Positive Skin Research Articles

Allergies aux fientes d’oiseaux

The problems of human–bird cohabitation are not a recent phenomenon even if today their importance has taken on an indisputable extent. Their droppings contain significant concentrations of microorganisms and can cause allergic diseases, such as hypersensitivity pneumonitis (HSP), formerly called extrinsic allergic alveolitis, but also rhinitis, asthma or conjunctivitis. We report a rare case of allergy to bird droppings in a patient who raises chickens and canaries, having consulted for rhinoconjunctivitis whose allergological assessment found sensitization of these droppings with positive skin and specific IgE tests. Its management consisted of avoiding the risk with medical treatment. It is a rare pathology that must be considered in the event of exposure to birds.

Impact of allergic rhinitis on quality of life in patients with chronic rhinosinusitis

ObjectivesTo evaluate the impact of allergic rhinitis (AR) on the quality of life (QoL) in patients with chronic rhinosinusitis (CRS). MethodsRetrospective cross-sectional study of adult patients with CRS presenting to our clinic between August 2020 and February 2023 was performed. AR was diagnosed based on a positive skin or blood allergy test. Patients' characteristics, AR status, comorbidities, endoscopy scores, and SNOT-22 scores were collected. ResultsA total of 514 CRS patients were included, with 265 (51.6 %) patients with AR. CRS patients with AR were younger (p = 0.004), more likely to be female (p < 0.001), and more likely to have asthma (p < 0.001). Polyp status and endoscopy scores did not differ between patients with and without AR. Baseline SNOT-22 scores were slightly worse in the AR cohort (43.6 vs 38.7, p = 0.007), which was mainly secondary to rhinologic (p = 0.002), extrarhinologic (p = 0.007), and ear/facial (p = 0.007) subdomains. Worse rhinologic and extrarhinologic scores were associated with the presence of AR after adjusting for confounding variables (Coef = 1.55, p = 0.011; and Coef = 0.83, p = 0.021 respectively). ConclusionThe impact of allergic rhinitis on QoL is mainly on the nasal symptoms. Further studies should look at the role of AR on the QoL of different CRS endotypes; and at the role of AR-specific treatment, such as immunotherapy, on the QoL of patients with CRS.

Performance Analysis of Water Injection Well BEL-13 and Production Well BEL-01 Using Hall Plot and Buckley-Leverett Methods

At first, the FLO field had an ability to flow fluids to the surface in a natural flow, but the production capacity decreased with time. Therefore, production is increased using the waterflooding method. The purpose of this study was to analyze the performance of waterflooding carried out on injection well BEL-13 and production well BEL-01. There are two methods used in this study to achieve the desired aims and objectives, namely the Hall Plot method and the Buckley-Leverett method. The Hall Plot method was used to see the connectivity conditions between injection and production wells after being injected with water periodically. Whereas the Buckley-Leverett method was used to estimate the time of water breakthrough, production amount (Np), the injection rate (Wi), water cut value (WC), and recovery factor (RF). Based on the Hall Plot method, it was found that the waterflooding carried out was stable or normal because there was no negative skin or positive skin. In addition, based on relative permeability curve, rock wettability of the reservoir rock is water wet. Analysis using Buckley-Leverett shows that the cumulative production at the time of water breakthrough from the injection well BEL-13 to the production well BEL-01 is 364,733.64 STB. When the water breakthrough occurs, the predictions of WOR, water cut, and recovery factor are 2.13, 68.08%, and 29.76%.

Severe Anaphylactic Reaction to Ferric Carboxymaltose With Positive Skin and Basophil Activation Tests.

Severe Anaphylactic Reaction to Ferric Carboxymaltose With Positive Skin and Basophil Activation Tests.

