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Background Data are sparse regarding the safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with multiple sclerosis (MS). Objective To estimate (1) the pooled proportion of MS patients experiencing relapse among vaccine recipients; (2) the rate of transient neurological worsening, adverse events, and serious adverse events; (3) the previous outcomes of interest for different SARS-CoV-2 vaccine types. Methods Systematic review and meta-analysis of pharmacovigilance registries and observational studies. Results Nineteen observational studies comprising 14,755 MS patients who received 23,088 doses of COVID-19 vaccines were included. Mean age was 43.3 years (95% confidence interval (CI): 40–46.6); relapsing-remitting, secondary-progressive, primary-progressive MS and clinically isolated syndrome were diagnosed in 82.6% (95% CI: 73.9–89.8), 12.6% (95% CI: 6.3–20.8), 6.7% (95% CI: 4.2–9.9), and 2.9% (95% CI: 1–5.9) of cases, respectively. The pooled proportion of MS patients experiencing relapse at a mean time interval of 20 days (95% CI: 12–28.2) from vaccination was 1.9% (95% CI: 1.3%–2.6%; I2 = 78%), with the relapse risk being independent of the type of administered SARS-CoV-2-vaccine ( p for subgroup differences = 0.7 for messenger RNA (mRNA), inactivated virus, and adenovector-based vaccines). After vaccination, transient neurological worsening was observed in 4.8% (95% CI: 2.3%–8.1%) of patients. Adverse events and serious adverse events were reported in 52.8% (95% CI: 46.7%–58.8%) and 0.1% (95% CI: 0%–0.2%) of vaccinations, respectively. Conclusion COVID-19 vaccination does not appear to increase the risk of relapse and serious adverse events in MS. Weighted against the risks of SARS-CoV-2-related complications and MS exacerbations, these safety data provide compelling pro-vaccination arguments for MS patients.

Previous data suggested the potential treatment effect of a proprietary quail eggs-based blend on allergic rhinitis (AR) symptoms, induced by allergen challenge. We herein aimed to investigate the efficacy and safety of a similar dietary supplement, comprising the bioactive ingredients of quail eggs and the zinc mineral, in the setting of active AR. Adult patients (

Η εμμηναρχή αποτελεί ορόσημο στη φυσιολογική ανάπτυξη κάθε γυναίκας γιατί σηματοδοτεί την έναρξη της περιόδου της γονιμότητας και αποτελεί αφετηρία για ποίκιλες μεταβολές στο ψυχισμό του ατόμου. Το γεγονός ότι επέρχεται αιφνίδια και συνδέεται με τη διαδικασία της αναπαραγωγής και τη γονιμότητα προσέδιδε στο θέμα μυστήριο και αποτελούσε ένα επιπλέον ερέθισμα για τους ερευνητές. Για τους παραπάνω λόγους η εμμηναρχή αποτέλεσε και εξακολουθεί να αποτελεί αντικείμενο εντατικής μελέτης. Ιδιαίτερο ενδιαφέρον έχει η χρονική στιγμή έλευσης της εμμηναρχής καθώς και τα βιολογικά γεγονότα που προηγούνται αυτής. Η μέση ηλικία εμμηναρχής τα τελευταία 150 χρόνια ελαττώνεται με ένα ρυθμό 2 3 μηνών ανά δεκαετία. Η μείωση της ηλικίας εμμηναρχής έχει αποδοθεί, από παλαιότερες μελέτες στην αυξημένη προσφορά και στη βελτιωμένη ποιότητα τροφής, καθώς και στην σημαντική αύξηση κατά την εφηβεία του ύψους και του βάρους. Επίσης, έχει βρεθεί ότι η έντονη φυσική δραστηριότητα επιβραδύνει την εμμηναρχή, ενώ δεν έχει διερευνηθεί ο ρόλος της συνήθους, μέτριας φυσικής δραστηριότητας στην ηλικία εμμηναρχής. Με σκοπό να καταγραφούν διάφορες παράμετροι που πιθανά επηρεάζουν την ηλικία εμμηναρχής έγινε μια επιδημιολογική μελέτη σε μαθήτριες (Δημοτικών και Γυμνασίων) της Αττικής. Ειδικότερα, έγινε προσπάθεια να απαντηθούν τα κάτωθι ερωτήματα; 1) εάν η προσλαμβανόμενη ενέργεια, ένας δείκτης φυσικής δραστηριότητας, σχετίζεται με αργότερη ηλικία εμμηναρχής, 2) εάν η προσλαμβανόμενη ενέργεια από τα λίπη σχετίζεται με πρωϊμότερη ηλικία εμμηναρχής και 3) εάν άλλα στοιχεία διατροφής και ανθρωπομετρικές μεταβλητές είναι προγνωστικά της ηλικίας εμμηναρχής. Στη μελέτη συμμετείχαν 345 κορίτσια ηλικίας 9-16 ετών, τα οποία φοιτούσαν σε οκτώ σχολεία της ευρύτερης περιοχής της Αθήνας. Μετά από προσωπική συνέντευξη έγινε καταγραφή των κοινωνικοοικονομικών, ανθρωπομετρικών, διατροφικών και οικογενειακών παραμέτρων των κοριτσιών αυτών. Η εμμηναρχή ήταν η μεταβλητή σε ένα μοντέλο αναλογικού κινδύνου αποτιμώντας την επίπτωση μιας σειράς προγνωστικών μεταβλητών. Σε συμπληρωματική ανάλυση η ηλικία εμμηναρχής ήταν η εξαρτημένη μεταβλητή ανάμεσα στα 166 κορίτσια τα οποία είχαν ήδη εμμηναρχή. Τα αποτελέσματα τόσο από την κύρια όσο και από τη συμπληρωματική ανάλυση ήταν παρόμοια Βρέθηκε ότι το αυξημένο ύψος και ο υψηλός δείκτης μάζας σώματος επιταχύνουν σημαντικά την εμφάνιση της εμμηναρχής και ότι η ηλικία εμμηναρχής της μητέρας και της κόρης συσχετίζονται σημαντικά. Βρέθηκε επίσης ότι η μέτρια φυσική δραστηριότητα καθώς και η συνολικά προσλαμβανόμενη ενέργεια συσχετίζονται με καθυστέρηση στην ηλικία εμμηναρχής. Όμως δεν βρέθηκε να υπάρχει συσχέτιση της ηλικίας εμμηναρχής με την εκπαίδευση του πατέρα, η οποία αποτελεί για την Ελλάδα το καλύτερο κριτήριο κοινωνικοοικονομικής τάξης, και η σύσταση της τροφής επίσης δεν βρέθηκε ότι επηρεάζει σημαντικά την ηλικία εμμηναρχής, αν και η αυξημένη πρόσληψη των πολυακόρεστων λιπών φαίνεται να συσχετίζεται με μια καθυστέρηση στην ηλικία εμμηναρχής. Διαφαίνεται λοιπόν ότι η σωματική δραστηριότητα καθυστερεί την εμμηναρχή, ενώ η σύσταση της τροφής που καταναλώνεται έχει μικρή επίδραση στην ηλικία εμμηναρχής.

