Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 707
Filtrar
1.
EClinicalMedicine ; : 100941, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34127959

RESUMO

Background: Effective home treatment algorithms implemented based on a pathophysiologic and pharmacologic rationale to accelerate recovery and prevent hospitalisation of patients with early coronavirus disease 2019 (COVID-19) would have major implications for patients and health system. Methods: This academic, matched-cohort study compared outcomes of 90 consecutive consenting patients with mild COVID-19 treated at home by their family physicians between October 2020 and January 2021 in Northern and Central Italy, according to the proposed recommendation algorithm, with outcomes for 90 age-, sex-, and comorbidities-matched patients who received other therapeutic regimens. Primary outcome was time to resolution of major symptoms. Secondary outcomes included prevention of hospitalisation. Analyses were by intention-to-treat. Findings: All patients achieved complete remission. The median [IQR] time to resolution of major symptoms was 18 [14-23] days in the 'recommended schedule' cohort and 14 [7-30] days in the matched 'control' cohort (p = 0·033). Other symptoms persisted in a lower percentage of patients in the 'recommended' than in the 'control' cohort (23·3% versus 73·3%, respectively, p<0·0001) and for a shorter period (p = 0·0107). Two patients in the 'recommended' cohort were hospitalised compared to 13 (14·4%) controls (p = 0·0103). The prevention algorithm reduced the days and cumulative costs of hospitalisation by >90%. Interpretation: Implementation of an early home treatment algorithm failed to accelerate recovery from major symptoms of COVID-19, but reduced the risk of hospitalisation and related treatment costs. Given the study design, additional research would be required to consolidate the proposed treatment recommendations. Funding: Fondazione Cav.Lav. Carlo Pesenti.

2.
Stem Cell Res Ther ; 12(1): 332, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34112227

RESUMO

Complement factor H (FH) is the main plasma regulator of the alternative pathway of complement. Genetic and acquired abnormalities in FH cause uncontrolled complement activation amplifying, with the consequent accumulation of complement components on the renal glomeruli. This leads to conditions such as C3 glomerulopathy (C3G) and atypical hemolytic uremic syndrome (aHUS). There is no effective therapy for these diseases. Half of the patients progress to end-stage renal disease and the condition recurs frequently in transplanted kidneys. Combined liver/kidney transplantation is a valid option for these patients, but the risks of the procedure and donor organ shortages hamper its clinical application. Therefore, there is an urgent need for alternative strategies for providing a normal FH supply. Human amnion epithelial cells (hAEC) have stem cell characteristics, including the capability to differentiate into hepatocyte-like cells in vivo.Here, we administered hAEC into the livers of newborn Cfh-/- mice, which spontaneously developed glomerular complement deposition and renal lesions resembling human C3G. hAEC engrafted at low levels in the livers of Cfh-/- mice and produced sufficient human FH to prevent complement activation and glomerular C3 and C9 deposition. However, long-term engraftment was not achieved, and eventually hAEC elicited a humoral immune response in immunocompetent Cfh-/- mice.hAEC cell therapy could be a valuable therapeutic option for patients undergoing kidney transplantation in whom post-transplant immunosuppression may protect allogeneic hAEC from rejection, while allogeneic cells provide normal FH to prevent disease recurrence.

