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John C Coffman,1 Justin Jones,2 Nasir Hussain,1 Mahmoud Abdel-Rasoul,3 Peter W Dienhart,1 Samiha M Nasser,1 Charles L Hamilton III,1 Jonathan A Lipps,1 Michael Kushelev1 1Department of Anesthesiology, The Ohio State University, Columbus, OH, USA; 2Department of Anesthesiology and Pain Management, The Metrohealth System, Cleveland, OH, USA; 3Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USACorrespondence: John C Coffman, Department of Anesthesiology, The Ohio State University, 410 W. 10th Ave, Columbus, OH, 43210, USA, Tel +1 614 293 8487, Email john.coffman@osumc.eduIntroduction: Hip arthroscopy is commonly performed as an outpatient procedure and effective postoperative pain management is important to provide quality patient care and enable timely discharge. Multiple regional nerve blocks have been described for pain relief after hip arthroscopy, but there is no consensus on the optimal technique. This retrospective investigation aimed to compare quadratus lumborum (QL) and pericapsular nerve group (PENG) blocks to determine if there are differences in analgesic outcomes after outpatient hip arthroscopy.Methods: A total of 50 consecutive patients that received QL block and 50 that received PENG block for outpatient hip arthroscopy were identified and compared to determine if there were any differences in the primary outcome of total perioperative opioid consumption prior to discharge from the surgery center. Important secondary analgesic outcomes include postoperative opioid consumption, verbal rating scale (VRS) pain scores or total time in the recovery area. Summary statistics of relevant variables are compared and reported between study groups (QL versus PENG).Results: For QL and PENG groups, no significant differences were observed in total perioperative oral morphine equivalents (OME) (69.5 vs 60mg; p=0.40), postoperative OME (15 vs 15.3mg; p=0.96) or maximum pain scores in the recovery area (7.0 vs 6.0; p=0.41). Postoperatively, QL block patients were in PACU for a greater length of time after surgery than PENG block patients (89.5 vs 72 minutes; p< 0.001). No patients had uncontrolled pain requiring emergency room visits or hospital admission within 24 hours. No neurologic complications or instances of motor weakness were reported after QL or PENG blocks.Conclusion: This retrospective study observed similar opioid requirements and pain scores for patients receiving QL versus PENG block for hip arthroscopy, though PENG block patients had shorter times in the recovery area. Prospective, controlled trials are required to further explore and confirm these findings.Keywords: quadratus lumborum, QL, pericapsular nerve group, PENG, Hip arthroscopy

Asthma is a heterogeneous disease commonly driven by allergic and/or eosinophilic inflammation, both of which may be present in severe disease. Most approved biologics for severe asthma are indicated for specific phenotypes and target individual downstream type 2 components of the inflammatory cascade. Tezepelumab, a human monoclonal antibody (immunoglobulin G2λ), binds specifically to thymic stromal lymphopoietin (TSLP), an epithelial cytokine that initiates and sustains allergic and eosinophilic inflammation in asthma. By blocking TSLP, tezepelumab has demonstrated efficacy across known asthma phenotypes and acts upstream of all current clinically used biomarkers. In a pooled analysis of the phase 2b PATHWAY (NCT02054130) and phase 3 NAVIGATOR (NCT03347279) studies, compared with placebo, tezepelumab reduced the annualized asthma exacerbation rate over 52 weeks by 62% (95% confidence interval [CI]: 53, 70) in patients with perennial aeroallergen sensitization (allergic asthma); by 71% (95% CI: 62, 78) in patients with a baseline blood eosinophil count ≥300 cells/μL; and by 71% (95% CI: 59, 79) in patients with allergic asthma and a baseline blood eosinophil count ≥300 cells/μL. This review examines the efficacy and mode of action of tezepelumab in patients with allergic asthma, eosinophilic asthma and coexisting allergic and eosinophilic phenotypes., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Introduction: Laparoscopic sleeve gastrectomy (LSG) has become a common surgical procedure. The value of routine histopathologic examination of the LSG specimens remains, however, a controversial issue. Helicobacter pylori was the most prevalent finding in several previous studies, but the overall results were dissimilar. We aim to assess the prevalence of Helicobacter pylori and other histopathologic findings in LSG specimens and the effect of increasing the number of sections for histology, from LSG specimens, on the rates of abnormal findings., Methods: We retrospectively reviewed the histopathologic data of all patients who had undergone LSG, in a tertiary care center, over a 4-year period ( n = 481). Patient characteristics and histopathologic findings were recorded and analyzed., Results: Inactive chronic gastritis was the most common histopathologic finding (62.16%) followed by Helicobacter pylori gastritis (35.34%). Intestinal metaplasia was identified in 1.66% of the cases. There was no diagnosis of malignancy. Increasing the number of sections submitted for histopathologic examination resulted in a significantly higher rate of H. pylori gastritis detection., Conclusion: Routine histopathologic examination of LSG specimens may detect H. pylori in a significant proportion of patients, and increasing the number of sections for histology from LSG specimens improves the rate of detection of this bacterium and identifies individuals who may benefit from treatment., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020 Nada A. Sabbah et al.)