Musculoskeletal Tuberculosis Involving Ribs, Spine, and Pelvis in a 17 year old Girl: A Case Report

Background: We present a case of progressive back pain associated with weight loss and low-grade fever in a 17-year-old patient previously diagnosed with spinal tuberculosis (TB) also known as tuberculous spondylitis or Pott’s disease. Case presentation: Upon the patient's presentation to the clinic, a differential diagnosis including infectious and non-infectious causes such as extra-pulmonary tuberculosis, septic arthritis, malignancy, rheumatologic diseases, and physical abuse was made. Her preliminary workup was suggestive of granulomatous disease. A positive tuberculin skin test (TST), and a polymerase chain reaction (PCR) test of the tissue with mycobacterium tuberculosis deoxyribonucleic acid (MTB DNA), confirmed the diagnosis of musculoskeletal TB. Conclusion: The patient was treated with anti-TB regimen and Pyridoxine to avoid peripheral neuropathy associated with isoniazid use. Her clinical follow-up showed improvement with a proper response to treatment and no sequelae.

Abstract 1760: The antibody-drug conjugate GENA-111 conjugated to auristatin F shows therapeutic potency in BCAM positive epithelial cancer

Abstract Antibody-drug conjugates (ADCs) are considered as promising cancer treatment modalities that combine the selectivity of antibodies and the cytotoxic properties of payloads using chemical linkers. However, despite their success, ADCs still suffer from drawbacks, e.g., systemic toxicity, which limit their potential clinical applications. The systemic toxicity of an ADC is mainly related to the stability of its linker, and to the selectivity of its antibody towards the targeted antigen expressed on cancer cells. Lu/BCAM (Lutheran/basal cell adhesion molecule) is a member of the immunoglobulin superfamily and is a receptor for laminin, a protein that facilitates cell adhesion, migration, and invasion. A growing number of studies show that BCAM plays an essential role in tumor progression and is overexpressed on epithelial cancers e.g., skin cancer. Here we describe GENA-111, a human monoclonal anti-BCAM IgG4 (S228P) antibody that binds to human BCAM with high affinity, and that is significantly internalized by BCAM-positive tumor cells. We also describe the GENA-111-auristatin F ADC, wherein the GENA-111 antibody has been armed with an auristatin F derivative using a new linker technology and a stabilized thiol maleimide conjugation. This new linker technology comprises a cleavable peptidic sequence that facilitates multidrug attachment and the production of ADCs with tailored drug-to-antibody ratios (DARs). Cytotoxic drugs are rapidly and selectively released from the linker by the carboxypeptidase activity of Cathepsin B. In vitro cytotoxicity examination showed the potent cytotoxic effects of this GENA-111-auristatin F ADC on BCAM-expressing tumor cells, with a positive correlation between cytotoxicity and BCAM expression. Moreover, this ADC was also shown to significantly reduce the growth of tumor cells, including A431, T47D, and Huh7. The GENA-111-auristatin F ADC was evaluated in a xenograft mouse model established by subcutaneous injection of A431 cells, a BCAM positive human skin cancer cell line. The results of this study will be presented and discussed. Taken together, our data suggest that an ADC targeting BCAM e.g., GENA-111-auristatin F, might be a promising treatment strategy for BCAM positive epithelial cancer patients. Citation Format: Hyunkyung Yu, Nathalie Bellocq, Youngeun Ha, Hyunuk Kim, Yunyeon Kim, Bu-Nam Jeon, Léo Marx, Mathilde Pantin, Hyunjin Yoo, Seungmin Byun, Joo-Yeon Chung, Mi Young Cha, Patrick Garrouste, Frédéric Lévy. The antibody-drug conjugate GENA-111 conjugated to auristatin F shows therapeutic potency in BCAM positive epithelial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1760.

