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1.
Clin Transplant ; : e14495, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34569101

RESUMO

Solid organ transplant patients are at higher risk for poor CoronaVirus Disease-2019 (COVID-19)-related outcomes and have been included as a priority group in the vaccination strategy worldwide. We assessed the safety and efficacy of a two-dose vaccination cycle with mRNA-based COVID-19 vaccine (BNT162b2) among 82 kidney transplant outpatients followed in our center in Rome, Italy. After a median of 43 post-vaccine days, a SARS-CoV-2 anti-Spike seroprevalence of 52.4% (n = 43/82) was observed. No impact of the vaccination on antibody-mediated rejection or graft function was observed, and no significant safety concerns were reported. Moreover, no de-novo HLA-donor-specific antibodies (DSA) were detected during the follow-up period. Only one patient with pre-vaccination HLA-DSA did not experience an increased intensity of the existing HLA-DSA. During the follow-up, only one infection (mild COVID-19) was observed in a patient after receiving the first vaccine dose. According to the multivariable logistic regression analysis, lack of seroconversion after two-dose vaccination independently associated with patient age ≥60 years (OR = 4.50; P-value = 0.02) and use of anti-metabolite as an immunosuppressant drug (OR = 5.26; P-value = 0.004). Among younger patients not taking anti-metabolites, the seroconversion rate was high (92.9%). Further larger studies are needed to assess the best COVID-19 vaccination strategy in transplanted patients. This article is protected by copyright. All rights reserved.

2.
Nutrients ; 13(8)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34445055

RESUMO

BACKGROUND: We previously reported that severe COVID-19 patients had higher chances of survival and a reduced risk of developing respiratory failure when administered with the probiotic formulation SLAB51. This study aimed to investigate further bacteriotherapy mechanisms and how early they are activated. METHODS: We performed an analysis on the blood oxygenation parameters collected in sixty-nine severe COVID-19 patients requiring non-invasive oxygen therapy and presenting a CT lung involvement ≥50%. Twenty-nine patients received low-molecular-weight heparin, azithromycin and Remdesivir. In addition, forty subjects received SLAB51. Blood gas analyses were performed before the beginning of treatments and at 24 h. RESULTS: The patients receiving only standard therapy needed significantly increased oxygen amounts during the 24 h observation period. Furthermore, they presented lower blood levels of pO2, O2Hb and SaO2 than the group also supplemented with oral bacteriotherapy. In vitro data suggest that SLAB51 can reduce nitric oxide synthesis in intestinal cells. CONCLUSIONS: SARS-CoV-2 infected patients may present lesions in the lungs compromising their gas exchange capability. The functionality of the organs essential for these patients' survival depends mainly on the levels of pO2, O2Hb and SaO2. SLAB51 contains enzymes that could reduce oxygen consumption in the intestine, making it available for the other organs.


Assuntos
COVID-19/terapia , Oxigênio/uso terapêutico , Probióticos/uso terapêutico , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Idoso , Alanina/análogos & derivados , Alanina/uso terapêutico , Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Gasometria , Linhagem Celular , Feminino , Heparina , Humanos , Hipóxia , Itália , Pulmão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
3.
Front Immunol ; 12: 708149, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335624

RESUMO

Microbial translocation (MT) and intestinal damage (ID) are poorly explored in COVID-19. Aims were to assess whether alteration of gut permeability and cell integrity characterize COVID-19 patients, whether it is more pronounced in severe infections and whether it influences the development of subsequent bloodstream infection (BSI). Furthermore, we looked at the potential predictive role of TM and ID markers on Intensive Care Unit (ICU) admission and in-hospital mortality. Over March-July 2020, 45 COVID-19 patients were enrolled. Markers of MT [LPB (Lipopolysacharide Binding Protein) and EndoCab IgM] and ID [I-FABP (Intestinal Fatty Acid Binding Protein)] were evaluated at COVID-19 diagnosis and after 7 days. As a control group, age- and gender-matched healthy donors (HDs) enrolled during the same study period were included. Median age was 66 (56-71) years. Twenty-one (46.6%) were admitted to ICU and mortality was 22% (10/45). Compared to HD, a high degree of MT and ID was observed. ICU patients had higher levels of MT, but not of ID, than non-ICU ones. Likewise, patients with BSI had lower EndoCab IgM than non-BSI. Interestingly, patients with high degree of MT and low ID were likely to be admitted to ICU (AUC 0.822). Patients with COVID-19 exhibited high level of MT, especially subjects admitted to ICU. COVID-19 is associated with gut permeability.


