Validation of the Italian version of the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire.

Objectives: The primary objective of this study was the translation and validation of the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire into Italian, denoted as AAV-PRO_ita. The secondary objective was to evaluate the impact of ANCA-associated vasculitis (AAV) on quality of life (QoL) and work impairment in a large cohort of Italian patients. Methods: The study design took a prospective cohort study approach. First, the AAV-PRO was translated into Italian following the step guidelines for translations. The new AAV-PRO_ita questionnaire covered three disease domains: organ-specific and systemic symptoms and signs; physical function; and social and emotional impact. Second, Italian-speaking AAV patients were recruited from 17 Italian centres belonging to the Italian Vasculitis Study Group. Participants completed the AAV-PRO_ita questionnaire at three time points. Participants were also requested to complete the work productivity and activity impairment: general health questionnaire. Results: A total of 276 AAV patients (56.5% women) completed the questionnaires. The AAV-PRO_ita questionnaire demonstrated a good internal consistency and test-retest reliability. Female AAV patients scored higher (i.e. worse) in all thee domains, especially in the social and emotional impact domain (P < 0.001). Patients on glucocorticoid therapy (n = 199) had higher scores in all domains, especially in the physical function domain (P < 0.001), compared with patients not on glucocorticoid therapy (n = 77). Furthermore, patients who had at least one relapse of disease (n = 114) had higher scores compared with those who had never had one (n = 161) in any domain (P < 0.05). Finally, nearly 30% of the patients reported work impairment. Conclusion: The AAV-PRO_ita questionnaire is a new 29-item, disease-specific patient-reported outcome measuring tool that can be used in AAV research in the Italian language. Sex, glucocorticoids and relapsing disease showed the greatest impact on QoL.

Efficacy of colchicine in addition to anakinra in patients with recurrent pericarditis.

AIM: Anakinra, an anti IL-1 agent targeting IL-1 alfa and beta, is available for the treatment of recurrent pericarditis in cases with corticosteroid dependence and colchicine resistance after failure of conventional therapies. However, it is unclear if the combination with colchicine, a non-specific inhibitor of the inflammasome targeting the same inflammatory pathway of IL-1, could provide additional benefit to prevent further recurrences. The aim of the present observational study is to assess whether the addition of colchicine on top of anakinra could prolong the time to first recurrence and prevent recurrences better than anakinra alone. METHODS: International, all-comers, multicentre, retrospective observational cohort study analysing all consecutive patients treated with anakinra for corticosteroid-dependent and colchicine-resistant recurrent pericarditis. The efficacy endpoint was recurrence rate and the time to the first recurrence. RESULTS: A total of 256 patients (mean age 45.0±15.4 years, 65.6% females, 80.9% with idiopathic/viral aetiology) were included. 64 (25.0%) were treated with anakinra as monotherapy while 192 (75.0%) with both anakinra and colchicine. After a follow-up of 12 months, 56 (21.9%) patients had recurrences. Patients treated with colchicine added to anakinra had a lower incidence of recurrences (respectively, 18.8% vs 31.3%; p=0.036) and a longer event-free survival (p=0.025). In multivariable analysis, colchicine use prevented recurrences (HR 0.52, 95% CI 0.29 to 0.91; p=0.021). CONCLUSIONS: The addition of colchicine on top of anakinra treatment could be helpful to reduce recurrences and prolong the recurrence-free survival.

Recipient hepatectomy technique may affect oncological outcomes of liver transplantation for hepatocellular carcinoma.

To date, caval sparing (CS) and total caval replacement (TCR) for recipient hepatectomy in liver transplantation (LT) have been compared only in terms of surgical morbidity. Nonetheless, the CS technique is inherently associated with an increased manipulation of the native liver and later exclusion of the venous outflow, which may increase the risk of intraoperative shedding of tumor cells when LT is performed for HCC. A multicenter, retrospective study was performed to assess the impact of recipient hepatectomy (CS vs. TCR) on the risk of posttransplant HCC recurrence among 16 European transplant centers that used either TCR or CS recipient hepatectomy as an elective protocol technique. Exclusion criteria comprised cases of non-center-protocol recipient hepatectomy technique, living-donor LT, HCC diagnosis suspected on preoperative imaging but not confirmed at the pathological examination of the explanted liver, HCC in close contact with the IVC, and previous liver resection for HCC. In 2420 patients, CS and TCR approaches were used in 1452 (60%) and 968 (40%) cases, respectively. Group adjustment with inverse probability weighting was performed for high-volume center, recipient age, alcohol abuse, viral hepatitis, Child-Pugh class C, Model for End-Stage Liver Disease score, cold ischemia time, clinical HCC stage within Milan criteria, pre-LT downstaging/bridging therapies, pre-LT alphafetoprotein serum levels, number and size of tumor nodules, microvascular invasion, and complete necrosis of all tumor nodules (matched cohort, TCR, n = 938; CS, n = 935). In a multivariate cause-specific hazard model, CS was associated with a higher risk of HCC recurrence (HR: 1.536, p = 0.007). In conclusion, TCR recipient hepatectomy, compared to the CS approach, may be associated with some protective effect against post-LT tumor recurrence.