Rifapentine and isoniazid for prevention of tuberculosis in people with diabetes (PROTID): protocol for a randomised controlled trial

BackgroundDiabetes mellitus (DM) increases the risk of tuberculosis (TB) and will hamper global TB control due to the dramatic rise in type 2 DM in TB-endemic settings. In this trial, we will examine the efficacy and safety of TB preventive therapy against the development of TB disease in people with DM who have latent TB infection (LTBI), with a 12-week course of rifapentine and isoniazid (3HP).MethodsThe ‘Prevention of tuberculosis in diabetes mellitus’ (PROTID) consortium will randomise 3000 HIV-negative eligible adults with DM and LTBI, as evidenced by a positive tuberculin skin test or interferon gamma release assay, to 12 weeks of 3HP or placebo. Participants will be recruited through screening adult patients attending DM clinics at referral hospitals in Tanzania and Uganda. Patients with previous TB disease or treatment with a rifamycin medication or isoniazid (INH) in the previous 2 years will be excluded. The primary outcome is the occurrence of definite or probable TB disease; secondary outcome measures include adverse events, all-cause mortality and treatment completion. The primary efficacy analysis will be intention-to-treat; per-protocol analyses will also be carried out. We will estimate the ratio of TB incidence rates in intervention and control groups, adjusting for the study site using Poisson regression. Results will be reported as efficacy estimates (1-rate ratio). Cumulative incidence rates allowing for death as a competing risk will also be reported. Approximately 1000 LTBI-negative, HIV-negative participants will be enrolled consecutively into a parallel cohort study to compare the incidence of TB in people with DM who are LTBI negative vs positive. A number of sub-studies will be conducted among others to examine the prevalence of LTBI and active TB, estimate the population impact and cost-effectiveness of LTBI treatment in people living with DM in these African countries and address gaps in the prevention and therapeutic management of combined TB-DM.DiscussionPROTID is anticipated to generate key evidence to guide decisions over the use of TB preventive treatment among people with DM as an important target group for better global TB control.Trial registrationClinicalTrials.govNCT04600167. Registered on 23 October 2020

White dot syndrome in a patient with presumed ocular tuberculosis: a case report

BackgroundThis manuscript describes a case of a patient with presumed ocular tuberculosis masquerading as multiple evanescent white dot syndrome.Case presentationA 32-year-old male patient presented with a complaint of reduced visual acuity in the left eye. Retinal fundus exam of the left eye revealed gray-whitish deep lesions predominantly nasal to the optic disc. The lesions were more clearly identifiable on fundus autofluorescence (FAF) imaging, fluorescein angiography (FA) and en face optical coherence tomography (OCT). FA also indicated retinal vasculitis and papillitis. Swept-source OCT B-scan demonstrated loss of the ellipsoid layer in the regions corresponding to the lesions detected by FAF. A positive tuberculin skin test (TST) confirmed presumed tuberculosis, and a related WDS diagnosis was made. Specific antituberculosis therapy was instituted with favorable anatomical recovery and visual outcome.ConclusionMultiple evanescent white dot syndrome (MEWDS) may be manifestation of presumed ocular tuberculosis, and multimodal retinal exams can provide a better understanding of atypical diseases and their follow-up.

Abstract P2-13-29: Analysis of GP2 immune response and relationship to recurrence in a prospective, randomized, placebo-controlled, single-blinded, multicenter, phase IIb study evaluating the reduction of recurrences using HER2/neu peptide GP2 (GLSI-100) vs. GM-CSF alone after adjuvant trastuzumab in HER2 positive women with operable breast cancer

