Paolo Severgnini

Background: Organ donation after determination of death by neurological criteria (DBD) remains a cornerstone of deceased donation programs, yet the full pathway from donor identification to organ retrieval, transplantation, and early graft function remains insufficiently described. A better understanding of where falls occurs along this trajectory may help identify modifiable barriers and improve donation‐system performance. Methods: We performed a retrospective single‐center observational study including all consecutive cases of patients who underwent determination of death by neurological criteria recorded between 2019–2025 in four intensive care units of a tertiary‐care hospital in Northern Italy. Data were extracted from institutional clinical and donation records and included donor characteristics, recorded donation preference, family authorization, causes of non‐retrieval, number and type of organs retrieved and transplanted, and early graft functional recovery (e.g., 24–48 h posttransplant). Results: 155 patients underwent determination of death by neurological criteria. Organ retrieval was performed in 111 cases (71.6%). Documented prior consent was present in 41 cases (26.4%), decline in 3 (1.9%), and no prior recorded donation preference in 106 cases (68.4%), requiring family authorization. In this subgroup, family decline occurred in 27 cases (25.5%) and represented the leading cause of non‐retrieval. Medical contraindications accounted for 12 further exclusions. Overall, 365 organs were retrieved, corresponding to 65.8% of potentially available organs; 343 (94.0%) were transplanted, and 332 (96.8% of transplanted organs) showed functional recovery at 24–48 h. Mean number of retrieved organs was 3.28, with 2.99 functioning grafts per donor. Conclusions: Family decline and non‐retrieval of organs judged unsuitable at retrieval were the main points of loss along the donation pathway. Systematic whole‐pathway data collection may help identify missed opportunities, guide quality‐improvement strategies, and optimize assessment at the organ retrieval stage.

Intestinal ischemia and reperfusion injury (IRI) can lead to multiple organ dysfunction, including the central nervous system (CNS), where a neuroinflammatory response may develop. Hyaluronan, a glycosaminoglycan component of the extracellular matrix, has been shown to modulate enteric neuronal and immune function during in vivo IRI in the rat small intestine. The aim of this study was to investigate the potential involvement of hyaluronan in the alterations induced by in vivo intestinal IRI in the rat hippocampus and striatum. Mesenteric ischemia was induced in anesthetized adult male rats for 60 min, followed by 24 h of reperfusion. Injured (IRI group), sham-operated (SHAM group), and non-injured (CTR group) animals were treated with the hyaluronan synthesis inhibitor 4-methylumbelliferone (4-MU; 25 mg/kg). In the hippocampus and striatum of the IRI group, levels of both hyaluronan and neurocan, a proteoglycan primarily found in the central nervous system extracellular matrix, as well as the hyaluronan synthesizing enzyme Has2, were significantly downregulated compared to the CTR and SHAM groups. These changes were associated with alterations in the TLR4-NFκB-pIκB pathway, with the effects being more prominent in the hippocampus than in the striatum. Increased levels of IL6, co-localizing with the microglial marker S100β, were observed in both regions and were attenuated by 4-MU only in the hippocampus. Overall, these findings suggest that intestinal IRI may disrupt extracellular matrix homeostasis and induce hyaluronan-mediated enhancement of local proinflammatory signaling, primarily involving IL6 and microglial cells, mainly in the hippocampus. Such changes may contribute to the development of cognitive deficits and memory dysfunction associated with intestinal IRI.

