Neutrophil Extracellular Traps and Thrombolysis Resistance: New Insights for Targeting Therapies.

BACKGROUND: Thrombosis is linked to neutrophil release of neutrophil extracellular traps (NETs). NETs are proposed as a mechanism of resistance to thrombolysis. This study intends to analyze the composition of thrombi retrieved after mechanical thrombectomy, estimate the age and organization of thrombi, and evaluate associations with the use of thrombolysis, antiplatelets, and heparin. METHODS: This retrospective observational study involved 72 samples (44 from cerebral and 28 coronary arteries), which were stained with hematoxylin and eosin, anti-NE (neutrophil elastase) antibody, and anti-histone H2B (histone H2B) antibody, representing different components in NET formation, all detectable during the later stages of NETosis, for histochemical and digital quantification of NET content. The histological and morphological evaluations of the specimens were correlated, through univariate and mediation analyses, with clinical information and therapy administered before intervention. RESULTS: The results demonstrated that the composition of cerebral and coronary thrombi differs, and there were significantly more lytic cerebral thrombi than coronary thrombi (66% versus 14%; P=0.005). There was a considerably higher expression of NETs in the cerebral thrombi as testified by the higher expression of H2B (P=0.031). Thrombolysis was remarkably associated with higher NE positivity (average marginal effect, 6.461 [95% CI, 0.7901-12.13]; P=0.02555), regardless of the origin of thrombi. There was no notable association between the administration of antiaggregant therapy/heparin and H2B/NE amount when adjusted for the thrombus location. Importantly, the age of the thrombus was the only independent predictor of NET content without any mediation of the thrombolytic treatment (P=0.014). CONCLUSIONS: The age of the thrombus is the driving force for NET content, which correlates with impaired clinical outcomes. The therapy that is currently administered does not modify NET content. This study supports the need to investigate new pharmacological approaches added to thrombolysis to prevent NET formation or enhance their disruption, such as recombinant human DNase I (deoxyribonuclease I).

Surveillance of Individuals at High Risk of Developing Pancreatic Cancer: A Prevalence Meta-analysis to Estimate the Rate of Low-yield Surgery.

OBJECTIVE: To quantify the rate of low-yield surgery, defined as no high-grade dysplastic precursor lesions or T1N0M0 pancreatic cancer at pathology, during pancreatic cancer surveillance. BACKGROUND: Global efforts have been made in pancreatic cancer surveillance to anticipate the diagnosis of pancreatic cancer at an early stage and improve survival in high-risk individuals (HRIs) with a hereditary predisposition. The negative impact of pancreatic cancer surveillance when surgery is performed for low-grade dysplasia or a non-neoplastic condition is not well quantified. MATERIALS AND METHODS: A systematic search and prevalence meta-analysis was performed for studies reporting surgery with final diagnoses other than those defined by the Cancer of the Pancreas Screening (CAPS) goals from January 2000 to July 2023. The secondary outcome was the pooled proportion of final diagnoses matching the CAPS goals (PROSPERO: #CRD42022300408). RESULTS: Twenty-three articles with 5027 patients (median 109 patients/study, interquartile range 251) were included. The pooled prevalence of low-yield surgery was 2.1% (95% CI: 0.9-3.7, I2 : 83%). In the subgroup analysis, this prevalence was nonsignificantly higher in studies that only included familial pancreatic cancer subjects without known pathogenic variants, compared with those enrolling pathogenic variant carriers. No effect modifiers were found. Overall, the pooled prevalence of subjects under surveillance who had a pancreatic resection that contained target lesions was 0.8% (95% CI, 0.3-1.5, I2 : 24%]. The temporal analysis showed that the rate of low-yield surgeries decreased in the last decades and stabilized at around 1% (test for subgroup differences P <0.01). CONCLUSIONS: The risk of "low-yield" surgery during pancreatic cancer surveillance is relatively low but should be thoroughly discussed with individuals under surveillance.

Cancer incidence (2000-2020) among individuals under 35: an emerging sex disparity in oncology.