3.
Orphanet J Rare Dis ; 16(1): 251, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078418

RESUMO

BACKGROUND: The European Rare Kidney Disease Reference Network (ERKNet) recently established ERKReg, a Web-based registry for all patients with rare kidney diseases. The main objectives of this core registry are to generate epidemiological information, identify current patient cohort for clinical research, explore diagnostic and therapeutic management practices, and monitor treatment performance and patient's outcomes. The registry has a modular design that allows to integrate comprehensive disease-specific registries as extensions to the core database. The diagnosis (Orphacode) and diagnostic information (clinical, imaging, histopathological, biochemical, immunological and genetic) are recorded. Anthropometric, kidney function, and disease-specific management and outcome items informing a set of 61 key performance indicators (KPIs) are obtained annually. Data quality is ensured by automated plausibility checks upon data entry and regular offline database checks prompting queries. Centre KPI statistics and benchmarking are calculated automatically. RESULTS: Within the first 24 months since its launch, 7607 patients were enrolled to the registry at 45 pediatric and 12 specialized adult nephrology units from 21 countries. A kidney disease diagnosis had been established in 97.1% of these patients at time of enrolment. While 199 individual disease entities were reported by Orphacode, 50% of the cohort could be classified with 11, 80% with 43 and 95% with 92 codes. Two kidney diagnoses were assigned in 6.5% of patients; 5.9% suffered from syndromic disease. Whereas glomerulopathies (54.8%) and ciliopathies including autosomal dominant polycystic kidney disease (ADPKD) (31.5%) were the predominant disease groups among adults, the pediatric disease spectrum encompassed congenital anomalies of the kidney and urinary tract (CAKUT) (33.7%), glomerulopathies (30.7%), ciliopathies (14.0%), tubulopathies (9.2%), thrombotic microangiopathies (5.6%), and metabolic nephropathies (4.1%). Genetically confirmed diagnoses were reported in 24% of all pediatric and 12% adult patients, whereas glomerulopathies had been confirmed by kidney biopsy in 80.4% adult versus 38.5% pediatric glomerulopathy cases. CONCLUSIONS: ERKReg is a rapidly growing source of epidemiological information and patient cohorts for clinical research, and an innovative tool to monitor management quality and patient outcomes.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33945051

RESUMO

Obesity is a major public health problem worldwide. Only relatively few treatment options are, at present, available for the management of obese patients. Furthermore, treatment of obesity is affected by the widespread misuse of drugs and food supplements. Ephedra sinica is an old medicinal herb, commonly used in the treatment of respiratory tract diseases. Ephedra species contain several alkaloids, including pseudoephedrine, notably endowed with indirect sympathomimetic pharmacodynamic properties. The anorexigenic effect of pseudoephedrine is attributable primarily to the inhibition of neurons located in the hypothalamic paraventricular nucleus (PVN), mediating satiety stimuli. Pseudoephedrine influences lipolysis and thermogenesis through interaction with ß3 adrenergic receptors and reduces fat accumulation through down-regulation of transcription factors related to lipogenesis. However, its use is associated with adverse events that involve to a large extent the cardiovascular and the central nervous system. Adverse events of pseudoephedrine also affect the eye, the intestine, and the skin, and, of relevance, sudden cardiovascular death related to dietary supplements containing Ephedra alkaloids has also been reported. In light of the limited availability of clinical data on pseudoephedrine in obesity, along with its significantly unbalanced risk/benefit profile, as well as of the psychophysical susceptibility of obese patients, it appears reasonable to preclude the prescription of pseudoephedrine in obese patients of any order and degree.

5.
Eur J Prev Cardiol ; 28(4): 385-396, 2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-33966080

RESUMO

AIMS: An exhaustive and updated estimation of cardiovascular disease burden and vascular risk factors is still lacking in European countries. This study aims to fill this gap assessing the global Italian cardiovascular disease burden and its changes from 1990 to 2017 and comparing the Italian situation with European countries. METHODS: All accessible data sources from the 2017 Global Burden of Disease study were used to estimate the cardiovascular disease prevalence, mortality and disability-adjusted life years and cardiovascular disease attributable risk factors burden in Italy from 1990 to 2017. Furthermore, we compared the cardiovascular disease burden within the 28 European Union countries. RESULTS: Since 1990, we observed a significant decrease of cardiovascular disease burden, particularly in the age-standardised prevalence (-12.7%), mortality rate (-53.8%), and disability-adjusted life years rate (-55.5%). Similar improvements were observed in the majority of European countries. However, we found an increase in all-ages prevalence of cardiovascular diseases from 5.75 m to 7.49 m Italian residents. Cardiovascular diseases still remain the first cause of death (34.8% of total mortality). More than 80% of the cardiovascular disease burden could be attributed to known modifiable risk factors such as high systolic blood pressure, dietary risks, high low density lipoprotein cholesterol, and impaired kidney function. CONCLUSIONS: Our study shows a decline in cardiovascular mortality and disability-adjusted life years, which reflects the success in reducing disability, premature death and early incidence of cardiovascular diseases. However, the burden of cardiovascular diseases is still high. An approach that includes the cooperation and coordination of all stakeholders of the Italian National Health System is required to further reduce this burden.

