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Abstract Background The efficacy and safety profile of mesenchymal stem cells (MSCs) augmentation in chondral procedures are controversial. This systematic review updated the current evidence on MSCs augmentation for chondral procedures in patients with symptomatic chondral defects of the knee. Methods This study followed the PRISMA guidelines. The literature search was updated in August 2022. Two independent authors accessed PubMed, Google scholar, Embase, and Scopus. No additional filters or time constrains were used for the search. A cross reference of the bibliographies was also performed. All the clinical studies investigating surgical procedures for chondral defects of the knee augmented with MSCs were accessed. Defects of both tibiofemoral and patellofemoral joints were included. The following patient reported outcomes measures (PROMs) were retrieved at baseline and last follow-up: Visual Analogic Scale (VAS), Tegner Activity Scale, Lysholm Knee Scoring System, International Knee Documentation Committee (IKDC). Return to daily activities and data on hypertrophy, failure, revision surgery were also collected. Failures were defined as the recurrence of symptoms attributable to the index procedure. Revisions were defined as any reoperation at the site of the index procedure. Results A total of 15 clinical studies (411 procedures) were included. Patients returned to their prior sport activity at 2.8 ± 0.4 months. All the PROMs improved at last follow-up: Tegner (P = 0.0002), Lysholm (P

Abstract Background Biochemical markers of bone turnover (BTMs), such as bone alkaline phosphatase (bALP), procollagen type I N propeptide (PINP), serum cross-linked C-telopeptides of type I collagen (bCTx), and urinary cross-linked N-telopeptides of type I collagen (NTx), are commonly used for therapy monitoring purposes for osteoporotic patients. The present study evaluated the potential role of BTMs as therapy monitoring. Methods All randomized clinical trials (RCTs) comparing two or more pharmacological treatments for postmenopausal osteoporosis were accessed. Only studies that reported the value of bALP, PINP, bCTx, and NTx at last follow-up were included. A multivariate analysis was performed to assess associations between these biomarkers and clinical outcomes and rate of adverse events in patients with postmenopausal osteoporosis. A multiple linear model regression analysis through the Pearson product-moment correlation coefficient was used. Results A total of 16 RCTs (14,446 patients) were included. The median age was 67 years, and the median BMI 25.4 kg/m2. The median vertebral BMD was 0.82, hip BMD 0.79, and femur BMD 0.64 g/cm2. The ANOVA test found optimal within-group variance concerning mean age, body mass index, and BMD. Greater bALP was associated with lower femoral BMD (P = 0.01). Greater NTx was associated with a greater number of non-vertebral fractures (P = 0.02). Greater NTx was associated with greater rate of therapy discontinuation (P = 0.04). No other statistically significant associations were detected. Conclusion Our analysis supports the adoption of BTMs in therapy monitoring of osteoporotic patients. Level of evidence Level I, systematic review of RCTs.

Francesco Giorgino,1 Alfred Penfornis,2 Valeria Pechtner,3 Raffaella Gentilella,4 Antonella Corcos4 1Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology, and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy; 2Service d’Endocrinologie, Diabétologie, et Maladies Métaboliques, Centre Hospitalier Sud-Francilien de Corbeil-Essonnes, Université Paris-Sud, Orsay, France; 3Lilly Diabetes, Eli Lilly & Company, Neuilly-sur-Seine, France; 4Eli Lilly Italia, Sesto Fiorentino, Italy Abstract: Adherence to antihyperglycemic medications is often suboptimal in patients with type 2 diabetes, and this can contribute to poor glycemic control, increased hospitalization, and the development of diabetic complications. Reported adherence rates to antihyperglycemics vary widely among studies, and this may be related to differences in methodology for measuring adherence, patient populations, and other factors. Poor adherence may occur regardless of the specific regimen used and whether therapy is oral or injectable, and can be especially common in chronic, asymptomatic conditions, such as type 2 diabetes. More convenient drug-administration regimens and advances in formulations and delivery devices are among strategies shown to improve adherence to antihyperglycemic therapy, especially for injectable therapy. This is exemplified by technological developments made in the drug class of glucagon-like peptide 1-receptor agonists, which are a focus of this narrative review. Dulaglutide, albiglutide, and prolonged-release exenatide have an extended duration of action and can be administered once weekly, whereas such agents as liraglutide require once-daily administration. The convenience of once-weekly versus once-daily administration is associated with better adherence in real-world studies involving this class of agent. Moreover, provision of a user-friendly delivery device has been shown to overcome initial resistance to injectable therapy among patients with type 2 diabetes. This suggests that recent innovations in drug formulation (eg, ready-to-use formulations) and delivery systems (eg, single-dose prefilled pens and hidden, ready-attached needles) may be instrumental in encouraging patient acceptance. For physicians who aim to improve their patients’ adherence to antihyperglycemic medications, it is thus important to consider the patient’s therapeutic experience (treatment frequency, drug formulation, delivery device). Better adherence, powered by recent technological advances in the delivery of glucagon-like peptide 1-receptor agonists, may thus lead to improved clinical outcomes in type 2 diabetes. Keywords: type 2 diabetes mellitus, adherence, compliance, glucagon-like peptide 1-receptor agonists

