First-line eradication rates comparing two shortened non-bismuth quadruple regimens against Helicobacter pylori: an open-label, randomized, multicentre clinical trial.

OBJECTIVES: Helicobacter pylori eradication remains a challenge. Non-bismuth-based quadruple regimens (NBQR) have shown high eradication rates (ER) elsewhere that need to be locally confirmed. The objective of this study was to compare the first-line ER of a hybrid therapy (20 mg of omeprazole twice daily and 1 g of amoxicillin twice daily for 10 days, adding 500 mg of clarithromycin twice daily and 500 mg of metronidazole every 8 h for the last 5 days; OA-OACM) with that of a 10 day concomitant regimen consisting of taking all four drugs twice daily every day (including 500 mg of metronidazole every 12 h; OACM). A 10 day arm with standard triple therapy (OAC; 20 mg of omeprazole/12 h, 1 g of amoxicillin/12 h and 500 mg of clarithromycin/12 h) was included. PATIENTS AND METHODS: Three hundred consecutive patients were randomized (1: 2: 2) into one of the three following regimens: (i) OAC (60); (ii) OA-OACM (120); and (iii) OACM (120). Eradication was generally confirmed by a [(13)C]urea breath test at least 4 weeks after the end of treatment. Adverse events and compliance were assessed. EudraCT: 2011-006258-99. RESULTS: ITT cure rates were: OAC, 70.0% (42/60) (95% CI: 58.3-81.7); OA-OACM, 90.8% (109/120) (95% CI: 85.6-96.0); and OACM, 90.0% (107/119) (95% CI: 84.6-95.4). PP rates were: OAC, 72.4% (42/58) (95% CI: 60.8-84.1); OA-OACM, 93.9% (108/115) (95% CI: 89.5-98.3); and OACM, 90.3% (102/113) (95% CI: 84.8-95.8). Both NBQR significantly improved ER compared with OAC (P < 0.01), but no differences were seen between them. Mean compliance was elevated [98.0% (SD = 9.8)] with no differences between groups. There were more adverse events in the quadruple arms (OACM, 65.8%; OA-OACM, 68.6%; OAC, 46.6%; P < 0.05), but no significant differences between groups in terms of severity were seen. CONCLUSIONS: Hybrid and concomitant regimens show good ER against H. pylori infection with an acceptable safety profile. They clearly displace OAC as first-line regimen in our area.

Varicella-zoster virus (VZV) infection as a possible cause of Ogilvie's syndrome in an immunocompromised host.

We describe an immunodeficient adult with Ogilvie's syndrome preceding a disseminated papulovesicular skin rash in whom varicella-zoster virus infection was demonstrated by PCR assay in cutaneous and colonic biopsy specimens. In view of the significant morbidity and mortality that this condition carries, early and accurate molecular diagnosis and timely treatment are strongly recommended.

Antimicrobial susceptibility of Helicobacter pylori to six antibiotics currently used in Spain.

BACKGROUND: Antibiotic resistance is directly related to the loss of efficacy of currently accepted Helicobacter pylori therapies. Knowledge of the antibiotic susceptibility in a local area can contribute to the design of specific 'à la carte' treatments. The aim of this study was to analyse the susceptibility of H. pylori isolates to six conventional antibiotics currently used in a northern region of Spain. METHODS: Seventy-one isolates were obtained from gastric biopsies of 76 consecutive adult patients suffering from peptic ulcer disease, dyspepsia or familial gastric cancer and known to be infected with H. pylori by conventional methods. Susceptibility testing was performed for amoxicillin, ciprofloxacin, levofloxacin, clarithromycin, metronidazole and tetracycline using the Etest method. RESULTS: The prevalence rates of resistance were as follows: amoxicillin, 1.4% [95% confidence interval (CI) 0.0-7.6]; clarithromycin, 14.7% (95% CI 7.3-25.4); ciprofloxacin, 14.3% (95% CI 7.1-24.7); levofloxacin, 14.5% (95% CI 7.2-25.0); metronidazole, 45.1% (95% CI 33.2-57.3); and tetracycline, 0% (95% CI 0.0-5.1). CONCLUSIONS: Our study confirms an increasing rate of resistance to levofloxacin that equals that of clarithromycin in our healthcare area. This fact may reflect a wide and indiscriminate use of the former antibiotic and could account for a loss of clinical effectiveness of levofloxacin-containing regimens. Moreover, clarithromycin resistance rates remain stable, which could allow us to maintain its use in our area.

Levofloxacin versus clarithromycin in a 10 day triple therapy regimen for first-line Helicobacter pylori eradication: a single-blind randomized clinical trial.

