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Transjugular intrahepatic portosystemic shunt (TIPS) has been demonstrated to be feasible in older adult patients (age ≥70 years), yet the selection criteria remain suboptimal. Sarcopenia, highly prevalent in elderly population, may be significantly associated with post-TIPS outcome. This study aimed at evaluating the impact of baseline sarcopenia on post-TIPS survival in older adults with cirrhosis. A retrospective analysis of the prospective Italian TIPS-Registry was conducted to identify patients ≥70 years who received TIPS from June 2015 to March 2023. The availability of baseline abdominal CT scan was a mandatory inclusion criterion. Skeletal muscle index (SMI) was evaluated at the L3-L4 level. Sarcopenia was defined as SMI <50 cm2/m2 for men and <39 cm2/m2 for women. Probability of liver-related death was evaluated by competing risks analysis. A prediction model for liver-related mortality was created. One-hundred and fifteen patients were included: median age 74 years (IQR 3.1), 62% male, median dry-BMI 25.7 (IQR 4.7), 60% prevalence of sarcopenia. The main etiologies were viral (40%), alcohol-associated cirrhosis (23%), and metabolic dysfunction-associated steatohepatitis (20%). Refractory ascites (57%) was the main indications for TIPS. During a mean follow up of 20 months (IQR 20), 40 (34.8%) patients died for liver-related causes and 16 (13.9%) for extrahepatic causes. Liver-related mortality was significantly higher in patients with sarcopenia than in those without (6-months: 25.0% vs. 2.2%; 1-year: 43.0% vs. 4.8%, respectively; p value <0.001). A predictive model including INR, creatinine, and sarcopenia was developed to estimate liver-related mortality. The model achieved good predictive performances with AUCs of 0.826, 0.788, and 0.712 at 6-month, 1-year, and 2-years, respectively. Due to its significant impact on survival, the evaluation of sarcopenia may improve the selection of older adults candidate to TIPS. The new predictive model for post-TIPS liver-related mortality deserves external validation. [ABSTRACT FROM AUTHOR]

Background. Childbirth education classes are antenatal support services offered to pregnant women or to the couple, aimed at increasing their knowledge regarding pregnancy, labour, delivery, breastfeeding, parenthood and newborn care. Objective. The aim was to evaluate the effectiveness of Birthing Classes through the analysis of the occurrence of C-section, epidural analgesia, behavior during labor and delivery of the women who participated to the course as compared to those who did not attend it. Moreover, the level of satisfaction of pregnant women who attended the course was measured with a questionnaire of 20 items handed out after the delivery. Methods. To measure the satisfaction level of pregnant women, in the period from February 2017 to October 2017, a questionnaire of 20 items was used. In order to analyze the results of the births the medical records were consulted. Results. In the period of time going from February 2017 to October 2017 there were 147 women who have delivered and who have filled in the questionnaire. According to the multivariable analysis, there were no differences in the frequency of C-sections between the two groups (OR=0.8, 95%CI=0.3-1.7, p=0.503), whereas the frequency of epidural analgesia was lower in women who attended the Birthing Class (OR=0.3, 95%CI=0.1-0.9, p=0.036). We also observed that women who attended the Birthing Class: 1) had a higher likelihood of using breathing techniques during the labor (OR=5.5, 95%CI=1.5-20.0, p=0.009); 2) had a higher likelihood of taking advantage of the visualization exercises during the labor (OR=2.5, 95%CI=1.1-6.0, p=0.039). There was no other relevant difference between the two groups. Discussion. The benefits of perinatal education are difficult to evaluate systematically, and further research would be required to determine real effects and agree upon reliable indicators of effectiveness. Conclusion. This study identified several positive factors that confirm the results of other studies indicating that antenatal classes are effective for women giving birth for the first time/nulliparous women, based on an analysis of childbirth outcomes, in order to improve maternal and neonatal health. [ABSTRACT FROM AUTHOR]