Background: Patients with severe eosinophilic asthma (SEA) frequently have comorbid chronic rhinosinusitis with nasal polyposis (CRSwNP). In this pilot study we aimed to assess the effect of mepolizumab on rhinitic symptoms and nasal hypersensitivity, as well as NP. Methods: Fifteen patients with SEA (eight patients with rhinitis/rhinosinusitis and seven patients with NP) have been included as yet. All patients underwent skin prick testing (SPTs), facial CT scan, nasal Peak Inspiratory Flow Rate (nPIFR) measurements, and nasal provocation testing (NPT) before, 6 months, and one year after mepolizumab treatment for SEA. Daily nasal symptoms were recorded, along with SNOT 22. Nasal secretion samples were collected at each point of nasal provocation and stored for the quantification of inflammatory mediators. Results: Ten patients had positive SPTs to common aeroallergens. Total IgE mean serum levels were 175 IU/mL (range 10-555 IU/mL) with mean blood eosinophil count 345 k/μL (range 100-540 k/μL). Four patients had a positive provocation test which turned to negative in three patients after one year of treatment. There was a significant decrease in daily symptom scores after six months (mean±SD, 4.5±3 vs 1.7±1, p=0.007) and a year of treatment (2.8±1, p=0.08), with SNOT-22 score significantly improving after a year of treatment (56±16 vs 32±24, p=0.048). In five patients NP was significantly improved. Mediators’ measurements are pending. Conclusions: In SEA patients with CRSwNP a positive effect in reducing symptoms, nasal hypersensitivity and NP was seen however, a larger number of patients is needed in order to have conclusive results

Background Previous clinical trials have demonstrated the efficacy and safety of the anti-IgE monoclonal antibody omalizumab in chronic spontaneous urticaria (CSU) not responding to antihistamine treatment. The primary aim of our study was to describe the response patterns of patients with refractory CSU treated with omalizumab in a real-world clinical setting. Methods A retrospective analysis of medical records of 20 patients with refractory CSU was performed. Demographic, clinical, and laboratory features were retrieved and analyzed in correlation with treatment data. Results Mean age of our patient population was 54.5 years, while the majority were females (15/20 cases, 75%). Mean disease duration prior to omalizumab administration was 21.8 months. All patients had a history of chronic urticaria, refractory to high antihistamine and corticosteroid treatment, and responded favorably to omalizumab after administration of 1–5 doses of omalizumab; complete response was observed in 17/20 patients (85%) and well-controlled disease in the remaining 3/20 patients (15%). In a subset of cases (6/20, 30%), best response to omalizumab was achieved after interval administration of a 9-day course of methylprednisolone (total dose of 188 mg). Late response to omalizumab (after three-month treatment) was significantly correlated (P = 0.026) with shorter disease duration before initiation of omalizumab. Conclusion In the present series, omalizumab, either alone or in combination with a short-term course of corticosteroids, was highly effective in resolution of refractory CSU. Furthermore, disease duration prior to omalizumab had a significant effect on timing of response.

Drug-induced acute generalized exanthematous pustulosis is a rare pustular skin reaction, most commonly triggered by antibiotics. Although its diagnosis is based primarily on the presence of specific clinical and histopathologic features, additional in vivo (patch testing) or in vitro testing may be required, especially in atypical cases, to more accurately determine the causative agent. The authors report a histologically confirmed case of acute generalized exanthematous pustulosis that was induced by amoxicillin/clavulanic acid, as documented by subsequent patch testing, and presented with generalized painful lymphadenopathy, mimicking an acute infectious process. This is a very rare and diagnostically challenging clinical presentation of acute generalized exanthematous pustulosis, which has been reported, to the best of our knowledge, only once previously.