BACKGROUND: Aggressive malignancies, such as pancreatic cancer, are increasingly impacting young, female populations. Our investigation centered on whether the observed trends in cancer incidence were unique to pancreatic cancer or indicative of a broader trend across various cancer types. To delve deeper into this phenomenon, we analyzed cancer incidence trends across different age and sex groups. Furthermore, we explored differences in cancer incidence within specific young subgroups aged 18 to 26 and 27 to 34, to better understand the emerging incidence trend among young individuals. METHODS: This study collected cancer incidence data from one of the Surveillance, Epidemiology, and End Results cancer registry databases (SEER22), with 10,183,928 total cases from 2000 to 2020. Data were analyzed through Joinpoint trend analysis approach to evaluate sex- and age-specific trends in cancer incidence. Exposure rates were reported as Average Annual Percentage Changes (AAPCs). RESULTS: The analysis revealed significant age and sex-specific disparities, particularly among individuals aged 18-26 and 27-34. Pancreatic cancer incidence rates increased more in females aged 18-26 (AAPC, 9.37% [95% CI, 7.36-11.41%]; p < .0001) than in males (4.43% [95% CI, 2.36-6.53%]; p < .0001). Notably, among gender, age, and other malignancies, young females had the highest AAPCs for pancreatic cancer. Additionally, the incidence of gastric cancer, myeloma, and colorectal malignancies also showed higher AAPCs in young females compared to males. CONCLUSIONS: Recognizing emerging risk populations for highly lethal malignancies is crucial for early detection and effective disease management.

Diaphragm Dysfunction Predicts Weaning Outcome after Bilateral Lung Transplant.

BACKGROUND: Diaphragm dysfunction and its effects on outcomes of ventilator weaning have been evaluated in mixed critical care populations using diaphragm thickening fraction (the ratio of the difference between ultrasound diaphragm thickness at end-inspiration and end-expiration to diaphragm thickness at end-expiration) or neuroventilatory efficiency (the ratio of tidal volume and peak electrical activity of the diaphragm). Such data are not available in bilateral-lung transplant recipients. The authors hypothesized that (1) diaphragm dysfunction, as defined by a diaphragm thickening fraction less than 29%, is more likely to occur in difficult weaning; (2) diaphragm thickening fraction and neuroventilatory efficiency predict weaning outcome; and (3) duration of mechanical ventilation before the first spontaneous breathing trial is associated with diaphragm dysfunction. METHODS: Adult bilateral-lung transplant patients admitted to the intensive care unit were screened at the time of the first spontaneous breathing trial (pressure-support of 5 cm H2O and 0 positive end-expiratory pressure). At the fifth minute, diaphragm thickening fraction and neuroventilatory efficiency were measured during three respiratory cycles. Weaning was classified as simple, difficult, or prolonged (successful extubation at the first spontaneous breathing trial, within three or after three spontaneous breathing trials, respectively). RESULTS: Forty-four subjects were enrolled. Diaphragm dysfunction occurred in 14 subjects (32%), all of whom had difficult weaning (78% of the subgroup of 18 patients experiencing difficult weaning). Both diaphragm thickening fraction (24 [20 to 29] vs. 39 [35 to 45]%) and neuroventilatory efficiency (34 [26 to 45] vs. 55 [43 to 62] ml/µV) were lower in difficult weaning (both P < 0.001). The areas under the receiver operator curve predicting difficult weaning were 0.88 (95% CI, 0.73 to 0.99) for diaphragm thickening fraction and 0.85 (95% CI, 0.71 to 0.95) for neuroventilatory efficiency. The duration of ventilation demonstrated a linear inverse correlation with both diaphragm thickening fraction and neuroventilatory efficiency. CONCLUSIONS: Diaphragm dysfunction is common after bilateral-lung transplantation and associated with difficult weaning. In such patients, average values for diaphragm thickening fraction and neuroventilatory efficiency were reduced compared to patients with simple weaning. Both parameters showed similar accuracy for predicting success of ventilator weaning, demonstrating an inverse relationship with duration of ventilation.

Mortality related to HCV and other chronic liver diseases in Veneto (Italy), 2008-2021: Changes in trends and age-period-cohort effects.