Objective: To identify the incidence of hypercalcemia and hypocalcemia in zoledronic acid and denosumab groups. Secondary objective was to determine the correlation between calcium supplement and calcium level control., Methods: An observational retrospective cohort study was conducted by reviewing patient electronic records, laboratory results, and medication charts from 1 August 2015 to 31 July 2016. Adult cancer patients who were diagnosed with bone metastasis secondary to a solid tumor or multiple myeloma and who received either zoledronic acid or denosumab were included. Other indications for bone targeting agents were excluded. Data of bone targeting agents administration encounters were collected, evaluated, and analyzed., Results: A total of 1141 encounters (for 271 patients) were included. The incidence of hypocalcemia was higher in denosumab compared to zoledronic acid group (5.5% vs. 3.1%, OR = 0.55, 95% CI [0.3-1.0]; P = 0.05). Hypercalcemia incidence was also higher in denosumab group (8.5% vs. 3.1%, OR = 2.9, 95% CI [1.68-5.03]; P < 0.0001). Breast cancer was the most common malignancy associated with hypocalcemia (27.3%) followed by ovarian cancer (25%) and multiple myeloma (22.7%). The risk of developing hypocalcemia was reduced by 16% in patients receiving calcium supplementation (RR = 0.84, 95% CI [0.55-1.20]; P = 0.39)., Conclusion: Denosumab use was associated with higher rates of both hypercalcemia and hypocalcemia compared to zoledronic acid. Adequate supplementation with calcium substantially reduced the risk of hypocalcemia. Our results highlight the importance of taking preventative measures upon bone targeting agents initiation and during treatment including regular monitoring of calcium levels and providing supplements accordingly.

The present study concerns measurement of the radon concentration in drinking and irrigation waters obtained from the eastern part of Oman, in particular in regard to water quality assessment of the region. The samples were collected from different places covering most types of water sources in the region. A passive and time-integrated track etch detector (LR-115 type II) combined with a high-resolution optical microscope has been used to obtain the radon concentration in the studied samples. Values of dissolved radon in water varied among the water sources; the highest concentration of radon was found to be 363 Bq m-3 in a drinking water sample while well water used for irrigation showed the lowest value, at 140 Bq m-3. Measured data for all water sources are below the permissible limit of 11.1 kBq m-3 recommended by the US-EPA. Annual effective doses for the studied samples were in the range 0.38-0.99 μSv y-1 which is significantly less than the action level recommended by the WHO (0.1 mSv y-1), indicating that the water sources in the Jalan BBH region of Oman are safe to use. The obtained data may serve as a reference for any future radiological study of the waterbody of this region., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

This is an updated guideline for the diagnosis and management of allergic and non-allergic rhinitis, first published in 2007. It was produced by the Standards of Care Committee of the British Society of Allergy and Clinical Immunology, using accredited methods. Allergic rhinitis is common and affects 10-15% of children and 26% of adults in the UK, it affects quality of life, school and work attendance, and is a risk factor for development of asthma. Allergic rhinitis is diagnosed by history and examination, supported by specific allergy tests. Topical nasal corticosteroids are the treatment of choice for moderate to severe disease. Combination therapy with intranasal corticosteroid plus intranasal antihistamine is more effective than either alone and provides second line treatment for those with rhinitis poorly controlled on monotherapy. Immunotherapy is highly effective when the specific allergen is the responsible driver for the symptoms. Treatment of rhinitis is associated with benefits for asthma. Non-allergic rhinitis also is a risk factor for the development of asthma and may be eosinophilic and steroid-responsive or neurogenic and non- inflammatory. Non-allergic rhinitis may be a presenting complaint for systemic disorders such as granulomatous or eosinophilic polyangiitis, and sarcoidoisis. Infective rhinitis can be caused by viruses, and less commonly by bacteria, fungi and protozoa., (© 2017 John Wiley & Sons Ltd.)

