Macrophage expression and prognostic significance of the long pentraxin PTX3 in COVID-19.

Long pentraxin 3 (PTX3) is an essential component of humoral innate immunity, involved in resistance to selected pathogens and in the regulation of inflammation1-3. The present study was designed to assess the presence and significance of PTX3 in Coronavirus Disease 2019 (COVID-19)4-7. RNA-sequencing analysis of peripheral blood mononuclear cells, single-cell bioinformatics analysis and immunohistochemistry of lung autopsy samples revealed that myelomonocytic cells and endothelial cells express high levels of PTX3 in patients with COVID-19. Increased plasma concentrations of PTX3 were detected in 96 patients with COVID-19. PTX3 emerged as a strong independent predictor of 28-d mortality in multivariable analysis, better than conventional markers of inflammation, in hospitalized patients with COVID-19. The prognostic significance of PTX3 abundance for mortality was confirmed in a second independent cohort (54 patients). Thus, circulating and lung myelomonocytic cells and endothelial cells are a major source of PTX3, and PTX3 plasma concentration can serve as an independent strong prognostic indicator of short-term mortality in COVID-19.

IELSG38: phase II trial of front-line chlorambucil plus subcutaneous rituximab induction and maintenance in mucosa-associated lymphoid tissue lymphoma.

The IELSG38 trial was conducted to investigate the effects of subcutaneous (SC) rituximab on the complete remission (CR) rate and the benefits of SC maintenance in patients with extranodal marginal zone lymphoma (MZL) who received frontline treatment with chlorambucil plus rituximab. Study treatment comprised an induction phase with chlorambucil 6 mg/m2/day orally on weeks 1-6, 9-10, 13-14, 17-18, and 21-22, and rituximab 375 mg/m2 intravenously on day 1 of weeks 1-4, and 1400 mg SC on weeks 9, 13, 17, and 21. Then, a maintenance phase followed with rituximab administered at 1400 mg SC every two months for two years. Of the 112 patients enrolled, 109 were evaluated for efficacy. The CR rates increased from 52% at the end of the induction phase to 70% upon completion of the maintenance phase. With a median follow-up of 5.8 years, the 5-year event-free, progression-free, and overall survival rates were 87% (95% CI, 78-92), 84% (95% CI, 75-89), and 93% (95% CI, 86-96), respectively. The most common grade ≥3 toxicities were neutropenia (33%) and lymphocytopenia (16%). Six patients experienced treatment-related serious adverse events, including fever of unknown origin, sepsis, pneumonia, respiratory failure, severe cerebellar ataxia, and fatal acute myeloid leukemia. The trial showed that subcutaneous rituximab did not improve the complete remission rate at the conclusion of the induction phase, which was the main endpoint. Nevertheless, SC maintenance might have facilitated long-term disease control, potentially contributing to enhanced event-free and progression-free survival.

Response rates and associated factors after a multicomponent intervention in frail older adults with diabetes.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and frailty are associated with functional decline in older population. OBJECTIVE: To explore the individual response to a multimodal intervention on functional performance. DESIGN: A cluster-randomised multicentre clinical trial. SETTING: Outpatients in hospital or primary care. SUBJECTS: 843 (77.83 years, 50.65% men) prefrail and frail individuals ≥70 years with T2DM. METHODS: Participants were allocated to usual care group (UCG) or a multicomponent intervention group (IG): 16-week progressive resistance training, seven nutritional and diabetological educational sessions and achievement of glycated haemoglobin (7-8%) and blood pressure (<150 mmHg) targets. Functional performance was assessed with the Short Physical Performance Battery (SPPB) at 1 year. We used multivariate binomial and multinomial logistic regression models to explore the effect of the IG, and adherence on the outcomes studied, in several adjusted models. RESULTS: 53.7% in the IG versus 38.0% in the UCG improved by at least 1 point in their SPPB score [OR (95% CI): 2.07 (1.43, 2.98), P value <0.001]. Age, SPPB score and number of frailty criteria met decreased the probability of improving the SPPB score. Factors associated with worsening were pertaining to IG (decreased), age, SPPB score and the number of frailty criteria (increased). An adherence ≥84% was needed to achieve benefits, reaching the peak in the probability of improving SPPB when this was ≥85% [OR(95%CI): 2.38 (1.29, 4.79), P value 0.014]. CONCLUSIONS: Factors predicting the likelihood of improvement in a multimodal programme in pre-frail and frail older adults with diabetes are age, basal SPPB score, the number of frailty criteria and adherence.