BACKGROUND AND AIMS: The objective of this study was to assess the impact of the COVID-19 pandemic and direct-acting antiviral (DAA) agents on mortality related to chronic liver diseases (CLD). METHODS: Age-standardized mortality rates were computed based on CLD as the underlying cause of death (UCOD) and as any mention in death certificates (multiple causes of death-MCOD). Time trends in age-standardized mortality rates were investigated using generalized estimation equation models. Additionally, we conducted age, period, and birth cohort (APC) analyses on CLD-related mortality associated with alcohol and hepatitis C virus (HCV). RESULTS: Between 2008 and 2021, among residents in the Veneto region (Northeastern Italy) aged ≥35 years, there were 20 409 deaths based on the UCOD and 30 069 deaths based on MCOD from all CLD. We observed a 4% annual decline in age-standardized MCOD-based mortality throughout 2008-2021, with minor peaks corresponding to COVID-19 epidemic waves. Starting in 2016, the decline in HCV-related mortality accelerated further (p < .001). A peak in HCV-related mortality in the 1963-1967 birth cohort was observed, which levelled off by the end of the study period. Mortality related to alcoholic liver disease declined at a slower pace, becoming the most common aetiology mentioned in death certificates. CONCLUSIONS: The study demonstrates a significant decrease in HCV-related mortality at the population level in Italy with the introduction of DAAs. Continuous monitoring of MCOD data is warranted to determine if this favourable trend will continue. Further studies utilizing additional health records are needed to clarify the role of other CLD etiologies.

Application of the Weighted-Incidence Syndromic Combination Antibiogram (WISCA) to guide the empiric antibiotic treatment of febrile neutropenia in oncological paediatric patients: experience from two paediatric hospitals in Northern Italy.

BACKGROUND: Guidelines about febrile neutropenia in paediatric patients are not homogeneous; the best empiric treatment of this condition should be driven by local epidemiology. The Weighted-Incidence Syndromic Combination Antibiogram (WISCA) addresses the need for disease-specific local susceptibility evidence that could guide empiric antibiotic prescriptions based on outcome estimates of treatment regimens obtained as a weighted average of pathogen susceptibilities. This study developed a WISCA model to inform empirical antibiotic regimen selection for febrile neutropenia (FN) episodes in onco-haematological paediatric patients treated at two Italian paediatric tertiary centres. METHODS: We included blood cultures from patients with a bloodstream infection and neutropenia admitted to the Paediatric Haematology-Oncology wards in Padua and Genoa Hospitals from 2016 to 2021. WISCAs were developed by estimating the coverage of 20 antibiotics as monotherapy and of 21 combined regimens with a Bayesian probability distribution. RESULTS: We collected 350 blood cultures, including 196 g-negative and 154 g-positive bacteria. Considering the most used antibiotic combinations, such as piperacillin-tazobactam plus amikacin, the median coverage for the pool of bacteria collected in the study was 78%. When adding a glycopeptide, the median coverage increased to 89%, while the replacement of piperacillin-tazobactam with meropenem did not provide benefits. The developed WISCAs showed that no monotherapy offered an adequate coverage rate for the identified pathogens. CONCLUSIONS: The application of WISCA offers the possibility of maximizing the clinical utility of microbiological surveillance data derived from large hospitals to inform the choice of the best empiric treatment while contributing to spare broad-spectrum antibiotics.

Nationwide cost-effectiveness and quality of life analysis of minimally invasive distal pancreatectomy.

BACKGROUND: This study analyzed the Quality of Life (QoL) and cost-effectiveness of laparoscopic (LDP) versus robotic distal pancreatectomy (RDP). METHODS: Consecutive patients submitted to LDP or RDP from 2010 to 2020 in four high-volume Italian centers were included, with a minimum of 12 months of postoperative follow-up were included. QoL was evaluated using the EORTC QLQ-C30 and EQ-5D questionnaires, self-reported by patients. After a propensity score matching, which included BMI, gender, operation time, multiorgan and vascular resections, splenic preservation, and pancreatic stump management, the mean differential cost and Quality-Adjusted Life Years (QALY) were calculated and plotted on a cost-utility plane. RESULTS: The study population consisted of 564 patients. Among these, 271 (49%) patients were submitted to LDP, while 293 (51%) patients to RDP. After propensity score matching, the study population was composed of 159 patients in each group, with a median follow-up of 59 months. As regards the QoL analysis, global health and emotional functioning domains showed better results in the RDP group (p = 0.037 and p = 0.026, respectively), whereas the other did not differ. As expected, the median crude costs analysis confirmed that RDP was more expensive than LDP (16,041 Euros vs. 10,335 Euros, p < 0.001). However, the robotic approach had a higher probability of being more cost-effective than the laparoscopic procedure when a willingness to pay more than 5697 Euros/QALY was accepted. CONCLUSION: RDP was associated with better QoL as explored by specific domains. Crude costs were higher for RDP, and the cost-effectiveness threshold was set at 5697 euros/QALY.