Abstract Background: Delayed type hypersensitivity (DTH) skin tests in the randomized, active-controlled, single-blinded, multicenter Phase IIb trial investigating GLSI-100 (GP2+GM-CSF) administered in the adjuvant setting to node-positive and high-risk node-negative breast cancer patients with tumors expressing any degree of HER2 (immuno-histochemistry [IHC] 1-3+) (NCT00524277) have been analyzed. The trial enrolled HLA-A*02 patients randomized to receive GLSI-100 versus GM-CSF alone. The trial's primary objective was to determine if treatment with GLSI-100, a HER2-derived peptide, reduces recurrence rates. Analyses for this trial showing GLSI-100 to be efficacious, safe and immunogenic have been previously reported by Patel et al. and Mittendorf et al.. Methods: Consented patients were randomized and scheduled to receive GLSI-100 (500 mcg GP2: 125 mcg GM-CSF) or control (GM-CSF only) via 6 intradermal injections every 3-4 weeks as part of the Primary Immunization Series (PIS) for the first 6 months and 4 booster intradermal injections every 6 months thereafter. Boosters were introduced during the trial, thus some patients did not receive all 4 boosters. DTH skin tests were assessed at baseline and after the 6th dose with the orthogonal mean of each skin reaction measured 48-72 hours after injection using the sensitive ballpoint-pen method.. Results: The study enrolled 180 patients across 16 clinical sites with both HER2 3+ positive and low HER2 expressors (1-2+). After 5 years of follow-up, the Kaplan-Meier estimated 5-year DFS rate in the 46 HER2 3+ patients treated with GLSI-100, if the patient completed the PIS, was 100% versus 89.4% (95% CI:76.2, 95.5%) in the 50 placebo patients treated with GM-CSF (p = 0.0338). GLSI-100 was shown to be well tolerated with no SAEs deemed related to study medication and elicited a potent immune response measured by local skin tests and immunological assays. Injection site reactions were common, occurring in almost 100% of patients treated with either GLSI-100 or GM-CSF alone. Previous publications have reported the increase in DTH response reported among patients after treatment with GLSI-100. However, it was of interest to understand the positive DTH responses to GP2 noted at baseline. 22.8% of patients reacted to GP2 at baseline with induration of 5mm or greater. In the subgroup of patients who later experienced a breast cancer recurrence, 36.4% (8/22) had such a baseline response. Analysis of the time to recurrence among those recurring found that the median time to recurrence was 0.6 years for those with a baseline response while those that did not have a positive baseline DTH response to GP2 took 1.2 years to recur.. Conclusions: This study demonstrated that GLSI-100 safely elicited a potent immune response as evidenced by increased DTH skin responses with treatment paired with improved disease-free survival. It is theorized that a positive baseline DTH skin test to GP2 may be evidence of an existing immune response to GP2 associated with residual disease, impending recurrence, or prior treatments. Further studies assessing if GP2 immune response is an important prognosticator of cancer disease state or recurrence are planned. Citation Format: Snehal S Patel, David B McWilliams, Mira S Patel, Christine T Fischette, Jaye Thompson, F. Joseph Daugherty. Analysis of GP2 immune response and relationship to recurrence in a prospective, randomized, placebo-controlled, single-blinded, multicenter, phase IIb study evaluating the reduction of recurrences using HER2/neu peptide GP2 (GLSI-100) vs. GM-CSF alone after adjuvant trastuzumab in HER2 positive women with operable breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-29.

Egg allergy. Diagnosis in immediate and delayed type allergy

Egg allergy is one of the most common food allergies in children. Common symptoms of egg protein-induced allergy frequently involve the skin as well as the gut, and in more severe cases lead to anaphylaxis. Non-IgE-mediated symptoms such as eosinophilic diseases of the digestive tract or egg-induced enterocolitis may also be encountered. Sensitization to egg white proteins can be encountered in young children in the absence of clinical symptoms. The egg allergy diagnosis is based on the suggestive clinical history, positive skin and/or serological tests and possibly the egg protein challenge test, the gold standard for confirming the diagnosis. Ovomucoid is identified as a major allergen contained in the egg white, and its identification allows to improve the diagnosis, to identify the patient who can tolerate the highly prepared thermally prepared egg, the patient with the risk of persistent egg allergy and with the risk of a severe reaction. Spontaneous remission and development of egg tolerance are common and occur in 60-75% of children before adolescence; however, the burden of disease is significant during childhood, making the early and accurate diagnosis a necessity.

Tuberculin skin tests following Bacille Calmette Guerin vaccination in Africa: a protocol for systematic review and meta-analysis.

