A.G. Gravina

Pyoderma gangrenosum: an updated review

Pyoderma gangrenosum is a rare, ulcerative, cutaneous condition. First described in 1930, the pathogenesis of pyoderma gangrenosum remains unknown, but it is probably related to a hyperergic reaction. There are various clinical and histological variants of this disorder. Pyoderma gangrenosum often occurs in association with a systemic disease such as inflammatory bowel disease, rheumatologic disease, paraproteinaemia, or haematological malignancy. The diagnosis, mainly based on the clinical presentation and course, is confirmed through a process of elimination of other causes of cutaneous ulcers. Local treatment may be sufficient for mild disease, while for severe cases, systemic immunosuppressants are the mainstay. Long‐term treatment with these agents is often required, but this can expose patients to adverse side‐effects.

Empirical levofloxacin-containing versus clarithromycin-containing sequential therapy for Helicobacter pylori eradication: a randomised trial

Background and aims Antimicrobial drug resistance is a major cause of the failure of Helicobacter pylori eradication and is largely responsible for the decline in eradication rate. Quadruple therapy has been suggested as a first-line regimen in areas with clarithromycin resistance rate >15%. This randomised trial aimed at evaluating the efficacy of a levofloxacin-containing sequential regimen in the eradication of H pylori-infected patients in a geographical area with >15% prevalence of clarithromycin resistance versus a clarithromycin-containing sequential therapy. Methods 375 patients who were infected with H pylori and naïve to treatment were randomly assigned to one of the following treatments: (1) 5 days omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by 5 days omeprazole 20 mg twice daily + clarithromycin 500 mg twice daily + tinidazole 500 mg twice daily; or (2) omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by omeprazole 20 mg twice daily + levofloxacin 250 mg twice daily + tinidazole 500 mg twice daily; or (3) omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by omeprazole 20 mg twice daily + levofloxacin 500 mg twice daily + tinidazole 500 mg twice daily. Antimicrobial resistance was assessed by the E-test. Efficacy, adverse events and costs were determined for each group. Results Eradication rates in the intention-to-treat analyses were 80.8% (95% CI, 72.8% to 87.3%) with clarithromycin sequential therapy, 96.0% (95% CI, 90.9% to 98.7%) with levofloxacin-250 sequential therapy, and 96.8% (95% CI, 92.0% to 99.1%) with levofloxacin-500 sequential therapy. No differences in prevalence of antimicrobial resistance or incidence of adverse events were observed between groups. Levofloxacin-250 therapy was cost-saving compared with clarithromycin sequential therapy. Conclusion In an area with >15% prevalence of clarithromycin resistant H pylori strains, a levofloxacin-containing sequential therapy is more effective, equally safe and cost-saving compared to a clarithromycin-containing sequential therapy.

Optimized Nonbismuth Quadruple Therapies Cure Most Patients With Helicobacter pylori Infection in Populations With High Rates of Antibiotic Resistance

BACKGROUND & AIMS Strategies to eradicate Helicobacter pylori infection could be improved by suppressing acid and extending the duration of therapy (optimization). We compared the efficacy of 2 different optimized nonbismuth quadruple regimens in areas of high resistance to antimicrobial agents. METHODS We performed a prospective noninferiority multicenter trial in which 343 consecutive individuals with H pylori infection were assigned randomly to groups given hybrid therapy (40 mg omeprazole and 1 g amoxicillin, twice daily for 14 days; 500 mg clarithromycin and 500 mg nitroimidazole were added, twice daily for the final 7 days) or concomitant therapy (same 4 drugs taken concurrently, twice daily for 14 days). We assessed bacterial resistance to these drugs in a subset of patients using the E-test. Efficacy, side effects, and compliance were determined. RESULTS In per-protocol analysis, rates of eradication for hybrid and concomitant therapies were 92% (95% confidence interval [CI], 87%-95%) and 96.1% (95% CI, 93%-99%), respectively (P = .07). In intention-to-treat analysis, rates were 90% (95% CI, 86%-93%) and 91.7% (95% CI, 87%-95%), respectively (P = .35). Almost all patients (95.5%) were fully compliant; 23.5% of patients had H pylori strains that were resistant to clarithromycin (Italy, 26%; Spain, 19.5%), 33% were resistant to metronidazole (Italy, 33%; Spain, 34%), and 8.8% were resistant to both drugs (Italy, 7.1%; Spain, 11.5%). Side effects (only mild) were reported in 51.5% of patients (47% hybrid vs 56% concomitant; P = .06). Compliance greater than 80% was the only significant predictor of eradication (odds ratio, 12.5; 95% CI, 3.1-52; P = .001). Significantly more patients were compliant with hybrid therapy (98.8%) than concomitant therapy (95.2%; P = .05). CONCLUSIONS Optimized nonbismuth quadruple hybrid and concomitant therapies cured more than 90% of patients with H pylori infections in areas of high clarithromycin and metronidazole resistance. ClinicalTrials.gov number NCT01464060.