Nationwide hospitalizations of patients with down syndrome and congenital heart disease over a 15-year period.

Down syndrome is one of the most common genetic diseases, generally associated with an increased probability of congenital heart diseases. This increased risk contributes to escalated levels of morbidity and mortality. In this study, we sought to analyze nationwide data of pediatric and adult patients with Down syndrome and congenital heart disease over a 15-year period. Data obtained from the hospital discharge form between 2001 and 2016 of patients diagnosed with Down syndrome in Italy and at least one congenital heart disease were included. Information on 12362 admissions of 6527 patients were included. Age at first admission was 6.2 ± 12.8 years and was a predictor of mortality (HR = 1.51, 95% CI 1.13-2.03, p = 0.006). 3923 (60.1%) patients underwent only one admission, while 2604 (39.9%) underwent multiple (> 1) admissions. There were 5846 (47.3%) admissions for cardiac related symptoms. Multiple admissions (SHR: 3.13; 95% CI: 2.99, 3.27; P < 0.01) and cardiac admissions (SHR: 2.00; 95% CI: 1.92, 2.09; P < 0.01) were associated with an increased risk of additional potential readmissions. There was an increased risk of mortality for patients who had cardiac admissions (HR = 1.45, 95% CI: 1.08-1.94, p = 0.012), and for those who underwent at least 1 cardiac surgical procedure (HR = 1.51, 95% CI 1.13-2.03, p = 0.006). CONCLUSIONS: A younger age at first admission is a predictor for mortality in patients with Down syndrome and congenital heart disease. If patients undergo more than one admission, the risk of further readmissions increases. There is a pivotal role for heart disease in influencing the hospitalization rate and subsequent mortality. WHAT IS KNOWN: • Down syndrome individuals often face an increased risk of congenital heart diseases. • Congenital heart diseases contribute significantly to morbidity and mortality in Down syndrome patients. WHAT IS NEW: • This study analyzes nationwide data covering a 15-year period of pediatric and adult patients in Italy with Down syndrome and congenital heart disease. • It identifies a younger age at first admission as a predictor for mortality in these patients, emphasizing the criticality of early intervention. • Demonstrates a correlation between multiple admissions, particularly those related to cardiac issues, and an increased risk of further readmissions, providing insights into the ongoing healthcare needs of these individuals.

Extracorporeal Cardiopulmonary Resuscitation Use Among Children With Cardiac Disease in the ICU: A Meta-Analysis and Meta-Regression of Data Through March 2024.

OBJECTIVE: Epidemiologic data on extracorporeal cardiopulmonary resuscitation (ECPR) use in children with cardiac disease after in-hospital cardiac arrest (IHCA) are lacking. We aimed to investigate trends in ECPR use over time in critically ill children with cardiac disease. DATA SOURCES: We performed a secondary analysis of a recent systematic review (PROSPERO CRD42020156247) to investigate trends in ECPR use in children with cardiac disease. PubMed, Web of Science, Embase, and Cumulative Index to Nursing and Allied Health Literature were screened (inception to September 2021). For completeness of this secondary analysis, PubMed was also rescreened (September 2021 to March 2024). STUDY SELECTION: Observational studies including epidemiologic data on ECPR use in children with cardiac disease admitted to an ICU. DATA EXTRACTION: Data were extracted by two independent investigators. The risk of bias was assessed using the National Heart Lung and Blood Institutes Quality Assessment Tools. Random-effects meta-analysis was used to compute a pooled proportion of subjects undergoing ECPR; meta-regression was used to assess trends in ECPR use over time. DATA SYNTHESIS: Of the 2664 studies identified, 9 (17,669 patients) included data on ECPR use in children with cardiac disease. Eight were cohort studies, 1 was a case-control, 8 were retrospective, 1 was prospective, 6 were single-center, and 3 were multicenter. Seven studies were included in the meta-analysis; all were judged of good quality. By meta-analysis, we found that a pooled proportion of 21% (95% CI, 15-29%) of pediatric patients with cardiac disease experiencing IHCA were supported with ECPR. By meta-regression adjusted for category of patients (surgical vs. general cardiac), we found that the use of ECPR in critically ill children with cardiac disease significantly increased over time ( p = 0 .026). CONCLUSIONS: About one-fifth of critically ill pediatric cardiac patients experiencing IHCA were supported with ECPR, and its use significantly increased over time. This may partially explain the increased trends in survival demonstrated for this population.