COVID-19-induced neuropsychiatric symptoms can persist long after acute infection: a 2-year prospective study of biobehavioral risk factors and psychometric outcomes.

OBJECTIVES: To assess the prevalence of neuropsychiatric symptoms 2 years after the COVID-19 acute phase and to identify biobehavioral risk factors. METHODS: This 2-year prospective study assessed adult individuals with COVID-19 via face-to-face interview and laboratory testing at onset, and via telephone interview at 2-year follow-up. Data collected included COVID-19 severity and management at onset, as well as depression, anxiety, insomnia, cognitive failure, and fatigue at follow-up using standardized assessment tools. RESULTS: Out of 1,067 screened COVID-19 patients, 230 completed the 2-year follow-up (female, 53.5%; aged>40, 80.9%; native Italian, 94.9%; medical comorbidity, 53.5%; chronic medication, 46.3%; moderate to severe COVID-19, 24.9%; hospital admission, 28.7%; ICU, 5.2%). At follow-up, 9.1% had anxiety, 11.3% depression, 9.1% insomnia, 18.3% cognitive failure, and 39.1% fatigue, of clinical relevance. Headache (OR = 2.49, 95% CI = 1.01-6.16, p = 0.048), dyspnea (OR = 2.55, 95% CI = 1.03-6.31, p = 0.043), and number of symptoms (OR = 1.23, 95% CI = 1.01-1.51, p = 0.047) at onset were associated with anxiety at follow-up; dyspnea at onset was associated with depression at follow-up (OR = 2.80, 95% CI = 1.22-6.41, p = 0.015); number of comorbidities at onset was associated with insomnia at follow-up (OR = 1.48, 95% CI = 1.06-2.08, p = 0.022); female gender (OR = 2.39, 95% CI = 1.14-5.00, p = 0.020) and number of symptoms (OR = 1.20, 95% CI = 1.02-1.42, p = 0.026) at onset was associated with cognitive failure at follow-up; number of comorbidities (OR = 1.33, 95% CI = 1.03-1.73, p = 0.029) and symptoms (OR = 1.19, 95% CI = 1.04-1.37, p = 0.013) and raised interleukin 6 levels (OR = 4.02, 95% CI = 1.42-11.36, p = 0.009) at onset was associated with fatigue at follow-up. CONCLUSIONS: COVID-19 survivors, especially if female, with preexisting health problems, and with a more severe acute phase, may present with long-lasting neuropsychiatric sequalae, urging interventions to sustain recovery particularly in these higher risk individuals.

Efficacy and safety of colchicine for the treatment of myopericarditis.

OBJECTIVE: Clinical trials have evaluated the efficacy and safety of colchicine only in simple pericarditis, excluding cases of concomitant myocarditis. The aim of this paper is to evaluate the efficacy and safety of colchicine for the treatment of the first attack of acute pericarditis with concomitant myocardial involvement. METHODS: Double-centre retrospective cohort study analysing consecutive patients admitted for first attack of pericarditis with myocarditis and treated with or without colchicine. The primary efficacy end point was the time to the first recurrence. Propensity score matching was used to generate two groups of patients with similar baseline characteristics. Colchicine-associated side effects were analysed as safety end-point. RESULTS: A total of 175 patients (mean age 46.2±20.1 years, 25.1% females, 88.6% with idiopathic/viral aetiology) were included. Seventy-nine (45.1%) patients were treated with colchicine. After a median follow-up of 25.3 (IQR 8.3-45.6) months, 58 (33.1%) patients had recurrences. The propensity score generated two groups of 73 patients with similar baseline characteristics but the use of colchicine. Patients treated with colchicine had a lower incidence of recurrences (respectively, 19.2% vs 43.8%; p=0.001) and a longer event-free survival (p=0.005). In multivariable analysis, women (HR 1.97, 95% CI 1.04 to 3.73; p=0.037) and corticosteroid use (HR 2.27, 95% CI 1.15 to 4.47; p=0.018) were independent risk factors for recurrences. Colchicine-associated side effects were mild and occurred in 3 (1.7%) patients. CONCLUSION: In patients with first attack of pericarditis associated with myocardial involvement, colchicine was safe and efficacious for the reduction of recurrences.