Assuntos
COVID-19/metabolismo , Mucosa Intestinal/metabolismo , SARS-CoV-2/fisiologia , Proteínas de Fase Aguda/metabolismo , Idoso , Biomarcadores/metabolismo , COVID-19/diagnóstico , COVID-19/mortalidade , COVID-19/patologia , Proteínas de Transporte/metabolismo , Progressão da Doença , Proteínas de Ligação a Ácido Graxo/metabolismo , Feminino , Humanos , Unidades de Terapia Intensiva , Mucosa Intestinal/patologia , Masculino , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Análise de Sobrevida , Junções Íntimas/metabolismo
4.
Int J Cardiol ; 339: 235-242, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34224766

RESUMO

BACKGROUND: Cardiovascular disease (CVD) can occur in COVID-19 and has impact on clinical course. Data on CVD prevalence in hospitalized COVID-19 patients and sequelae in survivors is limited. Aim of this prospective study carried out on consecutive unselected COVID-19 population, was to assess: 1) CVD occurrence among hospitalized COVID-19 patients, 2) persistence or new onset of CVD at one-month and one-year follow-up. METHODS: Over 30 days n = 152 COVID-19 patients underwent cardiovascular evaluation. Standard electrocardiogram (ECG), Troponin and echocardiography were integrated by further tests when indicated. Medical history, arterial blood gas, blood tests, chest computed tomography and treatment were recorded. CVD was defined as the occurrence of a new condition during the hospitalization for COVID-19. Survivors attended a one-month follow-up visit and a one-year telephone follow-up. RESULTS: Forty-two patients (28%) experienced a wide spectrum of CVD with acute myocarditis being the most frequent. Death occurred in 32 patients (21%) and more frequently in patients who developed CVD (p = 0.032). After adjustment for confounders, CVD was independently associated with death occurrence. At one-month follow-up visit, 7 patients (9%) presented persistent or delayed CVD. At one-year telephone follow-up, 57 patients (48%) reported persistent symptoms. CONCLUSION: Cardiovascular evaluation in COVID-19 patients is crucial since the occurrence of CVD in hospitalized COVID-19 patients is common (28%), requires specific treatment and increases the risk of in-hospital mortality. Persistence or delayed presentation of CVD at 1-month (9%) and persistent symptoms at 1-year follow-up (48%) suggest the need for monitoring COVID-19 survivors.


Assuntos
COVID-19 , Miocardite , Seguimentos , Hospitais , Humanos , Estudos Prospectivos , SARS-CoV-2
5.
Chemotherapy ; 66(1-2): 24-32, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33756475

RESUMO

Respiratory and gastrointestinal symptoms are the predominant clinical manifestations of the coronavirus disease 2019 (COVID-19). Infecting intestinal epithelial cells, the severe acute respiratory syndrome coronavirus-2 may impact on host's microbiota and gut inflammation. It is well established that an imbalanced intestinal microbiome can affect pulmonary function, modulating the host immune response ("gut-lung axis"). While effective vaccines and targeted drugs are being tested, alternative pathophysiology-based options to prevent and treat COVID-19 infection must be considered on top of the limited evidence-based therapy currently available. Addressing intestinal dysbiosis with a probiotic supplement may, therefore, be a sensible option to be evaluated, in addition to current best available medical treatments. Herein, we summed up pathophysiologic assumptions and current evidence regarding bacteriotherapy administration in preventing and treating COVID-19 pneumonia.