Abstract Obesity-related disability-adjusted life years (DALYs) are expected to increase by approximately 40% from 2020 to 2030. DALYs and mortality related to obesity are the consequence of multiple comorbidities such as cardiovascular (i.e., heart failure) and metabolic diseases (i.e. type 2 diabetes [T2D], metabolic dysfunction-associated steatotic liver disease [MASLD]). Lifestyle interventions represent the foundation of obesity treatment, yet an escalation to pharmacological and/or surgical interventions is often needed. Liraglutide, semaglutide and tirzepatide are incretin-based therapies currently approved by FDA for the management of obesity, while triple GIPR/GCGR/GLP-1R agonist retatrutide (LY3437943), the cagrilintide/semaglutide (CagriSema) 2.4 mg combination, high-dose oral semaglutide, and oral orforglipron are in advanced stages of development. Incretin-based therapies have been associated with a body weight (BW) reduction of ≥5% in at least half of patients in most randomized controlled trials (RCT) and real-world studies (RWS). Semaglutide and tirzepatide have also displayed a mean 60–69% 10-years relative risk reduction of T2D development. In line with evidence accrued in patients with T2D, incretin-based therapies produced a favorable effect on traditional cardiovascular risk factors, such as lipids and blood pressure, and even reduced the risk of major cardiovascular events and heart failure-related events in individuals with obesity, as recently demonstrated for the first time in the SELECT trial with semaglutide 2.4 mg once-weekly. Moreover, incretin-based therapies have also been proven beneficial on obesity-related comorbidities, such as knee osteoarthritis (KOA), obstructive sleep apnea (OSA) syndrome, and MASLD. Further research is needed to improve our understanding of their effects on obesity-related comorbidities and the underlying mechanism, whether involving direct effects on target tissues or mediated by improvement in BW, glucose levels and other CV risk factors.

Abstract Background The present experiment aimed to evaluate the effects of commercially processed former foodstuffs (cFF) as dietary substitutes of corn, soybean meal and soybean oil on the growth performance, apparent total tract digestibility (ATTD), hematobiochemical profiles, and liver gene abundance in broiler chickens. Two hundred one-day-old male ROSS-308 chicks were assigned to 4 dietary groups (5 replicates of ten birds per replicate) according to their average body weight (BW, 38.0 ± 0.11 g). All groups received a two-phase feeding program: starter, d 1–12 and grower, d 12–33. The control group (cFF0) was fed a standard commercial feed based on corn, soybean meal and soybean oil. The other three groups received diets in which the feed based on corn, soybean meal, and soybean oil was partially replaced with cFF at a substitution level of 6.25% (cFF6.25), 12.5% (cFF12.5) or 25% (cFF25) for the following 33 d. Results The growth performance data showed no differences in BW or average daily gain among groups, although the average daily feed intake decreased during the grower period (12–33 d) and over entire experimental period (1–33 d) in a linear manner as the cFF inclusion level rose (P = 0.026), positively affecting the gain to feed ratio (P = 0.001). The ATTD of dry matter of the cFF-fed groups were greater with respect to control group and increased throughout the experimental period, whereas the ATTD of ether extract linearly decreased with increasing levels of cFF-fed groups compared with control group and throughout the experimental period (P