The Conceptual Definition of Sarcopenia: Delphi Consensus from the Global Leadership Initiative in Sarcopenia (GLIS).

IMPORTANCE: Sarcopenia, the age-related loss of muscle mass and strength/function, is an important clinical condition. However, no international consensus on the definition exists. OBJECTIVE: The Global Leadership Initiative in Sarcopenia (GLIS) aimed to address this by establishing the global conceptual definition of sarcopenia. DESIGN: The GLIS steering committee was formed in 2019-21 with representatives from all relevant scientific societies worldwide. During this time, the steering committee developed a set of statements on the topic and invited members from these societies to participate in a two-phase International Delphi Study. Between 2022 and 2023, participants ranked their agreement with a set of statements using an online survey tool (SurveyMonkey). Statements were categorised based on predefined thresholds: strong agreement (>80%), moderate agreement (70-80%) and low agreement (<70%). Statements with strong agreement were accepted, statements with low agreement were rejected and those with moderate agreement were reintroduced until consensus was reached. RESULTS: 107 participants (mean age: 54 ± 12 years [1 missing age], 64% men) from 29 countries across 7 continents/regions completed the Delphi survey. Twenty statements were found to have a strong agreement. These included; 6 statements on 'general aspects of sarcopenia' (strongest agreement: the prevalence of sarcopenia increases with age (98.3%)), 3 statements on 'components of sarcopenia' (muscle mass (89.4%), muscle strength (93.1%) and muscle-specific strength (80.8%) should all be a part of the conceptual definition of sarcopenia)) and 11 statements on 'outcomes of sarcopenia' (strongest agreement: sarcopenia increases the risk of impaired physical performance (97.9%)). A key finding of the Delphi survey was that muscle mass, muscle strength and muscle-specific strength were all accepted as 'components of sarcopenia', whereas impaired physical performance was accepted as an 'outcome' rather than a 'component' of sarcopenia. CONCLUSION AND RELEVANCE: The GLIS has created the first global conceptual definition of sarcopenia, which will now serve to develop an operational definition for clinical and research settings.

Physical performance and negative events in very old adults: a longitudinal study examining the ilSIRENTE cohort.

BACKGROUND: Declining physical performance in old age is associated with a wide range of negative health-related outcomes. However, it is unclear which physical capabilities should be prioritized to obtain prognostic information in older adults. AIMS: To examine the associations between the performance on several physical function tests and falls, disability, and death in a well-characterized sample of very old Italian adults. METHODS: This was a prospective cohort study of older adults who lived in the mountain community of the Sirente geographic area in Central Italy. Physical performance was assessed using isometric handgrip strength (IHG), walking speed (WS) at a usual and fast pace, 5-time sit-to-stand test (5STS), and sit-to-stand power measures. Appendicular skeletal muscle mass was estimated from calf circumference using a validated equation. History of falls, incident falls, and disability status according to basic Activities of Daily Living (ADLs) were recorded over two years. Survival status was obtained from the participants' general practitioners and was confirmed by the National Death Registry over 10 years from enrolment. Linear, binary, and Cox regressions were performed to evaluate the association between physical performance measures and health outcomes. RESULTS: The mean age of the 255 participants was 84.2 ± 5.1 years, and 161 (63.1%) were women. Logistic regression indicated that IHG was significantly associated with incident ADL disability, whereas specific sit-to-stand muscle power was an independent predictor of death. No significant associations were observed between physical function and falls. CONCLUSIONS: Our findings indicate selective associations between physical function tests and the occurrence of negative events in very old adults, with poor IHG predicting disability and specific sit-to-stand muscle power being longitudinally associated with death.

Topical application of hyaluronic acid and amino acids in hard-to-heal wounds: a cost-effectiveness analysis.

