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| 1 | “Rescue” regimens after Helicobacter pylori treatment failure显示文摘Helicobacter pylori (H pylori) infection is the main cause of gastritis, gastroduodenal ulcer disease, and gastric cancer. After more than 20 years of experience in H pylori treatment, in my opinion, the ideal regimen to treat this infection is still to be found. Currently, apart from having to know first-line eradication regimens well, we must also be prepared to face treatment failures. Therefore, in designing a treatment strategy we should not focus on the results of primary therapy alone, but also on the final (overall) eradication rate. The choice of a 'rescue' treatment depends on which treatment is used initially. If a clarithromycin- based regimen was used initially, a subsequent metronidazole-based treatment (quadruple therapy) may be used afterwards, and then a levofloxacin- based combination would be a third 'rescue' option. Alternatively, it has recently been suggested that levofloxacin-based rescue therapy constitutes an encouraging second-line strategy, representing an alternative to quadruple therapy in patients with previous PPI-clarithromycin-amoxicillin failure, with the advantage of efficacy, simplicity and safety. In this case, a quadruple regimen may be reserved as a third-line rescue option. Finally, rifabutin-based rescue therapy constitutes an encouraging empirical fourth- line strategy after multiple previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole, tetracycline, and levofloxacin. Even after two consecutive failures, several studies have demonstrated that H pylori eradication can finally be achieved in almost all patients if several rescue therapies are consecutively given. Therefore, the attitude in H pylori eradication therapy failure, evenafter two or more unsuccessful attempts, should be to fight and not to surrender. | Javier P Gisbert | 2008 | World Journal of Gastroenterology2008，14，35： | 20 |
| 2 | 硅油填充术后眼组织病理改变显示文摘目的 探讨硅油对人眼内组织毒副作用的发生时间及机制。 方法 对19例因硅油填充术后严重并发症而摘除的眼球进行组织病理学观察。 结果 在感觉层视网膜、视网膜色素上皮(retinalpigm entepithelium ,RPE)细胞、视神经、视网膜前膜和下膜、虹膜、前房角、以及角膜内皮中均可见硅油小泡或小滴。在硅油填充短于9个月的眼中,硅油小泡仅见于视网膜表面(视网膜前膜及巨噬细胞内);硅油填充9个月以上的眼中,硅油小泡进入感觉层视网膜内。1例硅油填充39个月的眼中,视神经间质和蛛网膜下间隙受到硅油小泡弥漫性浸润。 结论 眼内硅油填充术后的并发症与硅油在眼内存留的时间长短有关。 | 马景学 Gisbert Richard Ulrich Schaudig Alexander A.Bialasiewicz | 1999 | 中华眼底病杂志1999，15，4： | 15 |
| 3 | Anemia and inflammatory bowel diseases显示文摘Too often anemia is considered a rare or unimportant manifestation in inflammatory bowel disease (IBD). However, over the last 10 years a number of studies have been conducted and the most relevant conclusions obtained are: (1) anemia is quite common in IBD; (2) although in many cases anemia parallels the clinical activity of the disease, many patients in remission have anemia, and iron, vitamin B12 and/or folic acid deficiency; (3) anemia, and also iron def iciency without anemia, have important consequences in the clinical status and quality of life of the patient; (4) oral iron can lead to gastrointestinal intolerance and failure of treatment; (5) intravenous iron is an effective and safe way to treat iron deficiency; (6) erythropoietin is needed in a significant number of cases to achieve normal hemoglobin levels. Thus, the clinician caring for IBD patients should have a comprehensive knowledge of anemia, and apply recently published guidelines in clinical practice. | Fernando Gomollón Javier P Gisbert | 2009 | World Journal of Gastroenterology2009，15，37： | 8 |
| 4 | Common misconceptions about 5-aminosalicylates and thiopurines in inflammatory bowel disease显示文摘Misconceptions are common in the care of patients with inflammatory bowel disease(IBD).In this paper,we state the most commonly found misconceptions in clinical practice and deal with the use of 5-aminosalicylates and thiopurines,to review the related scientificevidence,and make appropriate recommendations.Prevention of errors needs knowledge to avoid making such errors through ignorance.However,the amount of knowledge is increasing so quickly that one new danger is an overabundance of information.IBD is a model of a very