Antibody response and risk of reinfection over 2 years among the patients with first wave of COVID-19.

OBJECTIVES: To describe the dynamics and factors related to natural and hybrid humoral response against the SARS-CoV-2 and risk of reinfection among first-wave patients. METHODS: A prospective longitudinal study with periodic serological follow-up after acute onset of all recovered patients with SARS-CoV-2 infection cared in Udine Hospital (March-May 2020). Nucleocapsid (N) protein and spike receptor-binding domain (S-RBD) antibody tests were used to distinguish natural and vaccine-induced response. RESULTS: Overall, 153 patients (66 men, mean age 56 years) were followed for a median of 27.3 (interquartile range 26.9-27.8) months. Seroreversion was 98.5% (95% CI: 96.8-99.4) for SARS-CoV-2-N IgM at 1 year and 57.4% (95% CI: 51.5-63.5) for SARS-CoV-2-N IgG at 2 years. Initial serological response (hazard ratio [HR]: 0.99, 95% CI: 0.99-0.99, p 0.002 for IgM and HR: 0.97, 95% CI: 0.97-0.98, p < 0.001 for IgG) and severity of acute infection (HR: 0.62, 95% CI: 0.39-0.96, p 0.033 for IgM and HR: 0.60, 95% CI: 0.37-0.99, p < 0.001 for IgG) were independently associated with persistent SARS-CoV-2-N IgM/IgG response. Older age and smoker status were associated with long-term SARS-CoV-2-N IgM and SARS-CoV-2-N IgG, respectively (HR: 0.75, 95% CI: 0.57-0.98, p 0.038; HR: 1.77, 95% CI: 1.19-2.61, p 0.004 respectively). All patients maintained SARS-CoV-2-S-RBD IgG response at 24-month follow-up. Reinfections occurred in 25 of 153 (16.3%) patients, mostly during the omicron circulation. Reinfection rates did not differ significantly between SARS-CoV-2-N IgG seronegative and seropositive patients (14/89, 15.7% vs. 10/62, 16.1%, p 0.947). Unvaccinated patients had higher risk of reinfection (4/7, 57.1% vs. vaccinated 21/146, 14.4%, p 0.014). DISCUSSION: First-wave patients had durable natural humoral immunity in 40% and anti-S-RBD response in 100% up to 2 years after infection. Natural humoral response alone was not protective against reinfections with omicron SARS-CoV-2 variants, whereas vaccination was effective to reduce the risk of a new infection.

Prediction of resting energy expenditure in Italian older adults with severe obesity.

Background: In the last decade a large number of studies proposed and/or validated equations to estimate the Resting Energy Expenditure (REE) in adults and/or older adults, however, no equation currently available showed good accuracy for older adults with severe obesity. Thus, this study aimed to develop and validate new predictive equations for REE, based on data from the indirect calorimetry, in Italian older adults with severe obesity. Methods: A retrospective study was as conducted with 764 Caucasian older adults with severe obesity (age range: 60-74 years and BMI ≥ 35 kg/m/²). Four models were used to test the accuracy of anthropometry and body composition variables in multivariable prediction of REE. All models were derived by stepwise multiple regression analysis using a calibration group of 382 subjects [295 females and 87 males] and the equations were cross-validated in the remaining 382 subjects [295 females and 87 males] as validation group. The new prediction equations and the other published equations were tested using the Bland-Altman method. Prediction accuracy was defined as the percentage of subjects whose REE was predicted within ± 10% of measured REE. Results: All the equations analyzed predicted higher energy requirements for males than females, and most of them underestimated the energy requirement values of our sample. The highest accuracy values were observed in the new equations, with 62% in the anthropometric model and 63% in the body composition model. Conclusion: Although the accuracy of our equations was slightly higher in comparison with the other taken into consideration, they cannot be considered completely satisfactory for predicting REE in Italians older adults with severe obesity. When predicting equations cannot guarantee precise or acceptable values of REE, the use of indirect calorimetry (if available) should be always recommended, especially in clinical practice.