Objective: To compare bioelectrical impedance analysis (BIA)-derived parameters in healthy volunteers and critically ill patients and to assess its prognostic value in an ICU patient cohort. Design: Retrospective, observational data analysis. Setting: Single centre, tertiary-level ICU (Ziekenhuis Netwerk Antwerpen, ZNA Stuivenberg Hospital). Patients: 101 patients and 101 healthy subjects, participants of International Fluid Academy Days. Measurements and main results: Compared to healthy volunteers, both male and female ICU patients had significantly higher values for total body water (TBW), extracellular water (ECW), extracellular fluid (ECF), plasma, and interstitial fluid volumes. The phase angle was significantly lower and the malnutrition index was significantly higher in ICU patients, regardless of gender. Non-survivors in the ICU had significantly higher extracellular water content (ECW, 50.7 ± 5.1 vs. 48.9 ± 4.3%, p = 0.047) and accordingly significantly lower intracellular water (ICW, 49.2 ± 5.1 vs. 51.1 ± 4.3%, p = 0.047). The malnutrition index was also significantly higher in non-survivors compared to survivors (0.94 ± 0.17 vs. 0.87 ± 0.16, p = 0.048), as was the capillary leak index (ECW/ICW). Conclusions: Compared to healthy volunteers, this study observed a higher malnutrition index and TBW in ICU patients with an accumulation of fluids in the extracellular compartment. ICU non-survivors showed similar results, indicating that ICU patients and a fortiori non-survivors are generally overhydrated, with increased TBW and ECW, and more undernourished, as indicated by a higher malnutrition index.

Moderate and severe traumatic brain injury (TBI) are major causes of disability and death. In addition, when TBI occurs during pregnancy, it can lead to miscarriage, premature birth, and maternal/fetal death, engendering clinical and ethical issues. Several recommendations have been proposed for the management of TBI patients; however, none of these have been specifically applied to pregnant women, which often have been excluded from major trials. Therefore, at present, evidence on TBI management in pregnant women is limited and mostly based on clinical experience. The aim of this manuscript is to provide the clinicians with practical suggestions, based on 10 rules, for the management of moderate to severe TBI during pregnancy. In particular, we firstly describe the pathophysiological changes occurring during pregnancy; then we explore the main strategies for the diagnosis of TBI taking in consideration the risks related to mother and fetus, and finally we discuss the most appropriate approaches for the management in this particular condition. Based on the available evidence, we suggest a stepwise approach consisting of different tiers of treatment and we describe the specific risks according to the severity of the neurological and systemic conditions of both fetus and mother in relation to each trimester of pregnancy. The innovative feature of this approach is the fact that it focuses on the vulnerability and specificity of this population, without forgetting the current knowledge on adult non-pregnant patients, which has to be applied to improve the quality of the care process.

Paravalvular leak (PVL) is a well‐recognized complication after mitral valve replacement (MVR). However, there are only a few studies analyzing leak occurrence and postoperative results after surgical MVR. The aim of this study was to assess the rate and determinants of early mitral PVL and to evaluate the impact on survival. We performed a retrospective analysis involving patients who underwent MVR from January 2012 to December 2019 at our Institution. Postoperative transthoracic echocardiography evaluation was done for all subjects before hospital discharge. Multivariable analysis was carried out by constructing a logistic regression model to identify predictors for PVL occurrence. Four hundred ninety‐four patients were enrolled. Operative mortality was 4.9%. Early mitral PVL was found in 16 patients (3.2%); the majority were mild (75%). Leaks occurred more frequently along the posterior segment of the mitral valve annulus (62.5%). Only one individual with moderate‐to‐severe PVL underwent reoperation during the same hospital admission. Multivariable analysis revealed that preoperative diagnosis of infective endocarditis was the only factor associated with early leak after MVR (odds ratio: 4.96; 95% confidence interval: 1.45–16.99; p = .011). Overall mortality at follow‐up (mean follow‐up time: 4.7 [SD: 2.5] years) was 19.6% and favored patients without early mitral PVL. The incidence of early PVL after MVR is low. PVL is usually mild and develop more frequently along the posterior segment of the mitral valve annulus. Preoperative diagnosis of infective endocarditis increases the risk of PVL formation.

