Single-capsule bismuth-based quadruple therapy as a rescue therapy for Helicobacter pylori eradication.

INTRODUCTION: Helicobacter pylori (H. pylori) infection is highly prevalent in Portugal and its eradication is formally recommended. However, the indiscriminate use of antimicrobials has led to a drastic rise in antibiotic resistance, with the failure of traditional eradication schemes. A single-capsule bismuth-based quadruple therapy became recently available in Portugal. This study aims to evaluate the efficacy and safety of a bismuth-based quadruple therapy as a second-line or rescue therapy. PATIENTS AND METHODS: This was a multicentric study. All consecutive patients that were treated with bismuth-based quadruple therapy, as second-line or salvage treatment between July 2017 and April 2019 were enrolled. Their medical records were reviewed and clinical and laboratorial parameters, as well as data on treatment efficacy and adverse events were retrieved. Patients were also contacted by phone after treatment to confirm compliance, adverse events, and global satisfaction with this specific therapy. RESULTS: A total of 151 subjects were included (female-68.9%; mean age-56 ± 13.5 years). Patients were previously submitted to 212 eradication schemes (Median-1; 1-5; IQR:4): 33.5% triple clarithromycin-based, 25% sequential, 7.5% concomitant, 5.2% others, and in 28.8% it was not possible to know the previous eradication scheme(s) followed by the patient. The PPI of choice was esomeprazole (39.7%), followed by omeprazole (27.8%). Compliance was achieved in 93.4% and the overall eradication rate was 90.1% (95% CI: 84.6-94.2). Treatment-related adverse effects were experienced by 63 patients (41.7%; 95% CI: 34-49.7), being mild in 29, moderate in 19, and severe in 15. The main drawbacks of the treatment, from the patient's perspective, were the high price (47%) and the adverse effects (16.6%). Failure to eradicate H. pylori was correlated with the following: previous rifabutin-based scheme (0 vs. 100%; p = 0.010) and a higher number of previous treatment schemes (1.5 ± 0.7 vs. 2.3 ± 1.2; p < 0.001). CONCLUSION: In this South-European country a single-capsule bismuth-based quadruple therapy is an excellent option as a second-line or rescue therapy, with acceptable compliance and side effects.

Soluble human Suppression of Tumorigenicity 2 is associated with endoscopic activity in patients with moderate-to-severe ulcerative colitis treated with golimumab.

BACKGROUND: Suppressor of Tumorigenicity 2 (ST2) is an IL33 receptor detected in the mucosa and serum of ulcerative colitis (UC) patients. We evaluated soluble ST2 (sST2) as a surrogate biomarker of disease outcome and therapeutic response, in moderate-to-severe UC patients treated with golimumab. METHODS: We conducted an open-label single-arm multicentre prospective study. At screening/baseline, week 6 (W6) and week 16 (W16), clinical and endoscopic activity (total Mayo score), histologic activity (Geboes index) and biomarkers were evaluated. RESULTS: From 38 patients, 34 (89.5%) completed W6 and 29 (76.3%) completed W16. Mean age (±SD) was 34.6 ± 12.6 years; 55.9% were female. At W16, 62.1% achieved clinical response. Patients with endoscopic activity at W6 (n = 20) had higher baseline sST2 (median, 24.5 versus 18.7 ng/ml, p = 0.026) and no decrease from baseline (median change, 0.8 versus -2.7, p = 0.029). At W6, sST2 levels correlated with endoscopic activity (rs = 0.45, p = 0.007) but not with histological activity (rs = 0.25, p = 0.151). The best cut-offs for endoscopic activity were sST2 = 16.9 ng/ml (sensitivity = 85%; specificity = 71%) and faecal calprotectin (FC) = 353 µg/g (sensitivity = 90%, specificity = 67%). Patients with histological activity at W6 (n = 27) had higher baseline ST2 levels (median, 23.0 versus 13.7 ng/ml, p = 0.035). sST2 did not correlate with FC or serum C-reactive protein. FC levels correlated with histological activity and baseline FC were higher when Geboes ⩾3.1 at W6. CONCLUSIONS: sST2 may be a surrogate biomarker of UC activity and therapeutic response as it correlates with endoscopic and clinical activity at W6 of golimumab treatment, and subjects with endoscopic and histological activity at W6 had higher baseline ST2 levels.

Twelve-day quintuple regime containing four antibiotics as a rescue therapy for Helicobacter pylori eradication in the central region of Portugal

