Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

A variant of green fluorescent protein exclusively deposited to active intracellular inclusion bodies

Background: Inclusion bodies (IBs) were generally considered to be inactive protein deposits and did not hold any attractive values in biotechnological applications. Recently, some IBs of recombinant proteins were confirmed to show their functional properties such as enzyme activities, fluorescence, etc. Such biologically active IBs are not commonly formed, but they have great potentials in the fields of biocatalysis, material science and nanotechnology. Results: In this study, we characterized the IBs of DL4, a deletion variant of green fluorescent protein which forms active intracellular aggregates. The DL4 proteins expressed in Escherichia coli were exclusively deposited to IBs, and the IBs were estimated to be mostly composed of active proteins. The spectral properties and quantum yield of the DL4 variant in the active IBs were almost same with those of its native protein. Refolding and stability studies revealed that the deletion mutation in DL4 didn't affect the folding efficiency of the protein, but destabilized its structure. Analyses specific for amyloid-like structures informed that the inner architecture of DL4 IBs might be amorphous rather than well-organized. The diameter of fluorescent DL4 IBs could be decreased up to 100-200 nm by reducing the expression time of the protein in vivo. Conclusions: To our knowledge, DL4 is the first GFP variant that folds correctly but aggregates exclusively in vivo without any self-aggregating/assembling tags. The fluorescent DL4 IBs have potentials to be used as fluorescent biomaterials. This study also suggests that biologically active IBs can be achieved through engineering a target protein itself.open0

Haemostatic function measured by thromboelastography and metabolic activity of platelets treated with riboflavin and UV light

[eng] Background: Pathogen reduction technology (PRT) may damage platelet (PLT) components. To study this, metabolic activity and haemostatic function of buffy coat (BC) PLT concentrates, with or without riboflavin and UV light PRT treatment, were compared. Material and methods: Twenty-four BC PLT concentrates, leukoreduced and diluted in additive solution, were grouped into 12 type-matched pairs, which were pooled and divided into 12 non-PRT-treated BC PLT concentrates (control units) and 12 riboflavin and UV PRT-treated BC PLT concentrates (test units). Haemostatic function and metabolic parameters were monitored by thrombelastography at days 1, 3, 7 and 14 post collection in both PLT groups. Results: Loss of PLT discoid shape, glucose consumption, lactate production, and decrease in pH were greater in the PRT-treated PLTs than in control PLTs over time (p<0.001). PLT haemostatic function evaluated by clot strength was also significantly weaker in PRT-treated PLTs compared with the excellent clot quality of control PLTs at day 7 (maximum amplitude: 41.27 vs 64.27; p<0.001), and even at day 14 (21.16 vs 60.39; p<0.001) of storage. Discussion: Pathogen reduction technology treatment accelerates and increases platelet storage lesion, resulting in glucose depletion, lactate accumulation, PLT acidification, and discoid shape loss. The clots produced by control PLTs at day 14 were still remarkably strong, whereas at day 7 PRT-treated PLTs produced weaker clots compared to the control group. Clinical trials investigating the efficacy of PRT-treated PLTs transfused at the end of the storage period (day 7), when the in vitro clot strength is weaker, are needed.

Surfactant protein D concentration in a pediatric population with suspected sleep disorder.

[eng] Obstructive sleep apnea (OSA) affects between 2% and 4% in children andthere is a search for new biomarkers that can be useful both in the diagnosis andin the evolution of the disease. The surfactant protein D (SP‐D) is a collectionthat is part of the innate immune system exerting an anti‐inflammatory andantimicrobial effect. Thus, the objective of this study was to evaluate theconcentration of SP‐D in the suspect OSA pediatric population. A total of 178children were recruited in this prospective study. Blood samples, sleep para-meters, feeding habits, anthropometric, sociodemographic, and family datawere collected. Specific biochemical determinations were made, and the plas-matic concentrations of SP‐D were measured by enzyme‐linked immunosorbentassay. We found no statistical correlation between the SP‐D concentration andthe apnea‐hypopnea index (AHI) from the data. Nevertheless, the changes inSP‐D levels could be correlated to a large extent by the arousals that often goalong with hypopneas (r = −0.258, p = 0.011 unadjusted; r = −0.258, p = 0.014adjusted by age and body mass inded [BMI] Z‐score). Intermittent hypoxia wascorrelated with C‐reactive protein levels (r = 0.547, p < 0.001 unadjusted;r = 0.542, p < 0.001 adjusted by age and BMI Z‐score). Although AHI and SP‐Ddid not appear to correlate, a secondary analysis suggests that sleep fragmen-tation, which is produced by arousals, may do, and further research is needed todetermine the mechanisms by which changes in SP‐D occur in OS

Cryopreservation of platelets treated with riboflavin and UV light and stored at -80°C for 1 year

[eng] Background: The combination of pathogen reduction technologies (PRTs) and cryopreservation can contribute to building a safe and durable platelet (PLT) inventory. Information about cryopreserved riboflavin and UV lighttreated PLTs is scarce.Study Design and Methods: Twenty-four buffy coat (BC) PLT concentrates were grouped into 12 type-matched pairs, pooled, and divided into 12 non-PRT-treated control units and 12 riboflavin and UV light PRT-treated test units. Both were cryopreserved with 5% DMSO and stored at −80°C for 1 year. The cryopreservation method used was designed to avoid the formation of aggregates. PLT variables (PLT recovery, swirling, pH, MPV, and LDH) and hemostatic function measured by thromboelastography (TEG) were analyzed before cryopreservation (day 1) and post-cryopreservation at day 14 and months 3, 6, and 12 of storage at −80°C. The analyses were carried out within 1-h post-thaw. Results: No aggregates were found in either PLT group at any time. Swirling was observed in both groups. MPV increased and mean pH values decreased over time (p 6.4, and procoagulant potential, as evidenced by a reduced clotting time after 12 months of storage at −80°C. The clinical relevance of these findings should be further investigated in clinical trials

