Transthoracic impedance variability to assess quality of chest compression in out-of-hospital cardiac arrest.

BACKGROUND: Chest compression is a lifesaving intervention in out-of-hospital cardiac arrest (OHCA), but the optimal metrics to assess its quality have yet to be identified. The objective of this study was to investigate whether a new parameter, that is, the variability of the chest compression-generated transthoracic impedance (TTI), namely ImpCC , which measures the consistency of the chest compression maneuver, relates to resuscitation outcome. METHODS: This multicenter observational, retrospective study included OHCAs with shockable rhythm. ImpCC variability was evaluated with the power spectral density analysis of the TTI. Multivariate regression model was used to examine the impact of ImpCC variability on defibrillation success. Secondary outcome measures were return of spontaneous circulation and survival. RESULTS: Among 835 treated OHCAs, 680 met inclusion criteria and 565 matched long-term outcomes. ImpCC was significantly higher in patients with unsuccessful defibrillation compared to those with successful defibrillation (p = .0002). Lower ImpCC variability was associated with successful defibrillation with an odds ratio (OR) of 0.993 (95% confidence interval [95% CI], 0.989-0.998, p = .003), while the standard chest compression fraction (CCF) was not associated (OR 1.008 [95 % CI, 0.992-1.026, p = .33]). Neither ImpCC nor CCF was associated with long-term outcomes. CONCLUSIONS: In this population, consistency of chest compression maneuver, measured by variability in TTI, was an independent predictor of defibrillation outcome. ImpCC may be a useful novel metrics for improving quality of care in OHCA.

Changing the stroke network during pandemic scenarios does not affect the management of patients with a positive Cincinnati prehospital stroke scale.

INTRODUCTION: Time plays a crucial role in the management of stroke, and changing the prehospital emergency network, altering the HUB and spoke relationship in pandemic scenarios, might have an impact on time to fibrinolysis or thrombectomy. The aim of this study was to evaluate the time-dependent stroke emergency network in Lombardy region (Italy) by comparing 2019 with 2020 and early 2021. Three parameters were investigated: (i) time of arrival of the first vehicle at the scene, (ii) overall duration of missions, and (iii) number of patients transported by emergency vehicles. METHODS: Data analysis process conducted using the SAS-AREU portal (SAS Institute, USA). RESULTS: The number of patients with a positive CPSS was similar among the different pandemic waves. Mission duration increased from a mean time (SD) of 52.9 (16.1) min in 2019 to 64.1 (19.7) in 2020 and 55.0 (16.8) in 2021. Time to first vehicle on scene increased to 15.7 (8.4) min in 2020 and 16.0 (7.0) in 2021 compared to 2019, 13.6 (7.2) (P < 0.05). The number of hospital with available stroke units decreased from 46 in 2019 to 10 during the first pandemic wave. CONCLUSIONS: The pandemic forced changes in the clinical mission of many hospitals by reducing the number of stroke units. Despite this, the organization of the emergency system allowed to identify strategic hospitals and thus avoid excessive transport time. The result was an adequate time for fibrinolysis/thrombectomy, in agreement with the guidelines. Coordinated management in emergency situations makes it possible to maintain service quality standards, despite the unfavorable scenario.

Development and Validation of a New Tool to Improve the Accuracy of the Hospital Mass-Casualty Incident Response Plan Activation: The PEMAAF Score.