6.
Panminerva Med ; 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33908730

RESUMO

BACKGROUND: Differences between total deaths registered during the Covid-19 pandemic and those registered in a previous reference period is a valid measure of the pandemic effect. However, this does not consider demographic changes and temporal trends in mortality. OBJECTIVE: To estimate the excess mortality in 2020 in Italy considering demographic changes and temporal trends in mortality. METHODS: We used daily mortality and population data for the 2011-2019 period to estimate the expected deaths in 2020. Expected deaths were estimated, separately by sex, through an over-dispersed Poisson regression model including calendar year and age group as covariates, a smooth function of the year's week, and the logarithm of the population as offset. The difference between observed and expected deaths was considered a measure of excess mortality. RESULTS: In 2020, 746,146 deaths occurred in Italy. We estimated an excess mortality of 90,725 deaths (95% CI: 86,503-94,914), which became 99,289 deaths after excluding January and February, when mortality was lower than expected. The excess was higher among men (49,422 deaths) than women (41,303 deaths) and it was mostly detected at ages ≥80 (60,224 deaths) and ages 65-79 (25,791 deaths), while among the population aged 25-49 and 50-64 we estimated an excess of 281 and 4764 deaths, respectively. CONCLUSIONS: After considering demographic changes and temporal improvement in mortality the excess deaths in 2020 still remains above 90,000 deaths. More important, considering these factors, the excess at ages <80 years is revised upwards, while the excess at older ages is revised downwards.

7.
Nephron ; : 1-17, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910203

RESUMO

BACKGROUND/AIM: Necrotizing crescentic glomerulonephritis (GN) associated with anti-neutrophil cytoplasmic antibodies (ANCA) against myeloperoxidase (MPO) is a devastating disease that quickly progresses to kidney failure. Current therapies are broadly immunosuppressive and associated with adverse effects. We wanted to set up a model that could be suitable for testing narrowly targeted therapies. METHODS: The model was constructed in male Wistar Kyoto rats through injections of human MPO (hMPO) and pertussis toxin, followed by a sub-nephritogenic dose of sheep anti-rat glomerular basement membrane (GBM) serum to boost the disease. Rats were monitored for 35 days. Rats given hMPO alone, saline, or human serum albumin with or without anti-GBM serum were also studied. RESULTS: Rats receiving hMPO developed circulating anti-hMPO and anti-rat MPO antibodies. Challenging hMPO-immunized rats with the anti-GBM serum led to more glomerular neutrophil infiltration and MPO release, and severe haematuria, heavy proteinuria, and higher blood urea nitrogen than hMPO alone. Pauci-immune GN developed with crescents, affecting 25% of glomeruli. The majority of crescents were fibrocellular. Necrotizing lesions and Bowman capsule ruptures were detected. Cells double positive for claudin-1 (a marker of parietal epithelial cells [PECs]) and neural cell adhesion molecule (NCAM; progenitor PECs) were present in crescents. Double staining for NCAM and Ki-67 established proliferative status of progenitor PECs. Podocyte damage was associated with endothelial and GBM changes by electron microscopy. Monocyte/macrophages and CD4+ and CD8+ T cells accumulated in glomeruli and the surrounding area and in the tubulointerstitium. Lung haemorrhage also manifested. CONCLUSION: This model reflects histological lesions of human ANCA-associated rapidly progressive GN and may be useful for investigating new therapies.