Extracellular vesicle features are associated with COVID-19 severity.

COVID-19 is heterogeneous; therefore, it is crucial to identify early biomarkers for adverse outcomes. Extracellular vesicles (EV) are involved in the pathophysiology of COVID-19 and have both negative and positive effects. The objective of this study was to identify the potential role of EV in the prognostic stratification of COVID-19 patients. A total of 146 patients with severe or critical COVID-19 were enrolled. Demographic and comorbidity characteristics were collected, together with routine haematology, blood chemistry and lymphocyte subpopulation data. Flow cytometric characterization of the dimensional and antigenic properties of COVID-19 patients' plasma EVs was conducted. Elastic net logistic regression with cross-validation was employed to identify the best model for classifying critically ill patients. Features of smaller EVs (i.e. the fraction of EVs smaller than 200 nm expressing either cluster of differentiation [CD] 31, CD 140b or CD 42b), albuminemia and the percentage of monocytes expressing human leukocyte antigen DR (HLA-DR) were associated with a better outcome. Conversely, the proportion of larger EVs expressing N-cadherin, CD 34, CD 56, CD31 or CD 45, interleukin 6, red cell width distribution (RDW), N-terminal pro-brain natriuretic peptide (NT-proBNP), age, procalcitonin, Charlson Comorbidity Index and pro-adrenomedullin were associated with disease severity. Therefore, the simultaneous assessment of EV dimensions and their antigenic properties complements laboratory workup and helps in patient stratification.

Lessons learnt while designing and conducting a longitudinal study from the first Italian COVID-19 pandemic wave up to 3 years.

BACKGROUND: Several scientific contributions have summarized the "lessons learnt" during the coronavirus disease 2019 (COVID-19) pandemic, but only a few authors have discussed what we have learnt on how to design and conduct research during a pandemic. The main intent of this study was to summarize the lessons learnt by an Italian multidisciplinary research group that developed and conducted a longitudinal study on COVID-19 patients infected during the first wave in March 2020 and followed-up for 3 years. METHODS: A qualitative research approach embedded into the primary CORonavirus MOnitoRing study (CORMOR) study was developed, according to the the consolidated criteria for reporting qualitative research. Multiple data collection strategies were performed: each member was invited to report the main lessons learnt according to his/her perspective and experience from the study design throughout its conduction. The narratives collected were summarized and discussed in face-to-face rounds. The narratives were then thematically analysed according to their main topic in a list that was resent to all members to check the content and their organization. The list of the final "lessons learnt" has been agreed by all members, as described in a detailed fashion. RESULTS: Several lessons were learnt while designing and conducting a longitudinal study during the COVID-19 pandemic and summarised into ten main themes: some are methodological, while others concern how to conduct research in pandemics/epidemics/infectious disease emergencies. CONCLUSIONS: The multidisciplinary approach, which also included patients' perspective, helped us to protect the consistency and quality of the research provided in pandemic times. The lesson learnt suggest that our research approach may benefit from changes in education, clinical practice and policies.

Stem Cells mobilization and collection in allogeneic related and unrelated donors: a single center experience with focus on plerixafor.