OBJECTIVE: The aim of this cost-effectiveness analysis was to estimate the monetary cost required to achieve a gain in health benefit. An analytic model to evaluate the cost-effectiveness of a topical medical device comprising a mixture of hyaluronic acid and amino acids (HA+AA medical device) (Vulnamin, Professional Dietetics SpA, Italy) as compared to standard of care (SoC) for hard-to-heal (chronic) wounds is presented. METHOD: Retrospective data was analysed from a cohort of patients as well as information from published literature. For each paper, the following information was extracted: number of patients enrolled in each treatment arm and the results of prespecified reviewed outcomes. RESULTS: A total of six studies involving 378 patients were included in this pooled analysis. Findings showed that treatment with the HA+AA medical device has the potential to lower consumption of resources. With regards to wound healing, in both superficial and deep wounds, treatment benefits of the HA+AA medical device included: rapid wound size reduction; faster healing; reduction of dressing changes; reduced infection risk; and reduced treatment costs. Results showed the HA+AA medical device to be 32% more cost-effective than comparators in the treatment of hard-to-heal wounds (time horizon selected=six months). CONCLUSION: The findings of this analysis showed that treatment with the HA+AA medical device is a valid alternative to SoC care because it is cheaper, and its utility and effectiveness are greater. In addition, the results of the analysis showed a direct relationship between the time to complete healing and the increase in costs (increasing the period of time to reach complete healing increases the costs associated with the treatment).

Mitochondrial Quantity and Quality in Age-Related Sarcopenia.

Sarcopenia, the age-associated decline in skeletal muscle mass and strength, is a condition with a complex pathophysiology. Among the factors underlying the development of sarcopenia are the progressive demise of motor neurons, the transition from fast to slow myosin isoform (type II to type I fiber switch), and the decrease in satellite cell number and function. Mitochondrial dysfunction has been indicated as a key contributor to skeletal myocyte decline and loss of physical performance with aging. Several systems have been implicated in the regulation of muscle plasticity and trophism such as the fine-tuned and complex regulation between the stimulator of protein synthesis, mechanistic target of rapamycin (mTOR), and the inhibitor of mTOR, AMP-activated protein kinase (AMPK), that promotes muscle catabolism. Here, we provide an overview of the molecular mechanisms linking mitochondrial signaling and quality with muscle homeostasis and performance and discuss the main pathways elicited by their imbalance during age-related muscle wasting. We also discuss lifestyle interventions (i.e., physical exercise and nutrition) that may be exploited to preserve mitochondrial function in the aged muscle. Finally, we illustrate the emerging possibility of rescuing muscle tissue homeostasis through mitochondrial transplantation.

Platelets and Neurodegenerative Diseases: Current Knowledge and Future Perspectives.

Platelets have a fundamental role in mediating hemostasis and thrombosis. However, more recently, a new idea is making headway, highlighting the importance of platelets as significant actors in modulating immune and inflammatory responses. In particular, platelets have an important role in the development of vascular amyloid-b-peptide(ab) deposits, known to play a relevant role in Alzheimer's disease (AD) through accumulation and deposition within the frontal cortex and hippocampus in the brain. The involvement of platelets in the pathogenesis of AD opens up the highly attractive possibility of applying antiplatelet therapy for the treatment and/or prevention of AD, but conclusive results are scarce. Even less is known about the potential role of platelets in mild cognitive impairment (MCI). The aim to this brief review is to summarize current knowledge on this topic and to introduce the new perspectives on the possible role of platelet activation as therapeutic target both in AD and MCI.

Interleukin-1 Blockers in Recurrent and Acute Pericarditis: State of the Art and Future Directions.

Diseases of the pericardium encompass a spectrum of conditions, including acute and recurrent pericarditis, where inflammation plays a pivotal role in the pathogenesis and clinical manifestations. Anti-inflammatory therapy indeed forms the cornerstone of treating these conditions: NSAIDs, colchicine, and corticosteroids (as a second-line treatment) are recommended by current guidelines. However, these medications come with several contraindications and are not devoid of adverse effects. In recent years, there has been an increased focus on the role of the inflammasome and potential therapeutic targets. Recurrent pericarditis also shares numerous characteristics with other autoinflammatory diseases, in which interleukin-1 antagonists have already been employed with good efficacy and safety. The objective of this review is to summarize the available studies on the use of anti-IL-1 drugs both in acute and recurrent pericarditis.

Differential utility of various frailty diagnostic tools in non-geriatric hospital departments of several countries: A longitudinal study.