8.
BMC Pulm Med ; 21(1): 96, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33743654

RESUMO

BACKGROUND: Gender-related factors might affect vulnerability to Covid-19. The aim of this study was to describe the role of gender on clinical features and 28-day mortality in Covid-19 patients. METHODS: Observational study of Covid-19 patients hospitalized in Bergamo, Italy, during the first three weeks of the outbreak. Medical records, clinical, radiological and laboratory findings upon admission and treatment have been collected. Primary outcome was 28-day mortality since hospitalization. RESULTS: 431 consecutive adult patients were admitted. Female patients were 119 (27.6%) with a mean age of 67.0 ± 14.5 years (vs 67.8 ± 12.5 for males, p = 0.54). Previous history of myocardial infarction, vasculopathy and former smoking habits were more common for males. At the time of admission PaO2/FiO2 was similar between men and women (228 [IQR, 134-273] vs 238 mmHg [150-281], p = 0.28). Continuous Positive Airway Pressure (CPAP) assistance was needed in the first 24 h more frequently in male patients (25.7% vs 13.0%; p = 0.006). Overall 28-day mortality was 26.1% in women and 38.1% in men (p = 0.018). Gender did not result an independent predictor of death once the parameters related to disease severity at presentation were included in the multivariable analysis (p = 0.898). Accordingly, the Kaplan-Meier survival analysis in female and male patients requiring CPAP or non-invasive ventilation in the first 24 h did not find a significant difference (p = 0.687). CONCLUSION: Hospitalized women are less likely to die from Covid-19; however, once severe disease occurs, the risk of dying is similar to men. Further studies are needed to better investigate the role of gender in clinical course and outcome of Covid-19.


Assuntos
/epidemiologia , Idoso , Idoso de 80 Anos ou mais , /fisiopatologia , Comorbidade , Pressão Positiva Contínua nas Vias Aéreas/estatística & dados numéricos , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Hipóxia/epidemiologia , Hipóxia/fisiopatologia , Hipóxia/terapia , Itália/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Ventilação não Invasiva/estatística & dados numéricos , Índice de Gravidade de Doença , Fatores Sexuais , Fumar/epidemiologia
9.
Clin J Am Soc Nephrol ; 16(4): 575-587, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33782036

RESUMO

BACKGROUND AND OBJECTIVES: Renin-angiotensin system (RAS) inhibitors reduce cardiovascular morbidity and mortality in patients with CKD. We evaluated the cardioprotective effects of the angiotensin-converting enzyme inhibitor ramipril in patients on maintenance hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this phase 3, prospective, randomized, open-label, blinded end point, parallel, multicenter trial, we recruited patients on maintenance hemodialysis with hypertension and/or left ventricular hypertrophy from 28 Italian centers. Between July 2009 and February 2014, 140 participants were randomized to ramipril (1.25-10 mg/d) and 129 participants were allocated to non-RAS inhibition therapy, both titrated up to the maximally tolerated dose to achieve predefined target BP values. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the single components of the primary end point, new-onset or recurrence of atrial fibrillation, hospitalizations for symptomatic fluid overload, thrombosis or stenosis of the arteriovenous fistula, and changes in cardiac mass index. All outcomes were evaluated up to 42 months after randomization. RESULTS: At comparable BP control, 23 participants on ramipril (16%) and 24 on non-RAS inhibitor therapy (19%) reached the primary composite end point (hazard ratio, 0.93; 95% confidence interval, 0.52 to 1.64; P=0.80). Ramipril reduced cardiac mass index at 1 year of follow-up (between-group difference in change from baseline: -16.3 g/m2; 95% confidence interval, -29.4 to -3.1), but did not significantly affect the other secondary outcomes. Hypotensive episodes were more frequent in participants allocated to ramipril than controls (41% versus 12%). Twenty participants on ramipril and nine controls developed cancer, including six gastrointestinal malignancies on ramipril (four were fatal), compared with none in controls. CONCLUSIONS: Ramipril did not reduce the risk of major cardiovascular events in patients on maintenance hemodialysis. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: ARCADIA, NCT00985322 and European Union Drug Regulating Authorities Clinical Trials Database number 2008-003529-17.

10.
Hypertension ; 77(4): 1029-1035, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33583200

RESUMO

The General Data Protection Regulation (GDPR) became binding law in the European Union Member States in 2018, as a step toward harmonizing personal data protection legislation in the European Union. The Regulation governs almost all types of personal data processing, hence, also, those pertaining to biomedical research. The purpose of this article is to highlight the main practical issues related to data and biological sample sharing that biomedical researchers face regularly, and to specify how these are addressed in the context of GDPR, after consulting with ethics/legal experts. We identify areas in which clarifications of the GDPR are needed, particularly those related to consent requirements by study participants. Amendments should target the following: (1) restricting exceptions based on national laws and increasing harmonization, (2) confirming the concept of broad consent, and (3) defining a roadmap for secondary use of data. These changes will be achieved by acknowledged learned societies in the field taking the lead in preparing a document giving guidance for the optimal interpretation of the GDPR, which will be finalized following a period of commenting by a broad multistakeholder audience. In parallel, promoting engagement and education of the public in the relevant issues (such as different consent types or residual risk for re-identification), on both local/national and international levels, is considered critical for advancement. We hope that this article will open this broad discussion involving all major stakeholders, toward optimizing the GDPR and allowing a harmonized transnational research approach.