A randomized controlled trial of acarbose in hepatic encephalopathy

BACKGROUND & AIMS Hepatic encephalopathy in cirrhosis is contributed to by toxic products deriving from the proteolytic bacterial flora-related degradation of dietary nitrogen substances. Acarbose is a novel hypoglycemic agent acting through the inhibition of glucose absorption in the gut and the promotion of intestinal saccharolytic bacterial flora at the expense of proteolytic flora. We assessed whether acarbose exerts a beneficial effect on hepatic encephalopathy and on postprandial hyperglycemia in cirrhotic patients with low-grade hepatic encephalopathy and type 2 diabetes mellitus. METHODS One hundred seven cirrhotic patients with grade 1-2 hepatic encephalopathy and type 2 diabetes mellitus were randomized to acarbose 100 mg 3 times daily or placebo for 8 weeks; after a 2-week washout period, treatments were switched, and patients were followed for 8 more weeks. Ammonia blood levels, Reitans number connection test, intellectual function, fasting and postprandial glucose levels, glycated hemoglobin values, and C peptide values were determined 2 weeks before and 4, 8, 11, 14, and 18 weeks after treatment. RESULTS (1) Acarbose significantly decreased ammonia blood levels and improved Reitans test score and intellectual function score compared with placebo (P < .01). (2) Acarbose caused a 33% decrease in fasting glucose level and an approximately 50% decrease in postprandial glucose level compared with placebo (P < .01). (3) Acarbose significantly lowered glycated hemoglobin values and postprandial C peptide compared with baseline values, whereas placebo did not. (4) No change in biochemical parameters of liver function was observed after acarbose treatment. CONCLUSIONS Acarbose is a safe and effective drug in cirrhotic patients with low-grade hepatic encephalopathy and type 2 diabetes mellitus.

Efficacy of 5-Day Levofloxacin-Containing Concomitant Therapy in Eradication of Helicobacter pylori Infection

BACKGROUND & AIMS Helicobacter pylori have become resistant to antimicrobial agents, reducing eradication rates. A 10-day sequential regimen that contains levofloxacin was efficient, safe, and cost saving in eradicating H pylori infection in an area with high prevalence of clarithromycin resistance. We performed a noninferiority randomized trial to determine whether a 5-day levofloxacin-containing quadruple concomitant regimen was as safe and effective as the 10-day sequential regimen in eradicating H pylori in previously untreated patients. METHODS We randomly assigned patients with H pylori infection to groups that were given 5 days of concomitant therapy (esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, levofloxacin 500 mg twice daily, and tinidazole 500 mg twice daily; n = 90) or 10 days of sequential therapy (esomeprazole 40 mg twice daily, amoxicillin 1g twice daily for 5 days followed by esomeprazole 40 mg twice daily, levofloxacin 500 mg twice daily, and tinidazole 500 mg twice daily for 5 more days; n = 90). Antimicrobial resistance was assessed by the E-test. Efficacy, adverse events, and costs were determined. RESULTS Intention-to-treat analysis showed similar eradication rates for concomitant (92.2%; 95% confidence interval [CI], 84.0%-95.8%) and sequential therapies (93.3%; 95% CI, 86.9%-97.3%). Per-protocol eradication results were 96.5% (95% CI, 91%-99%) for concomitant therapy and 95.5% for sequential therapy (95% CI, 89.6%-98.5%). The differences between sequential and concomitant treatments were 1.1% in the intention-to-treat study (95% CI; -7.6% to 9.8%) and -1.0% in the per-protocol analysis (95% CI; -8.0% to 5.9%). The prevalence of antimicrobial resistance and incidence of adverse events were comparable between groups. Concomitant therapy cost

Helicobacter pylori second-line rescue therapy with levofloxacin- and bismuth-containing quadruple therapy, after failure of standard triple or non-bismuth quadruple treatments

9 less than sequential therapy. CONCLUSIONS Five days of levofloxacin-containing quadruple concomitant therapy is as effective and safe, and less expensive, in eradicating H pylori infection than 10 days of levofloxacin-containing sequential therapy.

Apple polyphenol extracts prevent aspirin-induced damage to the rat gastric mucosa

The most commonly used second‐line Helicobacter pylori eradication regimens are bismuth‐containing quadruple therapy and levofloxacin‐containing triple therapy, both offering suboptimal results. Combining bismuth and levofloxacin may enhance the efficacy of rescue eradication regimens.