In this paper, a new method for evaluating hot-electron degradation in p-GaN gate AlGaN/GaN power HEMTs is proposed. The method exploits a commercial parameter analyzer to study VTH and RON drifts induced by on-state stress at VDS = 50 V. The results show that VTH drift and part of the RON degradation induced by the on-state stress are recoverable and likely due to the ionization of C-related acceptors in the buffer. This was confirmed by a preliminary characterization of C-related buffer traps. Conversely, the remaining part of RON degradation (not recovered in 1000 s) was strongly affected by the surface treatment. The current level set during on-state stress affected the amount of non-recoverable degradation, confirming the involvement of hot electrons. Thanks to the monitoring of the parameters’ recovery, the proposed method provides important insights into the physical mechanisms governing the parameters’ degradation. This extends the capabilities of state-of-the art systems, without the need for custom setup development.

Coronaviruses (CoVs) share key genomic elements critical for viral replication, suggesting the feasibility of developing therapeutics with efficacy across different viruses. In a previous work, we demonstrated the antiviral activity of the antipsychotic drug lurasidone against both SARS-CoV-2 and HCoV-OC43. In this study, our investigations on the mechanism of action of lurasidone suggested that the drug exhibits antiviral activity by targeting the papain-like protease (PL-Pro) of both viruses, and the Spike protein of SARS-CoV-2, thereby hampering both the entry and the viral replication. In vitro assays demonstrate that lurasidone significantly reduces viral load in infected cells, showing that the drug is a promising candidate for further development as a dual-action antiviral, offering a potential new strategy in the fight against COVID-19 and other coronavirus-related diseases.

Objective: To analyze data available in the literature regarding a possible prognostic value of the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in prostate cancer (PCa) patients stratified in non-metastatic and metastatic diseases. Methods: A literature search process was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. In our meta-analysis, the pooled event rate estimated and the pooled hazard ratio were calculated using a random effect model. Results: Forty-two articles were selected for our analysis. The pooled risk difference for non-organ confined PCa between high and low NLR cases was 0.06 (95% confidence interval [CI]: −0.03–0.15) and between high and low PLR cases increased to 0.30 (95% CI: 0.16–0.43). In non-metastatic PCa cases, the pooled hazard ratio for overall mortality between high and low NLR was 1.33 (95% CI: 0.78–1.88) and between high and low PLR was 1.47 (95% CI: 0.91–2.03), whereas in metastatic PCa cases, between high and low NLR was 1.79 (95% CI: 1.44–2.13) and between high and low PLR was 1.05 (95% CI: 0.87–1.24). Conclusion: The prognostic values of NLR and PLR in terms of PCa characteristics and responses after treatment show a high level of heterogeneity of results among studies. These two ratios can represent the inflammatory and immunity status of the patient related to several conditions. A higher predictive value is related to a high NLR in terms of risk for overall mortality in metastatic PCa cases under systemic treatments.

Abstract The 9th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 30-December 1, 2023. This reference congress served as a platform for in-depth discussions and exchange on recently completed outcomes trials including dapagliflozin (DAPA-MI), semaglutide (SELECT and STEP-HFpEF) and bempedoic acid (CLEAR Outcomes), and the advances they represent in reducing the risk of major adverse cardiovascular events (MACE), improving metabolic outcomes, and treating obesity-related heart failure with preserved ejection fraction (HFpEF). A broad audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians participated in online discussions on guideline updates for the management of cardiovascular disease (CVD) in diabetes, heart failure (HF) and chronic kidney disease (CKD); advances in the management of type 1 diabetes (T1D) and its comorbidities; advances in the management of CKD with SGLT2 inhibitors and non-steroidal mineralocorticoid receptor antagonists (nsMRAs); and advances in the treatment of obesity with GLP-1 and dual GIP/GLP-1 receptor agonists. The association of diabetes and obesity with nonalcoholic steatohepatitis (NASH; metabolic dysfunction-associated steatohepatitis, MASH) and cancer and possible treatments for these complications were also explored. It is generally assumed that treatment of chronic diseases is equally effective for all patients. However, as discussed at the Summit, this assumption may not be true. Therefore, it is important to enroll patients from diverse racial and ethnic groups in clinical trials and to analyze patient-reported outcomes to assess treatment efficacy, and to develop innovative approaches to tailor medications to those who benefit most with minimal side effects. Other keys to a successful management of diabetes and comorbidities, including dementia, entail the use of continuous glucose monitoring (CGM) technology and the implementation of appropriate patient-physician communication strategies. The 10th Cardiovascular Outcome Trial Summit will be held virtually on December 5–6, 2024 ( http://www.cvot.org ).