BACKGROUND: There is limited knowledge on the performance of different frailty scales in clinical settings. We sought to evaluate in non-geriatric hospital departments the feasibility, agreement and predictive ability for adverse events after 1 year follow-up of several frailty assessment tools. METHODS: Longitudinal study with 667 older adults recruited from five hospitals in three different countries (Spain, Italy and United Kingdom). Participants were older than 75 years attending the emergency room, cardiology and surgery departments. Frailty scales used were Frailty Phenotype (FP), FRAIL scale, Tilburg and Groningen Frailty Indicators, and Clinical Frailty Scale (CFS). Analyses included the prevalence of frailty, degree of agreement between tools, feasibility and prognostic value for hospital readmission, worsening of disability and mortality, by tool and setting. RESULTS: Emergency Room and cardiology were the settings with the highest frailty prevalence, varying by tool between 40.4% and 67.2%; elective surgery was the one with the lowest prevalence (between 13.2% and 38.2%). The tools showed a fair to moderate agreement. FP showed the lowest feasibility, especially in urgent surgery (35.6%). FRAIL, CFS and FP predicted mortality and readmissions in several settings, but disability worsening only in cardiology. CONCLUSIONS: Frailty is a highly frequent condition in older people attending non-geriatric hospital departments. We recommend that based upon their current feasibility and predictive ability, the FRAIL scale, CFS and FP should be preferentially used in these settings. The low concordance among the tools and differences in prevalence reported and predictive ability suggest the existence of different subtypes of frailty.

Biochemical Markers of Musculoskeletal Health and Aging to be Assessed in Clinical Trials of Drugs Aiming at the Treatment of Sarcopenia: Consensus Paper from an Expert Group Meeting Organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the Centre Académique de Recherche et d'Expérimentation en Santé (CARES SPRL), Under the Auspices of the World Health Organization Collaborating Center for the Epidemiology of Musculoskeletal Conditions and Aging.

In clinical trials, biochemical markers provide useful information on the drug's mode of action, therapeutic response and side effect monitoring and can act as surrogate endpoints. In pharmacological intervention development for sarcopenia management, there is an urgent need to identify biomarkers to measure in clinical trials and that could be used in the future in clinical practice. The objective of the current consensus paper is to provide a clear list of biochemical markers of musculoskeletal health and aging that can be recommended to be measured in Phase II and Phase III clinical trials evaluating new chemical entities for sarcopenia treatment. A working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) proposed classifying biochemical markers into 2 series: biochemical markers evaluating musculoskeletal status and biochemical markers evaluating causal factors. For series 1, the group agreed on 4 biochemical markers that should be assessed in Phase II or Phase III trials (i.e., Myostatin-Follistatin, Brain Derived Neurotrophic Factor, N-terminal Type III Procollagen and Serum Creatinine to Serum Cystatin C Ratio - or the Sarcopenia Index). For series 2, the group agreed on 6 biochemical markers that should be assessed in Phase II trials (i.e., the hormones insulin-like growth factor-1 (IGF-I), dehydroepiandrosterone sulphate, and cortisol, and the inflammatory markers C-reactive protein (CRP), interleukin-6 and tumor necrosis factor-α), and 2 in Phase III trials (i.e., IGF-I and CRP). The group also proposed optional biochemical markers that may provide insights into the mode of action of pharmacological therapies. Further research and development of new methods for biochemical marker assays may lead to the evolution of these recommendations.

Continuous glucose monitoring (CGM) in a non-Icu hospital setting: The patient's journey.

AIMS: Although consistent data support the outpatient use of continuous glucose monitoring (CGM) to improve glycemic control and reduce hypoglycemic burden, and clinical outcomes, there are limited data regarding its use in the hospital setting, particularly in the non-intensive care unit (non-ICU) setting. The emerging use of CGM in the non-critical care setting may be useful in increasing the efficiency of hospital care and reducing the length of stay for patients with diabetes while improving glycemic control. DATA SYNTHESIS: The purpose of this Expert Opinion paper was to evaluate the state of the art and provide a practical model of how CGM can be implemented in the hospital. SETTING: A patient's CGM journey from admission to the ward to the application of the sensor, from patient education on the device during hospitalization until discharge of the patient to maintain remote control. CONCLUSIONS: This practical approach for the implementation and management of CGM in patients with diabetes admitted to non-ICUs could guide hospitals in their diabetes management initiatives using CGM, helping to identify patients most likely to benefit and suggesting how this technology can be implemented to maximize clinical benefits.