Tuberculin reactivity following tuberculin skin test which is the most common measure of the effect of the Bacille Calmette Guerin (BCG) vaccination has remained complex. This protocol is aimed to assess the effect of BCG vaccine on tuberculin skin test in Africa as a guide to better understanding or resolving this complexity. A search strategy is developed using MeSH, key words, text words, and entry terms. Five databases will be searched, including PubMed, African Journals Online (AJOL), Google Scholar, Research Gate, and Cochrane Library. Only observational studies conducted in Sub-Saharan Africa and retrievable in English language will be included. The primary measurable outcome of this study is pooled prevalence of positive tuberculin skin tests. Secondary outcomes are factors that influence Tuberculin Skin Test (TST) positivity such as BCG type, the dose of BCG, age at BCG vaccinates, time/interval between BCG vaccination and TST, and type of tuberculin unit used for TST. Identified studies will be screened and selected based on inclusion criteria. Data will be extracted into Zotero, Microsoft Excel and CMA software. Both quality scores and the risk of bias for individual studies will be reported. Studies will be assessed for methodological, clinical, and statistical heterogeneity. Funnel Plots will be used for assessing publication bias. The results will be presented in tabular format in addition to a narrative synthesis. The pooled prevalence of effect of BCG vaccine on TST in Africa will be examined in relation to factors that influence TST positivity.

Skirining fitokimia ekstrak etanol kulit buah sirsak (Annona muricata Linn) dan uji aktivitas antioksidan dengan metode DPPH

Phytochemical screening research on the ethanol extract of soursop (Annona muricata Linn) peel and antioxidant activity was tested using the DPPH method. The purpose of this study was to determine several classes of compounds found in soursop rind and to determine the antioxidant activity of ethanol extract of soursop rind against DPPH free radicals. The results showed ethanol extract of positive soursop fruit skin containing flavonoids, tannins, and terpenoids. of soursop fruit skin extract was carried out by DPPH method results obtained IC50 value of 192.13 µg / mL ± 5.198137 which was categorized as weak.

Skin and mucous membranes colonisation with Staphylococcus aureus or MRSA as a risk factor for surgical site infections in elective Caesarean Section

The purpose of this study was to determine if skin and mucous membrane colonisation with Staphylococcus aureus (S. aureus) and methicillin-resistant Staphylococcus aureus (MRSA) increases the incidence of surgical site infection (SSI) post-elective Caesarean Sections. A prospective study was conducted at a major centre in Jordan, involving 127 patients who underwent elective Caesarean Section surgeries during 2019. Participants were screened for skin and mucous membranes colonisation for S. aureus preoperatively and were followed for 90 days for any signs of SSI. The screening sites were on three parts of the patients’ bodies; nose, throat, and groyne. The total SSI incidence was 18.9%. Among participants with SSI; 66.7% had a superficial infection and 33.3% had deep tissue infection. Skin and mucous membrane colonisation was positive in 42 participants (33.1%) in one of the three screening sites. Participants with positive skin and mucous membrane colonisation were found to have SSI incidence 2.43 times more than the non-colonised participants (Fisher’s Exact test = 3.832, p = .05, CI: 0.098–6.02). Participants with S. aureus skin and mucous membranes colonisation were significantly 2.94 times with more SSI incidence than those who were not colonised (Fisher’s Exact test = 5.485, p = .02, CI: 1.164–7.439). Skin and mucous membrane colonisation was found to increase the incidence of SSI. More attention should be performed to screen for skin and mucous membranes colonisation and subsequent selective skin decolonisation to decrease SSI incidence. IMPACT STATEMENT What is already known on this subject? Surgical site infection (SSI) is a challenge that increases the costs of health care. Surgical site infection is associated with high costs mainly due to the increase in the length of hospital stay. Skin screening for S. aureus or MRSA colonisation was found to be important for selective skin decolonisation using appropriate antiseptic preparation and preoperative antibiotic prophylaxis. What do the results of this study add? The incidence of SSI in the colonised group was found to be 2.43 times higher than in the non-colonised group. What are the implications of these findings for clinical practice and/or further research? Screening for colonisation and subsequent selective skin decolonisation should be a part of SSI prevention policies.