INTRODUCTION: Poor CD34 + cells mobilization in allogeneic donors could affect transplant outcome. In a subgroup of patient mobilization with granulocyte colony-stimulating factor (G-CSF) alone is unsatisfactory, and Plerixafor could be used to enhance CD34 + cells release from bone marrow niche. MATERIALS AND METHODS: We conducted a retrospective single-center, cohort study on healthy allogeneic donors both related and unrelated, treated by Udine Transfusion Center over the last 10 years (2012-2022). In the 195 allogeneic donors treated we analyzed age, sex, body weight, BMI, comorbidities, G-CSF dosage and even baseline white blood cell count as possible predictor of insufficient CD34 + cells mobilization on day 5. In the subgroup of related donors we evaluated even baseline CD34 + cells (measured before mobilization start). Processed donor blood volume, collection efficiency and apheresis product were examined. Additionally a comparative analysis was conducted between G-CSF alone treated donors and poor mobilizing ones, in which Plerixafor was administered at a dose of 0.24 mg/kg as a pre-emptive or rescue agent. RESULTS: In 9 donors, due to poor mobilization (defined as CD34 + < 20/µL or estimated yield < 1 ×106 kg/recipient body weight), the use of plerixafor was necessary. PLX at a dose of 0.24 mg/kg was administered 5 h before collection, inducing an average increase of 5.1 (1.7-12.6) in CD34 + circulating cells. In this subgroup of patients, BMI and weight were significantly lower (p = 0.03). Interestingly, baseline CD34 + cells (measured before the onset of mobilization) also seems to predict poor mobilization (p = 0.003). In donors additionally treated with Plerixafor compared to those who received G-CSF alone, collection efficiency was higher (p = 0.02) and CD34 + cells collected were comparable (p = 0.2). Side effects related to the administration of plerixafor, if they occurred, were well tolerated. CONCLUSIONS: Plerixafor is a safe and effective drug in the rescue and prevention of poor mobilization. New prospective studies on allogeneic donors should be performed to increase the treatable population to avoid inadequate collection and mobilization. New laboratory predictors such as baseline CD34 + cells should be investigated in larger cohorts and then used as early screening.

Quality of life 1 year after hospital discharge in unvaccinated pregnant women with COVID-19 respiratory symptoms: a prospective observational study (ODISSEA-PINK study).

Introduction: Little is known about Quality of Life within the first court of unvaccinated COVID-19 pregnant women exposed to the pandemic stressor. Primary aim of this study was to evaluate 1 year after hospital discharge HRQoL in a cohort of COVID-19 unvaccinated pregnant patients with COVID-19. Methods: in this prospective observational study, all COVID-19 positive pregnant women at any gestational age, admitted to the Obstetric Department at the University Hospital of Udine, Italy, from 1 March 2020 to 1 March 2021, requiring or not oxygen supplementation due to SARS-CoV2 pneumonia were evaluated. Patients with a history of neurological or psychiatric disease, those with a previous abortion, and those who refused to provide written informed consent were excluded from the study. We investigated pregnant positive COVID-19 women Health-related quality of life (HRQoL) with the Short-Form Health Survey-36 (SF-36) and Post-traumatic Stress-Disorder (PTSD) with the Impact of Event Scale-Revised (IES-R). Results: 62 pregnant women respected the inclusion criteria of the study, and data from 33 patients were analyzed. The mean age was 32 ± 6 years, with a median gestational age of 38 weeks [IQR 34-40]. 15.2% of patients required oxygen therapy through noninvasive respiratory support (with high flow nasal cannula) for a median of 9 days [IQR 6-12]. The median Physical Component Summary (PCS) and Mental Component Summary (MCS) scores were 50.2 [IQR 46.7-53.7] and 56.0 [IQR 46.8-60.6] respectively. Ten patients out of 33 (30%) tested positive for PTSD. Maternal age, gestational age, and history of cardiac-pulmonary-kidney disease significantly affected HRQoL at multivariable analysis. Discussion: In COVID-19 pregnant unvaccinated women some physical impairments reducing HRQoL are still present 1 year after hospital discharge. Previous medical history such as history of cardiac-pulmonary-kidney disease significantly affected HRQoL. Long and repeated follow-up should be pursued in this category of patients.Clinical trial registration:ClinicalTrials.gov, Identifier NCT04860687.

Influence of a regional network combined with a systematic multidisciplinary approach on the outcomes of patients with acute type A aortic dissection.

BACKGROUND: Whether in patients with acute type A aortic dissection reduction of intervals between onset of symptoms and diagnosis influences patient outcomes is still not completely defined. METHODS: In 199 patients with acute type A aortic dissection, the efficacy of a systematic multidisciplinary approach and institution of a regional network were evaluated; 90 patients operated before 2016 (Group1) were compared with 109 repaired after 2016 (Group2) for early and late outcomes. RESULTS: Mortality was reduced from 13% in Group1 to 4% in Group2 (p = 0.013). In Group2 a more patients (46%) had arch replacement compared to Group1 (29%)(p = 0.06). In Group2 axillary artery cannulation was almost routinely used (91% vs 67%, p < 0.001) with shorter circulatory arrest time (37 vs 44 min, p < 0.001). The interval from diagnosis to surgery dropped from 210 min in Group1 to 160 min in Group2 (p < 0.001); this reduction was evident both in patients admitted to the emergency department of a spoke and/or a hub center. Patients presenting with or developing shock were reduced from Group1 to Group2 and in particular those reaching the hub center from spoke centers. Survival at 1 and 5 years was 82 ± 4% and 70 ± 5% in Group1 vs 92 ± 3% and 87 ± 8% in Group2 (p = 0.007). CONCLUSIONS: Outcomes of patients with acute type A aortic dissection improved using a systematic multidisciplinary approach while a network between spoke and hub centers reduced intervals between diagnosis, transportation to hub center and repair, limiting the incidence of tamponade and shock.

