RESUMO
BCG vaccination in children protects against heterologous infections and improves survival independently of tuberculosis prevention. The phase III ACTIVATE trial assessed whether BCG has similar effects in the elderly. In this double-blind, randomized trial, elderly patients (n = 198) received BCG or placebo vaccine at hospital discharge and were followed for 12 months for new infections. At interim analysis, BCG vaccination significantly increased the time to first infection (median 16 weeks compared to 11 weeks after placebo). The incidence of new infections was 42.3% (95% CIs 31.9%-53.4%) after placebo vaccination and 25.0% (95% CIs 16.4%-36.1%) after BCG vaccination; most of the protection was against respiratory tract infections of probable viral origin (hazard ratio 0.21, p = 0.013). No difference in the frequency of adverse effects was found. Data show that BCG vaccination is safe and can protect the elderly against infections. Larger studies are needed to assess protection against respiratory infections, including COVID-19 (ClinicalTrials.gov NCT03296423).
Assuntos
Vacina BCG/efeitos adversos , Vacina BCG/imunologia , Infecções Respiratórias/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Vacina BCG/administração & dosagem , Método Duplo-Cego , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Respiratórias/imunologia , Viroses/imunologia , Viroses/prevenção & controleRESUMO
Oral iron supplementation is the cornerstone for the management of iron-deficiency anemia. A new oral formulation of iron conjugated with N-aspartyl-casein (Fe-ASP) (Omalin®, Uni-Pharma) is studied in the ACCESS double-blind, double-dummy randomized clinical trial; 60 patients were randomized to 12-week oral treatment twice every day either with oral ferrous sulfate (FeSO4) delivering 47 mg elementary iron or oral Fe-ASP delivering 40 mg elementary iron. Participants had hemoglobin less than 10 g/dl, decreased red blood cell (RBC) count, and ferritin lower than 30 ng/ml; patients with a medical history of malignancy were excluded. The primary endpoint was the increase of Hb in the first 4 weeks of treatment, and the study was powered for non-inferiority. A new score of global improvement was introduced where all participants were given one point for any at least 10% increase of Hb, RBC, and reticulocytes. At week 4, the mean (SE) change of Hb was 0.76 g/dl in the FeSO4 group and 0.83 g/dl in the Fe-ASP group (p: 0.876). The odds for worse allocation of the global score were 0.35 in the Fe-ASP group compared to the FeSO4 group. Patients in the Fe-ASP group experienced a significant decrease in the number of IDA-related physical signs by week 4. No differences were found between the two groups in any of the patient-reported outcomes of fatigue and of gastrointestinal adverse events either at week 4 or at week 12. ACCESS is the most recent clinical trial showing the non-inferiority of Fe-ASP to FeSO4 for the primary endpoint of the Hb change.
Assuntos
Anemia Ferropriva , Ferro , Humanos , Ferro/uso terapêutico , Anemia Ferropriva/tratamento farmacológico , Caseínas/uso terapêutico , Ferritinas , Hemoglobinas/análiseRESUMO
BACKGROUND: AKI commonly occurs in patients with coronavirus disease 2019 (COVID-19). Its pathogenesis is poorly understood. The urokinase receptor system is a key regulator of the intersection between inflammation, immunity, and coagulation, and soluble urokinase plasminogen activator receptor (suPAR) has been identified as an immunologic risk factor for AKI. Whether suPAR is associated with COVID-19-related AKI is unknown. METHODS: In a multinational observational study of adult patients hospitalized for COVID-19, we measured suPAR levels in plasma samples from 352 adult patients that had been collected within 48 hours of admission. We examined the association between suPAR levels and incident in-hospital AKI. RESULTS: Of the 352 patients (57.4% were male, 13.9% were black, and mean age was 61 years), 91 (25.9%) developed AKI during their hospitalization, of whom 25 (27.4%) required dialysis. The median suPAR level was 5.61 ng/ml. AKI incidence rose with increasing suPAR tertiles, from a 6.0% incidence in patients with suPAR <4.60 ng/ml (first tertile) to a 45.8% incidence of AKI in patients with suPAR levels >6.86 ng/ml (third tertile). None of the patients with suPAR <4.60 ng/ml required dialysis during their hospitalization. In multivariable analysis, the highest suPAR tertile was associated with a 9.15-fold increase in the odds of AKI (95% confidence interval [95% CI], 3.64 to 22.93) and a 22.86-fold increase in the odds of requiring dialysis (95% CI, 2.77 to 188.75). The association was independent of inflammatory markers and persisted across subgroups. CONCLUSIONS: Admission suPAR levels in patients hospitalized for COVID-19 are predictive of in-hospital AKI and the need for dialysis. SuPAR may be a key component of the pathophysiology of AKI in COVID-19.
