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The aim of this study was to evaluate changes in the concentration of N-terminal type I collagen extension pro-peptide (PINP), tartrate-resistant acid phosphatase (TRAcP), and parathyroid hormone-related protein (PTHrP) in saliva during orthodontic treatment in order to evaluate whether changes in bone turnover marker (BTM) concentration can help highlight the effects of orthodontic mechanical loading in the absence of clinical evidence of tooth movement in terms of tooth movement. Saliva samples from 25 apparently healthy young subjects (10 females and 15 males) were collected using Salivette® (Sarstedt) with cotton swabs and the concentrations of PTHrP, TRAcP 5b, and PINP were analyzed at time 0 (T1), 25 days (T2), and at 45 days (T3). Differences in the median value of biomarker levels between baseline T1 and follow-up of the different groups (T2 and T3) were assessed using the non-parametric Mann-Whitney U test. Trough concentrations of P1NP, PTHrP, and TRAcP were 0.80 µg/L, 0.21 ng/mL, and 0.90 U/L above the method LOD. The non-parametric Mann-Whitney U test confirmed a statistically significant difference in T1 versus concentrations of T2 and T3. All subjects evaluated had a statistically significant difference between T1 vs. T3. when compared with the specific critical difference (RCV) for the analyte The results obtained demonstrate that the evaluation of BTM changes in saliva can help the evaluation of orthodontic procedures and the monitoring of biomechanical therapy.
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The purpose of the present study was to evaluate the concentrations of some bone turnover markers in preterm neonates with uncomplicated clinical course in the first month of life. Samples from 13 preterm neonates were collected at three different times: at birth (T0) from umbilical cord blood (UCB); and at 15 (T1) and 30 (T2) days of life from peripheral blood (PB). The concentrations of calcium (Ca), phosphate (P), total alkaline phosphatase (ALP), Collagen Type 1 Amino-terminal Propeptide (PINP), osteocalcin (OC), Collagen Type 1 Carboxyl-Terminal Telopeptide (CTX) and Leptin were assessed. A statistically significant difference for ALP concentration at birth versus T1 and T2 was found. An evident increase in the median concentrations of CTX, OC and PINP from T0 to T2 were observed. A significant difference was also found for Leptin concentration at T0 compared to T1. In preterm infants, in the absence of acute or chronic medical conditions and without risk factors for metabolic bone disease (MBD) of prematurity, there is a significant increase in bone turnover markers during the first month of life. The knowledge of the variations in these markers in the first weeks of life, integrated by the variations in the biochemical indicators of bone metabolism, could help in recognizing any conditions at risk of developing bone diseases.
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BACKGROUND: Immunocompromised patients show an impaired vaccine response and remain at high risk of severe COVID-19, despite vaccination. Neutralizing monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed for prophylaxis and treatment. The combination tixagevimab/cilgavimab (AZD7442) has been authorized for emergency use as pre-exposure prophylaxis for COVID-19, but data on safety and efficacy in kidney transplant recipients during the Omicron period are limited. METHODS: We conducted a multicenter retrospective cohort study including 253 kidney transplant recipients, of whom 98 were treated with tixagevimab/cilgavimab 150 mg/150 mg and 155 who received only four doses of the BNT162b2 mRNA vaccine. RESULTS: Only 13.3% of patients developed SARS-CoV-2 infection after the administration of tixagevimab/cilgavimab; in comparison, 34.2% of patients had been infected after the fourth dose of vaccine (p = 0.00013). Most infected patients in the AZD7442 group remained asymptomatic (92.3% vs 54.7%), 7.7% had mild symptoms and none had severe disease, need for hospitalization or died, while in the control group, 9.4% of patients had moderate or severe disease (p = 0.04). Using Kaplan-Meier curves we demonstrated that the controls presented early infection compared to the AZD7442 group (p = 0.000014). No changes in eGFR or proteinuria, assessed before and after the administration, were observed. CONCLUSIONS: In conclusion, our study showed that tixagevimab/cilgavimab 150/150 mg is effective and safe in preventing infection and severe disease when administered to patients with weak or no response to COVID-19 vaccine.