INTRODUCTION: Effective response to a mass-casualty incident (MCI) entails the activation of hospital MCI plans. Unfortunately, there are no tools available in the literature to support hospital responders in predicting the proper level of MCI plan activation. This manuscript describes the scientific-based approach used to develop, test, and validate the PEMAAF score (Proximity, Event, Multitude, Overcrowding, Temporary Ward Reduction Capacity, Time Shift Slot [Prossimità, Evento, Moltitudine, Affollamento, Accorpamento, Fascia Oraria], a tool able to predict the required level of hospital MCI plan activation and to facilitate a coordinated activation of a multi-hospital network. METHODS: Three study phases were performed within the Metropolitan City of Milan, Italy: (1) retrospective analysis of past MCI after action reports (AARs); (2) PEMAAF score development; and (3) PEMAAF score validation. The validation phase entailed a multi-step process including two retrospective analyses of past MCIs using the score, a focus group discussion (FGD), and a prospective simulation-based study. Sensitivity and specificity of the score were analyzed using a regression model, Spearman's Rho test, and receiver operating characteristic/ROC analysis curves. RESULTS: Results of the retrospective analysis and FGD were used to refine the PEMAAF score, which included six items-Proximity, Event, Multitude, Emergency Department (ED) Overcrowding, Temporary Ward Reduction Capacity, and Time Shift Slot-allowing for the identification of three priority levels (score of 5-6: green alert; score of 7-9: yellow alert; and score of 10-12: red alert). When prospectively analyzed, the PEMAAF score determined most frequent hospital MCI plan activation (>10) during night and holiday shifts, with a score of 11 being associated with a higher sensitivity system and a score of 12 with higher specificity. CONCLUSIONS: The PEMAAF score allowed for a balanced and adequately distributed response in case of MCI, prompting hospital MCI plan activation according to real needs, taking into consideration the whole hospital response network.

Management of possible stroke by laypeople in pre-hospital setting: who should we train?

BACKGROUND AND AIM: The pre-hospital management of a possible stroke is fundamental for the transport of patients to the correct HUB facility; thus, they must be transported to the Emergency Department (ED) by EMS vehicles. Our study aims to analyze the factors correlated with a higher probability of accessing the ED through the EMS in this event. METHODS: This is a retrospective observational study. All accesses in the 120 EDs of the Lombardy region, with a diagnosis of discharge whose symptoms could resemble CPSS, were analyzed between 1 January 2019 and 31 December 2019. RESULTS: We identified an increased probability of using the EMS vehicles of 0,05% (I.C. 95%: 0.04% - 0.06%; p<0.0001) for each additional year of age, considering patients aged 20 to 100 years and the percentage was significantly higher in the female population (58% vs 49%; p<0.001). Moreover, we calculated that the incidence of stroke was approximately 140 cases per 100,000 inhabitants. CONCLUSIONS: Only half of the citizens in the Lombardy region use the EMS in case of suspicion of stroke; further information campaigns are essential to educate citizens. Information strategies should be directed especially at men between 30 and 59 years old.

Detection of patients with COVID-19 by the emergency medical services in Lombardy through an operator-based interview and machine learning models.

BACKGROUND: The regional emergency medical service (EMS) in Lombardy (Italy) developed clinical algorithms based on operator-based interviews to detect patients with COVID-19 and refer them to the most appropriate hospitals. Machine learning (ML)-based models using additional clinical and geospatial epidemiological data may improve the identification of infected patients and guide EMS in detecting COVID-19 cases before confirmation with SARS-CoV-2 reverse transcriptase PCR (rtPCR). METHODS: This was an observational, retrospective cohort study using data from October 2020 to July 2021 (training set) and October 2021 to December 2021 (validation set) from patients who underwent a SARS-CoV-2 rtPCR test within 7 days of an EMS call. The performance of an operator-based interview using close contact history and signs/symptoms of COVID-19 was assessed in the training set for its ability to determine which patients had an rtPCR in the 7 days before or after the call. The interview accuracy was compared with four supervised ML models to predict positivity for SARS-CoV-2 within 7 days using readily available prehospital data retrieved from both training and validation sets. RESULTS: The training set includes 264 976 patients, median age 74 (IQR 55-84). Test characteristics for the detection of COVID-19-positive patients of the operator-based interview were: sensitivity 85.5%, specificity 58.7%, positive predictive value (PPV) 37.5% and negative predictive value (NPV) 93.3%. Contact history, fever and cough showed the highest association with SARS-CoV-2 infection. In the validation set (103 336 patients, median age 73 (IQR 50-84)), the best-performing ML model had an AUC of 0.85 (95% CI 0.84 to 0.86), sensitivity 91.4% (95 CI% 0.91 to 0.92), specificity 44.2% (95% CI 0.44 to 0.45) and accuracy 85% (95% CI 0.84 to 0.85). PPV and NPV were 13.3% (95% CI 0.13 to 0.14) and 98.2% (95% CI 0.98 to 0.98), respectively. Contact history, fever, call geographical distribution and cough were the most important variables in determining the outcome. CONCLUSION: ML-based models might help EMS identify patients with SARS-CoV-2 infection, and in guiding EMS allocation of hospital resources based on prespecified criteria.