Background: Comprehending and addressing the needs of caregivers during the post-intensive care unit (ICU) phase is vital for establishing sustainable support systems and improving the overall quality of life (QoL) for both patients and caregivers.Objective: To explore the experiences of family members (FMs) caring for loved ones three-months after ICU discharge and their related QoL.Methods and measures: A qualitative, descriptive research was conducted. Participants were recruited from two general ICUs in an Italian Academic Hospital. Data collection lasted two months and was performed with telephonic interviews led by ICU nurses. Thematic analysis was conducted using a hybrid approach, incorporating both deductive and inductive coding strategies. This process has been facilitated by Atlas.ti software.Results: Twenty-four FMs participated, representing a diverse range of familial relationships with the patients. Thematic analysis revealed four overarching themes: 1) QoL underwent transformations; 2) Positive emotions laden with significance; 3) Supporting role taken on by a caregiver; and 4) Life’s transience through the meaning-making of the illness event. These themes highlighted the multifaceted nature of the caregiving experience.Conclusions: This study provides valuable insights into the challenges and dynamics faced by FMs following ICU discharge. Findings underscore the importance of addressing environmental challenges, cultivating positive emotions, and strengthening caregiver-patient relationships to enhance the caregiving experience and promote overall QoL. FMs can adapt their personal concepts and reach their full potential by learning to coexist with the demanding role of caregiver and achieve a new level of resilience and fulfillment.

Cardiac computed tomography (CCT) has assumed an increasingly significant role in the evaluation of coronary artery disease (CAD) during the past few decades, whereas cardiovascular magnetic resonance (CMR) remains the gold standard for myocardial tissue characterization. The discovery of late myocardial enhancement following intravenous contrast administration dates back to the 1970s with ex-vivo CT animal investigations; nevertheless, the clinical application of this phenomenon for cardiac tissue characterization became prevalent for CMR imaging far earlier than for CCT imaging.Recently the technical advances in CT scanners have made it possible to take advantage of late contrast enhancement (LCE) for tissue characterization in CCT exams. Moreover, the introduction of extracellular volume calculation (ECV) on cardiac CT images combined with the possibility of evaluating cardiac function in the same exam is making CCT imaging a multiparametric technique more and more similar to CMR.The aim of our review is to provide a comprehensive overview on the role of CCT with LCE in the evaluation of a wide range of cardiac conditions.

BackgroundVeterinarians play an essential role in improving animal care, as they are often viewed as trusted advisors, particularly in relation to disease control and management; however, little is known about veterinarians’ perceptions and attitudes toward alternative feeds. The aim of this study was to investigate the influence of age, gender, and willingness to adopt on the attitudes of livestock veterinarians toward the use of alternative feeds in farm animals.MethodsA total of 136 active veterinarians completed the online survey, distributed through the main veterinary associations in Italy. The questionnaire contained items on dietary recommendation, awareness, benefit and safety perceptions, and a willingness to adopt former foodstuffs (FFs), complemented with socio-demographic questions.ResultsAlmost 90% of the population reported a willingness to adopt FFs as feed. Men and women did not share the same perceptions of the nutritional composition of FFs, while the importance of product availability was found to be a key factor driving the age difference. Participants willing to adopt FFs as feed linked positive attitudes to attributes such as digestibility, energy intake, and positive social implications.ConclusionOur findings provide a basic background on the current use of the FFs in Italy and suggest the need for the development of educational programs and marketing strategies to enhance the acceptability of FFs in farm animals to ultimately promote the transition toward more sustainable animal production. This study has limitations, including the number of recorded responses and reliance on national estimates. Future research is needed to investigate the perceptions of farmers and animal nutritionist from different countries. This could provide a more detailed picture of the current situation in Europe about the potential of using FFs in farm animals’ feed, thus further contributing toward a greener and safer livestock production sector.