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BACKGROUND: Sepsis is characterized by a dysregulated immune response and metabolic alterations, including decreased high-density lipoprotein cholesterol (HDL-C) levels. HDL exhibits beneficial properties, such as lipopolysaccharides (LPS) scavenging, exerting anti-inflammatory effects and providing endothelial protection. We investigated the effects of CER-001, an engineered HDL-mimetic, in a swine model of LPS-induced acute kidney injury (AKI) and a Phase 2a clinical trial, aiming to better understand its molecular basis in systemic inflammation and renal function. METHODS: We carried out a translational approach to study the effects of HDL administration on sepsis. Sterile systemic inflammation was induced in pigs by LPS infusion. Animals were randomized into LPS (n = 6), CER20 (single dose of CER-001 20 mg/kg; n = 6), and CER20 × 2 (two doses of CER-001 20 mg/kg; n = 6) groups. Survival rate, endothelial dysfunction biomarkers, pro-inflammatory mediators, LPS, and apolipoprotein A-I (ApoA-I) levels were assessed. Renal and liver histology and biochemistry were analyzed. Subsequently, we performed an open-label, randomized, dose-ranging (Phase 2a) study included 20 patients with sepsis due to intra-abdominal infection or urosepsis, randomized into Group A (conventional treatment, n = 5), Group B (CER-001 5 mg/kg BID, n = 5), Group C (CER-001 10 mg/kg BID, n = 5), and Group D (CER-001 20 mg/kg BID, n = 5). Primary outcomes were safety and efficacy in preventing AKI onset and severity; secondary outcomes include changes in inflammatory and endothelial dysfunction markers. RESULTS: CER-001 increased median survival, reduced inflammatory mediators, complement activation, and endothelial dysfunction in endotoxemic pigs. It enhanced LPS elimination through the bile and preserved liver and renal parenchyma. In the clinical study, CER-001 was well-tolerated with no serious adverse events related to study treatment. Rapid ApoA-I normalization was associated with enhanced LPS removal and immunomodulation with improvement of clinical outcomes, independently of the type and gravity of the sepsis. CER-001-treated patients had reduced risk for the onset and progression to severe AKI (stage 2 or 3) and, in a subset of critically ill patients, a reduced need for organ support and shorter ICU length of stay. CONCLUSIONS: CER-001 shows promise as a therapeutic strategy for sepsis management, improving outcomes and mitigating inflammation and organ damage. TRIAL REGISTRATION: The study was approved by the Agenzia Italiana del Farmaco (AIFA) and by the Local Ethic Committee (N° EUDRACT 2020-004202-60, Protocol CER-001- SEP_AKI_01) and was added to the EU Clinical Trials Register on January 13, 2021.
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Injúria Renal Aguda , Sepse , Humanos , Animais , Suínos , Lipoproteínas HDL , Apolipoproteína A-I/uso terapêutico , Apolipoproteína A-I/química , Apolipoproteína A-I/farmacologia , Lipopolissacarídeos , Pesquisa Translacional Biomédica , Inflamação , Sepse/tratamento farmacológico , Injúria Renal Aguda/tratamento farmacológico , Mediadores da InflamaçãoRESUMO
BACKGROUND: COVID-19 in kidney transplant recipients is associated with high morbidity and mortality. In this study we aimed to evaluate: (i) the seroconversion rate after BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 vaccine, (ii) factors associated with humoral response, (iii) clinical outcome of COVID-19 in kidney transplanted patients. METHODS: We enrolled a cohort of 743 kidney transplant recipients followed up from March 2020 until April 2022. A subset of 336 patients, who received three-doses of SARS-CoV-2 vaccine, was analyzed in terms of kinetics of humoral immune response and compared to a control group of 94 healthcare workers. Antibody response was tested before vaccination (T0), 15 and 90 days after the second dose (T1 and T2), on the day of the third dose (T3) and one month after the third dose (T4). RESULTS: We observed that 66 out of 743 subjects had COVID-19 infection pre-vaccination: 65.2% had severe symptoms, 27.3% were hospitalized (9 deaths), none were asymptomatic. After three doses, 51 patients had COVID-19 infection, 60.8% were asymptomatic, 27.5% reported mild symptoms, 3.9% showed severe symptoms, 7.8% were hospitalized (2 deaths). In the subset of 336 vaccinated patients, an antibody level > 0.8 U/ml was detected at T1, that increased at T2 and T3, peaking at T4. Independent factors associated with a negative antibody titer at T4 were decreasing estimated glomerular filtration rate, time from transplantation, and antimetabolites (all p < 0.001) and age (p = 0.007). CONCLUSIONS: The kinetics of humoral response after three doses of vaccine in kidney transplant patients is characterized by a late but effective immune response against SARS-CoV-2, reducing morbidity and mortality.
