The role of skin tests with polyethylene glycol and polysorbate 80 in the vaccination campaign for COVID-19: results from an Italian multicenter survey.

Summary: Background. International guidelines suggested skin tests with Polyethylene-glycol (PEG) and polysorbate 80 (PS-80), to investigate a possible hypersensitivity to these excipients either to identify subjects at risk of developing allergic reactions to Covid-19 vaccines, or in patients with suspected IgE mediated hypersensitivity reactions (HR) to the Covid-19 vaccine. The main purpose of this study was to investigate the prevalence of PEG and PS sensitization in patients with a clinical history of HR to drugs containing PEG/PS and in patients with a suspected Covid-19 vaccine immediate HR. Methods. This was a multicenter retrospective study conducted by allergists belonging to 20 Italian medical centers. Skin testing was performed in 531 patients with either a clinical history of suspected hypersensitivity reaction (HR) to drugs containing PEG and/or PS-80 (group 1:362 patient) or a suspected HR to Covid-19 vaccines (group 2: 169 patient), as suggested by the AAIITO/SIAAIC guidelines for the "management of patients at risk of allergic reactions to Covid-19 vaccines" [1]. Results. 10/362 (0.02%) had positive skin test to one or both excipients in group 1, 12/169 (7.1%) in group 2 (p less than 0.01). In group 2 HRs to Covid-19 vaccines were immediate in 10/12 of cases and anaphylaxis occurred in 4/12 of patients. Conclusions. The positivity of skin test with PEG and or PS before vaccination is extremely rare and mostly replaceable by an accurate clinical history. Sensitization to PEG and PS has to be investigated in patients with a previous immediate HR to a Covid-19 vaccine, in particular in patients with anaphylaxis.

Metaplastic squamous cell breast cancer: A case report and treatment strategy during covid-19 pandemic.

INTRODUCTION: Squamous carcinoma is a very rare breast cancer resulting from a differentiated squamous metaplasia. Its diagnosis is late due to the absence of specific clinical and radiological features. PRESENTATION OF CASE: The authors present the case of a 39-year-old patient with the clinical onset of an inflammatory cyst diagnosed with mammography and cytological examination. After segmentectomy, on histological examination was defined as: "squamous keratinizing aspect". In light of this report she was subjected to quadrantectomy with lymphadenectomy. She did not undergo radiotherapy treatment, which was delayed due to the ongoing pandemic. After a few months developed a local recurrence and underwent a mastectomy with multidisciplinary treatment. DISCUSSION: Squamously-differentiated metaplastic carcinoma of the breast is one of the rarest forms of breast cancer. Its etiopathogenesis is still unclear but some authors suggest that it originates from a squamous metaplasia deriving from the epithelium of cysts. This is a very aggressive and fast-growing tumour especially in young women, in fact the patient had a recurrence after a few months. She came to our attention 6 months after the initial surgery with a relapse at a local-regional level for which she was subjected to radical treatment and with a metastatic spread for which she was given the first-line chemotherapy treatment. CONCLUSION: There are no well-defined guidelines for the treatment of this rare form of cancer. The case illustrates how the rapid aggressiveness of the disease requires adequate and immediate multidisciplinary treatment from the very beginning.

Sensitization to Gibberellin-Regulated Protein (Peamaclein) Among Italian Cypress Pollen-Sensitized Patients.

BACKGROUND AND OBJECTIVES: Peach gibberellin-regulated protein (peamaclein) has recently emerged as a relevant food allergen in cypress pollen-hypersensitive patients. Objective: We investigated monosensitization to peamaclein among Italian cypress pollen-allergic patients. MATERIAL AND METHODS: A total of 835 cypress pollen-hypersensitive patients from 28 Italian allergy centers underwent a thorough work-up to determine food-allergic reactions and performed skin prick testing with a commercial peach extract containing peamaclein. IgE to rPru p 3 was measured in peach reactors, and those with negative results were enrolled as potentially monosensitized to peamaclein. IgE reactivity to rPru p 7 was evaluated using immunoblot and an experimental ImmunoCAP with rPru p 7. RESULTS: Skin prick tests were positive to peach in 163 patients (19.5%); however, 127 (77.9%) were excluded because they reacted to Pru p 3. Twenty-four patients (14.7%) corresponding to 2.8% of the entire study population) were considered potentially monosensitized to peamaclein. No geographic preference was observed. Seventeen of the 24 patients (70.8%) had a history of food allergy, mainly to peach (n=15). Additional offending foods included other Rosaceae, citrus fruits, fig, melon, tree nuts, and kiwi. On peach immunoblot, only 3 of 18 putative peamaclein-allergic patients reacted to a band at about 7 kDa; an additional 4 patients reacted at about 50-60 kDa. Ten of 18 patients (56%) had a positive result for Pru p 7 on ImmunoCAP. CONCLUSION: Allergy and sensitization to peamaclein seem rare in Italy. Most patients react to peach, although other Rosaceae fruits and several citrus fruits may also be offending foods. Peach and cypress pollen probably also share cross-reacting allergens other than peamaclein.