LDL-cholesterol control in the primary prevention of cardiovascular diseases: An expert opinion for clinicians and health professionals.

AIMS: Although adequate clinical management of patients with hypercholesterolemia without a history of known cardiovascular disease is essential for prevention, these subjects are often disregarded. Furthermore, the scientific literature on primary cardiovascular prevention is not as rich as that on secondary prevention; finally, physicians often lack adequate tools for the effective management of subjects in primary prevention and have to face some unsolved relevant issues. This document aims to discuss and review the evidence available on this topic and provide practical guidance. DATA SYNTHESIS: Available algorithms and risk charts represent the main tool for the assessment of cardiovascular risk in patients in primary prevention. The accuracy of such an estimate can be substantially improved considering the potential contribution of some additional risk factors (C-reactive protein, lipoprotein(a), family history of cardiovascular disease) and conditions (environmental pollution, sleep quality, socioeconomic status, educational level) whose impact on the cardiovascular risk has been better understood in recent years. The availability of non-invasive procedures to evaluate subclinical atherosclerosis may help to identify subjects needing an earlier intervention. Unveiling the presence of these conditions will improve cardiovascular risk estimation, granting a more appropriate intervention. CONCLUSIONS: The accurate assessment of cardiovascular risk in subjects in primary prevention with the use of algorithms and risk charts together with the evaluation of additional factors will allow physicians to approach each patient with personalized strategies, which should translate into an increased adherence to therapy and, as a consequence, a reduced cardiovascular risk.

Adherence to aerobic training combined with high protein intake is associated with low blood pressure in Italian older adults: a cross-sectional study.

BACKGROUND: Lifestyle habits have a key role in cardiometabolic health. The effects of combined aerobic training (AT) and high protein intake (HPI) on cardiometabolic parameters in older adults are not well established. AIMS: To investigate the association of AT and HPI with blood pressure (BP), blood glucose, and total blood cholesterol levels in a sample of Italian older adults enrolled in the Longevity Check-up 7 + (Lookup 7 +) study. METHODS: Lookup 7 + is an ongoing project started in June 2015 and conducted in unconventional settings (e.g., exhibitions, malls, health promotion campaigns) across Italy with the aim of fostering adoption of healthy lifestyles in the general population. For the present investigation, analyses were conducted in participants 65 + years and with body mass index values ≥ 18.5 kg/m2 (n = 3219). Systolic (SBP) and diastolic BP (DBP), blood glucose, and total blood cholesterol were measured. Protein intake was estimated using a 12-item food frequency questionnaire. HPI was operationalized as a daily protein intake ≥ 0.8 g/kg of body weight. AT was operationalized as the practice of running and/or swimming for 60 + minutes at least twice weekly during the previous year. RESULTS: The mean age of the 3219 participants was 72.7 ± 5.7 years, and 55.2% were women. Adherence to AT combined with a HPI was negatively and independently associated with SPB (ß: - 4.976; 95% confidence interval: - 9.8 to - 0.08). No other significant associations were observed. DISCUSSION AND CONCLUSIONS: Our results indicate that AT combined with HPI was negatively associated with SBP in a large and relatively unselected sample of Italian older adults living in the community. These findings need confirmation by ad hoc designed studies.

Malnutrition in COVID-19 survivors: prevalence and risk factors.

BACKGROUND: Nutritional status is a critical factor throughout COVID-19 disease course. Malnutrition is associated with poor outcomes in hospitalized COVID-19 patients. AIM: To assess the prevalence of malnutrition and identify its associated factors in COVID-19 survivors. METHODS: Study cohort included 1230 COVID-19 survivors aged 18-86 attending a post-COVID-19 outpatient service. Data on clinical parameters, anthropometry, acute COVID-19 symptoms, lifestyle habits were collected through a comprehensive medical assessment. Malnutrition was assessed according to Global Leadership Initiative on Malnutrition (GLIM) criteria. RESULTS: Prevalence of malnutrition was 22% at 4-5 months after acute disease. Participants who were not hospitalized during acute COVID-19 showed a higher frequency of malnutrition compared to those who needed hospitalization (26% versus 19%, p < 0.01). Malnutrition was found in 25% COVID-19 survivors over 65 years of age compared to 21% younger participants (p < 0.01). After multivariable adjustment, the likelihood of being malnourished increased progressively and independently with advancing age (Odds ratio [OR] 1.02; 95% CI 1.01-1.03) and in male participants (OR 5.56; 95% CI 3.53-8.74). Malnutrition was associated with loss of appetite (OR 2.50; 95% CI 1.73-3.62), and dysgeusia (OR 4.05; 95% CI 2.30-7.21) during acute COVID-19. DISCUSSION: In the present investigation we showed that malnutrition was highly prevalent in a large cohort of COVID-19 survivors at 4-5 months from acute illness. CONCLUSIONS: Our findings highlight the need to implement comprehensive nutritional assessment and therapy as an integral part of care for COVID-19 patients.