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COVID-19 , Transplante de Rim , Humanos , Vacinas contra COVID-19 , Imunidade Humoral , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Vacina BNT162 , Cinética , Transplante de Rim/efeitos adversos , Transplantados , Vacinas de mRNARESUMO
PURPOSE: to investigate the effects of intensive chemotherapy and glucocorticoid (GC) treatment on bone remodeling markers in children with acute lymphoblastic leukemia (ALL). METHODS: A cross-sectional study was carried out in 39 ALL children (aged 7.64 ± 4.47) and 49 controls (aged 8.7 ± 4.7 years). Osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL), osteocalcin (OC), C-terminal telopeptide of type I collagen (CTX), bone alkaline phosphatase (bALP), tartrate-resistant acid phosphatase 5b (TRACP5b), procollagen type I N-terminal propeptide (P1NP), Dickkopf-1 (DKK-1), and sclerostin were assessed. Statistical analysis was conducted using the principal component analysis (PCA) to study patterns of associations in bone markers. RESULTS: ALL patients showed significantly higher OPG, RANKL, OC, CTX, and TRACP5b than the controls (p ≤ 0.02). Considering ALL group, we found a strong positive correlation among OC, TRACP5b, P1NP, CTX, and PTH (r = 0.43-0.69; p < 0.001); between CTX and P1NP (r = 0.5; p = 0.001); and between P1NP and TRAcP (r = 0.63; p < 0.001). The PCA revealed OC, CTX, and P1NP as the main markers explaining the variability of the ALL cohort. CONCLUSIONS: Children with ALL showed a signature of bone resorption. The assessment of bone biomarkers could help identify ALL individuals who are most at risk of developing bone damage and who need preventive interventions.
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Mucin1 (MUC1), a glycoprotein associated with an aggressive cancer phenotype and chemoresistance, is aberrantly overexpressed in a subset of clear cell renal cell carcinoma (ccRCC). Recent studies suggest that MUC1 plays a role in modulating cancer cell metabolism, but its role in regulating immunoflogosis in the tumor microenvironment remains poorly understood. In a previous study, we showed that pentraxin-3 (PTX3) can affect the immunoflogosis in the ccRCC microenvironment by activating the classical pathway of the complement system (C1q) and releasing proangiogenic factors (C3a, C5a). In this scenario, we evaluated the PTX3 expression and analyzed the potential role of complement system activation on tumor site and immune microenvironment modulation, stratifying samples in tumors with high (MUC1H) versus tumors with low MUC1 expression (MUC1L). We found that PTX3 tissue expression was significantly higher in MUC1H ccRCC. In addition, C1q deposition and the expressions of CD59, C3aR, and C5aR were extensively present in MUC1H ccRCC tissue samples and colocalized with PTX3. Finally, MUC1 expression was associated with an increased number of infiltrating mast cells, M2-macrophage, and IDO1+ cells, and a reduced number of CD8+ T cells. Taken together, our results suggest that expression of MUC1 can modulate the immunoflogosis in the ccRCC microenvironment by activating the classical pathway of the complement system and regulating the immune infiltrate, promoting an immune-silent microenvironment.