complex disease and our goal with this review is to summarize the key evidence for the most common daily clinical problems.With regard to the use of 5-aminosalicylates,the best practice may to be consider abandoning the use of these drugs in patients withsmall bowel Crohn's disease.The combined approach with oral plus topical 5-aminosalicylates should be the first-line therapy in patients with active ulcerative colitis;once-daily treatment should be offered as a first choice regimen due to its better compliance and higher efficacy.With regard to thiopurines,they seem to be as effective in ulcerative colitis as in Crohn's disease.Underdosing of thiopurines is a form of undertreatment.Thiopurines should probably be continued indefinitely because their withdrawal is associated with a high risk of relapse.Mercaptopurine is a safe alternative in patients with digestive intolerance or hepatotoxicity due to azathioprine.Finally,thiopurine methyltransferase(TPMT)screening cannot substitute for regular monitoring because the majority of cases of myelotoxicity are not TPMT-related. | Javier P Gisbert María Chaparro Fernando Gomollón | 2011 | World Journal of Gastroenterology2011，17，30： | 8 |
| 5 | Optimizing clarithromycin-containing therapy for Helicobacter pylori in the era of antibiotic resistance显示文摘The efficacy of triple therapy for Helicobacter pylori infection has dramatically declined over the last decade,largely related to increasing clarithromycin resistance rates.From a microbiological standpoint,bismuth quadruple therapy is the ideal replacement since it combines drugs for which resistance does not impair its efficacy.Nonetheless,several obstacles such as availability,complexity or tolerance prevent a general implementation of bismuth quadruple therapy,so nonbismuth quadruple regimens remain the best firstline treatment in clinical practice in many geographical areas.We review the rationale and efficacy of several optimization tools(increasing the length of duration,high-dose acid suppression,probiotics),which have been largely evaluated over the last 5 years to increase the effectiveness of standard triple therapy.Then,we update available evidence on the effectiveness of several non-bismuth quadruple therapies(sequential,concomitant,hybrid,miscellaneous therapy),which have gained interest lately.We also revise evidence on the efficacy of the aforementioned optimization tools for non-bismuth quadruples schemes and,finally we provide a novel regionalized therapeutic algorithm,based on novel formulas recently developed for predicting the outcome of non-bismuth quadruple regimens,upon local antibiotic resistance rates. | Javier Molina-Infante Javier P Gisbert | 2014 | World Journal of Gastroenterology2014，20，30： | 7 |
| 6 | Second-line rescue triple therapy with levofloxacin after failure of non-bismuth quadruple “sequential” or “concomitant” treatment to eradicate H. pylori infection显示文摘 | Javier P. Gisbert Javier Molina-Infante Alicia C. Marin Gemma Vinagre Jesus Barrio Adrian Gerald McNicholl | 2013 | Scandinavian Journal of Gastroenterology2013，，6： | 6 |
| 7 | Second-line Therapy With Levofloxacin After Failure of Treatment to Eradicate Helicobacter pylori Infection: Time Trends in a Spanish Multicenter Study of 1000 Patients显示文摘 | Javier P. Gisbert ángeles Pérez-Aisa Fernando Bermejo Manuel Castro-Fernández Pedro Almela Jesús Barrio ángel Cosme Inés Modolell Felipe Bory Miguel Fernández-Bermejo Luis Rodrigo Jesús Ortu?o Pilar Sánchez-Pobre Sam Khorrami Alejandro Franco Albert Tomas | 2013 | Journal of Clinical Gastroenterology2013，，2： | 5 |
| 8 | Nonbismuth Quadruple (Concomitant) Therapy: Empirical and Tailored Efficacy versus Standard Triple Therapy for Clarithromycin‐Susceptible Helicobacter pylori and versus Sequential Therapy for Clarithromycin‐Resistant Strains显示文摘 | Javier Molina‐Infante Carmen Pazos‐Pacheco Gema Vinagre‐Rodriguez Belen Perez‐Gallardo Carmen Due?as‐Sadornil Moisés Hernandez‐Alonso Guadalupe Gonzalez‐Garcia Jose M. Mateos‐Rodriguez Miguel Fernandez‐Bermejo Javier P. Gisbert | 2012 | Helicobacter2012，，4： | 4 |