Measuring health-related quality of life in sarcopenia: summary of the SarQoL psychometric properties.

Patient perspectives are now widely recognized as a key element in the evaluation of health interventions. Therefore, the provision of specific and validated Patient Reported Outcome Measures that emphasize the lived experience of patients suffering from specific diseases is very important. In the field of sarcopenia, the only validated specific health-related quality of life (HRQoL) instrument available is the Sarcopenia Quality of Life questionnaire (SarQoL). This self-administrated HRQoL questionnaire, developed in 2015, consists of 55 items arranged into 22 questions and has currently been translated into 35 languages. Nineteen validation studies performed on SarQoL have consensually confirmed the capacity of SarQoL to detect difference in HRQoL between older people with and without sarcopenia, its reliability and its validity. Two further observational studies have also indicated its responsiveness to change. A short form SarQoL, including only 14 items has further been developed and validated to reduce the potential burden of administration. Research on the psychometric properties of SarQoL questionnaire is still encouraged as the responsiveness to change of SarQoL has not yet been measured in the context of interventional studies, as limited prospective data currently exist and as there is still not cut-off score to define a low HRQoL. In addition, SarQoL has mainly been used in community-dwelling older individuals with sarcopenia and would benefit to be studied in other types of populations. This review aims to provide to researchers, clinicians, regulators, pharmaceutical industries and other stakeholders a clear summary of comprehensive evidence on the SarQoL questionnaire published up to January 2023Query.

Mitochondrial-Derived Vesicles: The Good, the Bad, and the Ugly.

Mitophagy is crucial for maintaining mitochondrial quality. However, its assessment in vivo is challenging. The endosomal-lysosomal system is a more accessible pathway through which subtypes of extracellular vesicles (EVs), which also contain mitochondrial constituents, are released for disposal. The inclusion of mitochondrial components into EVs occurs in the setting of mild mitochondrial damage and during impairment of lysosomal function. By releasing mitochondrial-derived vesicles (MDVs), cells limit the unload of mitochondrial damage-associated molecular patterns with proinflammatory activity. Both positive and negative effects of EVs on recipient cells have been described. Whether this is due to the production of EVs other than those containing mitochondria, such as MDVs, holding specific biological functions is currently unknown. Evidence on the existence of different MDV subtypes has been produced. However, their characterization is not always pursued, which would be relevant to exploring the dynamics of mitochondrial quality control in health and disease. Furthermore, MDV classification may be instrumental in understanding their biological roles and promoting their implementation as biomarkers in clinical studies.

Effects of l-Arginine Plus Vitamin C Supplementation on l-Arginine Metabolism in Adults with Long COVID: Secondary Analysis of a Randomized Clinical Trial.

Altered l-arginine metabolism has been described in patients with COVID-19 and has been associated with immune and vascular dysfunction. In the present investigation, we determined the serum concentrations of l-arginine, citrulline, ornithine, monomethyl-l-arginine (MMA), and symmetric and asymmetric dimethylarginine (SDMA, ADMA) in adults with long COVID at baseline and after 28-days of l-arginine plus vitamin C or placebo supplementation enrolled in a randomized clinical trial, compared with a group of adults without previous history of SARS-CoV-2-infection. l-arginine-derived markers of nitric oxide (NO) bioavailability (i.e., l-arginine/ADMA, l-arginine/citrulline+ornithine, and l-arginine/ornithine) were also assayed. Partial least squares discriminant analysis (PLS-DA) models were built to characterize systemic l-arginine metabolism and assess the effects of the supplementation. PLS-DA allowed discrimination of participants with long COVID from healthy controls with 80.2 ± 3.0% accuracy. Lower markers of NO bioavailability were found in participants with long COVID. After 28 days of l-arginine plus vitamin C supplementation, serum l-arginine concentrations and l-arginine/ADMA increased significantly compared with placebo. This supplement may therefore be proposed as a remedy to increase NO bioavailability in people with long COVID.