11.
Curr Opin Nephrol Hypertens ; 30(2): 252-263, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33395036

RESUMO

PURPOSE OF REVIEW: We provide a comprehensive overview of angiotensin-converting enzyme 2 (ACE2) as a possible candidate for pharmacological approaches to halt inflammatory processes in different pathogenic conditions. RECENT FINDINGS: ACE2 has quickly gained prominence in basic research as it has been identified as the main entry receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This novel pathogen causes Coronavirus Disease 2019 (COVID-19), a pathogenic condition that reached pandemic proportion and is associated with unprecedented morbidity and mortality. SUMMARY: The renin-angiotensin system is a complex, coordinated hormonal cascade that plays a pivotal role in controlling individual cell behaviour and multiple organ functions. ACE2 acts as an endogenous counter-regulator to the pro-inflammatory and pro-fibrotic pathways triggered by ACE through the conversion of Ang II into the vasodilatory peptide Ang 1-7. We discuss the structure, function and expression of ACE2 in different tissues. We also briefly describe the role of ACE2 as a pivotal driver across a wide spectrum of pathogenic conditions, such as cardiac and renal diseases. Furthermore, we provide the most recent data concerning the possible role of ACE2 in mediating SARS-CoV-2 infection and dictating COVID-19 severity.


Assuntos
/metabolismo , /enzimologia , /genética , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Humanos , Sistema Renina-Angiotensina/efeitos dos fármacos
12.
Nephron ; 145(2): 137-149, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33486477

RESUMO

BACKGROUND: Biopsy-guided selection of older kidneys safely expands the organ pool, and pretransplant perfusion improves the preservation of these fragile organs. Herein, we studied morphofunctional variables associated with graft outcomes in perfused, histologically evaluated older kidneys. METHODS: This single-center prospective cohort pilot study evaluated the relationships between preimplantation histologic scores and renal perfusion parameters during hypothermic, pulsatile, machine perfusion (MP) and assessed whether these morphofunctional parameters associated with GFR (iohexol plasma clearance) at 6 months after transplantation in 20 consecutive consenting recipients of a biopsy-guided single or dual kidney transplant from >60-year-old deceased donors. RESULTS: The donor and recipient age was 70.4 ± 6.5 and 63.6 ± 7.9 years (p = 0.005), respectively. The kidney donor profile index (KDPI) was 93.3 ± 8.4% (>80% in 19 cases), histologic score 4.4 ± 1.4, and median (IQR) cold ischemia time 19.8 (17.8-22.8 h; >24 h in 5 cases). The 6-month GFR was 41.2 (34.9-55.7) mL/min. Vascular resistances positively correlated with global histologic score (p = 0.018) at MP start and then decreased from 0.88 ± 0.43 to 0.36 ± 0.13 mm Hg/mL/min (p < 0.001) in parallel with a three-fold renal flow increase from 24.0 ± 14.7 to 74.7 ± 31.8 mL/min (p < 0.001). Consistently, vascular resistance reductions positively correlated with global histologic score (p = 0.009, r = -0.429). Unlike KDPI or vascular resistances, histologic score was independently associated with 6-month GFR (beta standardized coefficient: -0.894, p = 0.005). CONCLUSIONS: MP safely improves graft perfusion, particularly in kidneys with severe histologic changes that would not be considered for transplantation because of high KDPI. The preimplantation histologic score associates with the functional recovery of older kidneys even in the context of a standardized program of pulsatile perfusion.