Background: Docetaxel (DT) is an extensively used taxane, frequently associated with hypersensitivity reactions. The aim of this study was to record the epidemiological and clinical features of hypersensitivity to DT in non-small cell lung cancer patients in order to obtain useful information concerning the management of these patients. We also developed a desensitization protocol and evaluated its clinical application. Methods: We retrospectively reviewed records of 620 non-small cell lung cancer patients treated with DT-containing regimens in the adjuvant, first-, second- or next-line setting. Data from 102 patients who had exhibited hypersensitivity reactions were analyzed according to the Common Toxicity Criteria for Adverse Events version 3.0. Five patients were chosen for the desensitization protocol. We applied the standard protocol for parenteral desensitization to β-lactam antibiotics, and DT treatment was carried out with a series of 10-fold dilutions in sufficient volume to administer the total dose. Results: One hundred and two patients (16.5%) were recorded as having hypersensitivity to DT. Reactions were observed after approximately 2.5 ± 1.0 cycles. Only 14 patients (14/620, 2%) developed grade 3–4 hypersensitivity. Reactions were more likely in patients during second- or third-line chemotherapy, but no other correlation (age, gender, atopic status) was observed. Five patients completed a parenteral desensitization protocol and continued their treatment uneventfully. Conclusions: Hypersensitivity reactions to DT respond quickly to discontinuation along with appropriate supportive care. Premedication and increased infusion time may allow readministration. The desensitization protocol that we developed provides a reliable alternative to permanent discontinuation of DT.

Keywords: food allergy; food intolerances; gluten-free diet; refractory coeliac disease

Platinum-containing chemotherapy agents (cisplatin, carboplatin, oxaliplatin) have been approved in the first-line setting of numerous malignancies, such as ovarian, bladder, head and neck, colorectal, and lung cancer. Their extensive use over the last decade has led to a significant increase in the incidence of hypersensitivity reactions, which are defined as unforeseen reactions whose signs and symptoms cannot be explained by the known toxicity of these drugs. Skin rash, flushing, abdominal cramping, itchy palms, and back pain are common symptoms. Cardiovascular and respiratory complications can prove fatal. Multiple pathogenetic mechanisms have been suggested. Hypersensitivity usually appears after multiple infusions, suggesting type I allergic reactions; however, other types of hypersensitivity also seem to be implicated. Several management options are available to treating physicians: discontinuation of chemotherapy, premedication, prolonging of infusion duration, desensitization protocols, and replacement with a different platinum compound after performing skin tests that rule out cross-reactions among platinum agents.

Background We recorded the epidemiologic and clinical features of hypersensitivity reactions (HSRs) to oxaliplatin in colorectal cancer (CRC) patients in order to provide information on the management of these patients. We also developed a desensitization protocol and evaluated its clinical application. For these reasons, we analyzed retrospectively the records of 215 CRC patients treated with oxaliplatin-containing regimens either as an adjuvant, first-line, second-line, or more. Patients and Methods Data from 52 patients with HSRs were analyzed according to the Common Toxicity Criteria for Adverse Events (CTCAE), v3.0. Three patients were chosen for the desensitization protocol. After determining the starting point for desensitization, we applied the standard protocol for parenteral desensitization to b-lactam antibiotics. Oxaliplatin treatment was then carried out with serial 10-fold dilutions in sufficient volume to administer the total dose. A total of 52 patients (24.2%) were recorded as having an allergic reaction to oxaliplatin. Results Hypersensitivity reactions were recorded after a mean of 6.5 (SD ± 4.5) cycles. Only 4 patients (4 of 215; 1.8%) developed CTCAE grade 3/4 HSRs. Hypersensitivity reactions were seen more likely in patients receiving second-line or more of chemotherapy compared with chemotherapy-naive patients. No other correlations were seen (the presence of atopic disease, positive skin prick test). The 3 patients, having completed the parenteral desensitization protocol, completed their treatment uneventfully as well. Conclusion Hypersensitivity reactions from oxaliplatin respond quickly to the discontinuation of the drug and appropriate support. Premedication and an increased infusion time could allow for readministration. The desensitization protocol we developed can provide a reliable alternative to permanent discontinuation of oxaliplatin.

Although the reported incidence of hypersensitivity reactions (HSR) to antineoplastic agents is considered to be uncommon, it is difficult to evaluate their exact prevalence, mainly because their definition is vast and pathogenic mechanisms are vague. HSR include facial flushing, erythema, pruritus, fever, tachycardia, dyspnea, tongue swelling, rash/hives, headache, chills, weakness, vomiting, burning sensations, dizziness, and edema. Treatment and prevention consists of slowing the infusion rate, steroids, and type 1 and 2 histamine receptor antagonists. Desensitization could allow the small number of patients who experience severe HSR to receive effective therapy for their cancer. Reintroductions have only been reported as single case studies or small cohorts. Large-scale validation on desensitization strategies is still missing. With regard to oxaliplatin, knowledge of its rare but eminent toxicity is paramount, because this drug is widely used in treating colorectal cancer, the second-highest cause of cancer mortality in the United States.

