Distinct platelet crosstalk with adaptive and innate immune cells after adenoviral and mRNA vaccination against SARS-CoV-2

Background: Genetic-based COVID-19 vaccines have proved highly effective in reducing the risk of hospitalization and death. As they were first distributed on a large-scale population, adenoviral-based vaccines were linked to a very rare thrombosis with thrombocytopenia syndrome and the interplay between platelets and vaccinations increasingly gained attention. Objective: To study the crosstalk between platelets and the vaccine-induced immune response. Methods: We prospectively enrolled young healthy volunteers who received the mRNA-based vaccine, BNT162b2 (n=15), or the adenovirus-based vaccine, AZD1222 (n=25) and studied their short-term platelet and immune response before and after vaccine injections. In a separate cohort, we retrospectively analysed the effect of aspirin on the antibody response 1 and 5 months after BNT162b2 vaccination. Results: Here we show that a faster antibody response to either vaccine is associated to the formation of platelet aggregates with marginal zone-like B-cells, a subset geared to bridge the temporal gap between innate and adaptive immunity. However, while the mRNA-based vaccine is associated with a more gradual and tolerogenic response that fosters the crosstalk between platelets and adaptive immunity, the adenovirus-based vaccine, the less immunogenic of the two, evokes an antiviral-like response during which platelets are cleared and less likely to cooperate with B-cells. Moreover, subjects taking aspirin (n=56) display lower antibody levels after BNT162b2 vaccination compared to matched individuals. Conclusions: Platelets are a component of the innate immune pathways that promote the B-cell response after vaccination. Future studies on the platelet-immune crosstalk post-immunization will improve safety, efficacy, and strategic administration of next-generation vaccines

Baker’s asthma with oculorhinitis: case report

Summary Introduction. Baker’s asthma is one of the most common causes of occupational asthma worldwide. Beside bread production, all occupations in contact with flour (confectioning, pastry making, milling, farming, cereal handling) can be affected. Objective. To illustrate, through the presentation of a clinical case, an updated interdisciplinary diagnostic approach for the evaluation of suspected occupational asthma, with the aim: to identify the possible causal link between the occupational exposure and the disease, and to formulate a correct judgment for job fitness. Materials and methods. Interdisciplinary (occupational medicine and allergology) specialist evaluation, blood and urine analysis, patch tests, total and specific IgE dosage, eosinophilic cationic protein assay, spirometry, non-specific metacholine bronchostimulation, specific inhalation challenge, with monitoring of airway resistance by FOT (forced oscillation technique), and of nasal and bronchial FeNO (fractional exhaled nitric oxide). Results. Fifty-four year-old man, baker since 1993. In recent months, dyspnoea and dry cough, accompanied by ocular and nasal flogosis, as well as itchy skin rash, mainly during work shifts. High total and specific IgE values. Increased eosinophilic cationic protein. Negative metacholine test. Specific inhalation challenge with buckwheat stopped after 15 minutes due to the onset of rhinitis, conjunctivitis, cough with shortness of breath and wheezing. Post-exposure FEV1 decrease (> 12%) and +76% FOT increase. Progressive and persistent nasal FeNO increase with normalization after 24 hours. These findings indicated bronchial and oculonasal allergic response to buckwheat and other cereals. Conclusion. The diagnostic protocol allowed demonstrating the causal link between occupational exposure and the disease, which was reported to the competent authorities. The patient was advised to refrain from further exposure. The evolution of processing techniques and the new substances used in bread production, require continuous updating of diagnostic and health surveillance protocols

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Asma professionale in panificatore: case report

Introduzione. L’asma dei panificatori è una delle più comuni cause di asma occupazionale. Descritta la prima volta nel 1700 da Bernardino Ramazzini, è tuttora assai attuale, soprattutto considerando la varietà di nuove sostanze potenzialmente allergizzanti. Gli addetti alla panificazione rappresentano la categoria più a rischio ma tutte le professioni a contatto con farine possono esserne colpite. Obiettivi. Illustrare, mediante la presentazione di un caso clinico, un aggiornato approccio diagnostico interdisciplinare per la valutazione dei lavoratori con sospetta asma professionale, ai fini dell’emissione di un corretto giudizio di idoneità alla mansione e del riconoscimento dell’eventuale nesso di causa tra l’esposizione lavorativa e la patologia presentata. Metodi. Il protocollo comprende visita specialistica di medicina del lavoro (con accurata anamnesi lavorativa), visita specialistica allergologica, esami ematochimici, dosaggio di IgE totali e specifiche, prove di funzionalità respiratoria associate (ove indicato) a test di broncoprovocazione aspecifica (TBPA) e specifica (TBPS), dosaggio del FeNO (frazione di Ossido Nitrico esalato) nasale e bronchiale, FOT (tecnica delle oscillazioni forzate) e dosaggio della proteina cationica eosinofila (ECP). Risultati. Il soggetto è un uomo di 54 anni che svolge la mansione di panificatore dal 1993. Il paziente riferiva da alcuni mesi comparsa di dispnea, tosse stizzosa e sintomatologia oculorinitica, prevalentemente durante il turno lavorativo. I test allergologici in vitro hanno rilevato elevati valori di IgE totali e specifiche per orzo, segale e grano saraceno. Il TBPA con metacolina è risultato negativo. Il paziente è stato dunque sottoposto a TBPS con grano saraceno. Il test è stato interrotto dopo 15 minuti per comparsa di rinocongiuntivite, tosse e dispnea. Il monitoraggio post-esposizione ha mostrato un decremento del FEV1 superiore al 12% e un incremento delle FOT del 76%. Il monitoraggio del FeNO a livello nasale ha mostrato progressivo e persistente decremento con normalizzazione dei valori intorno alla 24esima ora post-esposizione. La diminuzione dei valori sierici di ECP post-esposizione ha dimostrato sequestro degli eosinofili a livello degli organi bersaglio. Le variazioni descritte risultano compatibili con risposta allergica bronchiale e nasale all’allergene professionale. Conclusioni. L’iter descritto ha permesso di definire con certezza il nesso di causa tra l’esposizione lavorativa al grano saraceno e la patologia. Si è quindi provveduto alla segnalazione di malattia professionale alle Autorità competenti e consigliato al paziente di astenersi dall’esposizione agli allergeni testati. L’evoluzione delle tecniche di lavorazione, e le nuove sostanze utilizzate nella produzione del pane, richiedono continuo aggiornamento dei protocolli diagnostici e di sorveglianza sanitaria