Objectives: This study assesses the extent to which the strength of a recommendation in a World Health Organization (WHO) guideline affects uptake of the recommendation in national guidelines., Study Design and Setting: The uptake of recommendations included in HIV and TB guidelines issued by WHO from 2009 to 2013 was assessed across guidelines from 20 low- and middle-income countries in Africa and Southeast Asia. Associations between characteristics of recommendations (strength, quality of the evidence, type) and uptake were assessed using logistic regression., Results: Eight WHO guidelines consisting of 109 strong recommendations and 49 conditional recommendations were included, and uptake assessed across 44 national guidelines (1,255 recommendations) from 20 countries. Uptake of WHO recommendations in national guidelines was 82% for strong recommendations and 61% for conditional recommendations. The odds of uptake comparing strong recommendations and conditional recommendations was 1.9 (95% confidence interval: 1.4, 2.7), after adjustment for quality of evidence. Higher levels of evidence quality were associated with greater uptake, independent of recommendation strength., Conclusion: Guideline developers should be confident that conditional recommendations are frequently adopted. The fact that strong recommendations are more frequently adopted than conditional recommendations underscores the importance of ensuring that such recommendations are justified., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aim: To investigate the influence of proton pump inhibitors (PPIs) exposure on the diagnosis of Helicobacter pylori (H. pylori) gastritis and intestinal metaplasia., Methods: Chronic PPI use is associated with masking of H. pylori infection. Patients with H. pylori infection are predisposed to gastric and duodenal ulcers, and long-term infection with this organism has been associated with gastric mucosal atrophy and serious long-term complications, such as gastric lymphoma and adenocarcinoma. Three hundred patients diagnosed with gastritis between January 2008 and April 2010 were included in our study. The computerized medical database of these patients was reviewed retrospectively in order to assess whether the type of gastritis diagnosed (H. pylori vs non-H. pylori gastritis) is influenced by PPI exposure. H. pylori density was graded as low, if corresponding to mild density following the Updated Sydney System, or high, if corresponding to moderate or severe densities in the Updated Sydney System., Results: Patients were equally distributed between males and females with a median age at the time of diagnosis of 50 years old (range: 20-87). The histological types of gastritis were classified as H. pylori gastritis (n = 156, 52%) and non-H. pylori gastritis (n = 144, 48%). All patients with non-H. pylori gastritis had inactive chronic gastritis. Patients with no previous PPI exposure were more likely to be diagnosed with H. pylori gastritis than those with previous PPI exposure (71% vs 34.2%, P < 0.001). Intestinal metaplasia was more likely to be detected in the latter patients (1.4% vs 6.5%, P = 0.023). Multivariate analysis has also demonstrated that in the presence of previous PPI exposure (OR = 0.217, 95%CI: 0.123-0.385), GERD (OR = 0.317, 95%CI: 0.132-0.763, P = 0.01), alcohol intake (OR = 0.396, 95%CI: 0.195-0.804, P = 0.01), the detection of H. pylori was less likely. Chronic use of PPIs may mask H. pylori infections promoting the diagnosis of non-H. pylori gastritis and leads to a significant drop in H. pylori densities and to an increased risk of intestinal metaplasia., Conclusion: The use of PPIs masks H. pylori infection, promotes the diagnosis of non-H. pylori inactive chronic gastritis diagnosis, and increases the incidence of intestinal metaplasia.

Purpose: To assess the efficacy of chlorhexidine monotherapy for Acanthamoeba keratitis, and to determine the therapeutic outcomes of concomitant topical corticosteroids., Methods: In this prospective interventional case series, 31 eyes of 31 patients with Acanthamoeba keratitis (AK) were treated with chlorhexidine 0.02% as monotherapy, from April 2010 to April 2011. The diagnosis of AK was made based on clinical manifestations and positive confocal microscopic (confoscan 3.4, Nidek Co. Ltd., Gamagori, Japan) results. We report the percentage of a favorable clinical response within two weeks of initiating treatment, worsening of the infection while receiving chlorhexidine, recovery of visual acuity (VA), duration of treatment with chlorhexidine and corticosteroids, necessity for addition of other anti-Acanthamoeba agents, presence of corneal scar at the end of the treatment, and need for penetrating keratoplasty (PK)., Results: Two weeks after initiation of chlorhexidine, improvement in signs and symptoms was observed in 26 (83.9%) patients but 3 eyes required the addition of propamidine. After initial improvement in one patient, the infection worsened, necessitating the addition of Polyhexamethylene Biguanide (PHMB) and propamidine. A total of 26 (83.9%) patients received topical corticosteroids with mean duration of 65.8 ± 45.1 days. In 22 (71%) eyes, final visual acuity was ≥0.80. Improved VA occurred in 29 eyes (93.5%). Optical PK was considered in 3 (9.7%) eyes and a corneal scar developed in 8 (25.8%) eyes., Conclusion: Chlorhexidine is effective for monotherapy in AK and could be a good choice for initiating treatment. After the initial response to anti-Acanthamoeba agents, corticosteroids can be used as adjunctive therapy depending on the clinical condition.

This guidance for the management of patients with chronic urticaria and angioedema has been prepared by the Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI). The guideline is based on evidence as well as on expert opinion and is aimed at both adult physicians and paediatricians practising in allergy. The recommendations are evidence graded. During the development of these guidelines, all BSACI members were included in the consultation process using a Web-based system. Their comments and suggestions were carefully considered by the Standards of Care Committee. Where evidence was lacking, a consensus was reached by the experts on the committee. Included in this management guideline are clinical classification, aetiology, diagnosis, investigations, treatment guidance with special sections on children with urticaria and the use of antihistamines in women who are pregnant or breastfeeding. Finally, we have made recommendations for potential areas of future research., (© 2015 John Wiley & Sons Ltd.)

The Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI) and an expert panel have prepared this guidance for the management of immediate and non-immediate allergic reactions to penicillins and other beta-lactams. The guideline is intended for UK specialists in both adult and paediatric allergy and for other clinicians practising allergy in secondary and tertiary care. The recommendations are evidence based, but where evidence is lacking, the panel reached consensus. During the development of the guideline, all BSACI members were consulted using a Web-based process and all comments carefully considered. Included in the guideline are epidemiology of allergic reactions to beta-lactams, molecular structure, formulations available in the UK and a description of known beta-lactam antigenic determinants. Sections on the value and limitations of clinical history, skin testing and laboratory investigations for both penicillins and cephalosporins are included. Cross-reactivity between penicillins and cephalosporins is discussed in detail. Recommendations on oral provocation and desensitization procedures have been made. Guidance for beta-lactam allergy in children is given in a separate section. An algorithm to help the clinician in the diagnosis of patients with a history of penicillin allergy has also been included., (© 2015 John Wiley & Sons Ltd.)