Asymmetrical high-flow nasal cannula performs similarly to standard interface in patients with acute hypoxemic post-extubation respiratory failure: a pilot study.

BACKGROUND: Standard high-flow nasal cannula (HFNC) is a respiratory support device widely used to manage post-extubation hypoxemic acute respiratory failure (hARF) due to greater comfort, oxygenation, alveolar recruitment, humidification, and reduction of dead space, as compared to conventional oxygen therapy. On the contrary, the effects of the new asymmetrical HFNC interface (Optiflow® Duet system (Fisher & Paykel, Healthcare, Auckland, New Zealand) is still under discussion. Our aim is investigating whether the use of asymmetrical HFNC interface presents any relevant difference, compared with the standard configuration, on lung aeration (as assessed by end-expiratory lung impedance (EELI) measured by electrical impedance tomography (EIT)), diaphragm ultrasound thickening fraction (TFdi) and excursion (DE), ventilatory efficiency (estimated by corrected minute ventilation (MV)), gas exchange, dyspnea, and comfort. METHODS: Pilot physiological crossover randomized controlled study enrolling 20 adults admitted to the Intensive Care unit, invasively ventilated for at least 24 h, and developing post-extubation hARF, i.e., PaO2/set FiO2 < 300 mmHg during Venturi mask (VM) within 120 min after extubation. Each HFNC configuration was applied in a randomized 60 min sequence at a flow rate of 60 L/min. RESULTS: Global EELI, TFdi, DE, ventilatory efficiency, gas exchange and dyspnea were not significantly different, while comfort was greater during asymmetrical HFNC support, as compared to standard interface (10 [7-10] and 8 [7-9], p-value 0.044). CONCLUSIONS: In post-extubation hARF, the use of the asymmetrical HFNC, as compared to standard HFNC interface, slightly improved patient comfort without affecting lung aeration, diaphragm activity, ventilatory efficiency, dyspnea and gas exchange. CLINICAL TRIAL NUMBER: ClinicalTrial.gov. REGISTRATION NUMBER: NCT05838326 (01/05/2023). NEW & NOTEWORTHY: The asymmetrical high-flow nasal cannula oxygen therapy (Optiflow® Duet system (Fisher & Paykel, Healthcare, Auckland, New Zealand) provides greater comfort as compared to standard interface; while their performance in term of lung aeration, diaphragm activity, ventilatory efficiency, dyspnea, and gas exchange is similar.

Bilateral simultaneous cochlear implants in children: Best timing of surgery and long-term auditory outcomes.

PURPOSE: Evaluate the hearing outcomes of bilateral deaf children implanted simultaneously and define the most appropriate timing for surgery. MATERIALS AND METHODS: Audiological CI results were retrieved in both the short-term and long-term period and compared by stratifying the patients into different subcohorts according to their age at surgery. Additional data collected were age at implant activation, etiology and timing of onset of deafness, presence of psychomotor delay. RESULTS: fifty-six bilaterally implanted children were included. The short-term outcomes differed significantly when comparing groups of different ages at implantation: younger patients achieved better aided pure tone audiometry results. Considering long-term follow-up, a significant correlation was identified between an early age at implantation and the hearing outcome at ages 2 to 5 years. Perceptive levels were better at 4 years of age in the younger group. No significant differences were found between children implanted at before 12 months and between 12 and 16 months of age. CONCLUSIONS: The results of the analyzed follow-up data support the hypothesis that children implanted at before 24 months are expected to have better hearing performances. Nevertheless, these results are referred to a widely heterogeneous group of patients and the duration of auditory deprivation should be considered.

A tale of two constructs: combined assessment of demoralization and subjective incompetence.