Background: The long-term effects of COVID-19, which can vary significantly in type and timing, are considered relevant and impacting on the well-being of individuals. The present study aims to assess the incidence of outpatient care in the post-acute phase of SARS-CoV-2 infection in two Italian regions., Methods: The study has a multicentre, population-based, pre-post, repeated measures design to compare the incidence rate of access to outpatient visits and diagnostics before and after SARS-CoV-2 infection, considering a follow-up of 24 months. The study made use of previously recorded large-scale healthcare data available in the administrative databases of the Emilia-Romagna (E-R) and Veneto regions. Analyses were carried out separately in the two regions and results were pooled using random effects meta-analysis., Results: There were 27,140 subjects in E-R and 22,876 in Veneto who were included in the analysis. The pooled outputs showed an increase in rates of outpatient visits and diagnostics starting from month 2 after SARS-CoV-2 infection (IRR = 1.68, 95% CI = 1.56-1.81) with a peak at month 4 (IRR = 2.05, 95% CI = 1.95-2.15); the increase continued with reduced intensity up to month 15. Stratified analysis revealed that subjects with severe acute COVID-19 had a higher increase in rates (up to IRR = 3.96, 95% CI = 2.89-5.44), as well as patients with no comorbidities (up to IRR = 2.71, 95% CI = 2.60-2.83)., Conclusion: Long-term effects of COVID-19 include an increase in the healthcare burden especially in the first months after the acute infection. The increased demand for resources can last up to two years after infection in particular subgroups of patients such as subjects admitted to hospital during the acute phase due to the severe presentation of the disease., Competing Interests: Declarations. Ethics approval and consent to participate: This study involving human participants was reviewed and approved by Comitato Etico Area Vasta Emilia Nord (on 8-th February 2022), Comitato Etico Area Vasta Emilia Centro (on 19-th January 2022), and Comitato Etico della Romagna (on 18-th February 2022) for the E-R cohort, and by Comitato Etico per la Sperimentazione Clinica delle Province di Verona e Rovigo (on 21-st July 2021) for the Veneto Cohort. Written informed consent was not provided because this study was considered an exemption to Art. 14 of the General Data Protection Regulation (GDPR), due to the disproportionate effort to provide the information to data subjects about the existence of the study processing operation and that personal (health) data were processed for scientific purposes. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Introduction: T regulatory cells (Tregs) inversely correlate with disease progression in Amyotrophic Lateral Sclerosis (ALS) and fast-progressing ALS patients have been reported to exhibit dysfunctional, as well as reduced, levels of Tregs. This study aimed to evaluate the longitudinal changes in Tregs among ALS patients, considering potential clinical and biological modifiers of their percentages and concentrations. Additionally, we explored whether measures of ALS progression, such as the decline over time in the revised ALS Functional Rating Scale (ALSFRS-r) or forced vital capacity (FVC) correlated Treg levels and whether Treg phenotype varied during the course of ALS., Methods: Total Tregs (detected by CD3, CD4, FoxP3, CD25, and CD127) were quantified at five time points over 54 weeks in 21 patients in the placebo arm of the RAP-ALS trial; next they were characterized for the expression of surface markers including CD38, CD39, CXCR3, and PD1. Repeated measures mixed models were used to analyze the longitudinal course of Tregs, considering potential associations with other clinical and laboratory characteristics. Correlations between ALSFRS-r or FVC and Tregs over time were similarly investigated., Results: Our study showed that Treg levels did not change significantly on average during the observation period in our ALS cohort. However, PD1+Tregs decreased and CD39+Tregs increased over time. Male sex and cholesterol levels were associated with increasing Tregs (%) over time, while monocytes positively affected Treg concentrations. Treg concentrations showed a modesty association with FVC decline but were not associated with ALSFRS-r decline., Discussion: Treg levels remained stable during the ALS observation period and were not significantly associated with ALSFRS-r variations, suggesting that Treg numbers alone may have limited utility as a pharmaco-dynamic biomarker for ALS trials. However the observed changes in Treg phenotypes, such as the decrease in PD1+Tregs, indicate that phenotypic variations may warrant further investigation for their potential role in ALS progression and therapeutic targeting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Zucchi, Banchelli, Simonini, De Biasi, Martinelli, Gianferrari, Lo Tartaro, Cossarizza, D’Amico and Mandrioli.)