How to PROceed? Reviewing obstacles and perspectives in patient-centered digital care in radiation oncology

As the general public is increasing their online presence and is becoming confident with the digital infrastructure, an opportunity for patient-centered digital care has arisen. Electronic patient-reported outcomes, (e)PRO in short, may facilitate enhanced clinical management of radiation oncology patients. This might enable the physicians to take the initiative and counteract symptoms or undesired side effects before they aggravate and thus, reducing treatment-associated costs. In this article, we review the impetus for and modalities of (e)PRO-based data acquisition and handling in research and routine. We conclude that prospective and technical studies are needed to prove the clinical significance of (e)PROs to pave the way to monetary compensation and widespread application

Do Barrier Films Impact Long-Term Skin Toxicity following Whole-Breast Irradiation? Objective Follow-Up of Two Randomised Trials

Purpose: Hydrofilm, a polyurethane-based barrier film, can be used to prevent acute radiation dermatitis (RD) in adjuvant whole-breast irradiation (WBI) for breast cancer. This cost-effective prophylactic measure is currently being recommended to a growing number of patients, yet long-term safety data and its impact on late radiation-induced skin toxicity such as pigmentation changes and fibrosis have not been investigated. Methods: We objectively evaluated patients who were previously enrolled in either of two intrapatient-randomised (lateral versus medial breast halve) controlled trials on the use of Hydrofilm for RD prevention (DRKS00029665; registered on 19 July 2022). Results: Sixty-two patients (47.7% of the initial combined sample size) provided consent for this post-hoc examination, with a median follow-up time (range) of 58 (37–73) months. Following WBI, there was a significant increase in yellow skin tones of the entire breast when compared to baseline measurements before WBI (p p p p = 0.004, respectively). At follow-up, there were no significant differences in either pigmentation changes or skin fibrosis between the Hydrofilm and standard of care breast halves. Conclusion: These data suggest that Hydrofilm can be safely used in the context of acute RD prevention, without affecting late side effects, supporting its widespread use

Platelet and immune signature associated with a rapid response to the BNT162b2 mRNA COVID-19 vaccine

none18noMinistero Italiano Istruzione Università e Ricerca, Grant/Award Number: 2017ATZ2YK and 2017WJBKKW_003Background: A rapid immune response is critical to ensure effective protection against COVID-19. Platelets are first-line sentinels of the vascular system able to rapidly alert and stimulate the immune system. However, their role in the immune response to vaccines is not known. Objective: To identify features of the platelet-immune crosstalk that would provide an early readout of vaccine efficacy in adults who received the mRNA-based COVID-19 vaccine (BNT162b2). Methods: We prospectively enrolled 11 young healthy volunteers (54% females, median age: 28 years) who received two doses of BNT162b2, 21 days apart, and we studied their platelet and immune response before and after each dose of the vaccine (3 and 10 ± 2 days post-injection), in relation to the kinetics of the humoral response. Results: Participants achieving an effective level of neutralizing antibodies before the second dose of the vaccine (fast responders) had a higher leukocyte count, mounted a rapid cytokine response that incremented further after the second dose, and an elevated platelet turnover that ensured platelet count stability. Their circulating platelets were not more reactive but expressed lower surface levels of the immunoreceptor tyrosine-based inhibitory motif (ITIM)-coupled receptor CD31 (PECAM-1) compared to slow responders, and formed specific platelet-leukocyte aggregates, with B cells, just 3 days after the first dose, and with non-classical monocytes and eosinophils. Conclusion: We identified features of the platelet-immune crosstalk that are associated with the development of a rapid humoral response to an mRNA-based vaccine (BNT162b2) and that could be exploited as early biomarkers of vaccine efficacy.openFlego, Davide; Cesaroni, Simone; Romiti, Giulio F; Corica, Bernadette; Marrapodi, Ramona; Scafa, Noemi; Maiorca, Francesca; Lombardi, Ludovica; Pallucci, Davide; Pulcinelli, Fabio; Raparelli, Valeria; Visentini, Marcella; Cangemi, Roberto; Piconese, Silvia; Alvaro, Domenico; Polimeni, Antonella; Basili, Stefania; Stefanini, LuciaFlego, Davide; Cesaroni, Simone; Romiti, Giulio F; Corica, Bernadette; Marrapodi, Ramona; Scafa, Noemi; Maiorca, Francesca; Lombardi, Ludovica; Pallucci, Davide; Pulcinelli, Fabio; Raparelli, Valeria; Visentini, Marcella; Cangemi, Roberto; Piconese, Silvia; Alvaro, Domenico; Polimeni, Antonella; Basili, Stefania; Stefanini, Luci