In a prospective cohort study we investigated the course of allergic sensitization from childhood to puberty in a group of children with atopic asthma. An attempt was made to correlate the findings with the persistence of asthma. A total of 150 children with atopic asthma established at 7 years of age were evaluated when 8-10 years of age. A battery of skin-prick tests (SPTs) to common environmental allergens, a detailed clinical history for asthma severity classification, and spirometric analyses, were performed. In 127 of these children a re-evaluation was performed at puberty. A variety of statistical methods were used to analyze the results regarding changes in skin test reactivity to individual aeroallergens and atopic index (degree of atopy), as well as to determine any correlation between these changes and the persistence of asthma in puberty. A wide spectrum of modification in skin reactivity to common environmental allergens was observed, including the complete loss of sensitization to some allergens or the development of a new one to others. Specifically, 34% of asthmatic children sensitive to Dermatophagoides pteronyssinus and 52.7% sensitive to cat lost their sensitivity in puberty, while only 7.5% and 11.1%, respectively, became sensitized (p = 0.03 and p = 0.001, respectively). In contrast, regarding pollen sensitivity, 30.2% and 24% of asthmatic children became sensitive in puberty to olive pollen and grasses mix, respectively, and only 11.7% and 12.5%, respectively, lost their sensitivity to these allergens (p = 0.04). No correlation was shown between the skin test reactivity changes to individual allergens and the persistence of asthma, but a significant correlation was found between atopic index to indoor allergens in childhood and the persistence of asthma at puberty (p = 0.04). Interestingly, multi-sensitivity to allergens (>/= 4 allergens) in childhood was also found to correlate with the persistence of asthma at puberty [p = 0.05, odds ratio (OR) = 2.65, 95% confidence interval (CI) 1.2-7.2]. Our findings indicate that significant modification of skin reactivity to common environmental allergens in atopic children with asthma in puberty can occur. However, no association between these changes and the persistence of asthma could be demonstrated, although children with indoor allergic sensitization and multi-reactivity were found to have a higher probability of maintaining their asthma in puberty.

Rifampicin (also known as rifampin) is one of the most potent first-line antituberculosis drugs and an indispensable treatment option for isoniazid-resistant, rifampicin-sensitive tuberculosis (TB). Hypersensitivity reactions to rifampicin, mainly including fever, flu-like syndrome, rash, thrombocytopenia, acute renal failure, urticaria, and anaphylaxis, are considered rare but may occur among susceptible individuals and lead to premature discontinuation of the drug. Drug desensitization is a well-established procedure that may temporarily modify a patient’s immunologic response to the sensitizing agent, thus allowing for continuation of treatment. Desensitization to rifampicin has been previously described in rare case reports, almost invariably with successful results. We herein report a case of anaphylaxis during rapid oral desensitization to rifampicin in a male patient with active TB and a history of anaphylactic reactions to this agent. To the best of our knowledge, this is the first report in the English literature of a severe immediate-type reaction during desensitization to rifampicin. A 72-year-old man presented to the outpatient pulmonary clinic of “Sotiria” General Hospital, Athens, Greece, with fever, nonproductive cough, and weakness, lasting for 2 weeks. His medical history was significant for adult-onset diabetes mellitus and rheumatoid arthritis, treated with metformin and low-dose prednisone and intravenous infliximab, respectively. The patient was diagnosed with miliary TB and was started on anti-TB treatment with isoniazid (300 mg/day), rifampicin (600 mg/day), pyrazinamide (1500 mg/day), and ethambutol (1200 mg/day). Within 2 weeks after initiation of the above regimen, and 30 minutes after administration of the last dose of rifampicin, the patient developed fever and widespread urticaria; all drugs were subsequently discontinued and gradually reintroduced—after resolution of the cutaneous reaction—to identify the culprit drug. Urticaria, palmoplantar, and oropharyngeal pruritus were noted within 5 minutes after reintroduction of rifampicin and the drug was stopped; rifampicin was thereafter replaced with rifabutin. Ten days after initiation of rifabutin, the patient developed a maculopapular rash that affected the trunk and lower extremities. A skin biopsy was compatible with drug-induced eruption and rifabutin was discontinued. Approximately 3 years after his initial diagnosis of TB, the patient developed recurrent TB and was again started on a multidrug anti-TB regimen comprising isoniazid, rifabutin, pyrazinamide, and ethambutol. Twelve days after initiation of treatment a maculopapular rash appeared on the patient’s upper and lower extremities; rifabutin was again discontinued, followed by gradual resolution of the eruption, and the patient was referred to the Allergy Department of our hospital for further evaluation and management. At the time of the patient’s presentation to our department, skin prick test (SPT) and intradermal (ID) skin testing to rifampicin were performed, based on previous recommendations defining the highest nonirritant intradermal skin concentration of rifampicin (0.002 mg/mL). Histamine and saline were also used as positive and negative controls, respectively. SPT at a concentration of 2 mg/mL was negative, whereas a positive reaction (with a wheal of 15 17 mm and a flare of 42 44 mm) was shown on ID skin testing at a concentration of 0.002 mg/ mL. After obtaining the patient’s informed consent, oral desensitization to rifampicin was carried out in the intensive care unit. Premedication with antihistamines or steroids was not used (prednisone was discontinued for 3 days before the procedure) because these drugs may mask initial symptoms of anaphylaxis during desensitization, as previously emphasized, and the patient was not taking b-blockers or angiotensin-converting enzyme inhibitors. Increasing dosages of rifampicin were administered every 30 minutes, at a starting dose of 0.0002 mg followed by gradual dose escalation (Table I), as described in previously published desensitization protocols. Twenty minutes after administration of the 50 mg rifampicin dose, the patient started complaining of pruritus of the palms, soles, and groin followed by facial and trunk erythema, cough, generalized urticaria, hypotenstion, and sinus tachycardia followed by sinus bradycardia (without other ECG abnormalities). The desensitization procedure was discontinued, and the patient was treated with IV fluids, oxygen and nebulized salbutamol, intramuscular adrenaline, and intravenous methylprednisolone, dimetindene and ranitidine, with gradual recovery. Serum tryptase obtained at 1 hour after the onset of symptoms was 25 mg/L. Repeat serum tryptase, measured 1 week later, was found to be within normal limits (4 mg/L). Given the patient’s anaphylactic reaction during rapid desensitization, anti-IgE treatment and desensitization to rifampicin using slow dose increment over several days were recommended but the patient refused. Hypersensitivity reactions to anti-TB agents are relatively uncommon, encountered in approximately 4%-5% of the treated population, but may as well lead to withdrawal of the culprit drug and switching to an alternative agent. Rifampicin, in particular, is generally considered a well-tolerated drug with a low percentage of adverse events, especially when administered in usual therapeutic doses and outside the context of HIV infection. Delayed reactions, including a variety of cutaneous manifestations, are the commonest adverse reactions induced by rifampicin, whereas severe immediate reactions, such as anaphylaxis, are exceedingly rare.