Cancer stem cells (CSCs) may be dedifferentiated somatic cells following oncogenic processes, representing a subpopulation of cells able to promote tumor growth with their capacities for proliferation and self-renewal, inducing lineage heterogeneity, which may be a main cause of resistance to therapies. It has been shown that the "less differentiated process" may have an impact on tumor plasticity, particularly when non-CSCs may dedifferentiate and become CSC-like. Bidirectional interconversion between CSCs and non-CSCs has been reported in other solid tumors, where the inflammatory stroma promotes cell reprogramming by enhancing Wnt signaling through nuclear factor kappa B activation in association with intracellular signaling, which may induce cells' pluripotency, the oncogenic transformation can be considered another important aspect in the acquisition of "new" development programs with oncogenic features. During cell reprogramming, mutations represent an initial step toward dedifferentiation, in which tumor cells switch from a partially or terminally differentiated stage to a less differentiated stage that is mainly manifested by re-entry into the cell cycle, acquisition of a stem cell-like phenotype, and expression of stem cell markers. This phenomenon typically shows up as a change in the form, function, and pattern of gene and protein expression, and more specifically, in CSCs. This review would highlight the main epigenetic alterations, major signaling pathways and driver mutations in which CSCs, in tumors and specifically, in lung cancer, could be involved, acting as key elements in the differentiation/dedifferentiation process. This would highlight the main molecular mechanisms which need to be considered for more tailored therapies., Competing Interests: Conflict of interest The authors declare that have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Individuals with rare skeletal disorders like Multiple Osteochondromas and Ollier Disease often experience physical and psychological burdens. Adventure therapy, with activities like sailing in outdoor settings, promotes personal growth and psychological well-being, potentially improving health-related quality of life (HRQoL). This study aimed to evaluate the impact of a sailing program on health-related quality of life and participant satisfaction in individuals with Multiple Osteochondromas and Ollier Disease. A quasi-experimental one-group pre-post design was employed, with HRQoL assessed using the EQ-5D® instrument and participant satisfaction measured via a feedback survey. Data were collected before and after the five-day sailing program conducted in the Mediterranean Sea in 2022 and 2023, involving participants diagnosed with Multiple Osteochondromas and Ollier Disease. Statistical analyses were performed using the Wilcoxon signed-rank test and McNemar's test for paired data. A significance level of p < 0.05 and p < 0.10 was considered. A total of 25 participants, predominantly male (52%), with a median age of 16 years (ranking from 11 to 31), were included in the study. The sailing program had mixed impact on HRQoL. Specifically, individuals who were female (p = 0.03), aged 16 and older (p = 0.04), with higher educational attainment (p = 0.10) or stronger self-management (p = 0.09), resilience (p = 0.01) and self-engagement (p = 0.09) skills experienced enhanced HRQoL. Conversely, other participants exhibited an increase in self-care difficulties (p = 0.02) and a trend towards worsening pain/discomfort (p = 0.38). Overall satisfaction with the program was high, with 90% of participants expressing satisfaction.This is the first study which examined HRQoL in Multiple Osteochondromas and Ollier Disease patients within an outdoor adventure therapy setting. Findings suggest that adventure therapy, integrated into healthcare strategies, may offer a valuable complement to conventional treatments for rare skeletal disorders. Future research, including randomized controlled trials, are necessary to confirm these results and develop robust interventions for improving the well-being in this population., (© 2024. The Author(s).)