Meningioma-Related Epilepsy: A Happy Ending?

(1) Background: More than one-third of patients with meningiomas experience at least one seizure during the course of their disease, and in the 20-50% of cases, seizure represents the onset symptom. After surgery, up to 30% of patients continue to have seizures, while others may experience them later; (2) Methods: The study analyzed retrospectively the risk factors for pre-operative seizures in a large cohort of 358 patients who underwent surgery for newly diagnosed brain meningioma; (3) Results: We identified age, peritumor edema, and location as risk factors for seizure at the onset. Patients with seizures differed from patients without seizures for the following characteristics: younger average age, lower pre-operative Karnofsky Performance Status (KPS), location on the convexity, lower Simpson Grade, lower incidence of pre-operative neurological deficits, and higher incidence of pre-operative peritumor edema. After 24 months, 88.2% of patients were classified as Engel class Ia, and no correlation with disease progression was observed; (4) Conclusions: Meningioma-related epilepsy has generally a positive outcome following surgery and it seems not to be linked to disease progression, even if further studies are needed.

COVID-19 Survivors Are Still in Need of Neuropsychiatric Support Two Years after Infection.

COVID-19 survivors have been reported to be at risk of long-term neuropsychiatric sequalae; however, prospective evidence in this regard is lacking. We prospectively assessed the occurrence of mental-health-domain-related symptoms over a 24-month period following COVID-19 onset in a cohort of 230 patients. Of them, 36.1% were still presenting with at least one symptom 24 months later. Across the study period, a significant reduction in overall symptoms from the onset was observed (p < 0.001); however, symptom prevalence was unchanged between the 12- and 24-month follow-ups across most symptomatic domains. At the 24-month follow-up, mental-health-domain-related symptoms only were higher than at the onset and were the most frequently reported symptoms. Dyspnea at the onset predicted both symptoms of psychiatric disorders (OR = 3.26, 95% CI = 1.22-8.70, and p = 0.019) and a lack of concentration and focus (OR = 3.17, 95% CI = 1.40-7.16, and p = 0.005) 24 months post-infection, with the number of comorbidities at the onset also predicting the occurrence of a lack of concentration and focus (OR = 1.52, 95% CI = 1.12-2.08, and p = 0.008). The findings of this study may have important public health implications, as they underlie the fact that COVID-19 survivors are still in need of neuropsychiatric support two years after infection.

Post-COVID-19 Syndrome 2 Years After the First Wave: The Role of Humoral Response, Vaccination and Reinfection.

Background: The aim of this study was to describe the long-term evolution of post-COVID-19 syndrome over 2 years after the onset of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) in survivors of the first wave. Methods: This prospective study was based on interviews and investigated post-COVID-19 syndrome 6, 12, and 24 months after the disease onset in all adult in- and outpatients with COVID-19 followed at Udine Hospital (Italy) during the first wave (March-May 2020). Humoral response, vaccination status, and reinfection were assessed. Results: Overall, 230 patients (53.5% female; mean age 54.7 years) were interviewed 2.3 years (standard deviation = 0.11) after acute onset. Post-COVID-19 syndrome was observed in 36.1% of patients (n = 83) at 2 years. The most common persistent symptoms were fatigue (14.4%), rheumatological (14.4%), and psychiatric symptoms (9.6%). Overall, 55.4% (46 of 83) of long haulers searched for healthcare system support and 21 (45.7%) were visited by a specialist. Female gender (odds ratio [OR] = 2.50, P = .005), a proportional increase in the number of symptoms during acute COVID-19 (OR = 1.40, P = .001), and the presence of comorbidities (OR = 1.57, P = .004) were all independent risk factors for post-COVID-19 syndrome. Vaccination and reinfection had no impact on post-COVID-19 syndrome dynamics. The presence of receptor-binding domain (RBD) SARS-CoV-2 immunoglobulin G (IgG) and non-RBD SARS-CoV-2 IgG titers were not associated with the occurrence of post-COVID-19 syndrome. Conclusions: Two years after COVID-19, the burden of persistent symptoms remains high among in- and outpatients' population infected during the first wave. Post-COVID-19 dynamic does not seem to be influenced by SARS-CoV-2 immunization status and reinfection.