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Omicron SARS-CoV-2 infection management and outcomes in patients with hematologic disease and recipients of cell therapy

Introduction: Scarce real-life data exists for COVID-19 management in hematologic disease (HD) patients in the Omicron era. Purpose: To assess the current clinical management and outcome of SARS-CoV-2 infection diagnosed, identify the risk factors for severe outcomes according to the HD characteristics and cell therapy procedures in a real-world setting. Methods: A retrospective observational registry led by the Spanish Transplant Group (GETH-TC) with 692 consecutive patients with HD from December 2021 to May 2023 was analyzed. Results: Nearly one-third of patients (31%) remained untreated and presented low COVID-19-related mortality (0.9%). Nirmatrelvir/ritonavir was used mainly in mild COVID-19 cases in the outpatient setting (32%) with a low mortality (1%), while treatment with remdesivir was preferentially administered in moderate-to-severe SARS-CoV-2 infection cases during hospitalization (35%) with a mortality rate of 8.6%. The hospital admission rate was 23%, while 18% developed pneumonia. COVID-19-related mortality in admitted patients was 14%. Older age, autologous hematopoietic stem cell transplantation (SCT), chimeric antigen receptor T-cell therapy, corticosteroids and incomplete vaccination were factors independently associated with COVID-19 severity and significantly related with higher rates of hospital admission and pneumonia. Incomplete vaccination status, treatment with prior anti-CD20 monoclonal antibodies, and comorbid cardiomyopathy were identified as independent risk factors for COVID-19 mortality. Conclusions: The results support that, albeit to a lower extent, COVID-19 in the Omicron era remains a significant problem in HD patients. Complete vaccination (3 doses) should be prioritized in these immunocompromised patients. The identified risk factors may help to improve COVID-19 management to decrease the rate of severe disease, ICU admissions and mortality

Identification of COVID-19 patients at risk of hospital admission and mortality: a European multicentre retrospective analysis of mid-regional pro-adrenomedullin

Background: Mid-Regional pro-Adrenomedullin (MR-proADM) is an inflammatory biomarker that improves the prognostic assessment of patients with sepsis, septic shock and organ failure. Previous studies of MR-proADM have primarily focussed on bacterial infections. A limited number of small and monocentric studies have examined MR-proADM as a prognostic factor in patients infected with SARS-CoV-2, however there is need for multicenter validation. An evaluation of its utility in predicting need for hospitalisation in viral infections was also performed. Methods: An observational retrospective analysis of 1861 patients, with SARS-CoV-2 confirmed by RT-qPCR, from 10 hospitals across Europe was performed. Biomarkers, taken upon presentation to Emergency Departments (ED), clinical scores, patient demographics and outcomes were collected. Multiclass random forest classifier models were generated as well as calculation of area under the curve analysis. The primary endpoint was hospital admission with and without death. Results: Patients suitable for safe discharge from Emergency Departments could be identified through an MR-proADM value of ≤ 1.02&nbsp;nmol/L in combination with a CRP (C-Reactive Protein) of ≤ 20.2&nbsp;mg/L and age ≤ 64, or in combination with a SOFA (Sequential Organ Failure Assessment) score &lt; 2 if MR-proADM was ≤ 0.83&nbsp;nmol/L regardless of age. Those at an increased risk of mortality could be identified upon presentation to secondary care with an MR-proADM value of &gt; 0.85&nbsp;nmol/L, in combination with a SOFA score ≥ 2 and LDH &gt; 720 U/L, or in combination with a CRP &gt; 29.26&nbsp;mg/L and age ≤ 64, when MR-proADM was &gt; 1.02&nbsp;nmol/L. Conclusions: This international study suggests that for patients presenting to the ED with confirmed SARS-CoV-2 infection, MR-proADM in combination with age and CRP or with the patient’s SOFA score could identify patients at low risk where outpatient treatment may be safe

Strategies to reengage patients lost to follow up in HIV care in high income countries, a scoping review

Background: Despite remarkable achievements in antiretroviral therapy (ART), losses to follow-up (LTFU) might prevent the long-term success of HIV treatment and might delay the achievement of the 90-90-90 objectives. This scoping review is aimed at the description and analysis of the strategies used in high-income countries to reengage LTFU in HIV care, their implementation and impact. Methods: A scoping review was done following Arksey & O'Malley's methodological framework and recommendations from Joanna Briggs Institute. Peer reviewed articles were searched for in Pubmed, Scopus and Web of Science; and grey literature was searched for in Google and other sources of information. Documents were charted according to the information presented on LTFU, the reengagement procedures used in HIV units in high-income countries, published during the last 15 years. In addition, bibliographies of chosen articles were reviewed for additional articles. Results: Twenty-eight documents were finally included, over 80% of them published in the United States later than 2015. Database searches, phone calls and/or mail contacts were the most common strategies used to locate and track LTFU, while motivational interviews and strengths-based techniques were used most often during reengagement visits. Outcomes like tracing activities efficacy, rates of reengagement and viral load reduction were reported as outcome measures. Conclusions: This review shows a recent and growing trend in developing and implementing patient reengagement strategies in HIV care. However, most of these strategies have been implemented in the United States and little information is available for other high-income countries. The procedures used to trace and contact LTFU are similar across reviewed studies, but their impact and sustainability are widely different depending on the country studied