Pancreatic ductal adenocarcinoma (PDAC) still has a poor response to therapies, partly due to their cancer-associated fibroblasts (CAFs). Here, we investigate the synergistic impact of a combinatory approach between a known chemotherapy agent, such as gemcitabine (GEM), and gene-modified human mesenchymal stromal/stem cells (MSCs) secreting the pro-apoptotic soluble (s)TRAIL (sTRAIL MSCs) on both PDAC cells and CAFs. The combo significantly impacts on PDAC survival in 2D and 3D models. In orthotopic xenograft models, GEM and sTRAIL MSCs induce tumor architecture shredding with a reduction of CK7- and CK8/18-positive cancer cells and the abrogation of spleen metastases. A cytotoxic effect on primary human CAFs is also observed along with an alteration of their transcriptome and a reduction of the related desmoplasia. Collectively, we demonstrate a promising therapeutic profile of combining GEM and sTRAIL MSCs to target both tumoral and stromal compartments in PDAC., Competing Interests: Declaration of interests M. Dominici and G.G. hold patents in the field of cell and gene therapy. EIR Biotherapies srl holds patents related to the presented technologies. M. Dall’Ora and O.C. are employees of EVOTEC Modena Srl., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Although early palliative care (EPC) is beneficial in acute myeloid leukaemia, little is known about EPC value in multiple myeloma (MM). We compared quality indicators for palliative and end-of-life (EOL) care in patients with MM receiving EPC with those of patients who received usual haematological care (UHC)., Methods: This observational, retrospective study was based on 290 consecutive patients with MM. The following indicators were abstracted: providing psychological support, assessing/managing pain, discussing goals of care, promoting advance care plan, accessing home care services; no anti-MM treatment within 14 and 30 days and hospice length of stay >7 days before death; no cardiopulmonary resuscitation, no intubation, <2 hospitalisations and emergency department visits within 30 days before death. Comparisons were performed using unadjusted and confounder-adjusted regression models., Results: 55 patients received EPC and 231 UHC. Compared with UHC patients, EPC patients had a significantly higher number of quality indicators of care (mean 2.62±1.25 vs 1.12±0.95; p<0.0001)); a significant reduction of pain intensity over time (p<0.01) and a trend towards reduced aggressiveness at EOL, with the same survival (5.3 vs 5.46 years; p=0.74))., Conclusions: Our data support the value of integrating EPC into MM routine practice and lay the groundwork for future prospective comparative studies., Competing Interests: Competing interests: FF: advisory boards for Jannsen and Novartis and travel grants from Jazz Pharmaceuticals outside the submitted work. RM: honoraria from AbbVie, Roche, Janssen, and Shire, outside the submitted work. FE: consultancy for Abbvie, Amgen, Janssen, Orsenix, Takeda, and grants from Amgen (to his Institution), outside the submitted work. EB: grants from Helsinn Healthcare, outside of the submitted work. ML: advisory board Abbvie, Novartis, Gilead science, Jazz Pharmaceuticals, Sanofi, MSD, Daiichi-Sankyo, Travel grant Gilead science., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: In the early stages of the COVID-19 pandemic, preliminary results that later proved to be incorrect suggested the possible efficacy of anti-infective drugs such as azithromycin for the treatment of SARS-CoV-2 infection. These preliminary data may have influenced the prescription of azithromycin. However, no individual-level data linking the use of this antibiotic to acute SARS-CoV-2 infection are available. The present analysis aims to fill this gap., Methods: A retrospective population-based cohort design was used including patients diagnosed with SARS-CoV-2 infection in the period ranging from February 2020 to February 2022. The data source for antibiotic consumption was the drug database of outpatient prescriptions of Emilia-Romagna Region (Italy). Antibiotics were classified according to the Anatomical Therapeutic Chemical (ATC) classification system. Consumption rates and percentages of azithromycin DDDs (defined daily doses) during the acute phase of the infection were compared with a previous control period and with the post-acute phase. Analyses were stratified by four groups according to the prevalent virus variant at time of diagnosis., Results: Comparing the previous control period with the acute phase of infections, the rates of azithromycin consumption (DDD per 1000 individuals per day) increased from 1.17 to 23.11, from 0.80 to 33.03, from 0.81 to 21.01, and from 1.02 to 9.76, in the pre-Alpha, Alpha, Delta, and Omicron periods, respectively. Similarly, the percentages of individuals receiving azithromycin, and the azithromycin DDDs percentages over total systemic antibiotics DDDs increased in acute phases of infection compared with control periods. The consumption rates and percentages returned to preinfection levels in the post-acute phase. In the study period, 12.9% of the use of azithromycin in the entire adult population of Emilia-Romagna was attributable to acute SARS-CoV-2 infection., Conclusions: Considering the low likelihood of bacterial coinfections, the increased azithromycin consumption in the acute phase of SARS-CoV-2 infection suggests inappropriate prescribing of this antibiotic., (© 2024 The Author(s). Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Introduction: The effectiveness of early interventions in young autistic children is well established, but there is great interindividual variability in treatment response. Predictors of response to naturalistic developmental behavioral interventions (NDBI), like the Early Start Denver Model (ESDM), are needed., Methods: We conducted an exploratory study to prospectively seek predictors of response in 32 young children treated with ESDM after receiving an ASD diagnosis. All children were less than 39 months old (mean age: 29.7 mo), and received individualized ESDM for nine months. Tests were administered at the beginning, after 4 months, and at the end of treatment., Results: Four children (12.5%) were "strong responders", 8 children (25.0%) were "moderate responders", and 20 children (62.5%) were "poor responders". A more favorable response to ESDM was significantly predicted by higher PEP-3 Expressive Language, Receptive Language, Cognitive Verbal/Preverbal, Visuo-Motor Imitation scores, higher GMDS-ER Personal/Social, and VABS-II Communication scores, by lower ADI-R C restricted/stereotypic behaviors, and by joint attention level., Discussion: Most predictors showed a linear association with increasing response to ESDM, but GMDS-ER Personal-Social and joint attention level predicted strong response, while PEP-3 receptive language equally predicted moderate or strong response. Although larger samples will be necessary to reach definitive conclusions, in conjunction with prior reports our findings begin providing information able to assist clinicians in choosing the most appropriate treatment program for young autistic children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Asta, Di Bella, La Fauci Belponer, Bruschetta, Martines, Basile, Boncoddo, Bellomo, Cucinotta, Ricciardello, Turriziani, Colombi, Banchelli, Cuoghi Costantini, D’Amico and Persico.)

The complete and prolonged suppression of viral load is the primary objective of HAART in people living with HIV. Some people may experience therapeutic failure, while others may achieve virological suppression but are unable to maintain it, developing persistent or single detection of low-level viremia. This study aims to evaluate the determinants of a detectable viral load among patients on HAART to identify and address them promptly. In this retrospective study, all patients referring to the Infectious Disease Operative Unit of the Vito Fazzi Hospital in Lecce, Puglia, older than 18 years, receiving HAART for at least 12 months as of 30 June 2022, were included. For each patient, demographic characteristics such as age, sex, educational level, stable relationship, cohabitation, employment status, and information relating to habits and lifestyles such as physical activity, use of drugs, and substances or supplements for sport, abuse of alcohol, and smoking were collected. Degree of comorbidity was quantified according to the Charlson Comorbidity Index, and the presence of obesity and the COVID-19 infection was also considered. Univariable and multivariable logistic regression models were used to assess the association between patients' characteristics and the outcome. In the multivariable logistic regression model, the odds were lower for the duration of therapy (OR: 0.96; p = 0.0397), prescriber's perception of adherence to therapy (OR: 0.50; p < 0.0001), and Nadir CD4+ T-cell count (OR: 0.85; p = 0.0329), and higher for the presence of AIDS (OR: 1.89; p = 0.0423) and COVID-19 (OR: 2.31; p = 0.0182). Our findings support the early initiation of HAART to achieve virological suppression. Additionally, measures to improve adherence to therapy should be adopted to ensure better outcomes for patients.