Apple polyphenols extract (APE) improves colon damage in a rat model of colitis

Aspirin causes gastroduodenal ulcers and complications. Food bioactive compounds could exert beneficial effects in the gastrointestinal tract. We evaluated whether apple polyphenol extract (APE) reduced aspirin-induced injury to the rat gastric mucosa. Rats were treated with APE (10(-4) m catechin equivalent) before oral aspirin (200 mg/kg). Cyclo-oxygenase-2 (COX-2), transforming growth factor-alpha (TGF alpha) and heparin-binding epidermal-growth-factor-like growth factor (HB-EGF) mRNA and protein expression were assessed by RT-PCR and Western blot analysis, respectively; malondialdehyde (MDA) was determined by HPLC; gastric secretion was evaluated in pylorus-ligated rats. APE decreased acute and chronic aspirin injury both macroscopically and microscopically (approximately 50 % decrease in lesion score; P < 0.05). Aspirin up-regulated mRNA and protein expression of COX-2 and HB-EGF, but not of TGF alpha; APE reduced aspirin-induced mRNA and protein over-expression of COX-2 and HB-EGF; aspirin significantly increased gastric MDA and this effect was counteracted by APE pre-treatment. APE did not significantly affect gastric acid secretion. In conclusion, APE reduces aspirin-induced gastric injury independently of acid inhibition. We speculate that APE might be of therapeutic use in the prophylaxis of aspirin-related gastropathy.

Vascular endothelial growth factor and neo-angiogenesis in H. pylori gastritis in humans.

BACKGROUND AND AIM Searching for alternative therapies that are effective, safe and less expensive of those currently used for ulcerative colitis, we investigated the efficacy of a polyphenol extract from apple in rat colitis. METHODS Rats with trinitrobenzensulphonic acid-induced colitis were treated daily with rectal administration of apple polyphenols 10(-4) M for 14 days. COX-2, TNF-α, tissue transglutaminase and calpain in colon mucosa samples were assessed by reverse transcription-polymerase chain reaction and western blot analyses. To ascertain the role of tissue transglutaminase in mucosal healing, wounded rat fibroblasts were incubated with cystamine (a tissue transglutaminase activity inhibitor). RESULTS Colitis was associated with increased COX-2, TNF-α, calpain, and tissue transglutaminase mRNA. The protein expression of COX-2, TNF-α and calpain was increased whilst tissue transglutaminase was decreased. Apple extract treatment reduced the severity of colitis (p<0.05) and restored all the considered biomarkers at the baseline level. Apple polyphenols reduced the degradation of tissue transglutaminase protein occurring through calpain action. Apple polyphenols-treated wounded fibroblast recovered within 24h showing intense immunoreactivity for tissue transglutaminase. CONCLUSION The efficacy of apple extract is mediated by its effects on COX-2 and TNF-α. The unbalance between calpain and tissue transglutaminase may play a role in colonic damage and future therapeutic interventions in ulcerative colitis can target this mechanisms.

Helicobacter pylori infection but not small intestinal bacterial overgrowth may play a pathogenic role in rosacea

Host response plays a major role in the pathogenesis of Helicobacter pylori‐induced gastroduodenal disease including adenocarcinoma of the distal stomach. Vascular endothelial growth factor (VEGF) is an important modulator of gastric mucosal repair and is overexpressed in gastric cancer. The present study sought to evaluate the expression of VEGF in the gastric mucosa of H. pylori‐infected and H. pylori‐non‐infected dyspeptic patients. Fifteen H. pylori‐infected and 15 H. pylori‐non‐infected dyspeptic patients were studied. Diagnosis of H. pylori infection was based on rapid urease test and histology. VEGF protein expression was assessed by western blotting. VEGF mRNA expression was assessed by RT‐PCR. VEGF localization in the gastric mucosa and neo‐angiogenesis were determined by immunohistochemistry. VEGF protein and mRNA expression was significantly greater in H. pylori‐infected than in non‐infected patients. Immunohistochemistry showed that VEGF expression was more intense in the gastric gland compartment of H. pylori‐infected mucosa than in the non‐infected mucosa. The increase in VEGF expression was associated with a significant increase in neo‐angiogenesis as assessed by determination of CD34‐positive micro‐vessels. H. pylori gastritis is therefore associated with up‐regulation of VEGF expression, which parallels the increased formation of blood vessels in the gastric mucosa. It is postulated that increased VEGF expression and neo‐angiogenesis may contribute to H. pylori‐related gastric carcinogenesis. Copyright