Assuntos
COVID-19 , Disbiose , Microbioma Gastrointestinal/imunologia , Probióticos/farmacologia , COVID-19/imunologia , COVID-19/fisiopatologia , COVID-19/prevenção & controle , Suplementos Nutricionais , Disbiose/terapia , Disbiose/virologia , Humanos , SARS-CoV-2
6.
Adv Exp Med Biol ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33782903

RESUMO

Parathyroid disorders are characterized by alterations in calcium and phosphate homeostasis due to inappropriately high or low levels of parathyroid hormone (PTH). Despite PTH receptor type 1 has been described in almost all immune lineages and calcium signalling has been confirmed as a crucial mediator for immune response, in vitro studies on the physiological interactions between PTH and immunity are conflicting and not representative of the clinical scenarios seen in patients with parathyroid disorders. Infectious diseases are among the main causes of increased morbidity and mortality in patients with secondary hyperparathyroidism and chronic kidney disease. More, immune alterations have been described in primary hyperparathyroidism. Recent studies have unveiled an increased risk of infections also in hypoparathyroidism, suggesting that not only calcium, but also physiological levels of PTH may be necessary for a proper immune response. Finally, calcium/phosphate imbalance could affect negatively the prognosis of infectious diseases. Our review aimed to collect available data on infectious disease prevalence in patients with parathyroid disorders and new evidence on the role of PTH and calcium in determining the increased risk of infections observed in these patients.

7.
Adv Exp Med Biol ; 1323: 103-114, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33030706

RESUMO

BACKGROUND: Ventilator-associated pneumonia (VAP) is one of the most common nosocomial infection, associated with considerable mortality and morbidity in critically ill patients; however, its diagnosis and management remain challenging since clinical assessment is often poorly reliable. The aim of this systematic review was to evaluate the role of PCT in the diagnosis and management of critical ill patients affected by VAP. METHODS: We performed a systematic review of the evidence published over the last 10 years and currently available in medical literature search databases (Pubmed, Embase, Web of Knowledge, Cochrane Libraries) and searching clinical trial registries. We regarded as predefined outcomes the role of PCT in diagnosis, therapeutic monitoring, antibiotic discontinuation and prognosis. The Open Science Framework Registration number was doi.org/10.17605/OSF. IO/ZGFKQ RESULTS: 761 articles were retrieved and a total of 18 studies (n° of patients = 1774) were selected and analyzed according to inclusion criteria. In this 2020 update, the systematic review showed that currently, conflicting and inconclusive data are available about the role of PCT in the diagnosis of VAP and in the prediction (i) of the efficacy of antibiotic therapy, and (ii) of the clinical outcome. These studies, instead, seem to agree on the utility of PCT in the management of antibiotic therapy discontinuation. CONCLUSIONS: Currently there is insufficient evidence to support the role of PCT in the routine assessment of patients with VAP. The value of the results published appears to be limited by the deep methodological differences that characterize the various studies available at the present being.


Assuntos
Infecção Hospitalar , Pneumonia Associada à Ventilação Mecânica , Antibacterianos/uso terapêutico , Estado Terminal , Infecção Hospitalar/tratamento farmacológico , Humanos , Pneumonia Associada à Ventilação Mecânica/diagnóstico , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pró-Calcitonina
8.
Andrology ; 9(1): 33-38, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32526061

RESUMO

BACKGROUND: A pandemic outbreak of COVID-19 has been sweeping the world since December. It begins as a respiratory infection that, mainly in men with diabetes or renal impairment, evolves into a systemic disease, with SARDS, progressive endothelial cell damage, abnormal clotting and impaired cardiovascular and liver function. Some clinical trials are testing biological drugs to limit the immune system dysregulation, "cytokines storm," that causes the systemic complications of COVID-19. The contraindications of these drugs and their cost raise concerns over the implications of their widespread availability. OBJECTIVES: Numerous clinical and experimental studies have revealed a role for the nitric oxide (NO)-cyclic GMP-phosphodiesterase type 5 (PDE5) pathway in modulating low-grade inflammation in patients with metabolic diseases, offering cardiovascular protection. PDE5 inhibition favors an anti-inflammatory response by modulating activated T cells, reducing cytokine release, lowering fibrosis, increasing oxygen diffusion, stimulating vascular repair. PDE5 is highly expressed in the lungs, where its inhibition improves pulmonary fibrosis, a complication of severe COVID-19 disease. MATERIALS AND METHODS: We performed a systematic review of all evidence documenting any involvement of the NO-cGMP-PDE5 axis in the pathophysiology of COVID-19, presenting the ongoing clinical trials aimed at modulating this axis, including our own "silDEnafil administration in DiAbetic and dysmetaboLic patients with COVID-19 (DEDALO trial)." RESULTS: The reviewed evidence suggests that PDE5 inhibitors could offer a new strategy in managing COVID-19 by (i) counteracting the Ang-II-mediated downregulation of AT-1 receptor; (ii) acting on monocyte switching, thus reducing pro-inflammatory cytokines, interstitial infiltration and the vessel damage responsible for alveolar hemorrhage-necrosis; (iii) inhibiting the transition of endothelial and smooth muscle cells to mesenchymal cells in the pulmonary artery, preventing clotting and thrombotic complications. DISCUSSION AND CONCLUSION: If the ongoing trials presented herein should provide positive findings, the low cost, wide availability and temperature stability of PDE5 inhibitors could make them a major resource to combat COVID-19 in developing countries.