Evaluation of two commercial peach extracts for skin prick testing in the diagnosis of hypersensitivity to lipid transfer protein. A multicenter study.

Summary: The clinical usefulness of two commercial peach extracts for SPT (by Lofarma SpA and ALK-Abellò, respectively) was compared in a multicenter study carried out in Italy. Peach allergic patients were tested with the two extracts in parallel and underwent the detection of IgE specific for all three peach allergens currently available (Pru p1, Pru p3, and Pru p4, respectively). The two extracts were almost identical in terms of sensitivity and specificity, being able to detect virtually all patients sensitized to stable peach allergens (lipid transfer protein (LTP) and, presumably, peamaclein) but scoring negative in patients exclusively sensitive to labile allergens (either PR-10 and/or profilin). Thus, the two extracts represent an excellent tool to carry out a preliminary component-resolved diagnosis of peach allergy at the first patient visit.

Diabetes and severity of COVID-19: What is the link?

In Diabetes Mellitus the loss of capacity to regulate immunity, the reduction of pulmonary functions and the pro-thrombotic state determine the severity of COVID-19.

Metronidazole hypersensitivity in a patient with angioedema and widespread rash

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Diabetic foot infections: a comprehensive overview.

Diabetic foot ulcers (DFUs), a micro-vascular complication, are associated with a substantial increase in morbidity and mortality. DFUs are a complicated mixture of neuropathy, peripheral arterial diseases, foot deformities, and infections. Foot infections are frequent and potentially devastating complications. Infection prospers in more than half of all foot ulcers and is the factor that most often leads to lower extremity amputation. The complications of microbial flora span the spectrum from superficial cellulitis to chronic osteomyelitis and gangrenous extremity lower limb amputations. Wounds without confirmed soft tissue or bone infections do not require antibiotic therapy. Mild and moderate infections need empiric therapy covering Gram-positive cocci, while severe infections caused by drug-resistant organisms require broad-spectrum anti-microbials targeting aggressive Gram-negative aerobes and obligate anaerobes.

Gestational weight gain as an independent risk factor for adverse pregnancy outcomes in women with gestational diabetes.

OBJECTIVE: Obesity and gestational diabetes mellitus (GDM) are rising worldwide. This study retrospectively evaluated the role of excessive gestational weight gain (eGWG) in women with GDM and different pre-pregnancy body mass indices (BMIs). PATIENTS AND METHODS: Optimal glycaemic control was defined as achieving glucose target thresholds in more than 80% of measurements. 283 women with GDM were categorized as underweight, normal weight, overweight or obese based on WHO's classification scheme. eGWG was defined as >18.0 kilograms for women who were underweight, >15.8 kilograms for those who were normal weight, >11.3 kilograms for those who were overweight and >9.0 kilograms for those who were obese. For the analysis, women were divided into two groups: normal and excessive GWG. The main outcomes measured were incidences of large/small for gestational age (LGA/SGA), macrosomia, preterm delivery, hypertensive disorders and caesarean sections (CS). RESULTS: Excessive GWG was associated with higher birth weight and percentile (p<0.001), and with a higher prevalence of LGA (p<0.001), macrosomia (p=0.002) and hypertensive disorders (p=0.036). No statistical differences were found for the week of delivery, or prevalence of CS and SGA. The multivariate analysis highlighted both pre-pregnant BMI and eGWG as independent risk factors for LGA and macrosomia. Women with a pre-pregnant BMI of at least 25 and eGWG have a 5.43-fold greater risk of developing LGA (p=0.005). CONCLUSIONS: When combined with an inadequate pre-pregnant BMI, eGWG acts as a "synergic risk factor" for a poor outcome. When obesity or GDM occur, an optimal GWG can guarantee a better pregnancy outcome.