Introduction: The present study aims to describe a large cohort of Italian patients affected by osteogenesis imperfecta, providing a picture of the clinical bony and non-bony features and the molecular background to improve knowledge of the disease to inform appropriate management in clinical practice., Methods: A total of 568 subjects (from 446 unrelated Italian families) affected by osteogenesis imperfecta who received outpatient care at Istituto Ortopedico Rizzoli from 2006 to 2021 were considered in the present study., Results: Skeletal and extraskeletal features were analyzed showing a lower height (mean z-scores equal to -1.54 for male patients and -1.47 for female patients) compared with the general Italian population. Half of the patient population showed one or more deformities, and most of the patients had suffered a relatively low number of fractures (<10). An alteration in the sclera color was identified in 447 patients. Similarly, several extraskeletal features, like deafness, dental abnormalities, and cardiac problems, were investigated. Additionally, inheritance and genetic background were evaluated, showing that most of the patients have a positive family history and the majority of pathogenic variants detected were on collagen genes, as per literature., Conclusion: This study supports the definition of a clear picture of the heterogeneous clinical manifestations leading to variable severity in terms of skeletal and extra-skeletal traits and of the genetic background of an Italian population of osteogenesis imperfecta patients. In this perspective, this clearly highlights the crucial role of standardized and structured collection of high-quality data in disease registries particularly in rare disease scenarios, helping clinicians in disease monitoring and follow-up to improve clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision, (Copyright © 2024 Mordenti, Boarini, Banchelli, Antonioli, Corsini, Gnoli, Locatelli, Pedrini, Staals, Trisolino, Lanza and Sangiorgi.)

Background: In facioscapulohumeral muscular dystrophy (FSHD), it is not known whether physical activity (PA) practiced at young age is associated with the clinical presentation of disease. To assess this issue, we performed a retrospective cohort study concerning the previous practice of sports and, among them, those with medium-high cardiovascular commitment in clinically categorized carriers of a D4Z4 reduced allele (DRA)., Methods: People aged between 18 and 60 were recruited as being DRA carriers. Subcategory (classical phenotype, A; incomplete phenotype, B; asymptomatic carriers, C; complex phenotype, D) and FSHD score, which measures muscle functional impairment, were assessed for all participants. Information on PAs was retrieved by using an online survey dealing with the practice of sports at a young age., Results: 368 participants were included in the study, average age 36.6 years (SD = 9.4), 47.6% male. The FSHD subcategory A was observed in 157 (42.7%) participants with average (± SD) FSHD score of 5.8 ± 3.0; the incomplete phenotype (category B) in 46 (12.5%) participants (average score 2.2 ± 1.7) and the D phenotype in 61 (16.6%, average score 6.5 ± 3.8). Asymptomatic carriers were 104 (subcategory C, 28.3%, score 0.0 ± 0.2). Time from symptoms onset was higher for patients with A (15.8 ± 11.1 years) and D phenotype (13.3 ± 11.9) than for patients with B phenotype (7.3 ± 9.0). The practice of sports was associated with lower FSHD score (-17%) in participants with A phenotype (MR = 0.83, 95% CI = 0.73-0.95, p = 0.007) and by 33% in participants with D phenotype (MR = 0.67, 95% CI = 0.51-0.89, p = 0.006). Conversely, no improvement was observed in participants with incomplete phenotype with mild severity (B)., Conclusions: PAs at a young age are associated with a lower clinical score in the adult A and D FSHD subcategories. These results corroborate the need to consider PAs at the young age as a fundamental indicator for the correct clinical stratification of the disease and its possible evolution., (© 2024. The Author(s).)

Background: Knowledge about the dynamics of transmission of SARS-CoV-2 and the clinical aspects of COVID-19 has steadily increased over time, although evidence of the determinants of disease severity and duration is still limited and mainly focused on older adult and fragile populations., Methods: The present study was conceived and carried out in the Emilia-Romagna (E-R) and Veneto Regions, Italy, within the context of the EU's Horizon 2020 research project called ORCHESTRA (Connecting European Cohorts to increase common and effective response to SARS-CoV-2 pandemic) (www.orchestra-cohort.eu). The study has a multicenter retrospective population-based cohort design and aimed to investigate the incidence and risk factors of access to specific healthcare services (outpatient visits and diagnostics, drug prescriptions) during the post-acute phase from day-31 to day-365 after SARS-CoV-2 infection, in a healthy population at low risk of severe acute COVID-19. The study made use of previously recorded large-scale healthcare data available in the administrative databases of the two Italian Regions. The statistical analysis made use of methods for competing risks. Risk factors were assessed separately in the two Regions and results were pooled using random effects meta-analysis., Results: There were 35,128 subjects in E-R and 88,881 in Veneto who were included in the data analysis. The outcome (access to selected health services) occurred in a high percentage of subjects in the post-acute phase (25% in E-R and 21% in Veneto). Outpatient care was observed more frequently than drug prescriptions (18% vs. 12% in E-R and 15% vs. 10% in Veneto). Risk factors associated with the outcome were female sex, age greater than 40 years, baseline risk of hospitalization and death, moderate to severe acute COVID-19, and acute extrapulmonary complications., Conclusion: The outcome of interest may be considered as a proxy for long-term effects of COVID-19 needing clinical attention. Our data suggest that this outcome occurs in a substantial percentage of cases, even among a previously healthy population with low or mild severity of acute COVID-19. The study results provide useful insights into planning COVID-19-related services., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gagliotti, Banchelli, De Paoli, Buttazzi, Narne, Ricchizzi, Schievano, Bellio, Pitter, Tonon, Canziani, Rolli, Tacconelli, Berti, Russo and Moro.)