Emergency Department waiting-time in the post pandemic era: new organizational models, a challenge for the future.

BACKGROUND AND AIM: Covid-19 has profoundly changed the Emergency Department system in Lombardy, especially for the type of accesses and the number of diagnoses. Accordingly, the pre-hospital rescue system has undergone heavy changes, in particular regarding the times of rescue. Despite this, studies concerning the post-pandemic phase are lacking to understand whether the conditions of the emergency systems has resumed to the pre-pandemic period. The aim of the study is to evaluate the length of stay (LOS) phenomenon in the emergency departments (EDs) in the post-pandemic era. METHODS: a retrospective observational study was conducted, which analyzed the first six months of the years 2019, 2021 and 2022. The pandemic peak phase, corresponding to the first months of 2020, wasn't included. The investigated area included the provinces of Milan and Monza, a metropolitan area with 4 million inhabitants. RESULTS: The average time spent by patients in the ED increased by +3.8 hours in 2022 and by +1.3 hours in 2021 compared to 2019. The average time from ED access to hospitalization also increased by +4.8 hours in 2022 and +5.0 hours in 2021 compared to 2019. The percentage of time in ED recorded in a National Emergency Department Overcrowding Study (NEDOCS) in black code in 2022 reached 5.4% against 1.7% in 2021 and 0.5 % in 2019. CONCLUSIONS: data show an increase in the time spent in the EDs and an increase in the overcrowding, according to the NEDOCS index. New management models and a reorganization of EDs are needed as the workload has increased significantly.

Reconstructing the impact of COVID-19 on the immunity gap and transmission of respiratory syncytial virus in Lombardy, Italy.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of hospitalisation and mortality in young children globally. The social distancing measures implemented against COVID-19 in Lombardy (Italy) disrupted the typically seasonal RSV circulation during 2019-2021 and caused substantially more hospitalisations during 2021-2022. The primary aim of this study is to quantify the immunity gap-defined as the increased proportion of the population naïve to RSV infection following the relaxation of COVID-19 restrictions in Lombardy, which has been hypothesised to be a potential cause of the increased RSV burden in 2021-2022. METHODS: We developed a catalytic model to reconstruct changes in the age-dependent susceptibility profile of the Lombardy population throughout the COVID-19 pandemic. The model is calibrated to routinely collected hospitalisation, syndromic, and virological surveillance data and tested for alternative assumptions on age-dependencies in the risk of RSV infection throughout the pandemic. FINDINGS: We estimate that the proportion of the Lombardy population naïve to RSV infection increased by 60.8% (95% CrI: 55.2-65.4%) during the COVID-19 pandemic: from 1.4% (95% CrI: 1.3-1.6%) in 2018-2019 to 2.3% (95% CrI: 2.2-2.5%) before the 2021-2022 season, corresponding to an immunity gap of 0.87% (95% CrI: 0.87-0.88%). We found evidence of heterogeneity in RSV transmission by age, suggesting that the COVID-19 restrictions had variable impact on the contact patterns and risk of RSV infection across ages. INTERPRETATION: We estimate a substantial increase in the population-level susceptibility to RSV in Lombardy during 2019-2021, which contributed to an increase in primary RSV infections in 2021-2022. FUNDING: UK Medical Research Council (MRC), UK Foreign, Commonwealth & Development Office (FCDO), EDCTP2 programme, European Union, Wellcome Trust, Royal Society, EU-MUR PNRR INF-ACT.