Serum Sickness Reaction to Rituximab with Positive Immediate Intradermal Skin Test: A Case Report

Background: Rituximab is a chimeric murine/human monoclonal antibody against CD20. It can be used off-label in autoimmune diseases. Its administration can lead to several types of reactions; immediate infusional reactions and also delayed reactions like Serum Sickness Reaction (SSR). Case presentation: This is a case study of a 48 years old woman diagnosed with rheumatoid arthritis/systemic lupus erythematosus who developed refractory immune thrombocytopenic purpura and received treatment with rituximab. After treatment, she developed erythematous-violet lesions accompanied with fever of 38ºC, dyspnea, joints arthralgia and edema. In the emergency department, hypotension, fever, dyspnea, and shivering were observed, for which, intramuscular epinephrine, intravenous corticosteroids, antibiotics and salbutamol nebulization were administered. In our allergy unit, we performed an intradermal test (IDT) with rituximab (1mg/ml), which was positive at immediate (20min) and late (48h) reading. Based on the clinical manifestations and test carried out, she was diagnosed with rituximab SSR. We also studied the molecular mass of the IgE-reactive proteins present in rituximab product by SDS-PAGE Immunoblotting method according to Laemmli, in reducing and non-reducing conditions, with high sensitivity and using three different polyvinylidene difluoride (PVDF) membrane blocking substances (skimmed cow's milk, fish collagen and egg white). We did not detect IgE-binding to rituximab product. Conclusion: The pathogenesis of SSR is not well known. The patients after reinfusion can develop immediate reactions suggesting involvement of IgE hypersensitivity. Nevertheless, there are patients who tolerated reinfusion. Further studies and assays are needed for a better understanding of these reactions and to lead to a safer re-administration if needed.

Differentiating the endotypes in allergic rhinitis

Aim. The aim of the study was to differentiate the endotypes in allergic rhinitis by key allergy markers in a mixed group of patients.Material and Methods. The study comprised a total of 48 patients, men and women, aged 18-60 years suffering from three endotypes of allergic rhinitis including the classic, local, and dual allergic rhinitis. The standard diagnostics of allergic rhinitis included taking a history of allergies, family history of allergic disease, video rhinoscopy, serum total IgE level assessment, allergy skin tests to house dust mite and pollen allergens, and study of eosinophilic inflammation parameters (eosinophil cationic protein, interleukin-5 (IL5), and eosinophil counts in blood and nasal secretion).Results. Based on total IgE level, the general group of patients was divided to two subgroups: subgroup 1 comprised patients with high IgE level (n = 22); subgroup 2 comprised patients with low IgE level (n = 26). Most of patients in these groups had contradictory results of allergy skin tests i.e. positive allergy skin test results in case of high IgE level (group 1) and vice versa. Cluster analysis-based exminations of general group allowed to categorize three subgroups of patients: patients with classic allergic rhinitis (n = 22), local allergic rhinitis (n = 22), and dual allergic rhinitis (n = 4). Besides, an increased rate of anxiety disorder was found in patients with local allergic rhinitis (p &lt; 0.001).Conclusion. The obtained data showed promise for a new research trend in studying allergic rhinitis endotypes, namely: investigation of neuroimmune relationships in allergic tolerance disruption in the presence of this pathology.

Temporal dynamics of intradermal cytokine response to tuberculin in Mycobacterium bovis BCG-vaccinated cattle using sampling microneedles

Bovine tuberculosis (bTB) is a disease of livestock with severe and worldwide economic, animal welfare and zoonotic consequences. Application of test-and-slaughter-based control polices reliant on tuberculin skin testing has been the mainstay of bTB control in cattle. However, little is known about the temporal development of the bovine tuberculin skin test response at the dermal sites of antigen injection. To fill this knowledge gap, we applied minimally-invasive sampling microneedles (SMNs) for intradermal sampling of interstitial fluid at the tuberculin skin test sites in Mycobacterium bovis BCG-vaccinated calves and determined the temporal dynamics of a panel of 15 cytokines and chemokines in situ and in the peripheral blood. The results reveal an orchestrated and coordinated cytokine and local chemokine response, identified IL-1RA as a potential soluble biomarker of a positive tuberculin skin response, and confirmed the utility of IFN-γ and IP-10 for bTB detection in blood-based assays. Together, the results highlight the utility of SMNs to identify novel biomarkers and provide mechanistic insights on the intradermal cytokine and chemokine responses associated with the tuberculin skin test in BCG-sensitized cattle.