This is an observational multicentric cross-sectional study aiming at assessing the association between ABO blood groups and SARS-CoV-2 seroprevalence among the blood donors in Puglia region. Data on ABO and Rh blood groups and demographic characteristics were obtained from Blood Bank Information System. All donors were screened for SARS-CoV-2 IgG antibodies. Comparison of seroprevalence among blood groups and the association between the recorded variables and seroprevalence were evaluated. A total of 35,709 donors from 22 centers were included, with a seroprevalence of 6.8%. The distribution of ABO phenotypes was blood type O (46.8%), A (34.0%), B (14.7%), and AB (4.5%). Among the 2416 donors reactive for SARS-CoV-2 IgG, the prevalent phenotype was blood type O (43.1%), followed by A (37.7%), B (14.2%), and AB (5%). The seroprevalence of phenotype A and AB was 7.5%, followed by B (6.5%) and O (6.2%). According to the adjusted analysis, there was an increase in seroprevalence in groups A and AB, compared to group O, and an increase in males compared to females. A possible effect modification was observed after stratifying for sex (p = 0.0515). A significantly lower prevalence of blood type O was found compared to A and AB, whereas no association was observed between Rh factor and seroprevalence. We hypothesized that the A antigen present in blood type A and AB can play a role in the binding of SARS-CoV-2 to ACE2 receptors, resulting in an increased risk of infection. Furthermore, natural anti-A/anti-B antibodies produced in group O could block viral adhesion to cells and explain a lower risk of infection., (© 2023. The Author(s).)

Background and Aims: Bariatric Surgery (BS) is a therapeutic option in patients with severe obesity whose non-surgical techniques have failed. No work has previously explored trajectories of weight loss and how long this was maintained. Aim of study is to describe effect of BS and nutritional intervention on body weight trend in patients with obesity., Methods: 792 patients who underwent BS from 1996 to 2021 were included. The Protocol provides Laparoscopic Sleeve Gastrectomy (LSG), Vertical Gastroplasty (VBG) and Roux-en-Y Gastric Bypass (GB). %Total Weight Loss (%TWL) and %Excess Weight Loss (%EWL) were evaluated in three cohort of patients. Cumulative incidence of clinical goal after surgery was calculated at two and five years after BS., Results: At two years of follow-up, average %TWL and %EWL were 31.2% (95% CI = 29.0-33.4%) and 71% (95% CI = 65.4-76.5%) for VBG, 34.7% (95% CI = 33.8-35.6%) and 78.0% (95% CI = 75.9-89.1%) for GB and 33.8% (95% CI = 32.5-35.1%) and 68.8% (95% CI = 66.1-71.6%) for LSG. At two years from surgery the cumulative incidence of clinical goal was 70.7% (95% CI = 59.1-79.1%) for VBG, 86.4% (95% CI = 82.4-89.6%) for GB and 83.4% (95% CI = 76.0-87.1%) for LSG. At five years from surgery, average % TWL and % EWL were 22.5% (95% CI = 10.2-34.8%) and 58.2% (95% CI = 28.4-88.1%) for VBG, 31.8% (95% CI = 30.2-33.3%) and 70.8% (95% CI = 67.5-74.1%) for GB and 29.5% (95% CI = 26.2-32.8%) and 62.0% (95% CI = 53.4-70.6%) for LSG respectively. At five years after having reached clinical goal the share of people who were able to maintain their weight was 49.5% (95% CI = 30.8-79.6%) for VBG, 69.5% (95% CI = 58.3-82.8%) for GB and 55.9% (95% CI = 42.1-74.3%) for LSG. The median time of clinical goal maintaining was 4.8 years for VBG (95% CI lower limit = 4.1), 6.6 years for GB (95% CI lower limit = 6.2) and 5.3 years for LSG (95% CI lower limit = 4.8)., Conclusions: Our work confirm effectiveness of BS in patients with obesity and show that who do not reach clinical goal within 2 years, hardly will reach it later and suggest necessity for a medium and long-term follow-up to prevent weight regain., Competing Interests: Declaration of competing interest None of the authors have conflicts of interest to disclose., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