RhD immunoglobulin G (anti-D) administered to pregnant Rh(-) women prevents Rh isoimmunization. Its use has significantly reduced the incidence of haemolytic disease of the foetus and newborn previously responsible for one death in every 2200 births. In pregnancy, acute drug-induced hypersensitivity reactions including anaphylaxis can have serious deleterious effects on the mother and foetus/neonate. Women can be erroneously labelled as drug allergic as the investigation of hypersensitivity reactions in pregnancy is complex and drug challenges are usually contraindicated. We present three cases of suspected anti-D hypersensitivity clinically presenting as anaphylaxis and delayed transfusion-related reaction. We also propose a new algorithm for the investigations of such reaction. It relies on detailed history, cautious interpretation of skin tests, foetal Rh genotyping from maternal blood and, in some cases, anti-D challenges. This is not to deprive women of anti-D which might put their future pregnancies at risk., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To determine the feasibility of applying a postoperative clinical pathway after robotic nephroureterectomy (RNU) targeting safe omission of a pelvic drain and removal of the bladder catheter on the day after surgery with hospital discharge on postoperative day 1 (POD#1)., Methods: We reviewed a prospectively collected database of all RNUs performed by a single surgeon (R.A.) since institution of our clinical pathway in 2008 that includes pelvic drain omission, bladder catheter removal the morning after surgery, and discharge on POD#1. Patient demographics, and perioperative and postoperative outcomes were evaluated. Ability to adhere to the pathway and achieving the described parameters and whether any resulting complications occurred were determined., Results: RNU was performed in 29 patients with mean age and body mass index of 69 years (50-90 years) and 30 kg/m(2) (19-41 kg/m(2)), respectively. No patient required a pelvic drain, and 2 were discharged with a catheter. All but 2 patients (93%) were discharged on POD#1. Overall, successful pathway application was achieved in 26 of 29 patients (90%) including no drain, catheter removal on the morning after surgery, and discharge on POD#1. No patient developed urine leak or other complications related to early catheter removal., Conclusion: Our clinical pathway after RNU allows safe omission of a pelvic drain with early discontinuation of the bladder catheter and discharge on the POD#1 in most patients. To our knowledge, similar pathways have not been previously achieved with nephroureterectomy by any approach, but should be considered by surgeons treating urothelial carcinoma of the upper urinary tract., (Copyright © 2014 Elsevier Inc. All rights reserved.)

This guideline advises on the management of patients with cow's milk allergy. Cow's milk allergy presents in the first year of life with estimated population prevalence between 2% and 3%. The clinical manifestations of cow's milk allergy are very variable in type and severity making it the most difficult food allergy to diagnose. A careful age- and disease-specific history with relevant allergy tests including detection of milk-specific IgE (by skin prick test or serum assay), diagnostic elimination diet, and oral challenge will aid in diagnosis in most cases. Treatment is advice on cow's milk avoidance and suitable substitute milks. Cow's milk allergy often resolves. Reintroduction can be achieved by the graded exposure, either at home or supervised in hospital depending on severity, using a milk ladder. Where cow's milk allergy persists, novel treatment options may include oral tolerance induction, although most authors do not currently recommend it for routine clinical practice. Cow's milk allergy must be distinguished from primary lactose intolerance. This guideline was prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI) and is intended for clinicians in secondary and tertiary care. The recommendations are evidence based, but where evidence is lacking the panel of experts in the committee reached consensus. Grades of recommendation are shown throughout. The document encompasses epidemiology, natural history, clinical presentations, diagnosis, and treatment., (© 2014 John Wiley & Sons Ltd.)

Background: Beta lactams (BL) are the most widely prescribed antibiotics in the UK and the commonest cause of hypersensitivity reactions. There are no UK guidelines for BL testing and the most relevant guidelines were devised by the European Network for Drug Allergy (ENDA) on behalf of the European Academy of Allergy and Clinical Immunology., Objective: Delivery of allergy services differs across Europe, so this survey was designed to investigate how closely UK practice adhered to these guidelines., Methods: An online survey, using surveymonkey.com software, was sent to all consultants offering an allergy service in the UK and who were members of either BSACI or 'Travellers' (Immunology consultant group)., Results: The response rate was 48% (n=81/165) and BL allergy testing was undertaken by 78% of respondents. All responders requested SsIgE, although four responders stated they rarely requested. Skin testing was undertaken by 87% of respondents who perform beta lactam testing with 17% undertaking skin prick testing (SPT) only, 77% SPT followed by intra-dermal testing (IDT) if the former were negative or indeterminate and 6% SPT and IDT in all cases. The drugs, doses and protocols for skin testing varied considerably. Drug provocation testing was undertaken by 87% of respondents who undertake beta lactam testing with significant heterogeneity in protocols. Respondents that investigated ≤ 20 patients per year demonstrated lower adherence to ENDA recommendations compared to those who saw > 20. Following positive testing, 79% advised avoidance of all penicillins only and the remainder advised additional drug avoidance., Conclusion and Clinical Relevance: This survey revealed variation in the investigation and management of BL hypersensitivity in the UK with some centres reporting procedures that could potentially put patients at risk of anaphylaxis if allergy was falsely excluded. This survey highlights an urgent need for evidence based national guidelines and standardisation of practice., (© 2013 John Wiley & Sons Ltd.)