Assuntos
Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , GMP Cíclico/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/metabolismo , Óxido Nítrico/uso terapêutico , Inibidores da Fosfodiesterase 5/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Antivirais/efeitos adversos , COVID-19/enzimologia , COVID-19/virologia , Ensaios Clínicos como Assunto , Interações Hospedeiro-Patógeno , Humanos , Terapia de Alvo Molecular , Óxido Nítrico/efeitos adversos , Óxido Nítrico/metabolismo , Inibidores da Fosfodiesterase 5/efeitos adversos , SARS-CoV-2/patogenicidade , Transdução de Sinais , Resultado do Tratamento
11.
J Glob Antimicrob Resist ; 23: 292-296, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33065329

RESUMO

OBJECTIVE: This study presents real-life experience with cefiderocol used on a compassionate basis for treatment of three patients with severe infections caused by extensively/pan-drug resistant (XDR/PDR) Acinetobacter baumannii (Ab). METHODS: Serum bactericidal activity was determined and considered as a surrogate of cefiderocol susceptibility. RESULTS: Clinical improvement and microbiological eradication of A. baumannii were observed in all three patients, who were affected by extremely complex conditions either for type of infection, adverse effect or resistance profile of A. baumannii. CONCLUSION: Cefiderocol for XDR/PDR-Ab infections might be reconsidered, especially in light of the recent disappointing results of the CREDIBLE-CR study.


Assuntos
Acinetobacter baumannii , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cefalosporinas , Ensaios de Uso Compassivo , Farmacorresistência Bacteriana Múltipla , Humanos
12.
Sci Rep ; 10(1): 17419, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060700

RESUMO

Changes in immune and coagulation systems and possible viral spread through the blood-brain barrier have been described in SARS-CoV-2 infection. In this study, we evaluated the possible retinal involvement and ocular findings in severe COVID-19 pneumonia patients. A cross-sectional study was conducted on 46 patients affected by severe COVID-19 who were hospitalized in one intensive care unit (ICU) and in two infectious disease wards, including bedside eye screening, corneal sensitivity assessment and retinography. A total of 43 SARS-CoV-2-positive pneumonia patients affected with COVID-19 pneumonia were included, including 25 males and 18 females, with a median age of 70 years [IQR 59-78]. Except for one patient with unilateral posterior chorioretinitis of opportunistic origin, of whom aqueous tap was negative for SARS-CoV-2, no further retinal manifestation related to COVID-19 infection was found in our cohort. We found 3 patients (7%) with bilateral conjunctivitis in whom PCR analysis on conjunctival swabs provided negative results for SARS-CoV-2. No alterations in corneal sensitivity were found. We demonstrated the absence of retinal involvement in SARS-CoV-2 pneumonia patients. Ophthalmologic evaluation in COVID-19, particularly in patients hospitalized in an ICU setting, may be useful to reveal systemic co-infections by opportunistic pathogens.