Demoralization comprises multiple dimensions. Among them, Subjective Incompetence (SI) is the perception of being incapable of appropriate action in demanding circumstances. SI may be an early sign of demoralization preceding hopelessness, thus we aimed at integrating items related to Subjective Incompetence into the clinical assessment of demoralization. We assessed 414 subjects from the general population with the Demoralization Scale, 24 items (DS24) and the Subjective Incompetence Scale, 12 items (SIS12). We used multiple approaches to detect the optimal number of factors and their item structure, then conducted Bayesian Item Response Theory analyses to study item psychometric properties. Item Response Theory models were used to extrapolate latent severity ratings of clinical dimensions. We modelled the DS24 with five factors (Disheartenment, Sense of Failure, Helplessness, Irritability, Loss of Purpose) and the SIS12 with three (Subjective Incompetence, Inability to plan, Inability to Deal). The more complex IRT model had the best predictive value and helped to identify the items with better discrimination properties across the different dimensions. Twenty items were retained and used to develop the combined Demoralization and Subjective Incompetence Scale (DSIS20), which maintained high correlation with raw and latent trait scores of the longer versions. We combined selected items of the DS24 and the SIS12 to develop the DSIS20, a shorter assessment instrument that includes Subjective Incompetence as well as other clinical dimensions of demoralization. Further study may clarify if DSIS20 may be helpful for the early detection of demoralization.

Use of Sequential Multiple Assignment Randomized Trials (SMARTs) in oncology: systematic review of published studies.

Sequential multiple assignments randomized trials (SMARTs) are a type of experimental design where patients may be randomised multiple times according to pre-specified decision rules. The present work investigates the state-of-the-art of SMART designs in oncology, focusing on the discrepancy between the available methodological approaches in the statistical literature and the procedures applied within cancer clinical trials. A systematic review was conducted, searching PubMed, Embase and CENTRAL for protocols or reports of results of SMART designs and registrations of SMART designs in clinical trial registries applied to solid tumour research. After title/abstract and full-text screening, 33 records were included. Fifteen were reports of trials' results, four were trials' protocols and fourteen were trials' registrations. The study design was defined as SMART by only one out of fifteen trial reports. Conversely, 13 of 18 study protocols and trial registrations defined the study design SMART. Furthermore, most of the records considered each stage separately in the analysis, without considering treatment regimens embedded in the trial. SMART designs in oncology are still limited. Study powering and analysis is mainly based on statistical approaches traditionally used in single-stage parallel trial designs. Formal reporting guidelines for SMART designs are needed.

Physical activity assessment with wearable devices in rheumatic diseases: a systematic review and meta-analysis.

OBJECTIVES: In the management of rheumatic musculoskeletal disorders (RMDs), regular physical activity (PA) is an important recognized non-pharmacological intervention. This systematic review and meta-analysis aims to evaluate how the use of wearable devices (WDs) impacts physical activity in patients with noninflammatory and inflammatory rheumatic diseases. METHODS: A comprehensive search of articles was performed in PubMed, Embase, CINAHL and Scopus. A random-effect meta-analysis was carried out on the number of steps and moderate-vigorous physical activity (MVPA). Univariable meta-regression models were computed to assess the possibility that the study characteristics may act as modifiers on the final meta-analysis estimate. RESULTS: In the analysis, 51 articles were included, with a total of 7488 participants. Twenty-two studies considered MVPA outcome alone, 16 studies considered the number of steps alone, and 13 studies reported information on both outcomes. The recommended PA threshold was reached for MVPA (36.35, 95% CI 29.39, 43.31) but not for daily steps (-1092.60, -1640.42 to -544.77). Studies on patients with fibromyalgia report a higher number (6290, 5198.65-7381.62) of daily steps compared with other RMDs. Patients affected by chronic inflammatory arthropathies seemed to fare better in terms of daily steps than the other categories. Patients of younger age reported a higher overall level of PA than elderly individuals for both the number of steps and MVPA. CONCLUSION: Physical activity can be lower than the recommended threshold in patients with RMDs when objectively measured using WD. WDs could be a useful and affordable instrument for daily monitoring physical activity in RMDs and may support an increase in activity levels. PROSPERO TRIAL REGISTRATION: CRD42021227681, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=227681.

Vascular/epithelial changes as late sequelae after recovery from SARS-COV-2 infection: an in-vivo comparative study.

