EAACI guidelines on allergen immunotherapy: Prevention of allergy

Allergic diseases are common and frequently coexist. Allergen immunotherapy (AIT) is a disease‐modifying treatment for IgE‐mediated allergic disease with effects beyond cessation of AIT that may include important preventive effects. The European Academy of Allergy and Clinical Immunology (EAACI) has developed a clinical practice guideline to provide evidence‐based recommendations for AIT for the prevention of (i) development of allergic comorbidities in those with established allergic diseases, (ii) development of first allergic condition, and (iii) allergic sensitization. This guideline has been developed using the Appraisal of Guidelines for Research & Evaluation (AGREE II) framework, which involved a multidisciplinary expert working group, a systematic review of the underpinning evidence, and external peer‐review of draft recommendations. Our key recommendation is that a 3‐year course of subcutaneous or sublingual AIT can be recommended for children and adolescents with moderate‐to‐severe allergic rhinitis (AR) triggered by grass/birch pollen allergy to prevent asthma for up to 2 years post‐AIT in addition to its sustained effect on AR symptoms and medication. Some trial data even suggest a preventive effect on asthma symptoms and medication more than 2 years post‐AIT. We need more evidence concerning AIT for prevention in individuals with AR triggered by house dust mites or other allergens and for the prevention of allergic sensitization, the first allergic disease, or for the prevention of allergic comorbidities in those with other allergic conditions. Evidence for the preventive potential of AIT as disease‐modifying treatment exists but there is an urgent need for more high‐quality clinical trials.     

Exercise Doppler echocardiography in patients with pure mitral stenosis

Exercise increases heart rate and cardiac output and is helpful in the determination of dynamic mitral gradient in patients with mitral stenosis. However exercise is difficult to perform during cardiac catheterization in a premedicated recumbent patient and is only feasible when the brachial approach is used. Therefore, in the haemodynamic laboratory, exercise has important practical limitations. In order to obtain similar information using a reproducible and non-invasive technique, we tested the feasibility of combined two-dimensional and continuous wave Doppler echocardiography during exercise in a selected number of patients with pure mitral stenosis and in sinus rhythm. Seven patients, ranging from 14 to 48 years (average: 35 +/- 13), underwent baseline two-dimensional and continuous wave Doppler examinations, repeated after 2 minutes of supine bicycle exercise at a workload of 25, 50, 75 watts. The following parameters were derived and averaged: mean velocity of flow across the mitral valve, mean mitral valve gradient, diastolic filling period and heart rate. The increase in mitral valve flow was from 1.5 +/- 0.3 to 2.2 +/- 0.5 m/s (p less than 0.001); the corresponding increase in mean pressure gradient was from 11 +/- 3 to 21 +/- 8 mmHg (p less than 0.001). The decrease in the diastolic filling period was from 424 +/- 170 to 272 +/- 73 msec (p less than 0.005). The increase in heart rate was from 60 +/- 10 to 100 +/- 18 beats/minute (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Analgesic Efficacy of an Acetaminophen/Ibuprofen Fixed-dose Combination in Moderate to Severe Postoperative Dental Pain: A Randomized,Double-blind,Parallel-group,Placebo-controlled Trial

Purpose

Acute pain is a significant burden to the individual and to society. There is a clear need for a pain medication that provides improved analgesia over common analgesics, without compromising tolerability. The goal of this study was to determine the efficacy of a new fixed-dose combination of acetaminophen 975 mg and ibuprofen 292.5 mg (FDC 975/292.5) relative to acetaminophen or ibuprofen monotherapy, or placebo.

Microbiota That Affect Risk for Shigellosis in Children in Low-Income Countries

Pathogens in the gastrointestinal tract exist within a vast population of microbes. We examined associations between pathogens and composition of gut microbiota as they relate to Shigella spp./enteroinvasive Escherichia coli infection. We analyzed 3,035 stool specimens (1,735 nondiarrheal and 1,300 moderate-to-severe diarrheal) from the Global Enteric Multicenter Study for 9 enteropathogens. Diarrheal specimens had a higher number of enteropathogens (diarrheal mean 1.4, nondiarrheal mean 0.95; p<0.0001). Rotavirus showed a negative association with Shigella spp. in cases of diarrhea (odds ratio 0.31, 95% CI 0.17–0.55) and had a large combined effect on moderate-to-severe diarrhea (odds ratio 29, 95% CI 3.8–220). In 4 Lactobacillus taxa identified by 16S rRNA gene sequencing, the association between pathogen and disease was decreased, which is consistent with the possibility that Lactobacillus spp. are protective against Shigella spp.–induced diarrhea. Bacterial diversity of gut microbiota was associated with diarrhea status, not high levels of the Shigella spp. ipaH gene.     