Background: The population of large parts of Africa, South America and travellers to these areas are at risk of yellow fever (YF) with a 50% mortality risk. Yellow fever vaccine (YFV) propagated in hens' eggs confers protection in 95% of the vaccinated. The rate of anaphylaxis for YFV ranges from 0.42 to 1.8/100,000 doses with most cases considered to be due to egg allergy. Egg allergy is a contraindication for the YFV. Nevertheless, the potential fatal sequelae from YF give the incentive to protect everyone at risk irrespective of their allergic status., Methods: Six subjects who had had a recent reaction to egg and who were travelling to endemic areas (3 adults and 3 children) underwent skin prick tests (SPT) with undiluted YFV and egg extract. Intradermal tests for YFV were undertaken at a 1:10 dilution. In 4 egg-allergic patients with a positive SPT to YFV, a 7-step desensitization protocol was used. A 2-step (10 + 90%) protocol was used in the 2 subjects with a negative YFV SPT. Premedication was not administered., Results: All 6 patients were successfully vaccinated. Four patients completed desensitization: 1 developed mild local erythema at the injection site, 1 had fleeting generalized urticaria with local erythema/angioedema and 2 did not experience any adverse reactions. Patients who received YFV in 2 steps developed no adverse reactions., Conclusions: We describe the successful administration of YFV in 6 egg-allergic patients. The Cambridge Allergy 7-step protocol allows for its safe administration in patients with positive SPT to YFV. A 2-step protocol can be used in patients with negative YFV SPT., (Copyright © 2013 S. Karger AG, Basel.)

Introduction. Testicular lymphoma is an aggressive disease with a very poor prognosis. Nasal-type natural killer/T-cell lymphoma (NKTCL-N) in particular is very uncommon and has a rapidly progressive, fatal course. Case Report. We report a case of primary NKTCL-N of the testis in a 38-years-old Middle Eastern man. The patient had a history of primary right testicular tumor diagnosed at an outside institution as a seminoma and treated with orchiectomy followed by chemo/radiation. On admission, the patient had an enormous nasal granuloma with blood workup showing pancytopenia and elevated liver function tests due to active hepatitis B infection. CT scan of the sinuses showed a very large soft tissue mass, and PET scan showed splenomegaly with multiple lymph node masses in the pelvis and the chest areas. Bone marrow and nasal tumor biopsies as well as review of the slides from the initial orchiectomy were all in favor of NKTCL-N lymphoma. The patient was treated with CHOD based combination chemotherapy and responded dramatically to the first two cycles but passed away from fulminant hepatitis B infection. Conclusion. Despite all known treatments of NKTCL-N lymphoma of the testes, this disease has a very poor prognosis and invariably follows an aggressive clinical course.

Background: Paracetamol is a common antipyretic/analgesic and a component of many prescription and over- the- counter preparations. Hypersensitivity reactions to paracetamol appear to be increasing, but there are few prevalence data. The mechanism is poorly understood. We identified the clinical features of 32 patients with suspected paracetamol allergy, investigated the underlying mechanism and examined co-existing non-steroidal anti-inflammatory drug (NSAID) tolerance., Methods: A clinical history was taken and skin tests and an oral challenge were performed in 32 patients with suspected paracetamol allergy., Results: Patients presented with a combination of urticaria, angio-oedema (face, hands), erythema (cutaneous features in 94%), dyspnoea (including laryngeal oedema), rhinoconjunctivitis, cough, abdominal pain and anaphylaxis. Two patients had a positive skin prick test (SPT) and unequivocal history of acute urticaria/facial angio-oedema/conjunctivitis/cough after paracetamol with no other triggers. One patient had a positive intradermal test. Oral challenge was positive in 15 of 31 patients (including self-challenge in 4), triggering (a combination of) rhinitis, conjunctivitis, pruritus, erythema, urticaria, angio-oedema, dyspnoea and abdominal pain. Sensitivity was evident in 1 patient on the basis of the patient's history. Overall, paracetamol hypersensitivity was confirmed in 16 of the 32 patients (50%). Twelve of the 16 paracetamol-allergic patients (75%) tolerated NSAIDs (negative challenge in 6, negative history in 6). Four of these 16 patients (25%) were intolerant of NSAIDs (positive challenge in 1, self-challenge in 3)., Conclusions: In past reports on paracetamol hypersensitivity, only single cases of a positive SPT and detectable specific IgE have been described. Our data confirm that specific IgE may be a mechanism underlying paracetamol hypersensitivity, as in this series 18.8% of the patients had specific IgE. In 81.2% of patients, negative skin tests did not exclude paracetamol hypersensitivity, suggesting that it may be mediated by leukotrienes. However, three quarters of our patients tolerated NSAIDs, implicating an alternative mechanism. In patients with suspected paracetamol allergy, skin tests should be performed in addition to clinical history and oral challenge., (Copyright © 2012 S. Karger AG, Basel.)