Background: Helicobacter pylori eradication rates with standard triple therapy in many countries are clinically unacceptable. Fluoroquinolone resistance is increasing and jeopardizing secondline regimens. There is a growing need for an effective strategy in patients who failed previous therapies. Methods: This is a single-center, non-randomized clinical study conducted in the central region of Portugal. Sixty-four patients were included with a positive 13C-urea breath test (UBT) or histology for H. pylori, and at least one failed eradication attempt. The patient cohort included 71.7% of females with a median of age of 52 (range 23-87). They were treated with a twelve-day regimen consisting of a proton-pump inhibitor (PPI) bid, amoxicillin at 1,000 mg 12/12h and levofloxacin at 500 mg bid during the first seven days, followed by PPI bid, clarithromycin at 500 mg 12/12 h and either tinidazole or metronidazole at 500 mg bid/tid for five days. Eradication was assessed by UBT. The local Ethics Committee approved this study. Results: Eradication therapy was prescribed due to dyspepsia (66.7%), peptic ulcer (10%) and thrombocytopenia (8.3%). The median number of failed therapies was one (range 1-4). The eradication rate was 64.6% according to an intention-to-treat analysis (95% CI: 53-77%), and 70% by the per-protocol analysis (95% CI: 58-82%). Age, smoking, indication for eradication, previous therapies and the use of a second-generation or full-dose PPI did not affect success rates. Conclusions: Even though treatment with four antibiotics was used, this «reinforced» therapy achieved suboptimal results. This fact highlights the lack of effective H. pylori antimicrobials and suggests that second-line treatment in our region should be prescribed according to susceptibility testing (AU)

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Twelve-day quintuple regime containing four antibiotics as a rescue therapy for Helicobacter pylori eradication in the central region of Portugal.

BACKGROUND: Helicobacter pylori eradication rates with standard triple therapy in many countries are clinically unacceptable. Fluoroquinolone resistance is increasing and jeopardizing second-line regimens. There is a growing need for an effective strategy in patients who failed previous therapies. METHODS: This is a single-center, non-randomized clinical study conducted in the central region of Portugal. Sixty-four patients were included with a positive 13C-urea breath test (UBT) or histology for H. pylori, and at least one failed eradication attempt. The patient cohort included 71.7% of females with a median of age of 52 (range 23-87). They were treated with a twelve-day regimen consisting of a proton-pump inhibitor (PPI) bid, amoxicillin at 1,000 mg 12/12 h and levofloxacin at 500 mg bid during the first seven days, followed by PPI bid, clarithromycin at 500 mg 12/12h and either tinidazole or metronidazole at 500 mg bid/tid for five days. Eradication was assessed by UBT. The local Ethics Committee approved this study. RESULTS: Eradication therapy was prescribed due to dyspepsia (66.7%), peptic ulcer (10%) and thrombocytopenia (8.3%). The median number of failed therapies was one (range 1-4). The eradication rate was 64.6% according to an intention-to-treat analysis (95% CI: 53-77%), and 70% by the per-protocol analysis (95% CI: 58-82%). Age, smoking, indication for eradication, previous therapies and the use of a second-generation or full-dose PPI did not affect success rates. CONCLUSIONS: Even though treatment with four antibiotics was used, this "reinforced" therapy achieved suboptimal results. This fact highlights the lack of effective H. pylori antimicrobials and suggests that second-line treatment in our region should be prescribed according to susceptibility testing.

Levofloxacin or Clarithromycin-based quadruple regimens: what is the best alternative as first-line treatment for Helicobacter pylori eradication in a country with high resistance rates for both antibiotics?

BACKGROUND: Helicobacter pylori eradication rates in Portugal are declining, due to increased resistance of this bacterium to antimicrobial agents, especially Clarithromycin. Quadruple Levofloxacin-containing regimens could be an option for first-line treatment, but its efficacy should be evaluated as fluoroquinolone resistance is rapidly increasing. Our aim was to compare the efficacy of Clarithromycin and Levofloxacin-based sequential quadruple therapies as first-line treatment options and determine factors associated with treatment failure. METHODS: A total of 200 Helicobacter pylori infected patients were retrospectively included (female 57.5%; average age: 53.2 ± 15.7) and received either 10-day sequential therapy (Proton-Pump Inhibitor + Amoxicillin 1 g bid for 5 days and Proton-Pump Inhibitor + Clarithromycin 500 mg + Metronidazole/Tinidazole 500 mg bid/tid in the following 5 days; group A) or a 10-day modified sequential therapy with Levofloxacin 500 mg id instead of Clarithromycin (group B). Eradication was confirmed with urea breath test. Variables that could influence success rate were analyzed. RESULTS: There were no differences between groups in terms of gender, age, smoking habits and indications for treatment. The eradication rate obtained with Clarithromycin-based sequential treatment was significantly higher than with Levofloxacin-based therapy (90%, CI95%: 84-96% vs. 79%, CI95%: 71-87%, p = 0.001). Using full-dose proton-pump inhibitor and high-dose Metronidazole in group A, and full-dose proton-pump inhibitor and prescription from a Gastroenterologist in group B were associated with eradication success. CONCLUSIONS: Ten-day Levofloxacin-based sequential treatment achieved inadequate efficacy rate (<80%) and should not be adopted as first-line therapy. Standard sequential therapy showed significantly better results in this naïve population. Using full-dose proton-pump inhibitor and higher doses of Metronidazole is essential to achieve such results.

NOD2 mutations and colorectal cancer - Where do we stand?

