Assessment of continuous low-dose and high-dose burst of inhaled nitric oxide in spontaneously breathing COVID-19 patients: A randomized controlled trial.

BACKGROUND: Inhaled nitric oxide (iNO) showed to improve oxygenation at low doses by reducing intrapulmonary shunt and to display antiviral properties at high doses. To assess the safety and potential benefits, we designed an exploratory clinical trial comparing low-dose with intermittent high-dose iNO to only intermittent high-dose iNO in hypoxemic COVID-19 patients. METHODS: In this single-center interventional non-inferiority randomized trial (ClinicalTrials.gov, NCT04476992), twenty oxygen-dependent COVID-19 patients were randomly assigned to the high-dose (200 ppm for 30 min) + continuous low-dose (20 ppm) iNO group (iNO200/20) or the high-dose iNO group (iNO200). Methemoglobinemia (MetHb) assessed 48 h after iNO initiation was the primary endpoint. Reverse-transcription polymerase chain reaction for SARS-CoV-2, inflammatory markers during hospitalization, and heart ultrasounds during the iNO200 treatments were evaluated. RESULTS: MetHb difference between iNO groups remained within the non-inferiority limit of 3 %, indicating comparable treatments despite being statistically different (p-value<0.01). Both groups presented similar SpO2/FiO2 ratio at 48 h (iNO200 vs. iNO200/20 341[334-356] vs. 359 [331-380], respectively, p-value = 0.436). Both groups showed the same time to SARS-CoV-2 negativization, hospital length of stay, and recovery time. iNO-treated patients showed quicker SARS-CoV-2 negativization compared to a similar group of non-iNO patients (HR 2.57, 95%CI 1.04-6.33). During the 228 treatments, iNO200 and iNO200/20 groups were comparable for safety, hemodynamic stability, and respiratory function improvement. CONCLUSIONS: iNO200/20 and iNO200 are equally safe in non-intubated patients with COVID-19-induced respiratory failure with regards to MetHb and NO2. Larger studies should investigate whether iNO200/20 leads to better outcomes compared to non-iNO treated patients.

BABEL (Better tArgeting, Better outcomes for frail ELderly patients) advance care planning: a comprehensive approach to advance care planning in nursing homes: a cluster randomised trial.

BACKGROUND: Nursing home (NH) residents should have the opportunity to consider, discuss and document their healthcare wishes. However, such advance care planning (ACP) is frequently suboptimal. OBJECTIVE: Assess a comprehensive, person-centred ACP approach. DESIGN: Unblinded, cluster randomised trial. SETTING: Fourteen control and 15 intervention NHs in three Canadian provinces, 2018-2020. SUBJECTS: 713 residents (442 control, 271 intervention) aged ≥65 years, with elevated mortality risk. METHODS: The intervention was a structured, $\sim$60-min discussion between a resident, substitute decision-maker (SDM) and nursing home staff to: (i) confirm SDMs' identities and role; (ii) prepare SDMs for medical emergencies; (iii) explain residents' clinical condition and prognosis; (iv) ascertain residents' preferred philosophy to guide decision-making and (v) identify residents' preferred options for specific medical emergencies. Control NHs continued their usual ACP processes. Co-primary outcomes were: (a) comprehensiveness of advance care planning, assessed using the Audit of Advance Care Planning, and (b) Comfort Assessment in Dying. Ten secondary outcomes were assessed. P-values were adjusted for all 12 outcomes using the false discovery rate method. RESULTS: The intervention resulted in 5.21-fold higher odds of respondents rating ACP comprehensiveness as being better (95% confidence interval [CI] 3.53, 7.61). Comfort in dying did not differ (difference = -0.61; 95% CI -2.2, 1.0). Among the secondary outcomes, antimicrobial use was significantly lower in intervention homes (rate ratio = 0.79, 95% CI 0.66, 0.94). CONCLUSIONS: Superior comprehensiveness of the BABEL approach to ACP underscores the importance of allowing adequate time to address all important aspects of ACP and may reduce unwanted interventions towards the end of life.

Correction to: 2020 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference.

The abstract with Submission ID#809896 has been revised due to duplicate title and the missing main author.

Thyrotropin levels and severity of symptoms in migraine patients of tertiary headache center.

