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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.

OBJECTIVE Diabetes mellitus (DM) is a major risk factor for severe coronavirus disease 2019 (COVID-19) for reasons that are unclear. RESEARCH DESIGN AND METHODS We leveraged the International Study of Inflammation in COVID-19 (ISIC), a multicenter observational study of 2,044 patients hospitalized with COVID-19, to characterize the impact of DM on in-hospital outcomes and assess the contribution of inflammation and hyperglycemia to the risk attributed to DM. We measured biomarkers of inflammation collected at hospital admission and collected glucose levels and insulin data throughout hospitalization. The primary outcome was the composite of in-hospital death, need for mechanical ventilation, and need for renal replacement therapy. RESULTS Among participants (mean age 60 years, 58.2% males), those with DM (n = 686, 33.5%) had a significantly higher cumulative incidence of the primary outcome (37.8% vs. 28.6%) and higher levels of inflammatory biomarkers than those without DM. Among biomarkers, DM was only associated with higher soluble urokinase plasminogen activator receptor (suPAR) levels in multivariable analysis. Adjusting for suPAR levels abrogated the association between DM and the primary outcome (adjusted odds ratio 1.23 [95% CI 0.78, 1.37]). In mediation analysis, we estimated the proportion of the effect of DM on the primary outcome mediated by suPAR at 84.2%. Hyperglycemia and higher insulin doses were independent predictors of the primary outcome, with effect sizes unaffected by adjusting for suPAR levels. CONCLUSIONS Our findings suggest that the association between DM and outcomes in COVID-19 is largely mediated by hyperinflammation as assessed by suPAR levels, while the impact of hyperglycemia is independent of inflammation.

Background Venous thromboembolism (VTE) contributes significantly to COVID‐19 morbidity and mortality. The urokinase receptor system is involved in the regulation of coagulation. Levels of soluble urokinase plasminogen activator receptor (suPAR) reflect hyperinflammation and are strongly predictive of outcomes in COVID‐19. Whether suPAR levels identify patients with COVID‐19 at risk for VTE is unclear. Methods and Results We leveraged a multinational observational study of patients hospitalized for COVID‐19 with suPAR and D‐dimer levels measured on admission. In 1960 patients (mean age, 58 years; 57% men; 20% Black race), we assessed the association between suPAR and incident VTE (defined as pulmonary embolism or deep vein thrombosis) using logistic regression and Fine‐Gray modeling, accounting for the competing risk of death. VTE occurred in 163 (8%) patients and was associated with higher suPAR and D‐dimer levels. There was a positive association between suPAR and D‐dimer (β=7.34; P =0.002). Adjusted for clinical covariables, including D‐dimer, the odds of VTE were 168% higher comparing the third with first suPAR tertiles (adjusted odds ratio, 2.68 [95% CI, 1.51–4.75]; P Conclusions Higher suPAR was associated with incident VTE independently of D‐dimer in patients hospitalized for COVID‐19. Combining suPAR and D‐dimer identified patients at low VTE risk. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04818866.

Contains fulltext : 237989.pdf (Publisher’s version ) (Closed access) BACKGROUND: Anakinra might improve the prognosis of patients with moderate to severe COVID-19 (ie, patients requiring oxygen supplementation but not yet receiving organ support). We aimed to assess the effect of anakinra treatment on mortality in patients admitted to hospital with COVID-19. METHODS: For this systematic review and individual patient-level meta-analysis, a systematic literature search was done on Dec 28, 2020, in Medline (PubMed), Cochrane, medRxiv, bioRxiv, and the ClinicalTrials.gov databases for randomised trials, comparative studies, and observational studies of patients admitted to hospital with COVID-19, comparing administration of anakinra with standard of care, or placebo, or both. The search was repeated on Jan 22, 2021. Individual patient-level data were requested from investigators and corresponding authors of eligible studies; if individual patient-level data were not available, published data were extracted from the original reports. The primary endpoint was mortality after 28 days and the secondary endpoint was safety (eg, the risk of secondary infections). This study is registered on PROSPERO (CRD42020221491). FINDINGS: 209 articles were identified, of which 178 full-text articles fulfilled screening criteria and were assessed. Aggregate data on 1185 patients from nine studies were analysed, and individual patient-level data on 895 patients were provided from six of these studies. Eight studies were observational and one was a randomised controlled trial. Most studies used historical controls. In the individual patient-level meta-analysis, after adjusting for age, comorbidities, baseline ratio of the arterial partial oxygen pressure divided by the fraction of inspired oxygen (PaO(2)/FiO(2)), C-reactive protein (CRP) concentrations, and lymphopenia, mortality was significantly lower in patients treated with anakinra (38 [11%] of 342) than in those receiving standard of care with or without placebo (137 [25%] of 553; adjusted odds ratio [OR] 0·32 [95% CI 0·20-0·51]). The mortality benefit was similar across subgroups regardless of comorbidities (ie, diabetes), ferritin concentrations, or the baseline PaO(2)/FiO(2). In a subgroup analysis, anakinra was more effective in lowering mortality in patients with CRP concentrations higher than 100 mg/L (OR 0·28 [95% CI 0·17-0·47]). Anakinra showed a significant survival benefit when given without dexamethasone (OR 0·23 [95% CI 0·12-0·43]), but not with dexamethasone co-administration (0·72 [95% CI 0·37-1·41]). Anakinra was not associated with a significantly increased risk of secondary infections when compared with standard of care (OR 1·35 [95% CI 0·59-3·10]). INTERPRETATION: Anakinra could be a safe, anti-inflammatory treatment option to reduce the mortality risk in patients admitted to hospital with moderate to severe COVID-19 pneumonia, especially in the presence of signs of hyperinflammation such as CRP concentrations higher than 100 mg/L. FUNDING: Sobi.