Due to the overwhelming burden of colorectal cancer (CRC), great effort has been placed on identifying genetic mutations that contribute to disease development and progression. One of the most studied polymorphisms that could potentially increase susceptibility to CRC involves the nucleotide-binding and oligomerization-domain containing 2 (NOD2) gene. There is growing evidence that the biological activity of NOD2 is far greater than previously thought and a link with intestinal microbiota and mucosal immunity is increasingly sought after. In fact, microbial composition may be an important contributor not only to inflammatory bowel diseases (IBD) but also to CRC. Recent studies have showed that deficient NOD2 function confers a communicable risk of colitis and CRC. Despite the evidence from experimental models, population-based studies that tried to link certain NOD2 polymorphisms and an increase in CRC risk have been described as conflicting. Significant geographic discrepancies in the frequency of such polymorphisms and different interpretations of the results may have limited the conclusions of those studies. Since being first associated to IBD and CRC, our understanding of the role of this gene has come a long way, and it is tempting to postulate that it may contribute to identify individuals with susceptible genetic background that may benefit from early CRC screening programs or in predicting response to current therapeutic tools. The aim of this review is to clarify the status quo of NOD2 mutations as genetic risk factors to chronic inflammation and ultimately to CRC. The use of NOD2 as a predictor of certain phenotypic characteristics of the disease will be analyzed as well.

Drug-Induced Acute Pancreatitis and Pseudoaneurysms: An Ominous Combination.

Rupture of pseudoaneurysms is rare but can be life-threatening complications of acute or chronic pancreatitis, usually due to enzymatic digestion of vessel walls crossing peripancreatic fluid collections. We report the case of a 40 year-old female, with multisystemic lupus and anticoagulated for prior thrombotic events, admitted for probable cyclosporine-induced acute pancreatitis. Hemodynamic instability occurred due to abdominal hemorrhage from two pseudoaneurysms inside an acute peri-pancreatic collection. Selective angiography successfully embolized the gastroduodenal and pancreatoduodenal arteries. The hemorrhage recurred two weeks later and another successful embolization was performed and the patient remains well to date. The decision to restart anticoagulants and to suspend cyclosporine was challenging and required a multidisciplinary approach. Despite rare, bleeding from a pseudoaneurysm should be considered when facing a patient with pancreatitis and sudden signs of hemodynamic instability.

Os pseudoaneurismas são complicações raras mas graves da pancreatite aguda ou crónica. São causados pela digestão enzimática de artérias que atravessam colecções inflamatórias. Descreve-se o caso de uma doente do sexo feminino, de 40 anos, com lúpus sistémico e anticoagulada por trombose venosa profunda, admitida por pancreatite aguda associada à ciclosporina. Apresentou sinais de hemorragia abdominal causada por dois pseudoaneurismas dentro de uma colecção peri-pancreática. Foi então realizada angiografia com embolização da artéria gastroduodenal e pancreatoduodenal. Houve recidiva duas semanas depois, com necessidade de nova embolização bem-sucedida. A decisão de suspender a ciclosporina e reintroduzir anticoagulantes nesta doente de alto-risco é controversa. Apesar de raros, os pseudoaneurismas devem ser considerados perante um doente com pancreatite e sinais de hemorragia.

From past sailors' eras to the present day: scurvy as a surprising manifestation of an uncommon gastrointestinal disease.

A 45-year-old man presented with follicular exanthema in his lower limbs, alternating bowel habits and significant weight loss. His medical history included seronegative arthritis, bipolar disease and an inconclusive diagnostic laparoscopy. Diagnostic work up revealed microcytic anaemia and multivitamin deficiency. Skin biopsy of the exanthema suggested scurvy. Owing to these signs of malabsorption, upper endoscopy with duodenal biopsies was performed, exhibiting villous atrophy and extensive periodic acid-Schiff-positive material in the lamina propria, therefore diagnosing Whipple's disease (WD). After starting treatment with ceftriaxone and co-trimoxazole, an impressive recovery was noted, as the wide spectrum of malabsorption signs quickly disappeared. After a year of antibiotics, articular and cutaneous manifestations improved, allowing the patient to stop taking corticosteroids and antidepressants. This truly unusual presentation reflects the multisystemic nature of WD, often leading to misdiagnosis of other entities. Scurvy is a rare finding in developed countries, but its presence should raise suspicion for small bowel disease.

Mediastinitis by Actinomyces meyeri after oesophageal stent placement.

Actinomyces meyeri is a Gram-positive anaerobic forming bacterium of the genus Actinomyces, part of the oral cavity's flora, and its classification remains an unresolved issue. It is an extremely rare cause of disease, occurring in middle-aged immunocompetent patients and frequently misdiagnosed as malignancy or lung abscess. A 56-year-old man diagnosed with oesophageal squamous cell carcinoma had an endoscopically placed stent to palliate his dysphagia. Two weeks later he presented with thoracalgia and fever, interpreted as a common lung infection. Owing to lack of improvement, additional examinations were undertaken revealing mediastinum involvement. Unlike the good prognosis usually associated with this infection, the patient eventually died, reflecting the aggressive nature of his underlying condition. To our knowledge, this is the first report of mediastinitis by A. meyeri, supporting the described propensity of this agent to disseminate, particularly to the thoracic cavity, although probably in this case with an iatrogenic contribution.