In preclinical studies rapamycin was found to target neuroinflammation, by expanding regulatory T cells, and affecting autophagy, two pillars of amyotrophic lateral sclerosis (ALS) pathogenesis. Herein we report a multicenter, randomized, double-blind trial, in 63 ALS patients who were randomly assigned in a 1:1:1 ratio to receive rapamycin 2 mg/m 2 /day,1 mg/m 2 /day or placebo (EUDRACT 2016-002399-28; NCT03359538). The primary outcome, the number of patients exhibiting an increase >30% in regulatory T cells from baseline to treatment end, was not attained. Secondary outcomes were changes from baseline of T, B, NK cell subpopulations, inflammasome mRNA expression and activation status, S6-ribosomal protein phosphorylation, neurofilaments; clinical outcome measures of disease progression; survival; safety and quality of life. Of the secondary outcomes, rapamycin decreased mRNA relative expression of the pro-inflammatory cytokine IL-18, reduced plasmatic IL-18 protein, and increased the percentage of classical monocytes and memory switched B cells, although no corrections were applied for multiple tests. In conclusion, we show that rapamycin treatment is well tolerated and provides reassuring safety findings in ALS patients, but further trials are necessary to understand the biological and clinical effects of this drug in ALS., (© 2023. Springer Nature Limited.)

Patients with COVID-19 can develop different forms of the illness with more or less severe symptoms. A 2-year retrospective cohort study was conducted to evaluate the factors associated with the development of pneumonia in patients hospitalized with COVID-19 from March 2020 to February 2022. A total of 385 patients (59.0% males) with a mean age of 69.0 ± 16.0 years were included. At hospital admission, 318 patients (82.6%) reported one or more comorbidities, namely 201 (52.2%) subjects were affected by hypertension, 98 (25.5%) type 2 diabetes, 84 (21.8%) obesity, 36 (9.4%) cancer, and 14 (3.6%) suffered from kidney disease and were being treated with dialysis, and 76 (19.7%) resulted in being vaccinated with a higher prevalence of BNT162b2 vaccine (15.0%). Pneumonia was diagnosed in 276 (71.7%) patients. Multivariate regression analysis showed that pneumonia in COVID-19 patients was positively associated with type 2 diabetes (OR 1.81; 95% CI 1.00-3.27), obesity (OR 2.52; 95% CI 1.27-4.98), and negatively with hypertension (OR 0.58; 95% CI 0.35-0.96). Vaccination against SARS-CoV-2 resulted in a strongly protective factor against the development of pneumonia in COVID-19 patients (OR 0.49; 95% CI 0.28-0.85).

We aimed to identify prognostic laboratory markers during extracorporeal life support (ECLS) in patients with primary refractory cardiogenic shock (RCS) and to create a preliminary specific mortality score. All 208 consecutive subjects admitted for primary RCS and treated with ECLS between January-2009 and December-2018 were retrospectively analyzed. Multivariate regression analysis on laboratory markers during the first nine days of ECLS was used to develop a "Refractory End-stage Shock CUred with Ecls" (RESCUE) score. Serum creatinine (OR = 3.72, 95%CI: 2.01-6.88), direct bilirubin (OR = 1.40, 95%CI: 1.05-1.8), and platelet count (OR = 0.62, 95%CI: 0.42-0.94) were independent predictors of in-hospital mortality and were included in the score. The mean AUC was 0.763 (95%CI: 0.698-0.828) in the development cohort and 0.729 (95%CI: 0.664-0.794) in the bootstrap internal validation cohort. The RESCUE score represents a novel promising instrument to predict early mortality during the first critical days of ECLS and to help in properly guiding the therapeutic decision-making process., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The purpose of this multicenter, retrospective, observational study was to investigate the association between intraoperative component positioning and soft tissue balancing, as reported by robotic technology for a cohort of patients who received robotic arm-assisted lateral unicompartmental knee arthroplasty (UKA) as well as short-term clinical follow-up of these patients. Between 2013 and 2016, 78 patients (79 knees) underwent robotic arm-assisted lateral UKAs at two centers. Pre- and postoperatively, patients were administered the Knee Injury and Osteoarthritis Score (KOOS) and the Forgotten Joint Score-12 (FJS-12). Clinical results were dichotomized based upon KOOS and FJS-12 scores into either excellent or fair outcome, considering excellent KOOS and FJS-12 to be greater than or equal to 90. Intraoperative, postimplantation robotic data relative to computed tomography-based components placement were collected and classified. Following exclusions and loss to follow-up, a total of 74 subjects (75 knees) who received robotic arm-assisted lateral UKAs were taken into account with an average follow-up of 36.3 months (range: 25.0-54.2 months) postoperative. Of these, 66 patients (67 knees) were included in the clinical outcome analysis. All postoperative clinical scores showed significant improvement compared with the preoperative evaluation. No association was reported between three-dimensional component positioning and soft tissue balancing throughout knee range of motion with overall KOOS, KOOS subscales, and FJS-12 scores. Lateral UKA three-dimensional placement does not seem to affect short-term clinical performance. However, precise boundaries for lateral UKA positioning and balancing should be taken into account. Robotic assistance allows surgeons to acquire real-time information regarding implant alignment and soft tissue balancing., Competing Interests: F.Z., G.F., F.B., A.M., and A.E., or any member of their immediate family, have no funding or commercial associations (e.g., consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article. F.C. has received or will receive benefits for personal or professional use from a commercial party related directly or indirectly to the subject of this article from Stryker. F.C. reports consultancy fees, royalties, and fees for participation in review activities from Stryker related to this study. F.C. reports personal fees from Stryker Inc., personal fees from Stryker Inc., outside the submitted work. In addition, F.C. has a patent Stryker Inc. with royalties paid., (Thieme. All rights reserved.)