AIMS: While there is partial evidence of lung lesions in patients suffering from long COVID there are substantial concerns about lung remodelling sequelae after COVID-19 pneumonia. The aim of the present retrospective comparative study was to ascertain morphological features in lung samples from patients undergoing tumour resection several months after SARS-CoV-2 infection. METHODS AND RESULTS: The severity of several lesions with a major focus on the vascular bed was analysed in 2 tumour-distant lung fragments of 41 cases: 21 SARS-CoV-2 (+) lung tumour (LT) patients and 20 SARS-CoV-2 (-) LT patients. A systematic evaluation of several lesions was carried out by combining their scores into a grade of I-III. Tissue SARS-CoV-2 genomic/subgenomic transcripts were also investigated. Morphological findings were compared with clinical, laboratory and radiological data. SARS-CoV-2 (+) LT patients with previous pneumonia showed more severe parenchymal and vascular lesions than those found in SARS-CoV-2 (+) LT patients without pneumonia and SARS-CoV-2 (-) LT patients, mainly when combined scores were used. SARS-CoV-2 viral transcripts were not detected in any sample. SARS-CoV-2 (+) LT patients with pneumonia showed a significantly higher radiological global injury score. No other associations were found between morphological lesions and clinical data. CONCLUSIONS: To our knowledge, this is the first study that, after a granular evaluation of tissue parameters, detected several changes in lungs from patients undergoing tumour resection after SARS-CoV-2 infection. These lesions, in particular vascular remodelling, could have an important impact overall on the future management of these frail patients.

Comprehensive bronchoalveolar lavage characterization in COVID-19 associated acute respiratory distress syndrome patients: a prospective cohort study.

COVID-19-related acute respiratory distress syndrome (CARDS) is associated with high mortality rates. We still have limited knowledge of the complex alterations developing in the lung microenvironment. The goal of the present study was to comprehensively analyze the cellular components, inflammatory signature, and respiratory pathogens in bronchoalveolar lavage (BAL) of CARDS patients (16) in comparison to those of other invasively mechanically ventilated patients (24). In CARDS patients, BAL analysis revealed: SARS-CoV-2 infection frequently associated with other respiratory pathogens, significantly higher neutrophil granulocyte percentage, remarkably low interferon-gamma expression, and high levels of interleukins (IL)-1ß and IL-9. The most important predictive variables for worse outcomes were age, IL-18 expression, and BAL neutrophilia. To the best of our knowledge, this is the first study that was able to identify, through a comprehensive analysis of BAL, several aspects relevant to the complex pathophysiology of CARDS.

Knowledge assessment among subjects with chronic venous leg ulcer in outpatient setting: Translation and adaptation of a tool to identify subjects at risk of poor understanding.

Promotion of self-care is an important issue in the treatment of chronic diseases such as venous leg ulcers, as adequate self-care can prevent complications and ulcer recurrence. However, only a few tools have been developed and tested to assess the knowledge of patients with venous leg ulcers. This study aimed to translate, adapt and validate in an Italian language and context a questionnaire to assess the knowledge of patients with venous leg ulcers about their disease (pathophysiology, risk factors, lifestyle changes due to ulcer) and the proper management of the ulcer to prevent recurrence. This is a cross-sectional study divided into two phases: (1) translation and cross-cultural adaptation of the 'Educational Interventions in Venous Leg Ulcer Patients' tool in a six-stage process and (2) validation and reliability study with patients with active ulceration. There was great agreement for the English-to-Italian translation. In content validation, the tool showed good applicability among experts. Adjustments were made to improve semantic equivalence, and the questionnaire was made to be easy and quick to administer. The results of the target population showed a low level of knowledge among the patients. Knowing the deficiencies of the patients makes it possible to create educational projects to improve their abilities. Now more than ever, it is necessary to improve self-care and patient knowledge, allowing home care, improving autonomy, and avoiding hospital care that results in higher costs and risks. This questionnaire could be used in future studies to identify topics that need to be reinforced through education and to improve the awareness and self-care of these patients.

Validated Prognostic Scores to Predict Outcomes in ECLS-Bridged Patients to Lung Transplantation.