Platelet indices and glucose control in type 1 and type 2 diabetes mellitus: A case-control study.

BACKGROUND AND AIMS: The relationship between platelet indices and glucose control may differ in type 1 (T1DM) and type 2 (T2DM) diabetes. We aimed to investigate differences in mean platelet volume (MPV), platelet count, and platelet mass between patients with T1DM, T2DM, and healthy controls and to explore associations between these platelet indices and glucose control. METHODS AND RESULTS: A total of 691 T1DM and 459 T2DM patients and 943 control subjects (blood donors) were included. HbA1c was measured in all subjects with diabetes and 36 T1DM patients further underwent 24 h-continuous glucose monitoring to estimate short-term glucose control (glucose mean and standard deviation). Adjusting for age and sex, platelet count was higher and MPV lower in both T1DM and T2DM patients vs control subjects, while platelet mass (MPV × platelet count) resulted higher only in T2DM. Upon further adjustment for HbA1c, differences in platelet count and mass were respectively 19.5 × 109/L (95%CI: 9.8-29.3; p < 0.001) and 101 fL/nL (12-191; p = 0.027) comparing T2DM vs T1DM patients. MPV and platelet count were significantly and differently related in T2DM patients vs both T1DM and control subjects; this difference was maintained also accounting for HbA1c, age, and sex. Platelet mass and the volume-count relationship were significantly related to HbA1c only in T1DM patients. No associations were found between platelet indices and short-term glucose control. CONCLUSION: By accounting for confounders and glucose control, our data evidenced higher platelet mass and different volume-count kinetics in subjects with T2DM vs T1DM. Long-term glucose control seemed to influence platelet mass and the volume-count relationship only in T1DM subjects. These findings suggest different mechanisms behind platelet formation in T1DM and T2DM patients with long-term glycaemic control being more relevant in T1DM than T2DM.

Implementation of GOLD consensus report in real life: results from the Velletri-Lariano (VELA) cohort.

BACKGROUND: COPD is one of the leading causes of morbidity and mortality. Pharmacotherapy improves quality of life and reduces exacerbations although low adherence with prescribed treatments may represent a barrier to optimal disease management. The first objective of this paper is to report the distribution of COPD patients according to GOLD categories, in a sample of patients from a cohort study in an area of the Latium region in Italy. The second objective is to evaluate the agreement between the distributions of severity obtained from the HCPs and the experts included in the study board (Board). METHODS: COPD patients were given a card to collect demographic and clinical data at baseline. Information in those cards was independently evaluated by HCPs and Board to include each patient into one of the four GOLD categories. RESULTS: In a sample of 187 stable COPD patients, 59% male, mean age 70 year, the distribution of GOLD categories according to the Board was: 6% A, 34% B, 2% C, and 58% D. A discrepancy in GOLD classification was observed between the study board and field-based HCPs, regarding more than 50% of the patients, with a clear trend to underestimate the frequency of patients in D level (21%) and to overestimate the frequency in C level (21%). CONCLUSIONS: These results describe for the first time the distribution of COPD patients in an Italian cohort according to the GOLD categories, with the highest frequencies in levels B and D. The misclassification from HCPs may impact the therapeutic approach and the clinical outcomes.

Antinociceptive action of NOP and opioid receptor agonists in the mouse orofacial formalin test.

Nociceptin/orphanin FQ (N/OFQ) modulates several biological functions, including pain transmission via selective activation of a specific receptor named NOP. The aim of this study was the investigation of the antinociceptive properties of NOP agonists and their interaction with opioids in the trigeminal territory. The orofacial formalin (OFF) test in mice was used to investigate the antinociceptive potential associated to the activation of NOP and opioid receptors. Mice subjected to OFF test displayed the typical biphasic nociceptive response and sensitivity to opioid and NSAID drugs. Mice knockout for the NOP gene displayed a robust pronociceptive phenotype. The NOP selective agonist Ro 65-6570 (0.1-1mgkg-1) and morphine (0.1-10mgkg-1) elicited dose dependent antinociceptive effects in the OFF with the alkaloid showing larger effects; the isobologram analysis of their actions demonstrated an additive type of interaction. The mixed NOP/opioid receptor agonist cebranopadol elicited potent (0.01-0.1mgkg-1) and robust antinociceptive effects. In the investigated dose range, all drugs did not modify the motor performance of the mice in the rotarod test. Collectively the results of this study demonstrated that selective NOP agonists and particularly mixed NOP/opioid agonists are worthy of development as innovative drugs to treat painful conditions of the trigeminal territory.