BACKGROUND: There is growing evidence that the standard triple therapy against Helicobacter pylori infection is losing clinical effectiveness. A triple therapy regimen with levofloxacin, amoxicillin and a proton pump inhibitor has been reported to be effective and well tolerated, and this regimen has been suggested as an alternative first-line treatment. The aim of this single-blind randomized clinical trial was to compare the eradication success of two first-line triple therapy regimens in the north of Spain: clarithromycin, amoxicillin and omeprazole (CAO) versus levofloxacin, amoxicillin and omeprazole (LAO). MATERIALS AND METHODS: A total of 250 consecutive patients diagnosed by conventional methods with H. pylori infection were randomized into one of two 10 day therapeutic regimens: standard CAO (n = 128) or LAO (n = 122). Eradication was confirmed by the (13)C-urea breath test. Adverse effects and compliance were also assessed. The clinical trial registration number was HPL08001HCLAD (EudraCT: 2008-001892-31). RESULTS: Intention-to-treat cure rates were: CAO, 75.0% (96/128; 95% CI: 66.6%-82.2%) and LAO, 82.8% (101/122; 95% CI: 74.9%-89.0%). Per-protocol cure rates were: CAO, 78.0% (96/123; 95% CI: 69.7%-85.0%) and LAO, 83.1% (98/118; 95% CI: 75.0%-89.3%). There were no statistically significant differences in effectiveness between the two regimens. In addition, no relevant differences in compliance or adverse effects were demonstrated. CONCLUSIONS: Levofloxacin-based treatment for H. pylori infection did not improve upon the eradication rate of the standard clarithromycin-based triple therapy in this study. This may reflect the progressive increase in in vitro resistance rates to levofloxacin observed in our region.

Methylprednisolone in adults hospitalized with COVID-19 pneumonia : An open-label randomized trial (GLUCOCOVID).

PURPOSE: To determine whether a 6-day course of methylprednisolone (MP) improves outcome in patients with severe SARS-CoV­2 (Corona Virus Disease 2019 [COVID-19]). METHODS: The study was a multicentric open-label trial of COVID-19 patients who were aged ≥ 18 years, receiving oxygen without mechanical ventilation, and with evidence of systemic inflammatory response who were assigned to standard of care (SOC) or SOC plus intravenous MP (40 mg bid for 3 days followed by 20 mg bid for 3 days). The primary outcome was a composite of death, admission to the intensive care unit, or requirement for noninvasive ventilation. Both intention-to-treat (ITT) and per protocol (PP) analyses were performed. RESULTS: A total of 91 patients were screened, and 64 were randomized (mean age70 ± 12 years). In the ITT analysis, 14 of 29 patients (48%) in the SOC group and 14 of 35 (40%) in the MP group suffered the composite endpoint (40% versus 20% in patients under 72 years and 67% versus 48% in those over 72 years; p = 0.25). In the PP analysis, patients on MP had a significantly lower risk of experiencing the composite endpoint (age-adjusted risk ratio 0.42; 95% confidence interval, CI 0.20-0.89; p = 0.043). CONCLUSION: The planned sample size was not achieved, and our results should therefore be interpreted with caution. The use of MP had no significant effect on the primary endpoint in ITT analysis; however, the PP analysis showed a beneficial effect due to MP, which consistent with other published trials support the use of glucocorticoids in severe cases of COVID-19.

One not to miss: Tuberculous tracheal stenosis.

We describe a patient who developed severe tracheal stenosis while on treatment for pulmonary tuberculosis. Bronchoscopic-guided balloon dilatation succeeded in managing this disorder. Diagnosis of tracheobronchial tuberculosis requires a high index of suspicion because symptoms are usually attributed to co-existing pulmonary disease and airway lesions are not detectable on chest x-ray. Interventional bronchoscopy is employed to restore airway patency once significant stenosis develops. Should bronchoscopic measures fail, surgical options can be considered.

Fatal acute hepatitis after sequential treatment with levofloxacin, doxycycline, and naproxen in a patient presenting with acute Mycoplasma pneumoniae infection.