Abstract Background Anterior cruciate ligament (ACL) tears in skeletally immature patients are increasingly common. Evidence comparing the outcomes of all-epiphyseal versus trans-epiphyseal ACL reconstruction in skeletally immature patients is limited, and the current literature could benefit from a comprehensive systematic review. The present study compared all-epiphyseal versus trans-epiphyseal ACL reconstruction in skeletally immature patients. The outcomes of interest were to compare joint laxity, patient-reported outcome measures (PROMs), return to sport, and complications. Methods This study was conducted according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. In November 2023, the following databases were accessed: PubMed, Web of Science, Google Scholar, and Embase. No additional filters were used in the database search. All the clinical studies investigating ACL reconstruction in skeletally immature patients were accessed. Only articles that clearly stated the surgical technique (all- or trans-epiphyseal) were eligible. Only articles with a minimum of 6 months of follow-up were included. Only articles that clearly stated that surgeries were conducted in children with open physis were eligible. Results Data from 1489 patients (1493 procedures) were collected, of which 32% (490 of 1489 patients) were female. The mean length of follow-up was 46.6 months. The mean age of the patients was 12.7 years. No difference was found in joint laxity (Table 3): positive pivot shift (P = 0.4), positive Lachman test (P = 0.3), and mean arthrometer laxity (P = 0.1). No difference was found in PROMs (Table 4): International Knee Documentation Committee (IKDC) (P = 0.3), Lysholm (P = 0.4), and Tegner (P = 0.7). The trans-epiphyseal technique was associated with a greater rate of patients unable to return to sports (1% versus 7%, P = 0.0001) and with a longer time to return to sports (7.7 versus 8.6 months, P = 0.01). Though the trans-epiphyseal technique was associated with a lower rate of return to sport, this difference was not statistically significant (P = 0.8). No difference was evidenced in the rate of patients who had reduced their league or level of sports activity (P = 0.6) or in the rate of patients who had returned to their previous league or level of sports activity (P = 0.7). No difference was found in the rate of complication: re-tear (P = 0.8), reoperation (P = 0.7), increased laxity (P = 0.9), and persistent instability sensation (P = 0.3). Conclusion Trans-epiphyseal ACL reconstruction was associated with a greater rate of patients unable to return to sport and with a longer time to return to sport compared with the all-epiphyseal technique in skeletally immature patients. Level of evidence Level III, systematic review.

Abstract Background In the last years, the classical pattern of diabetic kidney disease (DKD) has been partially overcome, because of the uncovering of a new DKD phenotype with significant renal dysfunction without presence of albuminuria: the non-albuminuric DKD (NA-DKD). To date, the cardiovascular risk associated with this phenotype is still debated. We investigated the cardiovascular risk and renal injury profile of NA-DKD subjects in comparison with other DKD phenotypes. Methods Pulse wave velocity (PWV), intima-media thickness, presence of carotid atherosclerotic plaque, renal resistive index (RRI), and a panel of urinary biomarkers of kidney injury were evaluated in 160 subjects with type 2 diabetes, stratified according to estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR) into four groups: controls (UACR

Abstract It is unclear whether manual lymphatic drainage (MLD) following primary total knee arthroplasty (TKA) is effective in reducing pain and swelling and improving knee function. The present study investigated the efficacy of MLD after TKA. The outcomes of interest are the range of motion (ROM), pain (visual analogue scale, VAS), and circumference of the lower leg. This meta-analysis was conducted according to the 2020 PRISMA statement. In November 2023, the following databases were accessed: PubMed, Web of Science, Google Scholar, and Embase, with no time constraint. Only level I evidence studies, according to the Oxford Centre of Evidence-Based Medicine, were considered. All the randomised controlled trials (RCTs) comparing patients who have received MLD versus a group of patients who did not undergo MLD following primary TKA were accessed. Data from four RCTs (197 TKAs) were retrieved. 67% (132 of 197 patients) were women. The mean length of follow-up was 7.0 ± 5.8 weeks. The mean age of the patients was 69.6 ± 2.7 years, and the mean BMI was 28.7 ± 0.9 kg/m2. At baseline, between-group comparability was evidenced in the male:female ratio, mean age, mean BMI, knee flexion, and VAS. No difference was found in flexion (P = 0.7) and VAS (P = 0.3). No difference was found in the circumference of the thigh (P = 0.8), knee (P = 0.4), calf (P = 0.4), and ankle (P = 0.3). The current level I of evidence does not support the use of MLD in primary TKA.