13.
PLoS Med ; 18(1): e1003408, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33444372

RESUMO

BACKGROUND: Acute kidney injury (AKI) is increasingly encountered in community settings and contributes to morbidity, mortality, and increased resource utilization worldwide. In low-resource settings, lack of awareness of and limited access to diagnostic and therapeutic interventions likely influence patient management. We evaluated the feasibility of the use of point-of-care (POC) serum creatinine and urine dipstick testing with an education and training program to optimize the identification and management of AKI in the community in 3 low-resource countries. METHODS AND FINDINGS: Patients presenting to healthcare centers (HCCs) from 1 October 2016 to 29 September 2017 in the cities Cochabamba, Bolivia; Dharan, Nepal; and Blantyre, Malawi, were assessed utilizing a symptom-based risk score to identify patients at moderate to high AKI risk. POC testing for serum creatinine and urine dipstick at enrollment were utilized to classify these patients as having chronic kidney disease (CKD), acute kidney disease (AKD), or no kidney disease (NKD). Patients were followed for a maximum of 6 months with repeat POC testing. AKI development was assessed at 7 days, kidney recovery at 1 month, and progression to CKD and mortality at 3 and 6 months. Following an observation phase to establish baseline data, care providers and physicians in the HCCs were trained with a standardized protocol utilizing POC tests to evaluate and manage patients, guided by physicians in referral hospitals connected via mobile digital technology. We evaluated 3,577 patients, and 2,101 were enrolled: 978 in the observation phase and 1,123 in the intervention phase. Due to the high number of patients attending the centers daily, it was not feasible to screen all patients to assess the actual incidence of AKI. Of enrolled patients, 1,825/2,101 (87%) were adults, 1,117/2,101 (53%) were females, 399/2,101 (19%) were from Bolivia, 813/2,101 (39%) were from Malawi, and 889/2,101 (42%) were from Nepal. The age of enrolled patients ranged from 1 month to 96 years, with a mean of 43 years (SD 21) and a median of 43 years (IQR 27-62). Hypertension was the most common comorbidity (418/2,101; 20%). At enrollment, 197/2,101 (9.4%) had CKD, and 1,199/2,101 (57%) had AKD. AKI developed in 30% within 7 days. By 1 month, 268/978 (27%) patients in the observation phase and 203/1,123 (18%) in the intervention phase were lost to follow-up. In the intervention phase, more patients received fluids (observation 714/978 [73%] versus intervention 874/1,123 [78%]; 95% CI 0.63, 0.94; p = 0.012), hospitalization was reduced (observation 578/978 [59%] versus intervention 548/1,123 [49%]; 95% CI 0.55, 0.79; p < 0.001), and admitted patients with severe AKI did not show a significantly lower mortality during follow-up (observation 27/135 [20%] versus intervention 21/178 [11.8%]; 95% CI 0.98, 3.52; p = 0.057). Of 504 patients with kidney function assessed during the 6-month follow-up, de novo CKD arose in 79/484 (16.3%), with no difference between the observation and intervention phase (95% CI 0.91, 2.47; p = 0.101). Overall mortality was 273/2,101 (13%) and was highest in those who had CKD (24/106; 23%), followed by those with AKD (128/760; 17%), AKI (85/628; 14%), and NKD (36/607; 6%). The main limitation of our study was the inability to determine the actual incidence of kidney dysfunction in the health centers as it was not feasible to screen all the patients due to the high numbers seen daily. CONCLUSIONS: This multicenter, non-randomized feasibility study in low-resource settings demonstrates that it is feasible to implement a comprehensive program utilizing POC testing and protocol-based management to improve the recognition and management of AKI and AKD in high-risk patients in primary care.


Assuntos
Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/terapia , Injúria Renal Aguda/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Bolívia/epidemiologia , Criança , Pré-Escolar , Creatinina/sangue , Países em Desenvolvimento , Progressão da Doença , Estudos de Viabilidade , Feminino , Humanos , Lactente , Malaui/epidemiologia , Masculino , Pessoa de Meia-Idade , Nepal/epidemiologia , Testes Imediatos , Urinálise
16.
Am J Transplant ; 2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33370477