Assuntos
Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Retina/patologia , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/isolamento & purificação , COVID-19 , Conjuntivite/complicações , Conjuntivite/patologia , Conjuntivite/virologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Estudos Transversais , Feminino , Humanos , Retinopatia Hipertensiva/complicações , Retinopatia Hipertensiva/diagnóstico , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/virologia , RNA Viral/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Retina/virologia , SARS-CoV-2 , Índice de Gravidade de Doença
16.
Pharmaceutics ; 12(7)2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32709076

RESUMO

Brain infections as meningitis and encephalitis are attracting a great interest. Challenges in the treatment of these diseases are mainly represented by the blood brain barrier (BBB) that impairs the efficient delivery of even very potent drugs to reach the brain. The nose to the brain administration route, is a non-invasive alternative for a quick onset of action, and enables the transport of numerous medicinal agents straight to the brain thus workarounding the BBB through the highly vascularized olfactory region. In this report, Thymus vulgaris and Syzygium aromaticum essential oils (EOs) were selected to be included in chitosan coated nanoemulsions (NEs). The EOs were firstly analyzed to determine their chemical composition, then used to prepare NEs, that were deeply characterized in order to evaluate their use in intranasal administration. An in vitro evaluation against a collection of clinical isolated bacterial strains was carried out for both free and nanoemulsioned EOs. Chitosan coated NEs showed to be a potential and effective intranasal formulation against multi-drug resistant Gram-negative bacteria such as methicillin-susceptible Staphylococcus aureus and multi-drug resistant Gram-negative microorganisms including carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae.

17.
Metabolites ; 10(7)2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32635406

RESUMO

To investigate the effects of oral bacteriotherapy on intestinal phenylalanine and tyrosine metabolism, in this longitudinal, double-arm trial, 15 virally suppressed HIV+ individuals underwent blood and fecal sample collection at baseline and after 6 months of oral bacteriotherapy. A baseline fecal sample was collected from 15 healthy individuals and served as control group for the baseline levels of fecal phenylalanine and tyrosine. CD4 and CD8 immune activation (CD38+) was evaluated by flow cytometry. Amino acid evaluation on fecal samples was conducted by Proton Nuclear Magnetic Resonance. Results showed that HIV+ participants displayed higher baseline phenylalanine/tyrosine ratio values than healthy volunteers. A significand reduction in phenylalanine/tyrosine ratio and peripheral CD4+ CD38+ activation was observed at the end of oral bacteriotherapy. In conclusion, probiotics beneficially affect the immune activation of HIV+ individuals. Therefore, the restoration of intestinal amino acid metabolism could represent the mechanisms through which probiotics exert these desirable effects.

18.
PLoS One ; 15(6): e0234025, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32492045

RESUMO

Protecting Health Care Workers (HCWs) during routine care of suspected or confirmed COVID-19 patients is of paramount importance to halt the SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) pandemic. The WHO, ECDC and CDC have issued conflicting guidelines on the use of respiratory filters (N95) by HCWs. We searched PubMed, Embase and The Cochrane Library from the inception to March 21, 2020 to identify randomized controlled trials (RCTs) comparing N95 respirators versus surgical masks for prevention of COVID-19 or any other respiratory infection among HCWs. The grading of recommendations, assessment, development, and evaluation (GRADE) was used to evaluate the quality of evidence. Four RCTs involving 8736 HCWs were included. We did not find any trial specifically on prevention of COVID-19. However, wearing N95 respirators can prevent 73 more (95% CI 46-91) clinical respiratory infections per 1000 HCWs compared to surgical masks (2 RCTs; 2594 patients; low quality of evidence). A protective effect of N95 respirators in laboratory-confirmed bacterial colonization (RR = 0.41; 95%CI 0.28-0.61) was also found. A trend in favour of N95 respirators was observed in preventing laboratory-confirmed respiratory viral infections, laboratory-confirmed respiratory infection, and influenza like illness. We found no direct high quality evidence on whether N95 respirators are better than surgical masks for HCWs protection from SARS-CoV-2. However, low quality evidence suggests that N95 respirators protect HCWs from clinical respiratory infections. This finding should be contemplated to decide the best strategy to support the resilience of healthcare systems facing the potentially catastrophic SARS-CoV-2 pandemic.


Assuntos
Infecções por Coronavirus/prevenção & controle , Pessoal de Saúde , Controle de Infecções , Máscaras , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Dispositivos de Proteção Respiratória , Betacoronavirus/fisiologia , COVID-19 , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Humanos , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2
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