Unnoticed Adverse Effect of Isoniazid during Childhood Tuberculosis Preventive Treatment: Hyperuricemia

Abstract Objective Isoniazid for 6 to 9 months is the most widely used form of tuberculosis (TB) preventive treatment. We aimed to assess the adverse effects of isoniazid by using the serum levels of aspartate transaminase (AST), alanine transaminase (ALT), and uric acid (SUA) in children and adolescents receiving long-term isoniazid for latent TB infection. Methods The study included children ≤18 years of age who underwent TB preventive treatment with isoniazid (IPT) between 2015 and 2019 at a university hospital. Serum transaminase, SUA, urea, and creatinine levels of patients were measured before the initiation of IPT, 15th day, and once a month during treatment. Patients with ALT, AST, or SUA results above cut-off levels during treatment were evaluated. The final values in follow-up were included in the data analysis. Results A total of 141 children who underwent IPT were included. In total, 70 children had family members with confirmed TB disease, and 71 children had a positive tuberculin skin test. SUA increased above cut-off values in 16 children (11.3%), and half of them had uric acid levels over 7 mg/dL. The median duration of the development of hyperuricemia was 4.0 months. ALT or AST increased above cut-off values in 23 children (16.3%). ALT was above cut-off values in seven patients, AST was high in 20 patients. The median duration to the development of AST and/or ALT levels above cut-off was 4.0 months. Two patients had hepatotoxic transaminase levels. Three patients had both elevated transaminases and SUA levels. Conclusion Isoniazid may also cause hyperuricemia besides elevation in transaminases in children.

Piperacillin-Tazobactam Hypersensitivity: A Large, Multicenter Analysis

Piperacillin/tazobactam is a broad-spectrum penicillin. Hypersensitivity reactions are less commonly reported than with other penicillins except in patients with cystic fibrosis. Detailed clinical characterization of a patient cohort referred with suspected piperacillin-tazobactam hypersensitivity. Retrospective analysis of the demographic characteristics, clinical presentation, investigation, and management of 87 patients presenting to 5 European allergy centers. Patients underwent skin prick and intradermal testing with piperacillin/tazobactam, major (penicilloyl-polylysine) and minor (sodium penilloate) determinants, amoxicillin, benzylpenicillin, flucloxacillin, co-amoxiclav, clavulanic acid, and meropenem with immediate and, where appropriate, delayed reading of tests. Skin test-negative patients underwent drug provocation to piperacillin/tazobactam and/or other penicillins. A multistep protocol was used, depending on risk assessment. Forty-eight of 87 (55%) patients were diagnosed with hypersensitivity to piperacillin/tazobactam with either positive skin or drug provocation test results, of whom 10 (21%) had a diagnosis of cystic fibrosis. Twenty-six (54%) patients presented with immediate and 22 (45%) with nonimmediate hypersensitivity. Patients with cystic fibrosis predominantly presented with nonimmediate hypersensitivity (70%). Reactions were severe in 52% of immediate reactors (Brown's anaphylaxis grade 3) and moderately severe (systemic involvement) in 75% of nonimmediate reactors. The number of patients with negative skin test results tolerating reintroduction was comparable in immediate (80%) and nonimmediate (88%) hypersensitivity. One-third of patients were cross-sensitized to other penicillins. The cross-sensitization pattern raised the possibility of tazobactam allergy in 3 patients. In 21 patients selectively sensitized to piperacillin/tazobactam (12 immediate, 9 nonimmediate), tolerance to other beta-lactams was demonstrated by drug provocation testing. Piperacillin-tazobactam caused immediate and nonimmediate hypersensitivity with similar frequency. Most patients were selectively sensitized and tolerated other penicillins. Some patients may be allergic to the beta-lactamase inhibitor only.