This guidance for the management of patients with hymenoptera venom allergy has been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). The guideline is based on evidence as well as on expert opinion and is for use by both adult physicians and pediatricians practising allergy. During the development of these guidelines, all BSACI members were included in the consultation process using a web-based system. Their comments and suggestions were carefully considered by the SOCC. Where evidence was lacking, consensus was reached by the experts on the committee. Included in this guideline are epidemiology, risk factors, clinical features, diagnostic tests, natural history of hymenoptera venom allergy and guidance on undertaking venom immunotherapy (VIT). There are also separate sections on children, elevated baseline tryptase and mastocytosis and mechanisms underlying VIT. Finally, we have made recommendations for potential areas of future research., (© 2011 Blackwell Publishing Ltd.)

Allergic rhinitis (AR) affects more than 20% of the population in the United Kingdom and western Europe and represents a major cause of morbidity that includes interference with usual daily activities and impairment of sleep quality. This guidance prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI) is for the management of AR in patients that have failed to achieve adequate relief of symptoms despite treatment with intranasal corticosteroids and/or antihistamines. The guideline is based on evidence and is for use by both adult physicians and paediatricians practising allergy. During the development of these guidelines, all BSACI members were included in the consultation process using a web-based system. Their comments and suggestions were carefully considered by the SOCC. Where evidence was lacking, consensus was reached by the experts on the committee. Included in this guideline are indications and contraindications for immunotherapy, criteria for patient selection, the evidence for short- and long-term efficacy of subcutaneous and sublingual immunotherapy, and discussion on safety and the different modes of immunotherapy including, pre-seasonal and co-seasonal treatments. There are sections on children, allergen standardization, vaccines used in the United Kingdom, oral allergy syndrome, cost effectiveness of immunotherapy and practical considerations of undertaking immunotherapy including recommendations on who should undertake immunotherapy and dosing schedules. Finally, there is discussion on potential biomarkers of response to immunotherapy, the use of component-resolved diagnostics, novel approaches, alternative routes and potential areas for future research., (© 2011 Blackwell Publishing Ltd.)

Background: Sentinel lymph node (SLN) biopsy in patients undergoing prophylactic mastectomy (PM) remains controversial. We sought to determine the incidence of finding occult cancer and the frequency of SLN positivity in patients undergoing contralateral PM., Methods: Medical records of patients undergoing bilateral mastectomy at our institution from 2003 to 2008 were reviewed (n = 115). Eight patients (6.9%) had known bilateral cancer; an additional eight patients (6.9%) underwent BPM for risk reduction. The remaining 99 patients who had ipsilateral breast cancer and underwent contralateral PM formed the cohort of interest for this study. Univariate and multivariate analyses to determine factors correlating with occult malignancy and SLN positivity in the PM specimen were performed using SPSS ver. 17 (SPSS Inc., Chicago, IL)., Results: The median patient age was 50 y, and median ipsilateral tumor size was 1.7 cm. Occult contralateral malignancy was found in eight (8.1%); of these, six (75.0%) had DCIS only. A positive SLN was found on the prophylactic side in 2 (2.0%) patients. Both had ipsilateral inflammatory cancer, and over 15 positive ipsilateral lymph nodes post-neoadjuvant chemotherapy. Ipsilateral inflammatory breast cancer was correlated with the finding of invasive cancer in the contralateral PM (P = 0.006), and both the finding of ipsilateral inflammatory breast cancer and number of positive lymph nodes correlated with the finding of a positive contralateral SLN., Conclusion: The incidence of occult malignancy in PM is low (2%). However, patients with ipsilateral inflammatory cancer are at high risk of contralateral malignancy; SLN biopsy on the prophylactic side in these patients may be warranted., (Copyright © 2010 Elsevier Inc. All rights reserved.)

This guideline advises on the management of patients with egg allergy. Most commonly, egg allergy presents in infancy, with a prevalence of approximately 2% in children and 0.1% in adults. A clear clinical history and the detection of egg white-specific IgE (by skin prick test or serum assay) will confirm the diagnosis in most cases. Egg avoidance advice is the cornerstone of management. Egg allergy often resolves and re-introduction can be achieved at home if reactions have been mild and there is no asthma. Patients with a history of severe reactions or asthma should have reintroduction guided by a specialist. All children with egg allergy should receive measles, mumps and rubella (MMR) vaccination. Influenza and yellow fever vaccines should only be considered in egg-allergic patients under the guidance of an allergy specialist. This guideline was prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI) and is intended for allergists and others with a special interest in allergy. The recommendations are evidence-based but where evidence was lacking consensus was reached by the panel of specialists on the committee. The document encompasses epidemiology, risk factors, diagnosis, treatment, prognosis and co-morbid associations.