Amplitude Spectrum Area of ventricular fibrillation to guide defibrillation: a small open-label, pseudo-randomized controlled multicenter trial.

BACKGROUND: Ventricular fibrillation (VF) waveform analysis has been proposed as a potential non-invasive guide to optimize timing of defibrillation. METHODS: The AMplitude Spectrum Area (AMSA) trial is an open-label, multicenter randomized controlled study reporting the first in-human use of AMSA analysis in out-of-hospital cardiac arrest (OHCA). The primary efficacy endpoint was the termination of VF for an AMSA ≥ 15.5 mV-Hz. Adult shockable OHCAs randomly received either an AMSA-guided cardiopulmonary resuscitation (CPR) or a standard-CPR. Randomization and allocation to trial group were carried out centrally. In the AMSA-guided CPR, an initial AMSA ≥ 15.5 mV-Hz prompted for immediate defibrillation, while lower values favored chest compression (CC). After completion of the first 2-min CPR cycle, an AMSA < 6.5 mV-Hz deferred defibrillation in favor of an additional 2-min CPR cycle. AMSA was measured and displayed in real-time during CC pauses for ventilation with a modified defibrillator. FINDINGS: The trial was early discontinued for low recruitment due to the COVID-19 pandemics. A total of 31 patients were recruited in 3 Italian cities, 19 in AMSA-CPR and 12 in standard-CPR, and included in the data analysis. No difference in primary outcome was observed between the two groups. Termination of VF occurred in 74% of patients in the AMSA-CPR compared to 75% in the standard CPR (OR 0.93 [95% CI 0.18-4.90]). No adverse events were reported. INTERPRETATION: AMSA was used prospectively in human patients during ongoing CPR. In this small trial, an AMSA-guided defibrillation provided no evidence of an improvement in termination of VF. TRIAL REGISTRATION: NCT03237910. FUNDING: European Commission - Horizon 2020; ZOLL Medical Corp., Chelmsford, USA (unrestricted grant); Italian Ministry of Health - Current research IRCCS.

Mechanical chest compression and extracorporeal life support for out-of-hospital cardiac arrest. A 30-month observational study in the metropolitan area of Milan, Italy.

BACKGROUND: Return of spontaneous circulation (ROSC) is achieved in 25% of out-of-hospital cardiac arrest (OHCA) patients. Mechanical chest compression (mechCPR) may maintain better perfusion during transport, allowing hospital treatments like extracorporeal circulation life support (ECLS). We aim to assess the effectiveness of a pre-hospital protocol introduction. METHODS: Observational, retrospective study assessing all OHCA patients aged 12-75, with no-flow time <20 min in a metropolitan area (Milan, Italy, 2013-2016). PRIMARY OUTCOMES: ROSC and Cerebral Performance Category score (CPC) ≤2 at hospital discharge. Logistic regressions with multiple comparison adjustments balanced with propensity scores calculated with inverse probability of treatment weighting were performed. RESULTS: 1366 OHCA were analysed; 305 received mechCPR, 1061 manual chest compressions (manCPR), and 108 ECLS. ROSC and CPC ≤2 were associated with low-flow minutes (odds ratio [95% confidence interval] 0.90 [0.88-0.91] and 0.90 [0.87-0.93]), shockable rhythm (2.52 [1.71-3.72] and 10.68 [5.63-20.28]), defibrillations number (1.15 [1.07-1.23] and 1.15 [1.04-1.26]), and mechCPR (1.86 [1.17-2.96] and 2.06 [1.11-3.81]). With resuscitation times >13 min, mechCPR achieved more frequently ROSC compared to manCPR. Among ECLS patients, 70% had time exceeding protocol: 8 (7.5%) had CPC ≤2 (half of them with low-flow times between 45 and 90 min), 2 (1.9%) survived with severe neurological disabilities, and 13 brain-dead (12.0%) became organ donors. CONCLUSIONS: MechCPR patients achieved ROSC more frequently than manual CPR patients; mechCPR was a crucial factor in an ECLS protocol for refractory OHCA. ECLS offered a chance of survival to patients who would otherwise die.