Five-Fraction Stereotactic Radiotherapy for Brain Metastases—A Retrospective Analysis

Purpose: To determine the safety and outcome profile of five-fraction stereotactic radiotherapy (FSRT) for brain metastases (BM), either as a definitive or adjuvant treatment. Methods: We assessed clinical data of patients receiving five fractions of 7 Gy each (cumulative physical dose of 35 Gy) to BM or surgical cavities. The primary endpoints were toxicity and radiation necrosis (RN) rates. Secondary endpoints were 1-year cumulative local control rate (LCR) and estimated overall survival (OS). Results: A total of 36 eligible patients receiving FSRT to a total of 49 targets were identified and included. The median follow up was 9 (1.1–56.2) months. The median age was 64.5 (34–92) years, the median ECOG score was 1, and the median Diagnostic-Specific Graded Prognostic Assessment (DS-GPA) score was 2. Treatment was well tolerated and there were no grade 3 adverse events or higher. The overall RN rate was 14.3% and the median time to RN was 12.9 (1.8–23.8) months. RN occurrence was associated with immunotherapy, young age (≤45 years), and large PTV. The cumulative 1-year local control rate was 83.1% and the estimated median local progression free-survival was 18.8 months. The estimated median overall survival was 11 (1.1–56.2) months and significantly superior in those patients presenting with RN. Conclusions: FSRT with 5 × 7 Gy represents a feasible, safe, and efficient fast track approach of intensified FSRT with acceptable LC and comparable RN rates for both the adjuvant and definitive RT settings

Five-Fraction Stereotactic Radiotherapy for Brain Metastases—A Retrospective Analysis

Purpose: To determine the safety and outcome profile of five-fraction stereotactic radiotherapy (FSRT) for brain metastases (BM), either as a definitive or adjuvant treatment. Methods: We assessed clinical data of patients receiving five fractions of 7 Gy each (cumulative physical dose of 35 Gy) to BM or surgical cavities. The primary endpoints were toxicity and radiation necrosis (RN) rates. Secondary endpoints were 1-year cumulative local control rate (LCR) and estimated overall survival (OS). Results: A total of 36 eligible patients receiving FSRT to a total of 49 targets were identified and included. The median follow up was 9 (1.1–56.2) months. The median age was 64.5 (34–92) years, the median ECOG score was 1, and the median Diagnostic-Specific Graded Prognostic Assessment (DS-GPA) score was 2. Treatment was well tolerated and there were no grade 3 adverse events or higher. The overall RN rate was 14.3% and the median time to RN was 12.9 (1.8–23.8) months. RN occurrence was associated with immunotherapy, young age (≤45 years), and large PTV. The cumulative 1-year local control rate was 83.1% and the estimated median local progression free-survival was 18.8 months. The estimated median overall survival was 11 (1.1–56.2) months and significantly superior in those patients presenting with RN. Conclusions: FSRT with 5 × 7 Gy represents a feasible, safe, and efficient fast track approach of intensified FSRT with acceptable LC and comparable RN rates for both the adjuvant and definitive RT settings

Non-Invasive Physical Plasma for Preventing Radiation Dermatitis in Breast Cancer: A First-In-Human Feasibility Study

Radiation dermatitis (RD) is the most common acute side effect of breast irradiation. More than a century following the therapeutic utilisation of X-rays, potent preventative and therapeutic options are still lacking. Non-invasive physical plasma (NIPP) is an emerging approach towards treatment of various dermatological disorders. In this study, we sought to determine the safety and feasibility of a NIPP device on RD. Thirty patients undergoing hypofractionated whole-breast irradiation were included. Parallel to radiation treatment, the irradiated breast was treated with NIPP with different application regimens. RD was assessed during and after NIPP/radiation, using clinician- and patient-reported outcomes. Additionally, safety and feasibility features were recorded. None of the patients was prescribed topical corticosteroids and none considered the treatment to be unpleasant. RD was less frequent and milder in comparison with standard skin care. Neither NIPP-related adverse events nor side effects were reported. This proven safety and feasibility profile of a topical NIPP device in the prevention and treatment of RD will be used as the framework for a larger intrapatient-randomised double-blind placebo-controlled trial, using objective and patient-reported outcome measures as an endpoint