Background: Fall risk in the elderly is a major public health issue due to the injury-related consequences and the risk of associated long-term disability. However, delivering preventive interventions in usual clinical practice still represents a challenge., Aim: To evaluate the efficacy of a multiple-component combined with a multifactorial personalized intervention in reducing fall rates in a mixed population of community-dwelling elderly compared to usual care., Design: Randomized Controlled Trial (NCT03592420, clinicalTrials.gov)., Setting: Outpatients in two Italian centers., Population: 403 community-dwelling elderly at moderate-to-high fall risk, including subjects with Parkinson's Disease and stroke., Methods: After the randomization, the described interventions were administered to the intervention group ( n = 203). The control group ( n = 200) received usual care and recommendations to minimize fall risk factors. In addition, each participant received a fall diary, followed by 12 monthly phone calls. The primary endpoint was the total number of falls in each group over 12 months, while the secondary endpoints were other fall-related indicators recorded at one year. In addition, participants' functioning was assessed at baseline (T1) and 3-month (T3)., Results: 690 falls were reported at 12 months, 48.8% in the intervention and 51.2% in the control group, with 1.66 (± 3.5) and 1.77 (± 3.2) mean falls per subject, respectively. Subjects with ≥ 1 fall and ≥2 falls were, respectively, 236 (58.6%) and 148 (36.7%). No statistically significant differences were observed between groups regarding the number of falls, the falling probability, and the time to the first fall. According to the subgroup analysis, no significant differences were reported. However, a statistically significant difference was found for the Mini-BESTest ( p = 0.004) and the Fullerton Advanced Balance Scale ( p = 0.006) for the intervention group, with a small effect size (Cohen's d 0.26 and 0.32, respectively), at T1 and T3 evaluations., Conclusions: The intervention was ineffective in reducing the number of falls, the falling probability, and the time to the first fall at 12 months in a mixed population of community-dwelling elderly. A significant improvement for two balance indicators was recorded in the intervention group. Future studies are needed to explore different effects of the proposed interventions to reduce falls and consequences., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 La Porta, Lullini, Caselli, Valzania, Mussi, Tedeschi, Pioli, Bondavalli, Bertolotti, Banchelli, D'Amico, Vicini, Puglisi, Clerici, Chiari and the PRECISA Group.)

Purpose: Cancer stem cells (CSCs) are described as resistant to chemotherapy and radiotherapy. It has been shown that CSCs influence disease-free survival in patients undergoing surgery for lung cancer (NCT04634630). We recently described an overexpression of CSCs recurrence-related genes (RG) in lung cancer. This study aims to investigate CSC frequency and RG expression as predictors of disease-free survival in lung cancer., Experimental Design: This secondary analysis of a prospective cohort study involved 22 surgical tumor specimens from 22 patients harboring early (I-II) and locally advanced (IIIA) stages ACL and SCCL. Cell population frequency analysis of ALDHhigh (CSCs) and ALDHlow (cancer cells) was performed on each tumor specimen. In addition, RG expression was assessed for 31 target genes separately in ALDHhigh and ALDHlow populations. CSCs frequency and RG expression were assessed as predictors of disease-free survival by Cox analysis., Results: CSCs frequency and RG expression were independent predictors of disease-free survival. CSC frequency was not related to disease-free survival in early-stage patients (HR = 0.84, 95%CI = 0.53-1.33, P = .454), whereas it was a risk factor for locally advanced-stage patients (HR = 1.22, 95%CI = 1.09-1.35, P = .000). RG expression-if measured in CSCs-was related to a higher risk of recurrence (HR = 1.19, 95%CI = 1.03-1.39, P = .021). The effect of RG expression measured in cancer cells on disease-free survival was lower and was not statistically significant (HR = 1.12, 95%CI = 0.94-1.33, P = .196)., Conclusions: CSCs frequency and RG expression are independent predictors of relapse in lung cancer. Considering these results, CSCs and RG may be considered for both target therapy and prognosis., (© The Author(s) 2022. Published by Oxford University Press.)