Selection of patients who may benefit from extracorporeal life support (ECLS) as a bridge to lung transplant (LTx) is crucial. The aim was to assess if validated prognostic scores could help in selecting patients who may benefit from ECLS-bridging predicting their outcomes. Clinical data of patients successfully ECLS-bridged to LTx from 2009 to 2021 were collected from two European centers. For each patient, we calculated Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score III (SAPS III), Acute Physiology and Chronic Health Evaluation II (APACHE II), before placing ECLS support, and then correlated with outcome. Median values of SOFA, SAPS III, and APACHE II were 5 (IQR 3-9), 57 (IQR 47.5-65), and 21 (IQR 15-26). In-hospital, 30 and 90 days mortality were 21%, 14%, and 22%. SOFA, SAPS III, and APACHE II were analyzed as predictors of in-hospital, 30 and 90 days mortality (SOFA C-Index: 0.67, 0.78, 0.72; SAPS III C-index: 0.48, 0.45, 0.51; APACHE II C-Index: 0.49, 0.45, 0.52). For SOFA, the score with the best performance, a value ≥9 was identified to be the optimal cut-off for the prediction of the outcomes of interest. SOFA may be considered an adequate predictor in these patients, helping clinical decision-making. More specific and simplified scores for this population are necessary.

Laparoscopic right hemicolectomy with 2D or 3D video system technology: systematic review and meta-analysis.

BACKGROUND: Standard laparoscopic colorectal surgery relies on 2D image systems in most centers. However, 3D vision has gained popularity and is used nowadays in a constantly rising number of units. Right hemicolectomy with intracorporeal anastomosis and lymph node dissection represents a surgical procedure that may benefit the most from 3D vision. The aim of the study was to summarize the available literature on the use of 2D vs. 3D video imaging in patients undergoing laparoscopic right hemicolectomy. METHODS: A comprehensive literature review was conducted including Medline/PubMed, Embase, and Scopus (PROSPERO registration number CRD 42022344764) through October 2022. The systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The risk of bias was evaluated using the ROBINS-I tool. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines and GRADEpro to develop a summary of evidence tables. Random-effects meta-analyses were conducted. RESULTS: Five observational retrospective studies (496 patients, 275 2D and 216 3D) were included. One study was rated as having a critical risk of bias; the remaining had low to moderate risk. 2D laparoscopic right hemicolectomy patients showed longer anastomotic time in 3/3 studies (MD = 3.32; 95%CI, 1.58-5.05; p = 0.002) and an upward trend in operative time in 4/5 studies (MD = 9.98; 95%CI, -1.42, 21.37; p = 0.086) compared to 3D. The two image video systems had similar short-term outcomes, including the number of lymph nodes harvested (MD = -0.67; 95%CI, -2.47, 1.13; p = 0.47), morbidity (OR post-operative complications = 1.12; 95%CI, 0.71-1.77; p = 0.62), and length of stay (MD = 0.27; 95%CI, -0.59, 1.13; p = 0.9). CONCLUSIONS: 2D and 2D laparoscopic right hemicolectomy had similar complications rate, with a shorter anastomotic time along with a downward trend in overall operative time for 3D. Larger prospective randomized trials are awaited before definitive conclusions can be drawn.

Does 3D laparoscopic video technology affect long-term survival in right hemicolectomy for cancer compared to standard 2D? A propensity score study.

BACKGROUND: There are few studies focused on the short-term results of laparoscopic right hemicolectomy performed with 2D (two-dimension) or 3D (three-dimension) video technology and none on the oncologic effects. The aim of the study was to assess the long-term results of laparoscopic right hemicolectomy (LRH) with intracorporeal anastomosis using 3D or 2D video in patients with right colon cancer with at least three years of oncologic follow-up. METHODS: Data from patients undergoing laparoscopic right hemicolectomy (LRH) with intracorporeal anastomosis for cancer in an 11-year period (June 2008-June 2019) and ≥ 3 years of follow-up were prospectively collected. Surgical procedures were performed by two expert laparoscopic surgeons. RESULTS: 111 patients were included in the study: 56 (50.5%) in the 3D group and 55 (49.5%) in the 2D group. Tumor stage and number of lymph nodes harvested were similar. Overall and disease-free survival were not different in the two groups. Local recurrence occurred in none of the patients, and distant metachronous metastases were similar in the two groups. A propensity score weighting approach was used to account for potential confounding related to patients' nonrandom allocation to the 2 groups. The effects of the intervention on postoperative outcomes were assessed with a weighted regression approach. CONCLUSIONS: Laparoscopic 3D technology allows similar oncological results as 2D vision in LRH with intracorporeal anastomosis. Larger prospective randomized studies might confirm these results in the long-term follow-up.