Changes to the Major Trauma Pre-Hospital Emergency Medical System Network before and during the 2019 COVID-19 Pandemic.

Objectives: During the coronavirus disease 2019 pandemic, emergency medical services (EMSs) were among the most affected; in fact, there were delays in rescue and changes in time-dependent disease networks. The aim of the study is to understand the impact of COVID-19 on the time-dependent trauma network in the Lombardy region. Methods: A retrospective analysis on major trauma was performed by analysing all records saved in the EmMa database from 1 January 2019 to 31 December 2019 and from 1 January 2020 to 31 December 2020. Age, gender, time to first emergency vehicle on scene and mission duration were collected. Results: In 2020, compared to 2019, there was a reduction in major trauma diagnoses in March and April, during the first lockdown, OR 0.59 (95% CI 0.49−0.70; p < 0.0001), and a reduction in road accidents and accidents at work, while injuries related to falls from height and violent events increased. There was no significant increase in the number of deaths in the prehospital setting, OR 1.09 (95% CI 0.73−1.30; p = 0.325). Conclusions: The COVID-19 pandemic has changed the epidemiology of major trauma, but in the Lombardy region there was no significant change in mortality in the out-of-hospital setting.

The Impact of COVID-19 on Lombardy Region ST-Elevation Myocardial Infarction Emergency Medical System Network-A Three-Year Study.

Objectives: The COVID-19 pandemic had a significant impact on emergency medical systems (EMS). Regarding the ST-elevation myocardial infarction (STEMI) dependent time network, however, there is little evidence linked to the post-pandemic phase regarding this issue. Such information could prove to be of pivotal importance regarding STEMI clinical management, especially pre-hospital clinical protocols such as fibrinolysis. Methods: A retrospective observational cohort study of all STEMI rescues recorded in the Lombardy EMS registry from the 1st of January 2019 to the 30th of December 2021. Results: Regarding the number of STEMI diagnoses, March 2020 (first pandemic wave in Italy) saw a reduction compared to March 2019 (OR 0.76 [0.60-0.93], p = 0.011). The average time of the entire mission increased to 63.1 min in 2021, reaching 64.7 min in 2020, compared with 57.7 min in 2019. The number of HUBs for STEMI patients saw a reduction, falling from 52 HUBs in the pre-pandemic phase to 13 HUBs during the first wave. Conclusions: During the pandemic phase, there was an increase in the transportation times of STEMI patients from home to the hospital. Such changes did not alter the clinical approach in the out-of-hospital phase. Indeed, the implementation of fibrinolysis was not required.