Assuntos
Injúria Renal Aguda/etiologia , Betacoronavirus , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Injúria Renal Aguda/sangue , Injúria Renal Aguda/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2RESUMO
BACKGROUND: The accuracy of a new optical biosensor (OB) point-of-care device for the detection of severe infections is studied. METHODS: The OB emits different wavelengths and outputs information associated with heart rate, pulse oximetry, levels of nitric oxide and kidney function. At the first phase, recordings were done every two hours for three consecutive days after hospital admission in 142 patients at high-risk for sepsis by placing the OB on the forefinger. At the second phase, single recordings were done in 54 patients with symptoms of viral infection; 38 were diagnosed with COVID-19. RESULTS: At the first phase, the cutoff value of positive likelihood of 18 provided 100% specificity and 100% positive predictive value for the diagnosis of sepsis. These were 87.5 and 91.7% respectively at the second phase. OB diagnosed severe COVID-19 with 83.3% sensitivity and 87.5% negative predictive value. CONCLUSIONS: The studied OB seems valuable for the discrimination of infection severity.
Assuntos
Técnicas Biossensoriais/métodos , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Sepse/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Área Sob a Curva , Betacoronavirus/isolamento & purificação , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Curva ROC , SARS-CoV-2 , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
Investigations that focused on the protective role of probiotics against Surgical Site Infections (SSI) in multiple-trauma (MT) patients are generally few, probably due to the complexity of the concept of trauma. We aimed to assess the efficacy of a four-probiotic regime to reduce the incidence of SSI in MT patients, with a brain injury included. MT patients, being intubated and expected to require mechanical ventilation for >10 days, were randomly allocated into placebo (n = 50) or probiotic treatment (n = 53) comprising Lactobacillus acidophilus LA-5 (1.75 × 109 cfu), Lactiplantibacillus plantarum UBLP-40 (0.5 × 109 cfu), Bifidobacterium animalis subsp. lactis BB-12 (1.75 × 109 cfu), and Saccharomycesboulardii Unique-28 (1.5 × 109 cfu) in sachets. All patients received two sachets of placebo or probiotics twice/day for 15 days and were followed-up for 30 days. The operations were classified as neurosurgical, thoracostomies, laparotomies, orthopedics, and others; then, the SSI and the isolated pathogen were registered. A total of 23 (46.0%) and 13 (24.5%) infectious insults in 89 (50 placebo patients) and 88 (53 probiotics-treated) operations (p = 0.022) were recorded, the majority of them relating to osteosynthesis17 and 8, respectively. The most commonly identified pathogens were Staphylococcus aureus and Acinetobacter baumannii. Our results support published evidence that the prophylactic administration of probiotics in MT patients exerts a positive effect on the incidence of SSI.
Assuntos
Bifidobacterium animalis , Probióticos , Bifidobacterium , Método Duplo-Cego , Humanos , Lactobacillus acidophilus , Probióticos/uso terapêutico , Infecção da Ferida Cirúrgica/prevenção & controleRESUMO
The role of probiotics in the prevention of ventilator-associated pneumonia (VAP) remains inconclusive. The aim of this study was to assess the efficacy of a probiotic regimen for VAP prophylaxis in mechanically ventilated multi-trauma patients, intubated immediately after the injurious insult. In a randomized, placebo-controlled study enrolling multi-trauma patients, patients expected to require mechanical ventilation for >10 days were assigned at random to receive prophylaxis with a probiotic formula (n=59) or placebo (n=53). The probiotic formula was a preparation of Lactobacillus acidophilus LA-5 [1.75 × 109 colony-forming units (cfu)], Lactobacillus plantarum (0.5 × 109 cfu), Bifidobacterium lactis BB-12 (1.75 × 109 cfu) and Saccharomyces boulardii (1.5 × 109 cfu) in sachets. Each patient received two sachets twice daily for 15 days: one through the nasogastric tube and one spread on the oropharynx. The incidence of VAP was the primary endpoint. The incidence of other infections and sepsis, and the duration of hospital stay were the secondary endpoints. Administration of probiotics reduced the incidence of VAP [11.9% vs 28.3%, hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.13-0.92; P=0.034] and sepsis [6.8% vs 24.5%, odds ratio 0.22, 95% CI 0.07-0.74: P=0.016]. Furthermore, probiotic prophylaxis reduced the time of stay in the intensive care unit (ICU) and the length of hospital stay. The prophylactic use of probiotics with a combination of enteral and topical application to the oropharynx had a positive effect on the incidence of VAP and sepsis, as well as on ICU and total hospital stay in patients receiving protracted mechanical ventilation.
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Antibioticoprofilaxia , Bifidobacterium animalis/química , Lactobacillus acidophilus/química , Lactobacillus plantarum/química , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Probióticos/uso terapêutico , Saccharomyces boulardii/química , Adulto , Feminino , Grécia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
[This corrects the article DOI: 10.3389/fimmu.2022.873067.].