BACKGROUND: The diagnosis of drug-induced liver injury relies on comprehensive clinical assessments due to the absence of an established biomarker or pathognomonic features of liver histology. However, prompt recognition of a culprit drug as the cause of liver injury is the most important aspect in the management of hepatotoxicity. CASE SUMMARY: A 63-year-old white male (85 kg) was admitted because of community-acquired pneumonia with associated pericarditis and subclinical hepatitis, subsequently related to acute Mycoplasma pneumoniae infection (diagnostic positive immuno-globulin M enzyme immunoassay, on hospital days 5 and 20). The patient had received cisplatin and radiotherapy from March to May 2006, as treatment for pharyngolaryngeal squamous cell carcinoma T3N0M0 without subsequent evidence of localized or meta-static recurrent disease (last oncologic consultation, May 17, 2007). He reported alcohol ingestion until March 2006 but no known liver disease, blood transfusion, or exposure to mushrooms or industrial cleaning solvents. Results of serologic tests for viral and nonviral infectious hepatitis, iron and copper studies, and tests for autoantibodies were normal or negative. The patient became initially asymptomatic and fever disappeared following sequential treatment with levo-floxacin (500 mg BID), doxycycline (100 mg BID), and naproxen (500 mg TID). However, on hospital day 10 jaundice and a significant elevation (alanine aminotransferase, 1577 U/L; aspartate amino-transferase, 1754 U/L; alkaline phosphatase, 189 U/L) of serum transaminases appeared. Despite the discontinuation of all medication, the patient gradually deteriorated and died 27 days after admission due to acute fulminant hepatic failure. Autopsy revealed massive hepatic necrosis, inflammatory changes with presence of eosinophils, and cholestasis. An objective causality assessment scale (Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale) suggested that each of the 3 drugs could "probably" (score = 6) be related to the patient's fulminant hepatitis. The Naranjo Adverse Drug Reactions Probability Scale assessment for the same drugs indicated a "possible" causal relation (score = 2). CONCLUSION: We report a case of lethal hepatitis possibly/probably associated with levofloxacin, doxy-cycline, and naproxen in a patient with acute M pneumoniae infection.

Interstitial Lung Disease in a Patient Treated with Denosumab.

Denosumab is an antiresorptive agent widely used for treating osteoporosis. Atypical femur fractures, osteonecrosis of the jaw and hypocalcaemia are well-known possible adverse effects of this drug. We present, to our knowledge, the first case report in the English literature of clinically significant interstitial lung disease likely related to denosumab. LEARNING POINTS: Denosumab is a fully human monoclonal antibody which may rarely cause interstitial lung disease (ILD).The findings from this isolated case report of ILD in a patient taking denosumab do not prove causality.Nevertheless, we suggest that patient exposure to denosumab should be considered in a patient with ILD.

[Penetrating atherosclerotic ulcer of the aortic arch]. / Ulcera aterosclerótica penetrada en cayado aórtico.

Acute aortic syndrome is an acute lesion of the aortic wall involving the aortic tunica media, with a potencial risk of severe complications. The aortic dissection is the main cause (80%), but other entities, such as the intramural hematoma (15%) and the penetrating aortic ulcer (5%), are a less frequent cause. A 49-year-old man, hypertensive, dyslipemic, and without drug treatment, was admitted in the emergency service due to a sudden pain in the mid-chest approximately 3 hr previously. No pain radiation or hemodynamic affectation were apparent. The symptoms were resistant to nitroglycerin and morphine. The chest X rays, electrocardiograms and cardiac enzymes were normal. A computed tomographic angiography was taken because an acute aortic symdrome was suspected (figure 1A). It showed a sacular formation compatible with an aortic ulcer in the left contour of the aortic arch, and situated one-half cm beyond the left subclavian artery and above a zone of parietal calcification. The acute symtomatic penetrating aortic ulcer syndrome carries an equal or greater risk than the typical dissection; therefore invasive treatment was recommended. Because of the potential risk of severe complications and unpredictable prognosis, a self-expanding endoluminal prosthesis (stent graft), Relay 30 x 100 mm, was implanted for femoral artery access with satisfactory results (figure 1B and 1C).

Indacaterol-induced severe constipation and abdominal pain: is there a role for colonic ß3-adrenoceptors?

Indacaterol is an ultra-long-acting ß2-adrenoceptor agonist that is indicated for the maintenance treatment of chronic obstructive pulmonary disease. We present a patient with severe chronic constipation and abdominal pain most probably induced by this medicament. Symptoms rapidly disappeared within 2 days after the drug withdrawal. As far as we know, no reports describing severe chronic constipation associated with indacaterol have been published. The Naranjo algorithm score and the Edwards and Aronson scale for causality assessment of suspected adverse drug reactions indicated a probable relationship between indacaterol use and constipation. Indacaterol-induced constipation is an unusual event that could be accounted for the high intrinsic activity of the drug on colonic ß3-adrenoreceptors, resulting in an inhibitory control of smooth muscle function and intestinal secretion. Clinicians should monitor such a possibility when prescribing this drug and maybe avoid its use in patients with a history of difficult bowel evacuation.