Barotrauma during Noninvasive Respiratory Support in COVID-19 Pneumonia Outside ICU: The Ancillary COVIMIX-2 Study.

BACKGROUND: Noninvasive respiratory support (NIRS) has been extensively used during the COVID-19 surge for patients with acute respiratory failure. However, little data are available about barotrauma during NIRS in patients treated outside the intensive care unit (ICU) setting. METHODS: COVIMIX-2 was an ancillary analysis of the previous COVIMIX study, a large multicenter observational work investigating the frequencies of barotrauma (i.e., pneumothorax and pneumomediastinum) in adult patients with COVID-19 interstitial pneumonia. Only patients treated with NIRS outside the ICU were considered. Baseline characteristics, clinical and radiological disease severity, type of ventilatory support used, blood tests and mortality were recorded. RESULTS: In all, 179 patients were included, 60 of them with barotrauma. They were older and had lower BMI than controls (p < 0.001 and p = 0.045, respectively). Cases had higher respiratory rates and lower PaO2/FiO2 (p = 0.009 and p < 0.001). The frequency of barotrauma was 0.3% [0.1-1.3%], with older age being a risk factor for barotrauma (OR 1.06, p = 0.015). Alveolar-arterial gradient (A-a) DO2 was protective against barotrauma (OR 0.92 [0.87-0.99], p = 0.026). Barotrauma required active treatment, with drainage, in only a minority of cases. The type of NIRS was not explicitly related to the development of barotrauma. Still, an escalation of respiratory support from conventional oxygen therapy, high flow nasal cannula to noninvasive respiratory mask was predictive for in-hospital death (OR 15.51, p = 0.001). CONCLUSIONS: COVIMIX-2 showed a low frequency for barotrauma, around 0.3%. The type of NIRS used seems not to increase this risk. Patients with barotrauma were older, with more severe systemic disease, and showed increased mortality.

Multivariable stratification of PI-RADS version 2.1 categories for the risk of false-positive target biopsy: Impact on prostate biopsy decisions.

PURPOSE: To identify clinical and multiparametric magnetic resonance imaging (mpMRI) factors predicting false positive target biopsy (FP-TB) of prostate imaging reporting and data system version 2.1 (PI-RADSv2.1) ≥ 3 findings. METHOD: We retrospectively included 221 men with and without previous negative prostate biopsy who underwent 3.0 T/1.5 T mpMRI for suspicious clinically significant prostate cancer (csPCa) between April 2019-July 2021. A study coordinator revised mpMRI reports provided by one of two radiologists (experience of > 1500/>500 mpMRI examinations, respectively) and matched them with the results of transperineal systematic biopsy plus fusion target biopsy (TB) of PI-RADSv2.1 ≥ 3 lesions or PI-RADSv2.1 ≤ 2 men with higher clinical risk. A multivariable model was built to identify features predicting FP-TB of index lesions, defined as the absence of csPCa (International Society of Urogenital Pathology [ISUP] ≥ 2). The model was internally validated with the bootstrap technique, receiving operating characteristics (ROC) analysis, and decision analysis. RESULTS: Features significantly associated with FP-TB were age < 65 years (odds ratio [OR] 2.77), prostate-specific antigen density (PSAD) < 0.15 ng/mL/mL (OR 2.45), PI-RADS 4/5 category vs. category 3 (OR 0.15/0.07), and multifocality (OR 0.46), with a 0.815 area under the curve (AUC) in assessing FP-TB. When adjusting PI-RADSv2.1 categorization for the model, mpMRI showed 87.5% sensitivity and 79.9% specificity for csPCa, with a greater net benefit in triggering biopsy compared to unadjusted categorization or adjustment for PSAD only at decision analysis, from threshold probability ≥ 15%. CONCLUSION: Adjusting PI-RADSv2.1 categories for a multivariable risk of FP-TB is potentially more effective in triggering TB of index lesions than unadjusted PI-RADS categorization or adjustment for PSAD alone.