RESUMO

Mesenchymal stromal cells (MSC) have emerged as a promising therapy to minimize the immunosuppressive regimen or induce tolerance in solid organ transplantation. In this randomized open-label phase Ib/IIa clinical trial, 20 liver transplant patients were randomly allocated (1:1) to receive a single pretransplant intravenous infusion of third-party bone marrow-derived MSC or standard of care alone. The primary endpoint was the safety profile of MSC administration during the 1-year follow-up. In all, 19 patients completed the study, and none of those who received MSC experienced infusion-related complications. The incidence of serious and non-serious adverse events was similar in the two groups. Circulating Treg/memory Treg and tolerant NK subset of CD56bright NK cells increased slightly over baseline, albeit not to a statistically significant extent, in MSC-treated patients but not in the control group. Graft function and survival, as well as histologic parameters and intragraft expression of tolerance-associated transcripts in 1-year protocol biopsies were similar in the two groups. In conclusion, pretransplant MSC infusion in liver transplant recipients was safe and induced mild positive changes in immunoregulatory T and NK cells in the peripheral blood. This study opens the way for a trial on possible tolerogenic efficacy of MSC in liver transplantation. ClinicalTrials.gov identifier: NCT02260375.

17.
Panminerva Med ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33244949

RESUMO

BACKGROUND: Findings from February, 2020, indicate that the clinical spectrum of Covid-19 can be heterogeneous, probably due to the infectious dose and viral load of SARS-CoV-2 within the first weeks of the outbreak. The aim of this study was to investigate predictors of overall 28-day mortality at the peak of the Italian outbreak. METHODS: Retrospective observational study of all Covid-19 patients admitted to the main hospital of Bergamo, from February 23 to March, 14, 2020. RESULTS: 508 patients were hospitalized , predominantly male (72.4%), mean age of 66±15 years; 49.2% were older than 70 years. Most of patients presented with severe respiratory failure (median value [IQR] of PaO2/FiO2 233 [149-281]). Mortality rate at 28 days resulted of 33.7% (N=171). 39.0% of patients were treated with continuous positive airway pressure (CPAP), 9.5% with non-invasive ventilation (NIV) and 13.6% with endotracheal intubation. 9.5% were admitted to semi-intensive respiratory care unit, and 18.9% to ICU. Risk factors independently associated with 28-day mortality were advanced age (≥78 years: odds ratio, OR, 95% confidence interval [CI] 38.91 [10.67-141.93], p<0.001; 70-77 years: 17.30 [5.40-55.38], p<0.001; 60-69 years: 3.20 [1.00-10.20], p=0.049), PaO2/FiO2 <200 at presentation (3.50 [1.70-7.20], p=0.001), need for CPAP/NIV in the first 24 hours (8.38 [3.63-19.35], p <0.001), and blood urea value at admission (1.01 [1.00-1.02], p=0.015). CONCLUSIONS: At the peak of the outbreak, with a probable high infectious dose and viral load, older age, the severity of respiratory failure and renal impairment at presentation, but not comorbidities, are predictors of 28-day mortality in Covid-19.

18.
Front Med (Lausanne) ; 7: 579418, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33224962

RESUMO

Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare disease characterized by microangiopathic hemolysis, thrombocytopenia, and renal impairment and is associated with dysregulation of the alternative complement pathway on the microvascular endothelium. Outcomes have improved greatly with pharmacologic complement C5 blockade. Abnormalities in complement genes (CFH, CD46, CFI, CFB, C3, and THBD), CFH-CFHR genomic rearrangements, and anti-FH antibodies have been reported in 40-60% of cases. The penetrance of aHUS is incomplete in carriers of complement gene abnormalities; and multiple hits, including the CFH-H3 and CD46 GGAAC risk haplotypes and the CFHR1 * B risk allele, as well as environmental factors, contribute to disease development. Here, we investigated the determinants of penetrance of aHUS associated with CD46 genetic abnormalities. We studied 485 aHUS patients and found CD46 rare variants (RVs) in about 10%. The c.286+2T>G RV was the most prevalent (13/485) and was associated with <30% penetrance. We conducted an in-depth study of a large pedigree including a proband who is heterozygous for the c.286+2T>G RV who experienced a severe form of aHUS and developed end-stage renal failure. The father and paternal uncle with the same variant in homozygosity and six heterozygous relatives are unaffected. Flow cytometry analysis showed about 50% reduction of CD46 expression on blood mononuclear cells from the heterozygous proband and over 90% reduction in cells from the proband's unaffected homozygous father and aunt. Further genetic studies did not reveal RVs in known aHUS-associated genes or common genetic modifiers that segregated with the disease. Importantly, a specific ex vivo test showed excessive complement deposition on endothelial cells exposed to sera from the proband, and also from his mother and maternal uncle, who do not carry the c.286+2T>G RV, indicating that they share a circulating defect that results in complement dysregulation on the endothelium. These results highlight the complexity of the genetics of aHUS and indicate that CD46 deficiency may not be enough to induce aHUS. We hypothesize that the proband inherited from his mother a genetic abnormality in a complement circulating factor that has not been identified yet, which synergized with the CD46 RV in predisposing him to the aHUS phenotype.