Giant reactions to the tuberculin skin test are extremely rare and have been previously reported almost exclusively in patients with lepromatous leprosy. We herein report a giant tuberculin reaction associated with the homeopathic drug Tuberculinum in a patient with no evidence of active tuberculosis or leprosy.

The aims of this study were to evaluate the implication of food allergy as a cause of paediatric constipation and to determine the diet period needed to tolerate the constipation-causing foods. Fifty-four children aged 6 months to 14 years (median, 42 months) suffering from chronic constipation (without anatomic abnormalities, cοeliac disease or hypothyroidism), unresponsive to a 3-month laxative therapy, were prospectively evaluated. All participants were evaluated for allergy to cow's milk, egg, wheat, rice, corn, potato, chicken, beef and soy, using skin tests (SPT), serum specific IgE and atopy patch test (APT). A withdrawal of the APT-positive foods was instructed. Thirty-two children had positive APT; 15 were positive to one; six, to two and 11, to three or more food allergens, wheat and egg being the commonest. After withdrawing the APT-positive foods for an 8-week period, constipation had improved in 28/32 children, but a relapse of constipation was noticed after an oral food challenge, so they continued the elimination diet. Tolerance to food allergens was achieved in only 6/28 after 6 months, compared to 25/28 after 12 months and to all after a 2-year-long elimination. Food allergy seems to be a significant etiologic factor for chronic constipation not responding to treatment, in infants and young children. APT was found to be useful in evaluating non-IgE allergy-mediated constipation, and there was no correlation of APT with IgE detection. Tolerance was adequately achieved after 12 months of strict food allergen elimination.

Hypersensitivity reactions to antineoplastic agents are defined as unexpected reactions with signs and symptoms inconsistent with known toxicity of antineoplastic drugs. These reactions are uncommon and usually associated with certain antineoplastic categories, such as taxanes, platinum-containing compounds, epipodofyllotoxins, asparaginase, procarbazine and, more rarely, with doxorubicin and 6-mercaptopurine. The mechanisms that are responsible for hypersensitivity reactions are unclear and vary between agents. Symptoms of these reactions range from mild skin rashes to more severe reactions, such as arthralgia, respiratory arrest or even death in some cases. Once hypersensitivity reactions are observed, basic principles that allow their management and possible continuance and completion of the regimen should be followed.

Objectives To investigate the expression of heat shock protein-70 (HSP-70) in transitional cell bladder cancer and correlate it with normal and inflammatory bladder tissue samples. Methods We used a three-step avidin-biotin method to examine the localization of a rabbit anti-HSP-70 polyclonal antibody in normal (n = 10), inflammatory (n = 10), and malignant (n = 67) bladder tissue samples. Results Fifty-eight percent of the bladder cancer samples and only 10% and 20% of the normal and inflammatory bladder tissue samples, respectively, expressed HSP-70. Localization of the antibody correlated with the grade ( P P P Conclusions HSP-70 is frequently overexpressed by bladder cancer cells and could be used as biochemical marker in patients with bladder cancer.

Background The relationship between inflammation, air obstruction and lung cancer is complex and there is still great uncertainty regarding their underlying pathophysiology. Our aim was to investigate the inflammation pathways that are implicated in both chronic obstructive pulmonary disease (COPD) and lung cancer. Methods A literature search was performed in PubMed to identify relative studies published until June 2011. Results The pathophysiology of both COPD and lung cancer includes dysregulation of the inflammation process, but the cascade of signaling events is not yet fully understood. Both lung cancer and COPD are associated with cigarette smoking that induces a chronic inflammatory state in the lung by generating reactive oxidant species. It is considered that shared inflammatory pathways involve genetic and epigenetic changes due to chronic tissue injury and abnormal tumor immunity in susceptible hosts. The proposed role of chronic inflammation is based on the 2-stage model of carcinogenesis. According to this model, genotoxic injury is crucial in tumorigenesis, followed by promotional events that result in clonal growth of modulated cells. Research has shown that chronic inflammation creates the necessary environment for the development of lung cancer, acting as a tumor promoter. This environment, in combination with cigarette smoke, induces the upregulation of mediators of the inflammatory response, such as cyclooxygenase-2. This leads to the production of inflammatory cytokines through lymphocytes, such as IL-1, IL-6, IL-8 and IL-10, as well as to the increased formation of chemotactic factors. Some of the latter mediators may suppress cell mediated immune response and promote angiogenesis. They also impact cell growth, resulting in the inhibition of apoptosis. Inflammatory factors promote oxidative stress, contribute to the generation of reactive oxygen, and cause oxidative DNA base modification. COX-2 also plays an important role in promoting epithelial-to-mesenchymal transition, present in both lung cancer and COPD. Thus, chronic inflammation plays a pathogenic role in lung cancer by inducing preneoplastic mutations and cellular damage. Conclusions Additional research is required to understand the cellular and molecular mechanisms that link COPD and lung cancer, in an effort to discover new methods of prevention and treatment.