Grounded in reality: artificial intelligence in medical education.

Background: In a recent survey, medical students expressed eagerness to acquire competencies in the use of artificial intelligence (AI) in medicine. It is time that undergraduate medical education takes the lead in helping students develop these competencies. We propose a solution that integrates competency-driven AI instruction in medical school curriculum. Methods: We applied constructivist and backwards design principles to design online learning assignments simulating the real-world work done in the healthcare industry. Our innovative approach assumed no technical background for students, yet addressed the need for training clinicians to be ready to practice in the new digital patient care environment. This modular 4-week AI course was implemented in 2019, integrating AI with evidence-based medicine, pathology, pharmacology, tele-monitoring, quality improvement, value-based care, and patient safety. Results: This educational innovation was tested in 2 cohorts of fourth year medical students who demonstrated an improvement in knowledge with an average quiz score of 97% and in skills with an average application assignment score of 89%. Weekly reflections revealed how students learned to transition from theory to practice of AI and how these concepts might apply to their upcoming residency training programs and future medical practice. Conclusions: We present an innovative product that achieves the objective of competency-based education of students regarding the role of AI in medicine. This course can be integrated in the preclinical years with a focus on foundational knowledge, vocabulary, and concepts, and in clinical years with a focus on application of core knowledge to real-world scenarios.

Evaluation of Kinesio Taping for Edema, Ecchymosis, and Pain After Liposuction: A Prospective Pilot Study.

BACKGROUND: Liposuction is a safe, simple, and effective method of body contouring. Pain, ecchymosis, and edema are often local complications at the removal site, especially in the first weeks after surgery. Several studies have shown that kinesiology (kinesio) taping improves blood and lymphatic flow, removing congestions of lymphatic fluid and alleviating hemorrhage. However, there are limited data on the effect of kinesio taping in mitigating local complications at fat grafting donor sites. OBJECTIVES: The aim of this pilot study was to evaluate the impact of kinesio taping in reducing postoperative edema, pain, and ecchymosis in the liposuction area. METHODS: Over a period of 18 months (January 2021-June 2022), 52 patients underwent liposuction of both flanks with subsequent breast fat grafting. Immediately after the surgery, kinesio taping was used on the right abdomen flank in all patients. Degree of edema as well as ecchymosis and pain were quantified at 7, 14, and 21 days after surgery. RESULTS: There were statistically significant differences in the taping area for ecchymosis at 7 days after surgery, edema at 14 and 21 days after surgery, and in pain, rated on a visual analog scale, at 7, 14 and 21 days after surgery. CONCLUSIONS: Kinesio taping, as used in this study, is beneficial in the reduction of edema and pain and the resolution of ecchymosis after liposuction.

Cardiometabolic Index (CMI) and Visceral Adiposity Index (VAI) Highlight a Higher Risk of Metabolic Syndrome in Women with Severe Obesity.

Recent evidence shows that simple and inexpensive anthropometric measurements can be used to identify, at an early stage, women with obesity at increased risk of developing metabolic syndrome (MetS). Thus, the aim of this study was to compare the accuracy of five different indexes of adiposity and/or body composition in identifying MetS in a group of 876 women (mean age ± SD: 52.1 ± 13.8 years; body mass index (BMI): 43.6 ± 6.1 kg m-2). The following indexes were determined for each subject: waist-to-hip ratio (WHR), waist-to-height ratio (WtHR), body mass fat index (BMFI), visceral adiposity index (VAI), and cardiometabolic index (CMI). Overall, the presence of MetS was detected in 544 patients (62%). Pearson correlation coefficients were calculated to evaluate the relationships between body composition indexes and metabolic characteristics of the women. Receiver operating characteristic (ROC) analysis was used to determine the best predictor for each adiposity index among metabolic risk factors. The ROC analysis showed VAI (AUC = 0.84) and CMI (AUC = 0.86) showed the best performance in predicting MetS. Differences were found between the ROC area of CMI and VAI with all other indexes (p < 0.05). The optimal cutoff point for early diagnosis of MetS was >0.92 for WHR, >0.76 for WtHR, >30.1 kg m-1 for BMFI, >1.94 for VAI, and >0.84 for CMI. In addition, VAI and CMI were the most sensitive and specific indexes compared with other indexes. In conclusion, VAI and CMI represent the most useful and reliable indexes to be used for detecting MetS in women suffering from obesity in clinical practice.