19.
EBioMedicine ; 61: 103069, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33130396

RESUMO

BACKGROUND: Italy was the first western country to experience a large Coronavirus Disease 2019 (COVID-19) outbreak and the province of Bergamo experienced one of the deadliest COVID-19 outbreaks in the world. Following the peak of the epidemic in mid-March, the curve has slowly fallen thanks to the strict lockdown imposed by the Italian government on 9th March 2020. METHODS: We performed a cross-sectional study to assess the prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in 423 workers in Bergamo province who returned to the workplace after the end of the Italian lockdown on 5th May 2020. To this end, we performed an enzyme-linked immunosorbent assay (ELISA) to detect the humoral response against SARS-CoV-2 and a nasopharyngeal swab to assess the presence of SARS-CoV-2 RNA by real-time reverse transcription polymerase chain reaction (rRT-PCR). As a secondary aim of the study, we validated a lateral flow immunochromatography assay (LFIA) for the detection of anti-SARS-CoV-2 antibodies. FINDINGS: ELISA identified 38.5% positive subjects, of whom 51.5% were positive for both IgG and IgM, 47.3% were positive only for IgG, but only 1.2% were positive for IgM alone. Only 23 (5.4%) participants tested positive for SARS-CoV-2 by rRT-PCR, although with high cycle thresholds (between 34 and 39), indicating a very low residual viral load that was not able to infect cultured cells. All these rRT-PCR positive subjects had already experienced seroconversion. When the ELISA was used as the comparator, the estimated specificity and sensitivity of the rapid LFIA for IgG were 98% and 92%, respectively. INTERPRETATION: the prevalence of SARS-CoV-2 infection in the province of Bergamo reached 38.5%, significantly higher than has been reported for most other regions worldwide. Few nasopharyngeal swabs tested positive in fully recovered subjects, though with a very low SARS-CoV-2 viral load, with implications for infectivity and discharge policies for positive individuals in the post-pandemic period. The rapid LFIA used in this study is a valuable tool for rapid serologic surveillance of COVID-19 for population studies. FUNDING: The study was supported by Regione Lombardia, Milano Serravalle - Milano Tangenziali S.p.A., Brembo S.p.A, and by MEI System.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/genética , Betacoronavirus/imunologia , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , RNA Viral/metabolismo , Adulto , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Carga Viral
20.
Nat Rev Nephrol ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33077917

RESUMO

In December 2019, a novel coronavirus was isolated from the respiratory epithelium of patients with unexplained pneumonia in Wuhan, China. This pathogen, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes a pathogenic condition that has been termed coronavirus disease 2019 (COVID-19) and has reached pandemic proportions. As of 17 September 2020, more than 30 million confirmed SARS-CoV-2 infections have been reported in 204 different countries, claiming more than 1 million lives worldwide. Accumulating evidence suggests that SARS-CoV-2 infection can lead to a variety of clinical conditions, ranging from asymptomatic to life-threatening cases. In the early stages of the disease, most patients experience mild clinical symptoms, including a high fever and dry cough. However, 20% of patients rapidly progress to severe illness characterized by atypical interstitial bilateral pneumonia, acute respiratory distress syndrome and multiorgan dysfunction. Almost 10% of these critically ill patients subsequently die. Insights into the pathogenic mechanisms underlying SARS-CoV-2 infection and COVID-19 progression are emerging and highlight the critical role of the immunological hyper-response - characterized by widespread endothelial damage, complement-induced blood clotting and systemic microangiopathy - in disease exacerbation. These insights may aid the identification of new or existing therapeutic interventions to limit the progression of early disease and treat severe cases.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...