In a prospective cohort study we investigated the course of allergic sensitization from childhood to puberty in a group of children with atopic asthma. An attempt was made to correlate the findings with the persistence of asthma. A total of 150 children with atopic asthma established at 7 years of age were evaluated when 8-10 years of age. A battery of skin-prick tests (SPTs) to common environmental allergens, a detailed clinical history for asthma severity classification, and spirometric analyses, were performed. In 127 of these children a re-evaluation was performed at puberty. A variety of statistical methods were used to analyze the results regarding changes in skin test reactivity to individual aeroallergens and atopic index (degree of atopy), as well as to determine any correlation between these changes and the persistence of asthma in puberty. A wide spectrum of modification in skin reactivity to common environmental allergens was observed, including the complete loss of sensitization to some allergens or the development of a new one to others. Specifically, 34% of asthmatic children sensitive to Dermatophagoides pteronyssinus and 52.7% sensitive to cat lost their sensitivity in puberty, while only 7.5% and 11.1%, respectively, became sensitized (p = 0.03 and p = 0.001, respectively). In contrast, regarding pollen sensitivity, 30.2% and 24% of asthmatic children became sensitive in puberty to olive pollen and grasses mix, respectively, and only 11.7% and 12.5%, respectively, lost their sensitivity to these allergens (p = 0.04). No correlation was shown between the skin test reactivity changes to individual allergens and the persistence of asthma, but a significant correlation was found between atopic index to indoor allergens in childhood and the persistence of asthma at puberty (p = 0.04). Interestingly, multi-sensitivity to allergens (/= 4 allergens) in childhood was also found to correlate with the persistence of asthma at puberty [p = 0.05, odds ratio (OR) = 2.65, 95% confidence interval (CI) 1.2-7.2]. Our findings indicate that significant modification of skin reactivity to common environmental allergens in atopic children with asthma in puberty can occur. However, no association between these changes and the persistence of asthma could be demonstrated, although children with indoor allergic sensitization and multi-reactivity were found to have a higher probability of maintaining their asthma in puberty.

Background: Controversial results have been reported on the participation and diagnostic value of lymphocyte reactivity in cow’s milk (CM) allergy. In this study, we used a specific nuclear marker to evaluate lymphocyte proliferation in IgE–mediated CM allergy in infants, and examine its relation with diets containing different CM antigen loads. Methods: Infants with IgE–mediated CM allergy, as assessed by open provocation and RAST, were grouped according to their exclusive diet, either CM formulae, breast feeding, or hydrolysed whey formulae. A group of non–atopic infants receiving CM was also examined. Lymphocyte proliferation to β–lactoglobulin was evaluated by quantitation of the proliferating cell nuclear antigen (PCNA) expression in peripheral blood mononuclear cells, by flow cytometry. Immunophenotypic surface markers were also examined. Results: A marked difference of PCNA expression between CM–fed allergic infants and healthy controls was observed (pConclusions: PCNA could be a useful marker in the assessment of lymphocyte proliferation to CM antigens. Low CM antigen diets are related with reduced lymphocyte reactivity, which may partly explain the clinical benefit observed with such diets.

Aim Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus immune/antigens mediated. It is clinically characterised by symptoms related to esophageal dysfunction and associated with eosinophil-predominant esophageal inflammation. The role of atopy has been clearly demonstrated both in epidemiological and experimental studies and has important implications for diagnosis and therapy.The aim of this study was to assess the relationship between food allergy and eosinophilic esophagitis in the pediatric population, as well as the effect of dietary modifications in patients’ clinical symptoms. Methods Thirty-six children aged 7 months to 12 years (median age 80 months), with EoE (esophageal symptoms, biopsy with >15 eosinophils/HPF after the patients have been treated with aP PI for at least 4– 8w eeks and other causes have been excluded) were included to group I. Twenty age and sex matched, apparently healthy, infants and children were studied as control group(group II).Serum specific IgEs to cow milk, egg, wheat, rice, corn, soy, chicken, potato, beef, peanut and pork were measured with the CAP-FEIA. Skin prick tests and atopy patch tests (using fresh foods) were performed for the same allergens. Results All children in control group had negative CAP, SPT and APT to all food allergens. In group I 30/36 children (83%) had positive APT. Of these, 12/30 (40%) had also positive SPT and 16/30 (53%) had also positive CAP. Of the 30 positive children 4 (4/30, 13%) had positive APT to one food allergen, 3/30 (10%) had positive APT to two food allergens and 23/30 (77%) to 3 or more food allergens. In the APT-positive children, in group I, withdrawing the suspected food allergens for an 8 week period resulted in the improvement of symptoms. Conclusion Food allergens seem to be a significant etiologic factor for eosinophilic esophagitis in infants and young children. Skin tests are able to identify, in most of the cases, the responsible food allergens leading to dietary modifications and symptom remission.