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Carcinoma de Células Renais , Neoplasias Renais , Mucina-1 , Microambiente Tumoral , Humanos , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Ativação do Complemento , Complemento C1q/metabolismo , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Macrófagos/imunologia , Mucina-1/metabolismo , Microambiente Tumoral/imunologiaRESUMO
AIM OF THE STUDY: We evaluated and compared blood gas analysis (EGA) non-conformities (NC) considered operator-dependent performed in Point-Of-Care (POC) analyzer as quality indicators (IQ) of the pre-analytical phase. To this end, four different NC registered in the resuscitation departments of the Hospital Polyclinic Bari from the beginning of the pandemic (March 2020) until February 2022 were evaluated. The results obtained were compared with those recorded in the pre-COVID period (March 2018-February 2020) to check if there were differences in number and type. MATERIAL AND METHODS: GEM 4000 series blood gas analyzers (Instrumentation Laboratory, Bedford, MA, United States) are installed with integrated Intelligent Quality Management (iQM®), which automatically identify and log pre-analytical errors. All blood gas analyzers are connected to the company intranet and interfaced with the GEM Web Plus (Werfen Instrumentation Laboratory, Bedford, MA, United States) data management information system, which allows the core laboratory to remotely supervise all decentralized POC stations. The operator-dependent process NC were expressed in terms of absolute and relative proportions (percentiles and percentage changes). For performance evaluation, the Mann-Whitney U test, Chi-squared test and Six-Sigma Metric calculation for performance classification were performed. RESULTS: In the COVID period, 31,364 blood gas tests were performed vs. 16,632 tests in the pre-COVID period. The NC related to the suitability of the EGA sample and manageable by the operators were totals of 652 (3.9%) and 749 (2.4%), respectively, in the pre-COVID and COVID periods. The pre-analytical phase IQs used did not show statistically significant differences in the two periods evaluated. The Sigma evaluation did not show an increase in error rates. CONCLUSIONS: Considering the increase in the number of EGAs performed in the two periods, the training procedures performed by the core laboratory staff were effective; the clinical users of the POC complied with the indications and procedures shared with the core laboratory without increasing the operator-dependent NCs. Furthermore, the core laboratory developed monitoring activities capable of guaranteeing the maintenance of the pre-analytical quality.
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Brain-type creatine kinase (CK-BB) increases during osteoclastogenesis, with high circulating amounts in type I osteogenesis imperfecta (OI) following treatment with neridronate, a bisphosphonate able to inhibit osteoclast activity and survival. The aim of this study was to demonstrate the correlation between osteoclastogenesis and CK-BB release from OI patients' osteoclasts treated with different concentrations of neridronate. Our patients showed reduced bone quality, increased levels of CTX I, a marker of bone resorption, and decreased levels of OPG, an inhibitor of osteoclastogenesis. In OI patients, the presence of MCSF and RANKL determined an increased secretion of CK-BB from osteoclasts (p = 0.04) compared with control conditions without these cytokines; interestingly, in the absence of these factors, the secretion of CK-BB is significantly elevated at 3 µmol/L compared with 0.03 and 1 µmol/L (p = 0.007). In healthy donors' cultures, the higher concentration of CK-BB can be detected following stimulation with 3 µmol/L neridronate compared with the untreated condition both with and without MCSF and RANKL (p = 0.03 and p = 0.006, respectively). Consistently, in osteoclast cultures, neridronate treatment is associated with a decrease in multinucleated TRAP+ cells, together with morphology changes typical of apoptosis. Consistently, in the media of the same osteoclast cultures, we demonstrated a significant increase in caspase-3 levels. In conclusion, our findings support the idea that CK-BB levels increase in the serum of OI-treated patients.
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OBJECTIVES: The aim of this study was to relate IL-6 and IL-1ß serum levels with the severity of olfactory disorders and with the type of unperceived odors. METHODS: 82 inpatients (45 men aged 62.3 ± 14.2 and 37 women aged 57.1 ± 12.8) with only smell dysfunctions were divided into two groups. The evaluation of the smell disorder was carried out with a questionnaire to define which sensitivity is most compromised in COVID-19 patients. Cytokine levels were measured with chemiluminescence and ELISA assay. Statistical analyses were performed with the Wilcoxon Rank test, Welch's T-test, and Mann-Whitney test (p < 0.05). RESULTS: Statistically significant differences in IL-6 and IL-1 ß levels were found in moderate disease patients when there was an impairment of trigeminal sensitivity (p <0.05) and trigeminal and olfactory sensitivity. CONCLUSIONS: The results obtained showed that in COVID-19 patients the impairment of trigeminal sensitivity in association with olfactory sensitivity was more prevalent in moderate than in mild forms.