RESUMO
In a recent study of our group with the acronym ACTIVATE, Bacillus Calmete-Guérin (BCG) vaccination reduced the occurrence of new infections compared to placebo vaccination in the elderly. Most benefit was found for respiratory infections. The ACTIVATE-2 study was launched to assess the efficacy of BCG vaccination against coronavirus disease 2019 (COVID-19). In this multicenter, double-blind trial, 301 volunteers aged 50 years or older were randomized (1:1) to be vaccinated with BCG or placebo. The trial end points were the incidence of COVID-19 and the presence of anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) antibodies, which were both evaluated through 6 months after study intervention. Results revealed 68% relative reduction of the risk to develop COVID-19, using clinical criteria or/and laboratory diagnosis, in the group of BCG vaccine recipients compared with placebo-vaccinated controls, during a 6-month follow-up (OR 0.32, 95% CI 0.13-0.79). In total, eight patients were in need of hospitalization for COVID-19: six in the placebo group and two in the BCG group. Three months after study intervention, positive anti-SARS-CoV-2 antibodies were noted in 1.3% of volunteers in the placebo group and in 4.7% of participants in BCG-vaccinated group. These data indicate that BCG vaccination confers some protection against possible COVID-19 among patients older than 50 years with comorbidities. BCG vaccination may be a promising approach against the COVID-19 pandemic.
Assuntos
Bacillus , COVID-19 , Idoso , Anticorpos Antivirais , Vacina BCG , COVID-19/prevenção & controle , Humanos , Pandemias/prevenção & controle , VacinaçãoRESUMO
Early increase of soluble urokinase plasminogen activator receptor (suPAR) serum levels is indicative of increased risk of progression of coronavirus disease 2019 (COVID-19) to respiratory failure. The SAVE-MORE double-blind, randomized controlled trial evaluated the efficacy and safety of anakinra, an IL-1α/ß inhibitor, in 594 patients with COVID-19 at risk of progressing to respiratory failure as identified by plasma suPAR ≥6 ng ml-1, 85.9% (n = 510) of whom were receiving dexamethasone. At day 28, the adjusted proportional odds of having a worse clinical status (assessed by the 11-point World Health Organization Clinical Progression Scale (WHO-CPS)) with anakinra, as compared to placebo, was 0.36 (95% confidence interval 0.26-0.50). The median WHO-CPS decrease on day 28 from baseline in the placebo and anakinra groups was 3 and 4 points, respectively (odds ratio (OR) = 0.40, P < 0.0001); the respective median decrease of Sequential Organ Failure Assessment (SOFA) score on day 7 from baseline was 0 and 1 points (OR = 0.63, P = 0.004). Twenty-eight-day mortality decreased (hazard ratio = 0.45, P = 0.045), and hospital stay was shorter.
Assuntos
Tratamento Farmacológico da COVID-19 , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Idoso , COVID-19/virologia , Método Duplo-Cego , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Masculino , Pessoa de Meia-Idade , Placebos , SARS-CoV-2/isolamento & purificaçãoRESUMO
Background The prevalence of latent tuberculosis infection (LTBI) increases with age. Interferon-gamma release assay (IGRA) is a T-cell based assay widely used for the detection of LTBI. Objectives To identify the prevalence of LTBI among an elderly Greek population using IGRA and to evaluate comorbidities associated with LTBI. Methods Individuals aged at least 65 years who were non-immunocompromised and had no history of active tuberculosis infection (TBI) underwent IGRA to identify LTBI. Participant characteristics were compared between the LTBI and non-LTBI groups. Interferon-gamma (INFγ) levels were analysed in each group. Results A total of 130 (38.7%) participants with LTBI and 206 (61.3%) participants without LTBI were included. Multivariate logistic regression analysis identified the following features that were independently associated with a positive IGRA result: female sex (odds ratio [OR]: 0.45; 95% confidence interval [CI]: 0.28-0.72; P=0.001), chronic heart failure (OR: 0.41; 95% CI: 0.22-0.77; P=0.005), history of major surgery (OR: 0.55; 95% CI: 0.33-0.92; P=0.022) and Charlson Comorbidity Index >3 (OR: 3.06; 95% CI: 1.46-6.40; P=0.003). Production of stimulated INFγ was significantly lower in the non-LTBI group. Conclusions Female sex, history of chronic heart failure and history of any surgical intervention were independently associated with a negative IGRA result, and CCI >3 was associated with a positive IGRA result. These results indicate careful interpretation of IGRA is required among elderly individuals with these characteristics.
Assuntos
Cirurgia Geral/estatística & dados numéricos , Insuficiência Cardíaca/epidemiologia , Testes de Liberação de Interferon-gama/métodos , Interferon gama/sangue , Tuberculose Latente/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Grécia/epidemiologia , Humanos , Tuberculose Latente/diagnóstico , Masculino , PrevalênciaRESUMO
CASE PRESENTATION: An 80-year-old man presented with a 5-day history of hemoptysis, mild shortness of breath on exertion, fatigue, and malaise. He denied chest pain or fever. He had a history of hypertension, congestive heart failure, and left nephrectomy for renal cancer 10 years earlier; he was a former cigarette smoker with a 50 pack-year history, having quit 5 years prior to presentation. The patient did not report any recent travel history or occupational or animal exposures, and he did not have gastroesophageal reflux. Medications included diltiazem hydrochloride, irbesartan, hydrochlorothiazide, and ranitidine.