| 9 | Severe ulcerative colitis: At what point should we define resistance to steroids?显示文摘Corticoesteroids are still the first-line treatment for active ulcerative colitis more than 50 years after the publication of trials assessing their beneficial effect, with about a 50% remission rate in cases of severe disease. The mortality related to severe attacks of ulcerative colitis has decreased dramatically, to less than 1%, in experienced centers, due to the appropriate use of intensive therapeutic measures (intravenous steroids, fluids and electrolytes, artificial nutritional support, antibiotics, etc), along with timely decision-making about second-line medical therapy and early identification of patients requiring colectomy. One of the most difficult decisions in the management of severe ulcerative colitis is knowing for how long corticosteroids should be administered before deciding that a patient is a non-responder. Studies assessing the outcome of acute attacks after steroid initiation have demonstrated that, in steroid-sensitive patients, the response generally occurs early on, in the first days of treatment. Different indexes to predict treatment failure, when applied on the third day of treatment, have demonstrated a high positive predictive value for colectomy. In contrast to this resolute approach, which is the most widely accepted, other authors have suggested that in some patients a completeand prolonged response to steroids may take longer. Either way, physicians taking care of these patients need to recognize that severe ulcerative colitis may be life-threatening, and they need to be careful with excessively prolonged medical treatment and delayed surgery. | Maria Esteve Javier P Gisbert | 2008 | World Journal of Gastroenterology2008，14，36： | 3 |
| 10 | Preclinical evaluation of azathioprine plus buthionine sulfoximine in the treatment of human hepatocarcinoma and colon carcinoma显示文摘AIM: To evaluate the efficacy and the safety of azathioprine (AZA) and buthionine sulfoximine (BSO) bylocalized application into HepG2 tumor in vivo.METHODS: Different hepatoma and colon carcinoma cell lines (HepG2, HuH7, Chang liver, LoVo, RKO, SW-48, SW-480) were grown in minimal essencial medium supplemented with 10% fetal bovine serum and 1% antibiotic/antimycotic solution and maintained in a humidified 37 ℃ incubator with 5% CO2. These cells were pretreated with BSO for 24 h and then with AZA for different times. We examined the effects of this combination on some proteins and on cellular death. We also studied the eff icacy and the safety of AZA (6 mg/kg per day) and BSO (90 mg/kg per day) in HepG2 tumor growth in vivo using athymic mice. We measured safety by serological markers such as aminotransferases and creatine kinase.RESULTS: The in vitro studies revealed a new mechanism of action for the AZA plus BSO combination in the cancer cells compared with other thiopurines (6-mercaptopurine, 6-methylmercaptopurine, 6-thioguanine and 6-methylthioguanine) in combination with BSO. The cytotoxic effect of AZA plus BSO in HepG2 cells resulted from necroptosis induction in a mitochondrial-dependent manner. From kinetic studies we suggest that glutathione (GSH) depletion stimulates c-Jun amino-terminal kinase and Bax translocation in HepG2 cells with subsequent deregulation of mitochondria (cytochrome c release, loss of membrane potential), and proteolysis activation leading to loss of membrane integrity, release of lactate dehydrogenase and DNA degradation. Some of this biochemical and cellular changes could be reversed by N-acetylcysteine (a GSH replenisher). In vivo studies showed that HepG2 tumor growth was inhibited when AZA was combined with BSO.CONCLUSION: Our studies suggest that a combination of AZA plus BSO could be useful for localizedtreatment of hepatocellular carcinoma as in the currently used transarterial chemoembolization method. | Borja Hernández-Breijo Jorge Monserrat Sara Ramírez-Rubio Eva P Cuevas Diana Vara Inés Díaz-Laviada M Dolores Fernández-Moreno Irene D Román Javier P Gisbert Luis G Guijarro | 2011 | World Journal of Gastroenterology2011，17，34： | 2 |