Transient Diagnosis of Fines Migration Integrating Core Testing and Numerical Reservoir Modeling

SummaryTo manage well productivity, an effort was undertaken to identify fines migration by means of transient diagnosis, quantify its effect on productivity, model the production history, and forecast well performance. Because of its distinguishable transient behavior, mechanical fines migration can be identified among other factors that contribute to productivity decline. Pressure transient analysis (PTA), production data analysis (PDA), laboratory experiments, and numerical-flow-simulation techniques were used to understand the physics of fines migration, quantify its characteristic parameters, validate the model with production history, and verify its efficacy in a field application. Results are consistent with laboratory observations, synthetic studies leveraging a geomechanics reservoir simulator, and field data for moderate to severe fines migration.A new integrated approach was developed to accurately identify and depict declining productivity caused by fines migration through PTA, core testing, and reservoir flow modeling. Previous research has proposed a permeability-reduction flow function that correlates with extended coreflood data to predict the key parameters that characterize the fines-migration effects: critical velocity, permeability-reduction rate, and ultimate residual permeability. From the transient-behavior observations on wells experiencing fines migration, the obvious damage is represented by a positive skin as a function of time in the near-wellbore region. This concurs with the realization that interstitial velocity decreases with the distance from the wellbore. For severe fines migration observed in both synthetic cases and field data, two permeability regions could be identified and described by a radial composite model allowing the damage radius and the average permeabilities of each zone be estimated. Incorporation of a new technique, which correlates the skin-time function with the fines-migration flow relation, enables the calculation of key parameter ranges. These can be integrated with coreflood data for use as initial values in numerical reservoir modeling, potentially simplifying history-matching efforts before performance forecast.The novelty of this workflow is in the ability to identify and quantify the potential influence of mechanical fines migration with PTA and PDA techniques, and incorporation of the fines-migration flow relation to estimate the ranges of the characteristic parameters used in numerical modeling. Understanding the impact of fines migration on well productivity allows engineers to more accurately predict production decline, identify the benefit of remediation, and select optimal development strategies.

Does the principle of homologous groups allow a reduction of allergens in the skin prick test panel?

Regulatory and economic conditions drive the application of the concept of homologous groups on therapeutic and diagnostic formulations. In this context, a possible reduction of allergens in the skin prick test panel in the clinical routine should be investigated for the grass, birch and Dermatophagoides homologous group. Grass and cultivated rye skin prick test results of 1101 patients, birch/hazel/alder skin prick test results of 1131 patients and 1068 Dermatophagoides pteronyssinus and farinae skin prick tests were retrospectively evaluated with regard to sensitivity and false-negative rate detecting sensitization against cultivated rye with grass skin prick test, sensitization against hazel and/or alder with birch skin prick test and sensitization towards Dermatophagoides farinae with Dermatophagoides pteronyssinus skin prick test. Skin prick test results in all groups highly correlated in Spearman Rank Order correlation. Sensitivity of grass skin prick test detecting sensitization against cultivated rye was highest with 98.9%, sensitivity of birch skin prick test detecting sensitization toward hazel and alder was 95.6 and 90.0%, respectively. Sensitivity of skin prick test with Dermatophagoides pteronyssinus detecting sensitization towards Dermatophagoides farinae was 93.6%. Only 26 patients with positive rye, hazel, alder or Dermatophagoides farinae skin prick test that were overlooked by grass, birch or Dermatophagoides pteronyssinus skin prick test reported allergic symptoms. In routine clinical practice, sensitization against cultivated rye can safely be detected by skin prick test with grass allergen. In addition, the sensitivity of birch skin prick test is high in terms of sensitization towards hazel, but lower for alder. Sensitivity of Dermatophagoides pteronyssinus skin prick test also is high to detect sensitization towards Dermatophagoides farinae. Further research will indicate if several skin prick test allergens will disappear and be completely replaced by a single skin prick test based on the principle of homologous groups.