Asthma management among allergists in Italy: results from a survey.

BACKGROUND: In Europe more than 50% of asthmatic treated patients have not well-controlled asthma. Asthma affects about 2.5 million of patients in Italy. AIMS AND OBJECTIVES: The present survey aims at investigating how Italian allergists approach asthmatic patients, in order to highlight pitfalls and unmet needs concerning real-life asthma management. METHODS: An anonymous 16 item web questionnaire was available (April-October 2015) to all allergists who visited the web site of SIAAIC (Società Italiana di Allergologia, Asma Immunologia Clinica). Those who wished to give their contribution had the opportunity to answer about epidemiology, risk factors, treatment approaches, and adherence to therapy. RESULTS: One hundred and seventy four allergists answered the survey. 54% of them reported up to 10 patient visits per week and 35.3% between 10 and 30. The most frequent reasons of follow up visits are routine check-up (56.5% of allergists), and worsening of symptoms (41% of allergists). Nocturnal apnoeas, gastro-esophageal reflux and obesity are the most important comorbidities/risk factors of poorly controlled asthma. Bronchial hyper-responsiveness, increased NO levels and reduced exercise tolerance are the most important indicators of asthma severity. Concerning therapy, ICS combined with LABA is the treatment of choice suitable for the majority of patients. A rapid onset of action and a flexible ICS dosage are indicated as the optimal characteristics for achieving the therapeutic goals. Poor adherence to therapy is an important reason for symptom worsening for the majority of allergists. Complex dosage regimens and economic aspects are considered the most important factors impacting on adherence. CONCLUSIONS: Allergists are involved in the management of asthma, regularly seeing their patients. Co-morbidities are frequent in asthmatic patients and may impact negatively on disease control, thus identifying patients who need a more careful and strict monitoring. Airway hyper-responsiveness to methacholine challenge test and nitric oxide are considered important indicators of asthma severity. The combination of LABA and inhaled steroids is considered the treatment of choice for most asthmatic patients, in keeping with broad evidence indicating that the combination therapy is more effective and rapid in gaining asthma control than inhaled corticosteroids alone. Adherence to medication regimens is considered of essence to achieve the therapeutic goals.

Polarity dependent strongly inhomogeneous In-incorporation in GaN nanocolumns.

In this work, GaN/InGaN/GaN nanocolumns (NCs) have been grown by molecular beam epitaxy. Selective area growth (SAG) and self-organized growth (SOG) were performed simultaneously in patterned and unpatterned regions of the same substrate, respectively. The resulting structures show different tip morphologies and structural properties due to the different polarity along the growth direction, namely Ga-polar with r-plane faceted tips for the SAG NCs and N-polar with c-plane top facet for the SOG ones. When growing Ga-polar GaN/InGaN NCs, no indium is incorporated at a substrate temperature of [Formula: see text]°C. Rather, indium incorporation takes place under the same growth conditions on the N-polar NCs. The In-incorporation is investigated by means of nano x-ray fluorescence and diffraction, high-angle annular dark-field scanning transmission electron microscopy and high-resolution transmission electron microscopy.

Cross-reactivity and Tolerability of Ertapenem in Patients With IgE-Mediated Hypersensitivity to ß-Lactams.