Cardiopulmonary resuscitation missed by bystanders: Collateral damage of coronavirus disease 2019.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic changed the time-dependent cardiac arrest network. This study aims to understand whether the rescue standards of cardiopulmonary resuscitation (CPR) and out-of-hospital cardiac arrest (OHCA) were handled differently during pandemic compared to the previous year. METHODS: Data for the years 2019 and 2020 were provided by the records of the Lombardy office of the Regional Agency for Emergency and Urgency. We analysed where the cardiac arrest occurred, when CPR started and whether the bystanders used public access to defibrillation (PAD). RESULTS: During 2020, there was a reduction in CPRs performed by bystanders (odds ratio [OR] = 0.936 [95% confidence interval (CI95% ) 0.882-0.993], p = .029) and in the return of spontaneous circulation (ROSC) (OR = 0.621 [CI95% 0.563-0.685], p < .0001), while there was no significant reduction in the use of PAD. Analysing only March, the period of the first wave in Lombardy, the comparison shows a reduction in bystanders CPRs (OR = 0.727 [CI95% 0.602-0.877], p = .0008), use of PAD (OR = 0.441 [CI95% 0.272-0.716], p = .0009) and in ROSC (OR = 0.179 [CI95% 0.124-0.257], p < .0001). These phenomena could be influenced by the different settings in which the OHCAs occurred; in fact, those that occurred in public places with a mandatory PAD were strongly reduced (OR = 0.49 [CI95% , 0.44-0.55], p < .0001). CONCLUSIONS: COVID-19 had a profound impact on the time-dependant OHCA network. During the first pandemic wave, CPR and PAD used by bystanders decreased. The different contexts in which OHCAs occurred may partially explain these differences.

Rapid reorganization of the Milan metropolitan public safety answering point operations during the initial phase of the COVID-19 outbreak in Italy.

Objective: To quantify how the first public announcement of confirmed coronavirus disease 2019 (COVID-19) in Italy affected a metropolitan region's emergency medical services (EMS) call volume and how rapid introduction of alternative procedures at the public safety answering point (PSAP) managed system resources. Methods: PSAP processes were modified over several days including (1) referral of non-ill callers to public health information call centers; (2) algorithms for detection, isolation, or hospitalization of suspected COVID-19 patients; and (3) specialized medical teams sent to the PSAP for triage and case management, including ambulance dispatches or alternative dispositions. Call volumes, ambulance dispatches, and response intervals for the 2 weeks after announcement were compared to 2017-2019 data and the week before. Results: For 2 weeks following outbreak announcement, the primary-level PSAP (police/fire/EMS) averaged 56% more daily calls compared to prior years and recorded 9281 (106% increase) on Day 4, averaging ∼400/hour. The secondary-level (EMS) PSAP recorded an analogous 63% increase with 3863 calls (∼161/hour; 264% increase) on Day 3. The COVID-19 response team processed the more complex cases (n = 5361), averaging 432 ± 110 daily (∼one-fifth of EMS calls). Although community COVID-19 cases increased exponentially, ambulance response intervals and dispatches (averaging 1120 ± 46 daily) were successfully contained, particularly compared with the week before (1174 ± 40; P = 0.02). Conclusion: With sudden escalating EMS call volumes, rapid reorganization of dispatch operations using tailored algorithms and specially assigned personnel can protect EMS system resources by optimizing patient dispositions, controlling ambulance allocations and mitigating hospital impact. Prudent population-based disaster planning should strongly consider pre-establishing similar highly coordinated medical taskforce contingencies.

Early vascular complications after percutaneous cannulation for extracorporeal membrane oxygenation for cardiac assist.

BACKGROUND: Extracorporeal membrane oxygenation (VA ECMO) demonstrated an advantage in survival and neurological outcome in patients with cardiogenic shock and, in selected population, in victims of refractory cardiac arrest. The incidence of vascular complications ranges in recent series from 10 to 70% including both early and late complications. The aim of the present study was to determine the incidence of early vascular complications and the effectiveness of the prevention of limb ischemia by the insertion of a catheter for distal perfusion. METHODS: Data from our registry of 100 patients treated with VA ECMO implanted via percutaneous femoral approach for cardiogenic shock or refractory cardiac arrest were analyzed. If the leg perfusion was inadequate, an additional 7-9 Fr percutaneous catheter distal to the ECMO arterial cannula was placed into the femoral artery to prevent limb ischemia. RESULTS: Thirty-five patients had early vascular complications. Thirty patients with early ischemia were cannulated with a small reperfusion cannula to obtain antegrade perfusion of the limb. Twenty-six had an effective reperfusion. Seven patients developed a compartment syndrome of the leg requiring urgent fasciotomy that led to clinical improvement and recovery in five, while the other two patients progressed to irreversible ischemia requiring amputation of the limb. CONCLUSION: The majority of ischemic episodes were resolved with the insertion of a distal perfusion catheter. We did not observe any mortal vascular complication, nor any of the observed complications was related to increased mortality.