Patent blue V is widely used in the identification of sentinel lymph nodes in patients with breast cancer and other malignancies. Individual case reports of allergy to patent blue V have been described in the medical literature since the 1960s. However, there is little data on clinical features and little experience of which allergy tests are appropriate or useful. We gathered all cases of patent blue V allergy that had been seen and diagnosed in the Department of Allergy, Addenbrooke's Hospital over a 3-year period. We collected clinical details of each case including skin test results. For comparison we recruited 12 healthy control subjects who then underwent skin testing to patent blue V. Six cases of patent blue V allergy were identified, all occurring during sentinel lymph node identification for breast carcinoma. All 6 had positive skin prick tests to neat patent blue V (25 mg/ml). Skin prick testing with a 1 : 10 dilution (2.5 mg/ml) produced positive results in 3 of 4 patients tested, and intradermal testing at a 1 : 100 dilution was (0.25 mg/ml) was positive in all patients tested. Of 12 control subjects, 11 had negative skin prick tests to both neat and 1 : 10 patent blue V with one subject showing a positive reaction to the higher concentration only. On the basis of our experience of patent blue V allergy, we propose a diagnostic protocol that can be safely and reliably utilised in centres equipped for allergy testing.

Investigation of anaphylaxis during general anaesthesia requires an accurate record of events including information on timing of drug administration provided by the anaesthetist, as well as timed acute tryptase measurements. Referrals should be made to a centre with the experience and ability to investigate reactions to a range of drug classes/substances including neuromuscular blocking agents (NMBAs) intravenous (i.v.) anaesthetics, antibiotics, opioid analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), local anaesthetics, colloids, latex and other agents. About a third of cases are due to allergy to NMBAs. Therefore, investigation should be carried out in a dedicated drug allergy clinic to allow seamless investigation of all suspected drug classes as a single day-case. This will often require skin prick tests, intra-dermal testing and/or drug challenge. Investigation must cover the agents administered, but should also include most other commonly used NMBAs and i.v. anaesthetics. The outcome should be to identify the cause and a range of drugs/agents likely to be safe for future use. The allergist is responsible for a detailed report to the referring anaesthetist and to the patient's GP as well as the surgeon/obstetrician. A shorter report should be provided to the patient, adding an allergy alert to the case notes and providing an application form for an alert-bracelet indicating the wording to be inscribed. The MHRA should be notified. Investigation of anaphylaxis during general anaesthesia should be focussed in major allergy centres with a high throughput of cases and with experience and ability as described above. We suggest this focus since there is a distinct lack of validated data for testing, thus requiring experience in interpreting tests and because of the serious consequences of diagnostic error.

Thunderstorm-related asthma is increasingly recognized in many parts of the world. This review focuses on important advances in the understanding of the mechanism of the role of allergens, in particular fungal spores such as Alternaria, in asthma epidemics associated with thunderstorms. From our observations, we have proposed that the prerequisites for this phenomenon are as follows: 1) a sensitized, atopic, asthmatic individual; 2) prior airway hyperresponsiveness before a sudden, large allergen exposure; 3) a large-scale thunderstorm with cold outflow occurring at a time and location during an allergen season in which large numbers of asthmatics are outdoors; and 4) sudden release of large amounts of respirable allergenic fragments, particularly fungal spores such as Alternaria.

"Flat epithelial atypia" is the adopted term by the WHO working group on breast tumor referring to an early neoplastic breast lesion affecting the terminal duct-lobular units. Pathologists have described this lesion under a variety of names including columnar cell lesions and low-grade clinging carcinoma in situ. It is usually encountered on breast biopsies performed for mammographically-identified microcalcifications. Because of its relatively frequent association with carcinomas, its recognition in biopsy specimens is important. This review will focus on the histopathologic features, differential diagnosis, biologic potential, clinical significance and management of this lesion.

Gene expression profiling has been increasingly used to determine new cancer markers. This technology holds major promises for improving the management of patients with breast cancer in which traditional clinicopathologic parameters do not account for all the heterogeneity of this disease and its distinct prognostic groups. Gene expression profiling has resulted in new classification of breast cancer and new assays are being developed and commercialized as prognostic and predictive tests. However, the use of these tests in a clinical setting presents many issues. The accuracy of this new technology is often overestimated and its limitations should be addressed. Although early results are promising, further validation and well designed clinical trials are required before incorporating these tests in routine clinical practice.

These guidelines have been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI) and are intended for allergists and others with a special interest in allergy. As routine or validated tests are not available for the majority of drugs, considerable experience is required for the investigation of allergic drug reactions and to undertake specific drug challenge. A missed or incorrect diagnosis of drug allergy can have serious consequences. Therefore, investigation and management of drug allergy is best carried out in specialist centres with large patient numbers and adequate competence and resources to manage complex cases. The recommendations are evidence-based but where evidence was lacking consensus was reached by the panel of specialists on the committee. The document encompasses epidemiology, risk factors, clinical patterns of drug allergy, diagnosis and treatment procedures. In order to achieve a correct diagnosis we have placed particular emphasis on obtaining an accurate clinical history and on the physical examination, as these are critical to the choice of skin tests and subsequent drug provocation. After the diagnosis of drug allergy has been established, communication of results and patient education are vital components of overall patient management.