Stenting for cervical tracheo-esophageal malignant fistula: a case report

Esophago-respiratory neoplastic fistulas present serious problems of management, mostly because of the severe status of the patient. The authors present the case of a 49-year-old patient with a malignant eso-tracheal fistula manifesting as mild dysphagia and dyspnoea. An endoscopic palliative treatment of the fistula was performed introducing a metallic coated stent into the esophagus. The multiple stent displacement required a definitive, very high positioning of the stent in the lower pharynx, with significant discomfort. Severe respiratory conditions regressed and the patient survived 6 months after the initial placement. The authors suggest endoscopic palliation with esophageal prosthesis as the therapeutic choice in those cases not amenable to surgery.     

Pharmacodynamic studies in suicidal digoxin poisoning (author's transl)

In two patients with suicidal digoxin poisoning the correlations between serum digoxin concentration and changes in the duration of QTc and the flattening of the T-waves were studied. The digoxin serum half-life following suicidal digoxin poisoning was in the first patient (10 mg beta-acetyl derivative of digoxin) 77 h, prolonged cause of renal insufficiency, and in the second patient 39.6 h. (20 mg beta-acetyl derivative of digoxin). In both patients the digoxin induced flattening of the T-wave reached a plateau of maximum efficacy at a serum level of 2-3 ng/ml with no further change up to a serum level of 13.2 ng/ml and 9.6 ng/ml respectively. A linear correlation, however, was found between the digoxin serum concentration and the digoxin induced shortening of QTc, r = 0.88 and r = 0.92 respectively. A plateau maximum efficacy was not found. The regression equations were y = -12.0 chi + 430.8 and y = -8.0 chi + 391.9 respectively. The shortening of QTc is therefore an important parameter for the diagnosis of digoxin poisoning. It can be determined very quick with no methodical problems.     

Downregulation of the renal outer medullary K+ channel ROMK by the AMP-activated protein kinase

The 5′-adenosine monophosphate-activated serine/threonine protein kinase (AMPK) is stimulated by energy depletion, increase in cytosolic Ca²⁺ activity, oxidative stress, and nitric oxide. AMPK participates in the regulation of the epithelial Na⁺ channel ENaC and the voltage-gated K⁺ channel KCNE1/KCNQ1. It is partially effective by decreasing PIP₂ formation through the PI3K pathway. The present study explored whether AMPK regulates the renal outer medullary K⁺ channel ROMK. To this end, cRNA encoding ROMK was injected into Xenopus oocytes with and without additional injection of constitutively active AMPK^γR70Q (AMPK^α1-HA+AMPK^β1-Flag+AMPKγ1^R70Q), or of inactive AMPK^αK45R (AMPK^α1K45R+AMPK^β1-Flag+AMPK^γ1-HA), and the current determined utilizing two-electrode voltage-clamp and single channel patch clamp. ROMK protein abundance was measured utilizing chemiluminescence in Xenopus oocytes and western blot in whole kidney tissue. Moreover, renal Na⁺ and K⁺ excretion were determined in AMPK^α1-deficient mice (ampk ^?/? ) and wild-type mice (ampk ^+/+ ) prior to and following an acute K⁺ load (111 mM KCl, 30 mM NaHCO₃, 4.7 mM NaCl, and 2.25 g/dl BSA) at a rate of 500 μl/h. As a result, coexpression of AMPK^γR70Q but not of AMPK^αK45R significantly decreased the current in ROMK1-expressing Xenopus oocytes. Injection of phosphatidylinositol PI_(4,5)P₂ significantly increased the current in ROMK1-expressing Xenopus oocytes, an effect reversed in the presence of AMPK^γR70Q. Under control conditions, no significant differences between ampk ^?/? and ampk ^+/+ mice were observed in glomerular filtration rate (GFR), urinary flow rate, serum aldosterone, plasma Na⁺, and K⁺ concentrations as well as absolute and fractional Na⁺ and K⁺ excretion. Following an acute K⁺ load, GFR, urinary flow rate, serum aldosterone, plasma Na⁺, and K⁺ concentration were again similar in both genotypes, but renal absolute and fractional Na⁺ and K⁺ excretion were higher in ampk ^?/? than in ampk ^+/+ mice. According to micropuncture following a K⁺ load, delivery of Na⁺ to the early distal tubule but not delivery of K⁺ to late proximal and early distal tubules was increased in ampk ^?/? mice. The upregulation of renal ROMK1 protein expression by acute K⁺ load was more pronounced in ampk ^?/? than in ampk ^+/+ mice. In conclusion, AMPK downregulates ROMK, an effect compromising the ability of the kidney to excrete K⁺ following an acute K⁺ load.     

Atrial Fibrillation: Inflammation in Disguise?

Atrial fibrillation is highly prevalent, and affected patients are at an increased risk of a number of complications, including heart failure and thrombo‐embolism. Over the past years, there has been increasing interest in the role of inflammatory processes in atrial fibrillation, from the first occurrence of the arrhythmia to dreaded complications such as strokes or peripheral emboli. As the standard drug combination which aims at rate control and anticoagulation only offers partial protection against complications, newer agents are needed to optimize treatment. In this paper, we review recent knowledge regarding the impact of inflammation on the occurrence, recurrence, perpetuation and complications of the arrhythmia, as well as the role of anti‐inflammatory therapies in the treatment for the disease.