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COVID-19 , Transtornos do Olfato , Masculino , Humanos , Feminino , SARS-CoV-2 , Estudos Retrospectivos , Interleucina-6 , Pacientes Internados , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/etiologiaRESUMO
A large percentage of coronavirus disease 2019 (COVID-19) patients have taste dysfunction. Interleukin 6 (IL-6) levels in mild and moderate COVID-19 patients with the type (quantitative or qualitative) of taste disorders were compared in this observational study. The 208 COVID-19 patients (118 men and 90 women) revealing only taste dysfunctions as prodromic symptoms were classified as mild and moderate patients. Survey results were used to evaluate the taste disorder. The IL-6 levels were measured using a chemiluminescence assay. Statistical analysis was conducted using the Wilcoxon rank, Welch's, and Mann-Whitney tests. The findings revealed that neither the presence of dysgeusia or phantogeusia nor the perception of sour and salty, differed statistically significantly between moderate and mild patients (P > 0.05). But between moderate and mild patients, there were statistically significant differences in how umami, bitter, sweet, and parageusia were perceived (P < 0.05). There was an impairment of multiple tastes up to ageusia in patients with high IL-6 levels. The findings demonstrated that parageusia and dysfunctions in umami, bitter, and sweet taste perception can be indicators of more severe forms of COVID-19.
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COVID-19 , Paladar , Masculino , Humanos , Feminino , Disgeusia/etiologia , Interleucina-6 , Percepção Gustatória , Distúrbios do Paladar/etiologiaRESUMO
Background: The measurement of Fibroblast growth factor 23 (FGF23) may be useful in the diagnosis and management of abnormal phosphate metabolism in both patients with preserved renal function or with chronic kidney disease (CKD). FGF-23 tests differ considerably by molecule assayed (iFGF23 or cFGF23), analytical performance and reference ranges. We establish iFGF23 Upper Reference Limits (URL) in apparently healthy pediatric individuals using automated immunochemiluminescent assay. Methods: We measured the levels of plasma iFGF23 from 115 samples from apparently healthy pediatric subjects [59 (51.3%) individuals were male; median age 10 years (range 1-18)] included in an observational study conducted at Policlinico University Hospital of Bari. The method used for the iFGF23 assay was immunochemiluminescent sandwich assay developed by DiaSorin on the Liaison XL platform. Statistical calculation of 95% reference interval, right-sided (CLSI C28-A3) and verification of age and sex covariables was performed for the calculation of the URL. Results: The URL concentration of iFGF23 was 61.21 pg/mL (58.63 to 63.71, 90% CI). No significant differences were found between the median concentrations of iFGF23 differentiated by sex and age. Conclusions: The dosage of iFGF23 is important both for the differential diagnosis of the various forms of rickets, and for the subsequent monitoring of the effectiveness of drug treatment. We have established the URL for the iFGF23 Liaison test in apparently healthy pediatric subjects. The availability of iFGF23 pediatric reference values will allow a better clinical use of the test.
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Fatores de Crescimento de Fibroblastos , Insuficiência Renal Crônica , Humanos , Masculino , Criança , Lactente , Pré-Escolar , Adolescente , Feminino , Insuficiência Renal Crônica/diagnóstico , Valores de Referência , Fosfatos , Nível de SaúdeRESUMO
Serological assays are useful in investigating the development of humoral immunity against SARS-CoV-2 in the context of epidemiological studies focusing on the spread of protective immunity. The plaque reduction neutralization test (PRNT) is the gold standard method to assess the titer of protective antibodies in serum samples. However, to provide a result, the PRNT requires several days, skilled operators, and biosafety level 3 laboratories. Therefore, alternative methods are being assessed to establish a relationship between their outcomes and PRNT results. In this work, four different immunoassays (Roche Elecsys® Anti SARS-CoV-2 S, Snibe MAGLUMI® SARS-CoV-2 S-RBD IgG, Snibe MAGLUMI® 2019-nCoV IgG, and EUROIMMUN® SARS-CoV-2 NeutraLISA assays, respectively) have been performed on individuals healed after SARS-CoV-2 infection. The correlation between each assay and the reference method has been explored through linear regression modeling, as well as through the calculation of Pearson's and Spearman's coefficients. Furthermore, the ability of serological tests to discriminate samples with high titers of neutralizing antibodies (>160) has been assessed by ROC curve analyses, Cohen's Kappa coefficient, and positive predictive agreement. The EUROIMMUN® NeutraLISA assay displayed the best correlation with PRNT results (Pearson and Spearman coefficients equal to 0.660 and 0.784, respectively), as well as the ROC curve with the highest accuracy, sensitivity, and specificity (0.857, 0.889, and 0.829, respectively).