Heparin-induced thrombocytopenia (HIT) is a prothrombotic condition caused by platelet-activating antibodies that react with platelet factor 4 (PF4)/heparin complexes. Delayed-onset HIT occurs after heparin is stopped. Fondaparinux, a synthetic pentasaccharide, is thought to be a safe alternative anticoagulant in HIT. We describe a patient with delayed-onset HIT triggered by low-molecular-weight heparin (LMWH) which occurred during fondaparinux prophylaxis and which was complicated by microangiopathic hemolytic anemia. Patient serum contained high-titer anti-PF4/heparin antibodies demonstrating heparin-dependent platelet activation with serial dilutions. Confirmed delayed-onset HIT with LMWH has not been previously reported. Low dose fondaparinux does not necessarily prevent thrombotic complications of HIT., (Copyright 2008 Wiley-Liss, Inc.)

This guidance for the management of patients with rhinosinusitis and nasal polyposis has been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). The recommendations are based on evidence and expert opinion and are evidence graded. These guidelines are for the benefit of both adult physicians and paediatricians treating allergic conditions. Rhinosinusitis implies inflammation of the nose and sinuses which may or may not have an infective component and includes nasal polyposis. Acute rhinosinusitis lasts up to 12 weeks and resolves completely. Chronic rhinosinusitis persists over 12 weeks and may involve acute exacerbations. Rhinosinusitis is common, affecting around 15% of the population and causes significant reduction in quality of life. The diagnosis is based largely on symptoms with confirmation by nasendoscopy. Computerized tomography scans and magnetic resonance imaging are abnormal in approximately one third of the population so are not recommended for routine diagnosis but should be reserved for those with acute complications, diagnostic uncertainty or failed medical therapy. Underlying conditions such as immune deficiency, Wegener's granulomatosis, Churg-Strauss syndrome, aspirin hypersensitivity and allergic fungal sinusitis may present as rhinosinusitis. There are few good quality trials in this area but the available evidence suggests that treatment is primarily medical, involving douching, corticosteroids, antibiotics, anti-leukotrienes, and anti-histamines. Endoscopic sinus surgery should be considered for complications, anatomical variations causing local obstruction, allergic fungal disease or patients who remain very symptomatic despite medical treatment. Further well conducted trials in clearly defined patient groups are needed to improve management.

This guidance for the management of patients with allergic and non-allergic rhinitis has been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). The guideline is based on evidence as well as on expert opinion and is for use by both adult physicians and paediatricians practicing in allergy. The recommendations are evidence graded. During the development of these guidelines, all BSACI members were included in the consultation process using a web-based system. Their comments and suggestions were carefully considered by the SOCC. Where evidence was lacking, consensus was reached by the experts on the committee. Included in this guideline are clinical classification of rhinitis, aetiology, diagnosis, investigations and management including subcutaneous and sublingual immunotherapy. There are also special sections for children, co-morbid associations and pregnancy. Finally, we have made recommendations for potential areas of future research.

Background: After July 29, 2002, an epidemic of asthma admissions was associated with a thunderstorm in the United Kingdom., Objective: We sought to study the cause of epidemics of asthma associated with thunderstorms., Methods: We performed a case-control study of 26 patients presenting to Cambridge University Hospital with asthma after the thunderstorm. Control subjects were 31 patients with summer seasonal asthma. Subjects underwent skin tests and specific IgE serology to inhaled aeroallergens. Meteorologic and aerobiologic data correlated with asthma admissions were analyzed., Results: Twenty-three of 26 cases had IgE sensitization to Alternaria species. Eleven of 31 control subjects gave a history of asthma exacerbation during thunderstorms. Ten of these 11 control subjects were sensitive to Alternaria species on skin testing, but Alternaria species sensitivity was only identified in 4 of the 20 remaining control subjects who did not report thunderstorm-related asthma symptoms. The odds ratio of having epidemic thunderstorm-related asthma if sensitive to Alternaria species was 9.31 (95% CI, 2.305-37.601; P = .0008) and 63.966 (95% CI, 3.577-1143.9; P < .0001) if sensitive to Alternaria species, Cladosporium species, or both. Poisson regression analysis showed that counts of broken Alternaria species and Didymella and Cladosporium species were significantly correlated with each other and with asthma admissions. The thunderstorm was associated with increased levels of Alternaria, Cladosporium, and Didymella species., Conclusions: Alternaria alternata sensitivity is a compelling predictor of epidemic asthma in patients with seasonal asthma and grass pollen allergy and is likely to be the important factor in thunderstorm-related asthma., Clinical Implications: Alternaria species sensitization in asthmatic subjects with grass pollen sensitivity predicts susceptibility to thunderstorm-associated asthma.

This guidance for the management of patients with chronic urticaria and angio-oedema has been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). The guideline is based on evidence as well as on expert opinion and is aimed at both adult physicians and paediatricians practising in allergy. The recommendations are evidence graded. During the development of these guidelines, all BSACI members were included in the consultation process using a web-based system. Their comments and suggestions were carefully considered by the SOCC. Where evidence was lacking a consensus was reached by the experts on the committee. Included in this guideline are clinical classification, aetiology, diagnosis, investigations, treatment guidance with special sections on children with urticaria, and the use of antihistamines in women who are pregnant or breastfeeding. Finally, we have made recommendations for potential areas of future research.