BACKGROUND AND OBJECTIVE: Administration of carbapenems to ß-lactam-allergic patients has always been considered potentially harmful because of a 47.4% rate of cross-reactivity to imipenem reported in a single study. Nevertheless, recent studies have shown that the rate of cross-reactivity of imipenem and meropenem with penicillins is lower than 1%. The aim of this study was to evaluate the possibility of using ertapenem in patients with an established IgE-mediated ß-lactam allergy. PATIENTS AND METHODS: We studied all participants who came to our allergy unit and had a clinical history of immediate hypersensitivity reactions to ß-lactams. The inclusion criteria were a positive skin test result to at least 1 ß-lactam molecule and/or positive specific IgE (when available). All participants underwent immediate-type skin tests with several ß-lactam molecules including ertapenem. Challenges with intravenous ertapenem were performed on 2 different days in patients with negative skin test results. RESULTS: We examined 49 patients with a clinical history of immediate reactions to ß-lactams. All the patients had positive skin tests and/or positive specific IgE to at least 1 ß-lactam reagent and negative carbapenem skin tests. Thirty-six patients agreed to undergo the challenges and 35 tolerated the full dose of ertapenem. CONCLUSIONS: The practice of avoiding carbapenems in patients with ß-lactam allergy should be abandoned considering the very low rate of cross-reactivity. ß-Lactam-allergic patients who need ertapenem therapy should undergo skin tests and, if negative, a graded challenge to assess tolerability.

Cross-reactivity and tolerability of Ertapenem in patients with IgE-mediated hypersensitivy to Beta-lactams

Background and Objective: Administration of carbapenems to β-lactam-allergic patients has always been considered potentially harmful because of a 47.4% rate of cross-reactivity to imipenem reported in a single study. Nevertheless, recent studies have shown that the rate of cross-reactivity of imipenem and meropenem with penicillins is lower than 1%. The aim of this study was to evaluate the possibility of using ertapenem in patients with an established IgE-mediated β-lactam allergy. Patients and Methods: We studied all participants who came to our allergy unit and had a clinical history of immediate hypersensitivity reactions to β-lactams. The inclusion criteria were a positive skin test result to at least 1 β-lactam molecule and/or positive specific IgE (when available). All participants underwent immediate-type skin tests with several β-lactam molecules including ertapenem. Challenges with intravenous ertapenem were performed on 2 different days in patients with negative skin test results. Results: We examined 49 patients with a clinical history of immediate reactions to β-lactams. All the patients had positive skin tests and/or positive specific IgE to at least 1 β-lactam reagent and negative carbapenem skin tests. Thirty-six patients agreed to undergo the challenges and 35 tolerated the full dose of ertapenem. Conclusions: The practice of avoiding carbapenems in patients with β-lactam allergy should be abandoned considering the very low rate of cross-reactivity. β-Lactam-allergic patients who need ertapenem therapy should undergo skin tests and, if negative, a graded challenge to assess tolerability (AU)

Introducción y Objetivo: Siempre se ha considerado peligrosa la administración de carbapenems a pacientes alérgicos a betalactámicos por la presencia de reactividad cruzada en el 47,4% de los casos descrita en un estudio previo. Sin embargo, estudios recientes han mostrado que la reactividad cruzada de imipenem y meropenem con penicilinas es inferior al 1%. El objetivo de este estudio es valorar el uso de ertapenem en pacientes diagnosticado de alergia IgE mediada a betalactámicos. Pacientes y Métodos: Se incluyeron todos los pacientes que acudieron a nuestra unidad de Alergia con historia clínica de alergia inmediata a betalactámicos. Los criterios de inclusión fueron prueba cutánea positiva con al menos un betalactámico y/o IgE específica positiva (cuando estuviese disponible). Se realizaron pruebas cutáneas con betalactámicos, incluyendo ertapenem, con lectura inmediata en todos los pacientes. Se realizaron pruebas de provocación endovenosas con ertapenem en los pacientes con pruebas cutáneas negativas frente al mismo en dos días diferentes. Resultados: Se incluyeron 49 pacientes con historia clínica de alergia inmediata a betalactámicos. Todos los pacientes tenían pruebas cutáneas positivas y/o IgE específica positiva al menos a uno de los betalactámicos así como prueba cutánea negativa con carbapenémicos. Treinta y seis pacientes aceptaron la realización de pruebas de provocación con ertapenem que fueron tolerados por treinta y cinco de dichos pacientes. Conclusión: El hecho de recomendar evitar carbapenems en pacientes con alergia a betalactámicos debería ser abandonado, dada la baja reactividad cruzada que presentan. En los pacientes con alergia a betalactámicos que necesiten ertapenem se deberían realizar pruebas cutáneas con el fármaco y en caso de ser negativas, realizar un test de exposición progresiva para confirmar su tolerancia (AU)