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COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/diagnóstico , Teste para COVID-19 , Humanos , Imunoglobulina G , Sensibilidade e Especificidade , Testes Sorológicos/métodosRESUMO
Parathyroid hormone-related peptide (PTHrP) is expressed at a wide range of sites in the body and performs different functions including vasodilation, relaxation of smooth muscle cells, and regulation of bone development. PTHrP also mediates hypercalcemia related to neoplastic diseases. However, reference ranges specific method and age were not evaluated. We establish PTHrP reference ranges in apparently healthy, normocalcemic, normophosphatemic pediatric individuals. In this observational prospective, study we measured PTHrP in serum from 178 samples (55.06% male 44.94% female) from apparently healthy pediatric subjects [median age 10 years (range 1-18)] subunit ELISA method The statistical analysis performed provided for the calculation of the 95% reference interval, right-sided, with a non-parametric percentile method (CLSI C28-A3). Upper reference limits (URL) for PTHrP was 2.89 ng/mL (2.60 to 3.18; 90% CI). No significant differences were found between the median PTHrP concentrations in males vs females and in the age range categories selected. Comprehensive normal values for PTHrP are indispensable to the assessment of calcium phosphorus dysfunction in children. Severe hypercalcemia is a rare, but clinically significant condition, in infancy and childhood. PTHrP values higher than the reference value may help to distinguish the hypercalcemic product of a malignancy, paraneoplastic syndromes mediated by PTHrP, from other causes.
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Background: Charcot-Marie-Tooth (CMT) indicates a group of inherited polyneuropathies whose clinical phenotypes primarily include progressive distal weakness and muscle atrophy. Compelling evidence showed that the exercise-mimetic myokine irisin protects against muscle wasting in an autocrine manner, thus possibly preventing the onset of musculoskeletal atrophy. Therefore, we sought to determine if irisin serum levels correlate with biochemical and muscle parameters in a cohort of CMT patients. Methods: This cohort study included individuals (N=20) diagnosed with CMT disease. Irisin and biochemical markers were quantified in sera. Skeletal muscle mass (SMM) was evaluated by bioelectric impedance analysis, muscle strength by handgrip, and muscle quality was derived from muscle strength and muscle mass ratio. Results: CMT patients (m/f, 12/8) had lower irisin levels than age and sex matched healthy subjects (N=20) (6.51 ± 2.26 vs 9.34 ± 3.23 µg/ml; p=0.003). SMM in CMT patients was always lower compared to SMM reference values reported in healthy Caucasian population matched for age and sex. Almost the totality of CMT patients (19/20) showed low muscle quality and therefore patients were evaluated on the basis of muscle strength. Irisin was lower in presence of pathological compared to normal muscle strength (5.56 ± 1.26 vs 7.67 ± 2.72 µg/ml; p=0.03), and directly correlated with the marker of bone formation P1PN (r= 0.669; 95%CI 0.295 to 0.865; p=0.002), but inversely correlated with Vitamin D (r=-0.526; 95%CI -0,791 to -0,095; p=0.017). Surprisingly, in women, irisin levels were higher than in men (7.31 ± 2.53 vs 5.31 ± 1.02 µg/ml, p=0.05), and correlated with both muscle strength (r=0.759; 95%CI 0.329 to 0.929; p=0.004) and muscle quality (r=0.797; 95%CI 0.337 to 0.950; p=0.006). Conclusion: Our data demonstrate lower irisin levels in CMT patients compared to healthy subjects. Moreover, among patients, we observed, significantly higher irisin levels in women than in men, despite the higher SMM in the latter. Future studies are necessary to establish whether, in this clinical contest, irisin could represent a marker of the loss of muscle mass and strength and/or bone loss.