Background Chest radiation is a common therapeutic approach in the management of lung cancer, as well as in other malignancies, rendering radiation-induced pneumonitis a rather commonly reported adverse event. A large proportion of patients undergoing radiation have underlying chronic obstructive pulmonary disease (COPD). We aim to elucidate the pathogenetic pathways implicated in radiation-induced pneumonitis particularly in this subgroup of patients. Methods A literature search was performed in PubMed to identify relative studies published until June 2011. Results The incidence of radiation-induced pneumonitis after conventional irradiation in COPD is about 7 to 10% in the moderate although symptomatic forms and about 1 to 3% in the severe forms. Radiation-induced pneumonitis seems to be an acute-phase reaction, taking primarily place in the most radiosensitive subunit of the lung, the alveolar/capillary complex. Reactive oxygen species, generated by radiation, initiate a cascade of molecular events that alter the cytokine milieu of the microenvironment, creating inflammation and chronic oxidative stress. COPD is characterized by a chronic inflammatory state in the lung, also generating reactive oxidant species. Biological markers intrinsic to the patient, such as early variations of certain cytokines (IL-6, IL-10, TGF-β) seem to be implicated and studies are under way to determine their role. The standard dose-volume metrics, such as V20, V13 and mean lung dose, are major factors influencing the clinical course of radiation-induced pneumonitis. Conclusions Understanding the underlying pathogenesis of radiation-induced pneumonitis may help improve optimal delivery of treatment plans, minimize the risks and increasing the therapeutic ratio in patients with COPD.

Background Lung resection is still the only potentially curative therapy for patients with localised non-small lung cancer (NSCLC). However, the presence of cardiovascular comorbities and pulmonary function impairment increase the risk of perioperative death and postoperative complications. Various studies have evaluated the use of different preoperative tests aiming to identify asthma patients at greater risk for complications. Methods A literature search was performed in Pubmed to identify relative studies published until June 2011. Results Postoperative complications are associated with prolonged hospital stays and excessive morbidity and mortality especially in this group of patients. According to the ACCP/BTS guidelines, patients without known underlying lung disease with a preoperative FEV1 in excess of 2 L, generally tolerate pneumonectomy whereas those with FEV1 greater that 1.5 L, tolerate lobectomy. Although spirometric values strongly correlate with the severity of obstruction, they do not provide direct information regarding the degree of gas exchange impairment or the status of cardiovascular function. Cardiopulmonary exercise testing (CPET) is a preoperative test suggested before lung resection in patients with known underlying cardiovascular or lung disease. It is based on the interactions among pulmonary function, cardiovascular function and oxygen absorption from the peripheral tissues. Patients with maximal oxygen consumption (VO2 max)

Background Pulmonary toxicity and respiratory failure are major adverse events complicating the use of novel antineoplastic agents in the treatment of lung cancer. We aim to investigate the risk and characteristics of cytostatic-induced pulmonary toxicity caused by agents currently used to treat lung cancer. Methods A literature search was performed in PubMed to identify relative studies published until June 2011. Results Almost all categories of antineoplastic agents have been associated with some kind of pulmonary complications. Taxanes have been linked to acute pneumonitis, pleural effusion and reactions during infusion. Nucleoside analogs can cause diffuse alveolar damage, bronchospasm and acute respiratory distress syndrome (ARDS). Monoclonal antibodies are associated with pulmonary hemorrhage and hemoptysis. Acute pneumonitis and hypersensitivity reactions have been reported with podophyllotoxins, while diffuse interstitial pneumonia has been attributed to pemetrexed. Tyrosine kinase inhibitors of the epidermal growth factor receptor have been associated with acute pneumonitis, diffuse alveolar damage and pulmonary fibrosis. The exact incidence of lung toxicity caused by these agents remains unclear, although it seems relatively low. Clinical manifestation includes cough, fever, dyspnea and hypoxemia. Chest imaging reveals diffuse or patchy, unilateral or bilateral, ground-glass opacities or consolidations. It is important that other possible causes of respiratory failure be excluded when treating a lung cancer patient receiving chemotherapy. Conclusions Physicians should be aware of the potential of lung toxicities from antineoplastic agents, especially when they are combined with other cytotoxic drugs or radiation.

Background Lung cancer remains the leading cause of cancer-related deaths among men and women in the civilized world. A notable number of patients undergo radiation in various stages of the treatment process and its main respiratory side effect is pneumonitis. Our aim was to investigate the diagnostic and treatment methods of post-radiation pneumonitis particularly in asthma patients. Methods A literature search was performed in Pubmed to identify relative studies published until June 2011. Lung cancer, post-radiation pneumonitis, therapy and asthma were the key words used for the search. Results Post-radiation pneumonitis is a clinical situation demanding early diagnosis in asthma patients, but the latter is often underestimated. Pneumonitis is clinically revealed by dyspnea, cough, fever and usually begins up to 12 weeks after the start of radiation treatment. Radiographically, it appears as diffuse or patchy consolidation and/or ground glass opacities. Pulmonary function decline is correlated to decreased values of forced expiratory volume in the 1st second (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO). The effects on normal tissue may mimic or hide tumor recurrence. Smoking cessation causes changes of total lung capacity and vital capacity and this may have consequences on lung volume results in dose volume histogram analysis, targeting precision, oxygenation changes, tumor biology (gene expression) and prognosis. NCI Common Toxicity Criteria (CTC) V3.0 assessments are usually preformed weekly during radiotherapy and at regular follow-up visits. Complication rates vary with dose, fractionation, schedule duration, technique, photons' energy, irradiated volume, dose escalation, accelerated fractionation schemes, fields, co-morbidities and concurrent chemo-radiotherapy. Conclusions The crucially deteriorating on therapy effect of pneumonitis leads to the realization that alertness and constant attention is not only strongly advised, but compulsory in asthma patients.