BACKGROUND: The role of thyroid regulation in migraine is poorly understood, and data is contradictory. OBJECTIVE: To study the possible association of clinical features of migraine with patients' thyroid function. PATIENTS AND METHODS: One hundred and thirty migraine patients of a tertiary headache center took part in an open-label, cross-sectional comparative study. The Migraine Disability Assessment questionnaire, Spielberger State-Trait Anxiety Inventory, Beck Depression Inventory, Vanderbilt's Questionnaire of Pain Management, Gothenburg Quality of Life Questionnaire and Migraine-Specific Quality of Life questionnaire were used. The effectiveness of the attacks' therapy was assessed according to the Migraine Assessment of Current Therapy questionnaire. Levels of thyrotropine (thyroid stimulating hormone), thyroxine, and triiodothyronine were studied by standard immune chemiluminescent method using the Immulite-2000 set. RESULTS: An inverse correlation between levels of thyroid stimulating hormone in serum and duration of headache attacks was revealed. The effectiveness of abortive therapy for attacks showed a statistically significant positive correlation with thyroid stimulating hormone level. Quality of life measured by a general quality of life questionnaire, as well as the functional and social indices of a migraine-specific questionnaire, showed direct correlation with serum thyroid stimulating hormone. CONCLUSION: These results show an association of a more severe clinical course of migraine with lower thyroid stimulating hormone levels.

One-pot DTECT enables rapid and efficient capture of genetic signatures for precision genome editing and clinical diagnostics.

The detection of genomic sequences and their alterations is crucial for basic research and clinical diagnostics. However, current methodologies are costly and time-consuming and require outsourcing sample preparation, processing, and analysis to genomic companies. Here, we establish One-pot DTECT, a platform that expedites the detection of genetic signatures, only requiring a short incubation of a PCR product in an optimized one-pot mixture. One-pot DTECT enables qualitative, quantitative, and visual detection of biologically relevant variants, such as cancer mutations, and nucleotide changes introduced by prime editing and base editing into cancer cells and human primary T cells. Notably, One-pot DTECT achieves quantification accuracy for targeted genetic signatures comparable with Sanger and next-generation sequencing. Furthermore, its effectiveness as a diagnostic platform is demonstrated by successfully detecting sickle cell variants in blood and saliva samples. Altogether, One-pot DTECT offers an efficient, versatile, adaptable, and cost-effective alternative to traditional methods for detecting genomic signatures.

Macro- and Microstructure of In Situ Composites Prepared by Friction Stir Processing of AA5056 Admixed with Copper Powders.

This paper is devoted to using multi-pass friction stir processing (FSP) for admixing 1.5 to 30 vol.% copper powders into an AA5056 matrix for the in situ fabrication of a composite alloy reinforced by Al-Cu intermetallic compounds (IMC). Macrostructurally inhomogeneous stir zones have been obtained after the first FSP passes, the homogeneity of which was improved with the following FSP passes. As a result of stirring the plasticized AA5056, the initial copper particle agglomerates were compacted into large copper particles, which were then simultaneously saturated by aluminum. Microstructural investigations showed that various phases such as α-Al(Cu), α-Cu(Al) solid solutions, Cu3Al and CuAl IMCs, as well as both S and S'-Al2CuMg precipitates have been detected in the AA5056/Cu stir zone, depending upon the concentration of copper and the number of FSP passes. The number of IMCs increased with the number of FSP passes, enhancing microhardness by 50-55%. The effect of multipass FSP on tensile strength, yield stress and strain-to-fracture was analyzed.

Evolution of Microstructure in Friction Stir Processed Dissimilar CuZn37/AA5056 Stir Zone.

Dissimilar friction stir processing on CuZn37/AA5056 was performed to study structural and phase evolution of a friction stir zone. Formation of 5-10 µm intermetallic compounds (IMCs) such as Al2Cu was the main type of diffusion reaction between copper and aluminum. Other alloying elements such as Mg and Zn were forced out of the forming Al2Cu grains and dissolved in the melt formed due to exothermic effect of the Al2Cu formation. When solidified, these Zn-enriched zones were represented by α-Al+Al2Cu+Zn phases or α-Al+Al2Cu+Zn+MgZn regions. Eutectic Zn+MgZn was undoubtedly formed the melt after stirring had stopped. These zones were proven to be weak ones with respect to pull-off test since MgZn was detected on the fracture surface. Tensile strength of the stirred zone metal was achieved at the level of that of AA5056.