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Doença de Charcot-Marie-Tooth , Fibronectinas , Força da Mão , Atrofia Muscular , Biomarcadores , Doença de Charcot-Marie-Tooth/diagnóstico , Estudos de Coortes , Feminino , Fibronectinas/sangue , Humanos , Masculino , Músculo Esquelético , Atrofia Muscular/etiologiaRESUMO
BACKGROUND: Risky alcohol consumption can occur from a young age and affects people of all age groups, sometimes requiring the intervention of the emergency medical services. OBJECTIVES: Determining the timing and characteristics of emergency calls (to the "118" emergency number) relating to subjects in all age groups, in which alcohol was a contributing factor, along with the biochemical correlates, in a great metropolitan area. On the basis of these, future interventions would target specific training for nurses and paramedics working in emergency medical services. METHOD: An observational single-centre retrospective study carried out from 1 January 2014 to 31 December 2018 involving patients requiring emergency care and attending the Emergency Department of an University Hospital. RESULTS: Out of a total of 47,252 emergency calls, 2.22% were for alcohol-related conditions and mainly involved male patients (78.4%). A high incidence of alcoholic coma was found in patients aged 11 to 17 years. Emergency medical assistance was required mainly at night on weekdays by patients aged 11-17, 25-44 years and during the weekend and on weekdays by patients aged 18-24 years. A blood alcohol concentration higher than 50 mg/dL was found in more than 67% of patients aged 11-17 and 18-24 years at weekends. CONCLUSIONS: The most alarming finding from our data is that, despite prevention policies, young people requiring emergency medical assistance showed similar alcohol levels as adults and a high incidence of alcoholic coma.
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Intoxicação Alcoólica , Serviços Médicos de Emergência , Adolescente , Adulto , Intoxicação Alcoólica/complicações , Intoxicação Alcoólica/epidemiologia , Concentração Alcoólica no Sangue , Serviço Hospitalar de Emergência , Hospitais Universitários , Humanos , Masculino , Estudos RetrospectivosRESUMO
The coronavirus disease 2019 (COVID-19) pandemic has affected hundreds of millions of individuals and caused millions of deaths worldwide. Predicting the clinical course of the disease is of pivotal importance to manage patients. Several studies have found hematochemical alterations in COVID-19 patients, such as inflammatory markers. We retrospectively analyzed the anamnestic data and laboratory parameters of 303 patients diagnosed with COVID-19 who were admitted to the Polyclinic Hospital of Bari during the first phase of the COVID-19 global pandemic. After the pre-processing phase, we performed a survival analysis with Kaplan-Meier curves and Cox Regression, with the aim to discover the most unfavorable predictors. The target outcomes were mortality or admission to the intensive care unit (ICU). Different machine learning models were also compared to realize a robust classifier relying on a low number of strongly significant factors to estimate the risk of death or admission to ICU. From the survival analysis, it emerged that the most significant laboratory parameters for both outcomes was C-reactive protein min; HR=17.963 (95% CI 6.548-49.277, p < 0.001) for death, HR=1.789 (95% CI 1.000-3.200, p = 0.050) for admission to ICU. The second most important parameter was Erythrocytes max; HR=1.765 (95% CI 1.141-2.729, p < 0.05) for death, HR=1.481 (95% CI 0.895-2.452, p = 0.127) for admission to ICU. The best model for predicting the risk of death was the decision tree, which resulted in ROC-AUC of 89.66%, whereas the best model for predicting the admission to ICU was support vector machine, which had ROC-AUC of 95.07%. The hematochemical predictors identified in this study can be utilized as a strong prognostic signature to characterize the severity of the disease in COVID-19 patients.
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COVID-19 , Mortalidade Hospitalar , Humanos , Aprendizado de Máquina , Prognóstico , Estudos Retrospectivos , SARS-CoV-2 , Análise de SobrevidaRESUMO
OBJECTIVES: Galectin-3 is ß-galactoside-binding lectin with several roles in immune-inflammatory response. To date, there is no evidence of Galectin-3 role as a prognostic biomarker in COVID-19 disease. The aim of this study is to clarify the prognostic role of Galectin-3 in patients with COVID 19 acute respiratory failure. METHODS: We enrolled 156 consecutive patients with COVID-19 disease. Routine laboratory test, arterial blood gas, chest X-ray or Computed Tomography and Galectin-3 dosage were performed. The primary outcome was to assess Galectin-3 predictive power for 30-day mortality. Secondary outcomes were 30-day Intensive Care Unit admission and Acute Respiratory Distress Syndrome stratification according to Galectin-3 dosage. We performed Mann-Whitney U and Kruskal-Wallis tests for continuous variables comparison. Fisher's exact test or Chi-square test were used for categorical variables analysis. Receiver Operating Characteristic curves estimated Galectin-3 predictive power for the endpoints. With a fixed cut-off of 35.3 ng/ml, Kaplan-Meier with Log-Rank test and Cox Regression were performed to assess mortality and Intensive Care Unit admission risk. RESULTS: Galectin-3 correlated with many other prognostic predictors tested in our analysis. Moreover, patients with serum levels of Galectin-3 above 35.3 ng/ml had increased risk for mortality, Intensive Care Unit admission and severe Acute Respiratory Distress Syndrome. CONCLUSIONS: Our study demonstrates the role of Galectin-3 as a predictor of mortality, Intensive Care Unit access and ARDS stratification in patients with COVID 19 acute respiratory failure.