M O N D A Y 700 Identification of Structural Determinants Supporting The Absence of IgE Cross-Reactivity Between Caprine and Bovine b-Caseins In Patients Allergic to Goat's Milk But Tolerant To Cow's Milk S. Hazebrouck, S. Ah-Leung, E. Paty, E. Bidat, M. F. Drumare, S. Tilleul, K. Adel-Patient, J. M. Wal, H. Bernard; Laboratoire d’Immuno-Allergie Alimentaire INRA, Gif sur Yvette, FRANCE, Hopital Necker Enfants Malades, Paris, FRANCE, Hopital Ambroise Pare, Boulogne-Billancourt, FRANCE. RATIONALE: Despite a sequence homology of 90%, IgE antibodies from patients allergic to goat’s milk (GM) but tolerant to cow’s milk (CM) recognize the caprine b-casein without cross-reacting with the bovine b-casein. Primary structure differences between the two b-caseins, which probably account for this restricted IgE specificity, were thus investigated. METHODS: Recombinant caprine b-casein mutants were produced in E. coli by performing residue substitutions with the corresponding amino acids found in bovine b-casein. The alteration of immunoreactivity was then assessed by IgE binding studies using sera of 12 GM-allergic patients. Twenty CM-allergic patients were used as controls. The allergenic potency was also evaluated by performing mediator release assay using mast cells passively sensitized with human IgE. RESULTS: All b-casein constructs, whatever the mutations generated, exhibited the same IgE reactivity with sera from CM-allergic patients. In contrast to the recombinant caprine b-casein, the bovine counterpart was poorly recognized by IgE from GM-allergic/CM-tolerant patients. Five residues, out of the 17 amino acid residues differing between the two b-caseins, were identified for their critical role in the restricted IgE specificity of GM-allergic/CM-tolerant patients. Accordingly, the mutant of caprine b-casein containing the five bovine substitutions was unable to induce the degranulation of mast cells passively sensitized with IgE from GM-allergic/CM-tolerant patients. CONCLUSION: The restricted binding of IgE from GM-allergic/CMtolerant patients to the caprine b-casein is principally supported by three different residues located in the N-terminus and two residues located in the C-terminus of the protein.

Carboplatin is a chemotherapeutic agent approved in the first-line setting of numerous malignancies. Hypersensitivity to carboplatin has been reported in up to 44% of patients receiving this antineoplastic agent, usually occurring after several courses of treatment. The aim of this study was to determine the usefulness of skin tests in ruling out cross-reaction to cisplatin to continue platinum-based chemotherapy in patients who are responsive to these agents. Prick tests and intradermal tests with a series of dilutions of carboplatin and cisplatin were performed on three patients who had exhibited medium and severe hypersensitivity reactions to carboplatin. Prick tests were negative in both the antineoplastic agents. Intradermal tests with carboplatin were positive in all three patients and negative with cisplatin. In all patients, the administration of cisplatin instead of carboplatin was well tolerated without the need of premedication. In conclusion, intradermal skin tests can be a useful tool for detecting a potential cross-reaction between platinum salts. It allows safe administration of a different platinum agent in patients who seem to benefit from platinum-based therapy. Discontinuation of chemotherapy, desensitization protocols and steroid premedication can be avoided.

Hypersensitivity reactions to chemotherapy agents are defined as unexpected reactions with signs and symptoms not consistent with known toxicity of these drugs. These reactions range from mild to life-threatening and are difficult to predict. Symptoms include flushing, nausea, difficulty breathing, back pain, hypotension and tachycardia. Hypersensitivity is commonly encountered owing to the increasing use of chemotherapy drugs in clinical practice. The pathogenetic mechanisms are not fully understood but they seem to vary between agents. Reactions to taxanes usually occur during the first few minutes of the first or second infusion, whereas acute reactions to platinum agents usually occur after multiple cycles of therapy. Basic principles that allow management and possible completion of the regimen should be followed. Certain protocols aim to prevent acute reactions by slowing the infusion rate and by administering steroid and histamine receptor antagonists. Skin testing and desensitization protocols have also been successfully used in case of hypersensitivity to various chemotherapy drugs. Knowledge of all available management options assists physicians in making the most appropriate decision regarding further treatment.

Interferon-gamma (IFN-gamma) is considered an important determinant of the balance between T-helper type 1 and 2 cytokines and has been used experimentally for the treatment of atopic dermatitis. However, contrasting results have been reported relative to the Th-1/Th-2 cytokine profile in atopic patients. In this study, we examined cytokine production by polyclonally activated peripheral blood mononuclear cells (PBMC) from children with atopic dermatitis, and assessed the influence of in vitro IFN-gamma pretreatment on these cells. A fraction of PBMC isolated from children with severe atopic dermatitis, as well as from age-matched controls, was initially exposed to IFN-gamma. After washing, both treated and untreated cells were then put into culture either alone or with the addition of phytohemagglutinin (PHA) or phorbol myristate acetate (PMA) plus ionomycin. IL-4, IL-5, IL-10 and IFN-gamma production were measured in the supernatants using commercially available ELISAs. PBMC from atopic patients produced more IL-4 (P = 0.04) and IL-10 (P = 0.03) and less IFN-gamma (P = 0.01) than controls, when stimulated with PHA. Interestingly, in PMA + ionomycin stimulated cultures, the atopic cytokine profile was different with more IL-5 (P = 0.0068) and less IFN-gamma production (P = 0.00046) than the control group. When cells were pretreated with IFN-gamma, there were no significant differences between patients and controls. PBMC from children with atopic dermatitis show alterations in cytokine production, compatible in general terms with the Th-1/Th-2 model. Exposure of PBMC to IFN-gamma before activation results in a reduction of these differences, so that cytokine production becomes similar in the atopic and normal groups.