Introduction: The aims of this study were to assess the concordance of different tools and to describe the accuracy of a multimodal approach to predict unfavorable neurological outcome (UO) in cardiac arrest patients. Methods: Retrospective study of adult (>18 years) cardiac arrest patients who underwent multimodal monitoring; UO was defined as cerebral performance category 3–5 at 3 months. Predictors of UO were neurological pupillary index (NPi) ≤ 2 at 24 h; highly malignant patterns on EEG (HMp) within 48 h; bilateral absence of N20 waves on somato-sensory evoked potentials; and neuron-specific enolase (NSE) > 75 μg/L. Time-dependent decisional tree (i.e., NPi on day 1; HMp on day 1–2; absent N20 on day 2–3; highest NSE) and classification and regression tree (CART) analysis were used to assess the prediction of UO. Results: Of 137 patients, 104 (73%) had UO. Abnormal NPi, HMp on day 1 or 2, the bilateral absence of N20 or NSE >75 mcg/L had a specificity of 100% to predict UO. The presence of abnormal NPi was highly concordant with HMp and high NSE, and absence of N20 or high NSE with HMp. However, HMp had weak to moderate concordance with other predictors. The time-dependent decisional tree approach identified 73/103 patients (70%) with UO, showing a sensitivity of 71% and a specificity of 100%. Using the CART approach, HMp on EEG was the only variable significantly associated with UO. Conclusions: This study suggests that patients with UO had often at least two predictors of UO, except for HMp. A multimodal time-dependent approach may be helpful in the prediction of UO after CA. EEG should be included in all multimodal prognostic models.

Objectives: The aim of this study was to assess the diagnostic role of eosinophils count in COVID-19 patients. Methods: Retrospective analysis of patients admitted to our hospital with suspicion of COVID-19. Demographic, clinical and laboratory data were collected on admission. Eosinopenia was defined as eosinophils < 100 cells/mm³. The outcomes of this study were the association between eosinophils count on admission and positive real-time reverse transcription polymerase chain reaction (rRT-PCR) test and with suggestive chest computerized tomography (CT) of COVID-19 pneumonia. Results: A total of 174 patients was studied. Of those, 54% had positive rRT-PCR for SARS-CoV-2. A chest CT-scan was performed in 145 patients; 71% showed suggestive findings of COVID-19. Eosinophils on admission had a high predictive accuracy for positive rRT-PCR and suggestive chest CT-scan (area under the receiver operating characteristic—ROC curve, 0.84 (95% CIs 0.78–0.90) and 0.84 (95% CIs 0.77–0.91), respectively). Eosinopenia and high LDH were independent predictors of positive rRT-PCR, whereas eosinopenia, high body mass index and hypertension were predictors for suggestive CT-scan findings. Conclusions: Eosinopenia on admission could predict positive rRT-PCR test or suggestive chest CT-scan for COVID-19. This laboratory finding could help to identify patients at high-risk of COVID-19 in the setting where gold standard diagnostic methods are not available.

Article: Early versus late tracheal intubation in COVID-19 patients: a pro-con debate also considering heart-lung interactions - Minerva Cardioangiologica 2020 Oct 15 - Minerva Medica - Journals

Postoperative pulmonary complications (PPC) may result in longer duration of in-hospital stay and even mortality. Both thoracic surgery and intraoperative mechanical ventilation settings add considerably to the risk of PPC. It is unclear if one-lung ventilation (OLV) for thoracic surgery with a strategy of intraoperative high positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM) reduces PPC, compared to low PEEP without RM. PROTHOR is an international, multicenter, randomized, controlled, assessor-blinded, two-arm trial initiated by investigators of the PROtective VEntilation NETwork. In total, 2378 patients will be randomly assigned to one of two different intraoperative mechanical ventilation strategies. Investigators screen patients aged 18 years or older, scheduled for open thoracic or video-assisted thoracoscopic surgery under general anesthesia requiring OLV, with a maximal body mass index of 35 kg/m2, and a planned duration of surgery of more than 60 min. Further, the expected duration of OLV shall be longer than two-lung ventilation, and lung separation is planned with a double lumen tube. Patients will be randomly assigned to PEEP of 10 cmH2O with lung RM, or PEEP of 5 cmH2O without RM. During two-lung ventilation tidal volume is set at 7 mL/kg predicted body weight and, during OLV, it will be decreased to 5 mL/kg. The occurrence of PPC will be recorded as a collapsed composite of single adverse pulmonary events and represents the primary endpoint. PROTHOR is the first randomized controlled trial in patients undergoing thoracic surgery with OLV that is adequately powered to compare the effects of intraoperative high PEEP with RM versus low PEEP without RM on PPC. The results of the PROTHOR trial will support anesthesiologists in their decision to set intraoperative PEEP during protective ventilation for OLV in thoracic surgery. The trial was registered in clinicaltrials.gov ( NCT02963025 ) on 15 November 2016.