Assuntos
COVID-19/sangue , COVID-19/mortalidade , Galectinas/sangue , Síndrome do Desconforto Respiratório/sangue , Síndrome do Desconforto Respiratório/virologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteínas Sanguíneas , COVID-19/complicações , Cuidados Críticos , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Síndrome do Desconforto Respiratório/mortalidade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
The aim of this study was to evaluate the levels of vitamin D (25OHD) and other bone biomarkers in patients with third molar impaction (TMI). Thirty males and 30 females with unilateral or bilateral impacted mandibular third molar, and 15 males and 15 females as a control group (CG) were recruited. Rx-OPT was used to evaluate dental position and Pederson index to measure the difficulty of the intervention. Bone biomarkers were measured through blood venous sample in TMI group and CG. Mann-Whitney test, Pearson's correlation coefficient, linear regression model were used to compare the different parameters in the two groups. 25OHD showed lower values in TMI group than in CG (p < 0.05) with values significantly lower in bilateral impaction (p < 0.05). Pearson's coefficient for 25OHD presented a negative correlation with the Pederson index (ρ = -0.75). Bone alkaline phosphatase (BALP) showed significantly lower dosage in TMI group than CG (p = 0.02), Pearson's coefficient for BALP presented a negative correlation with the Pederson index. Serum calcium, serum phosphorus, ionized calcium levels in TMI and CG groups were similar and Mann-Whitney test did not significantly differ between TMI and CG. TMI could be a sign of vitamin D deficiency and of low BALP levels that should be investigated.
Assuntos
Fosfatase Alcalina/sangue , Cálcio/sangue , Dente Serotino , Fósforo/sangue , Dente Impactado/sangue , Vitamina D/sangue , Adolescente , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Dente Serotino/patologia , Dente Impactado/etiologia , Dente Impactado/patologia , Deficiência de Vitamina D/complicações , Adulto JovemRESUMO
BACKGROUND: Hypothyroidism is a frequently observed comorbidity in patients with chronic heart failure (CHF), possibly giving rise to unfavorable outcomes. AIM: The aim of the study was to evaluate the impact of TSH changes over time on cardiac function and prognosis of outpatients with CHF. METHODS: Patients underwent clinical, electrocardiographic, and echocardiographic evaluations at baseline and after 12 months. Moreover, blood chemistry tests were performed to evaluate renal function, cardiac biomarkers, fT3, fT4, and TSH levels. Based on TSH serum levels, patients were retrospectively classified into four categories: Group 1, patients with improved thyroid function at one-year follow up vs. baseline; Group 2, patients with stable and mildly high TSH values (3.74 - 10 mUI/L); Group 3, patients with worsening thyroid function; Euthyroid patients Group, TSH levels within the normal range of reference at baseline as well as at 12 months follow-up. We considered as end-points: one-year changes of laboratory and echocardiographic parameters; hospitalizations due to worsening of HF (acute decompensated heart failure - ADHF); death for all causes. RESULTS: Among 257 patients, 174 (67.7%) were euthyroid at baseline and after 12 months. Group 1 patients (n. 22, 8.6%) showed a significant improvement in systolic and diastolic function, filling pressures, NT-proBNP and Galectin-3. Group 2 patients (n. 34, 13.2%) did not exhibit significant modifications in studied parameters. Group 3 patients (n. 27, 10.5%) showed worsening of diastolic function and NT-proBNP and a greater risk of ADHF (HR: 2.12; 95%CI: 1.20-3.74; p: 0.009) and death (HR: 4.05; 95%CI: 2.01-8.15; p<0.001). CONCLUSION: In patients with CHF, changes in thyroid function over time influenced echocardiographic parameters and biomarkers reflecting modifications of cardiac function and prognosis, thus suggesting the clinical relevance of thyroid deficiency screening and correction.