chain reaction and restriction enzyme analysis in 75 Italian subjects affected by PAOD and 227 controls. The distribution of ICAM-1 genotypes in patients affected by PAOD was 32.1% EE, 50.6% EK, and 17.3% KK. The distribution of ICAM-1 genotypes in control subjects was 17.2% EE, 55.1% EK, and 27.7% KK. The EE genotype was significantly more common in patients than controls (P = 0.006). Logistic regression analysis indicated that the presence of the EE genotype significantly increases the risk of PAOD (odds ratio, 3.5; 95% confidence interval, 1.5-8.4; P = 0.004). This is the first study documenting a role of the ICAM-1 gene polymorphism in the pathogenesis of a cardiovascular disease, such as PAOD. Our data support the hypothesis that inflammatory mechanisms are important in the pathophysiology of vascular diseases with an atherosclerotic basis.