Early recognition of risk and start of treatment may improve unfavorable outcome of COVID-19. In the SAVE-MORE double-blind randomized trial, 594 patients with pneumonia without respiratory dysfunction at risk as defined by plasma suPAR (soluble urokinase plasminogen activator receptor) ≥ 6 ng/ml were 1:2 randomized to subcutaneous placebo or 100 mg anakinra once daily for 10 days; 85.9% were co-administered dexamethasone. After 28 days, anakinra-treated patients were distributed to lower strata of the 11-point World Health Organization ordinal Clinical Progression Scale (WHO-CPS) (adjusted odds ratio-OR 0.36; 95%CI 0.26–0.50; P

SUMMARYBCG vaccination induces heterologous protection against respiratory tract infections, and in children improves survival independently of tuberculosis prevention. The phase III ACTIVATE-2 study assessed whether BCG could also protect against COVID19 in the elderly. In this double-blind, randomized trial, elderly Greek patients were randomized (1:1) to receive either BCG revaccination or placebo at hospital discharge, followed by 6 months observation for incidence of COVID19 infection. BCG revaccination resulted in 68% risk reduction for total COVID19 clinical and microbiological diagnoses (OR 0.32, 95% CI 0.13-0.79). Five patients in the placebo group and one in the BCG-vaccinated group had severe COVID19 that necessitated hospitalization. 3 months after BCG vaccination 1.3% of placebo and 4.7% of BCG-vaccinated volunteers had anti-SARS-CoV-2 antibodies. These data argue that BCG revaccination is safe and protects the elderly against COVID19. BCG revaccination may represent a viable preventive measure against COVID19.

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 osteosynthesis—17 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.

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/β 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, The SAVE-MORE phase 3 study demonstrates the efficacy of anakinra, an IL-1α/β inhibitor, in patients with COVID-19 and high serum levels of soluble plasminogen activator receptor.

Objectives: This study aims to develop the Greek version of the Herth Hope Index (HHI) and assess its psychometric properties to a palliative care patient sample, using a cross-sectional design. Materials and Methods: The HHI was translated into Greek (HHI-Gr) using the ‘forward-backward’ procedure. It was administered to 130 eligible cancer patients, while for the stability of patients’ responses, 40 of these patients completed the HHI-Gr 3 days later. Along with the HHI-Gr, patients also completed the Hospital Anxiety and Depression Scale (HADS) and the Beck Hopelessness Scale (BHS). The HHI-Gr internal consistency reliability (Cronbach’s a), stability (intraclass correlation coefficient [ICC]), factor structure (factor analysis) and convergent validity (correlation with the HADS and the BHS questionnaires) were examined using the Eastern Cooperative Oncology Group (ECOG) performance status. Results: The HHI-Gr yielded a one-factor model and a Cronbach alpha (0.860) with excellent internal consistency reliability and stability ICC (>0.90). Satisfactory convergent validity was supported by the correlation analysis between the HHI-Gr and BHS (r = 0.718, P < 0.001). Overall test-retest reliability was satisfactory with a range between 0.77 and 0.96 (P < 0.001). Conclusion: These results demonstrate that the HHI-Gr is an instrument with satisfactory psychometric properties and is a valid research tool for the measurement of the levels of hope among Greek oncology patients.

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.

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)., Graphical Abstract, Highlights • ACTIVATE is a prospective randomized trial of BCG vaccination in the elderly • BCG increased the time to first infection and decreased the incidence of new infection • Strongest protection was found against viral respiratory tract infections • Epigenetic reprogramming and increased cytokine production was found in monocytes, Interim analysis of the phase III ACTIVATE trial to evaluate protection against infection in elderly patients reveals that BCG vaccination is safe, increases the time to first infection, and shows protection against viral respiratory infections.

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.

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.

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.