| 11 | Update on non-bismuth quadruple (concomitant) therapy for eradication of Helicobacter pylori显示文摘 | Javier Gisbert Calvet | 2012 | Clinical and Experimental Gastroenterology (default)2012，，： | 2 |
| 12 | Current Management of Iron Deficiency Anemia in Inflammatory Bowel Diseases: A Practical Guide显示文摘 | Fernando Gomollón Javier P. Gisbert | 2013 | Drugs2013，，16： | 2 |
| 13 | The course of inflammatory bowel disease during pregnancy and postpartum: a prospective European ECCO‐EpiCom Study of 209 pregnant women显示文摘 | N. Pedersen A. Bortoli D. Duricova R. D′Inca M. R. Panelli J. P. Gisbert G. Zoli A. López‐Sanromán F. Castiglione G. Riegler V. Annese P. Gionchetti A. Prada E. D. Pont A. Timmer C. Felley M. Shuhaibar E. V. Tsianos C. Dejaco F. J. Baert T. Jess M. Lebech | 2013 | Aliment Pharmacol Ther2013，，5： | 2 |
| 14 | A review of rescue regimens after clarithromycin-containing triple therapy failure (for Helicobacter pylori eradication)显示文摘 | Alicia C Marin Adrian G McNicholl Javier P Gisbert | 2013 | Expert Opinion on Pharmacotherapy2013，，7： | 2 |
| 15 | Rescue Therapy for Helicobacter pylori Infection 2012显示文摘 | Javier P. Gisbert Ping-I Hsu | 2012 | Gastroenterology Research and Practice2012，，： | 2 |
| 16 | Systematic review with meta‐analysis: the declining risk of colorectal cancer in ulcerative colitis显示文摘 | C. Casta?o‐Milla M. Chaparro J. P. Gisbert | 2014 | Aliment Pharmacol Ther2014，，7： | 2 |
| 17 | Update on non-bismuth quadruple (concomitant) therapy for eradication of Helicobacter pylori显示文摘 | Javier Gisbert Calvet | 2012 | Clinical and Experimental Gastroenterology (default)2012，，： | 2 |
| 18 | Anemia and digestive diseases: An update for the clinician显示文摘Anemia and iron deficiency are so common in digestive diseases that often are underestimated and undertreated. Our goal is to review from classif ication to treatment of the diverse types of anemias in different digestive diseases to update our knowledge on diagnosis and treatment. With the goal of improving the prognosis and quality of life of digestive diseases patients, we will review current transfusion, intravenous iron, and erythropoietin roles in the treatment of anemia. | Fernando Gomollón Javier P Gisbert | 2009 | World Journal of Gastroenterology2009，15，37： | 2 |
| 19 | N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis: Randomized,placebo-controlled pilot study显示文摘AIM: To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine (NAC) co-administration with mesalamine in ulcerative colitis (UC) patients. METHODS: Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine (2.4 g/d) plus N-acetyl-L-cysteine (0.8 g/d) (group A) or mesalamine plus placebo (group B). Patients were monitored using the Modified Truelove-Witts Severity Index (MTWSI). The primary endpoint was clinical remission (MTWSI ≤ 2) at 4 wk. Secondary endpoints were clinical response (defined as a reduction from baseline in the MTWSI of ≥ 2 points) and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS: Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine (group A) and mesalamine plus placebo (group B) respectively (OR = 1.71; 95% CI: 0.46 to 6.36; P = 0.19; NNT = 7.7). Analysis of variance (ANOVA) of data indicated a significant reduction of MTWSI in group A (P = 0.046) with respect to basal condition without significant changes in the group B (P = 0.735) during treatment. Clinical responses were 66% (group A) vs 44% (group B) after 4 wk of treatment (OR = 2.5; 95% CI: 0.64 to 9.65; P = 0.11; NNT = 4.5). Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups. CONCLUSION: In group A (oral NAC combined with mesalamine) contrarily to group B (mesalamine alone), the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects. | Luis G Guijarro Jose Mate Javier P Gisbert Jose Luis Perez-Calle Ignacio Marín-Jimenez Encarna Arriaza Tomás Olleros Mario Delgado Maria S Castillejo David Prieto-Merino Venancio Gonzalez Lara Amado Salvador Pea | 2008 | World Journal of Gastroenterology2008，14，18： | 2 |
| 20 | Treatment of H elicobacter pylori Infection 2013显示文摘 | Anthony O’Connor Javier Molina‐Infante Javier P. Gisbert Colm O’Morain | 2013 | Helicobacter2013，，： | 2 |
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