New treatment bundles improve survival in out-of-hospital cardiac arrest patients: a historical comparison.

INTRODUCTION: Before the introduction of the new international cardiac arrest treatment guidelines in 2005, patients with out-of-hospital cardiac arrest (OHCA) of cardiac origin in Northern Italy had very poor prognosis. Since 2006, a new bundle of care comprising use of automated external defibrillators (AEDs) and therapeutic hypothermia (TH) was started, while extracorporeal CPR program (ECPR) for selected refractory CA and dispatcher-assisted cardio-pulmonary resuscitation (CPR) was started in January 2010. OBJECTIVES: We hypothesized that a program of bundled care might improve outcome of OHCA patients. METHODS: We analyzed data collected in the OHCA registry of the MB area between September 2007 and August 2011 and compared this with data from 2000 to 2003. RESULTS: Between 2007 and 2011, 1128 OHCAs occurred in the MB area, 745 received CPR and 461 of these had a CA of presumed cardiac origin. Of these, 125 (27%) achieved sustained ROSC, 60 (13%) survived to 1 month, of whom 51 (11%) were discharged from hospital with a good neurological outcome (CPC≤2), and 9 with a poor neurological outcome (CPC>2). Compared with data from the 2000 to 2003 periods, survival increased from 5.6% to 13.01% (p<0.0001). In the 2007-2011 group, low-flow time and bystander CPR were independent markers of survival. CONCLUSIONS: OHCA survival has improved in our region. An increased bystander CPR rate associated with dispatcher-assisted CPR was the most significant cause of increased survival, but duration of CA remains critical for patient outcome.

Implementation and outcomes of a transfusion-related acute lung injury surveillance programme and study of HLA/HNA alloimmunisation in blood donors.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated mortality. Antibodies against human leucocyte antigens (HLA) and human neutrophil antigens (HNA) are often detected in the implicated donors. We investigated the incidence and aetiology of TRALI in Lombardy. Moreover, we determined the rate of HLA and HNA alloimmunisation and the HNA genotype in a cohort of local blood donors. MATERIALS AND METHODS: During a 2-year observational study in eight blood transfusion services, suspected TRALI cases were collected and characterised by means of HLA and HNA antibody screening of implicated donors, donor/recipient cross-matching and HLA/HNA molecular typing. In addition, 406 Italian donors were evaluated for alloimmunisation and in 102 of them HNA gene frequencies were determined. RESULTS: Eleven cases were referred to the central laboratory, of whom three were diagnosed as having TRALI, seven as having possible TRALI and one as having transfusion-associated circulatory overload. Seven TRALI cases were immune-mediated whereas in three we did not find either alloantibodies in implicated donors or a positive reaction in the cross-match. The most frequently implicated blood component was red blood cells (in 5 males and in 1 female), whereas four cases of TRALI were associated with transfusion of fresh-frozen plasma (in 3 females and in 1 male). The frequency of reported TRALI/possible TRALI cases was 1:82,000 for red blood cells and 1:22,500 for fresh-frozen plasma. No cases were observed for platelets. Overall, the frequency of HLA or HNA alloimmunisation in blood donors was 29% for females and 7% for males. The latter could be related, at least in part, to natural antibodies. HNA gene frequencies showed that HNA-1b is more frequent than HNA-1a in our sample of donors. DISCUSSION: The recently adopted national policy to prevent TRALI, i.e. using only plasma donated by males, would have had a positive impact in our setting.