The Relationship between Post-COVID Syndrome and the Burden of Comorbidities Assessed Using the Charlson Comorbidity Index.

Introduction: The post-COVID-19 syndrome is a clinical entity characterized by the manifestation of signs and symptoms that develop after the acute phase of COVID-19, which persist for a duration of more than 12 weeks and are not explained by any alternative diagnosis. It has been observed that individuals with pre-existing chronic diseases, including cardiovascular and pulmonary diseases, are at a greater risk of developing post-COVID-19 syndrome. The Charlson Comorbidity Index (CCI) is a useful tool employed to evaluate the burden of comorbidities and predict the prognosis of patients with post-COVID-19 syndrome. The present study aims to assess whether the burden of comorbidities, evaluated using the CCI, correlates with post-COVID-19 syndrome. Materials and Methods: Between 21 April 2020 and 15 May 2023, we enrolled all consecutive outpatients with previous COVID-19 admissions to a post-acute day-hospital service three months after a negative SARS-CoV-2 molecular test. We assessed age, sex, BMI, acute COVID-19 and post-COVID-19 signs, and symptoms and calculated CCI according to its current definition. Post-COVID-19 syndrome was defined as the persistence of at least one sign or symptom lasting more than 12 weeks after COVID-19 resolution and not explained by an alternative diagnosis. The relationship between post-COVID-19 and CCI was explored first with the chi-squared test, then with different binary logistic regression models. We considered significant values of p lower than 0.05. Results: We obtained a cohort of 3636 patients and observed a significant association between the number of post-COVID-19 symptoms and CCI. Patients developing post-COVID-19 were more commonly affected by a greater burden of comorbidities. Patients with at least one CCI point had an increased risk of post-COVID-19 syndrome (OR:2.961; 95%CI: 2.269-3.863; p < 0.0001), which increased further for CCI ≥ 4 (OR:6.062; 95%CI: 3.163-11.618; p < 0.0001). Conclusions: Patients affected by post-COVID-19 show a greater clinical complexity and a larger burden of comorbidities, synthesized by a higher CCI; moreover, a higher CCI seems to correlate with an increasing post-COVID-19 risk, being the presence of ≥1 or ≥4 CCI points associated with a 3-fold and 6-fold increased risk of post-COVID-19 syndrome, respectively.

Role of Intestinal Inflammation and Permeability in Patients with Acute Heart Failure.

Background and Objectives: Heart failure (HF) represents a major health burden. Although several treatment regimens are available, their effectiveness is often unsatisfactory. Growing evidence suggests a pivotal role of the gut in HF. Our study evaluated the prognostic role of intestinal inflammation and permeability in older patients with acute HF (AHF), and their correlation with the common parameters traditionally used in the diagnostic-therapeutic management of HF. Materials and Methods: In a single-center observational, prospective, longitudinal study, we enrolled 59 patients admitted to the Emergency Department (ED) and then hospitalized with a diagnosis of AHF, from April 2022 to April 2023. Serum routine laboratory parameters and transthoracic echocardiogram were assayed within the first 48 h of ED admission. Fecal calprotectin (FC) and both serum and fecal levels of zonulin were measured, respectively, as markers of intestinal inflammation and intestinal permeability. The combined clinical outcome included rehospitalizations for AHF and/or death within 90 days. Results: Patients with increased FC values (>50 µg/g) showed significantly worse clinical outcomes (p < 0.001) and higher median levels of NT-proBNP (p < 0.05). No significant correlation was found between the values of fecal and serum zonulin and the clinical outcome. Median values of TAPSE were lower in those patients with higher values of fecal calprotectin (p < 0.05). After multivariate analysis, NT-proBNP and FC values > 50 µg/g resulted as independent predictors of a worse clinical outcome. Conclusions: Our preliminary finding supports the hypothesis of a close relationship between the gut and heart, recognizing in a specific marker of intestinal inflammation such as FC, an independent predictive prognostic role in patients admitted for AHF. Further studies are needed to confirm these results, as well as investigate the reliability of new strategies targeted at modulation of the intestinal inflammatory response, and which are able to significantly impact the course of diseases, mainly in older and frail patients.