Acquired von Willebrand Syndrome and Desmopressin Resistance During Venovenous Extracorporeal Membrane Oxygenation in Patients With COVID-19: A Prospective Observational Study.

OBJECTIVES: Although COVID-19 is associated with high von Willebrand factor (vWF) parameters promoting thrombosis, venovenous extracorporeal membrane oxygenation (vvECMO) is associated with the development of acquired von Willebrand syndrome (AVWS) promoting bleeding. This study was designed to assess both the incidence and severity of AVWS in COVID-19 patients undergoing vvECMO, and the benefit of comprehensive vWF analyses. DESIGN: Prospective observational study. SETTING: ICU at a tertiary-care center. PATIENTS: Twenty-seven consecutive COVID-19 patients with acute respiratory distress syndrome (ARDS) requiring vvECMO. MEASUREMENTS AND MAIN RESULTS: Comprehensive vWF analyses (including sodium dodecyl-sulfate polyacrylamide gel electrophoresis) were performed before, during, and after vvECMO. In a subgroup of 12 patients with AVWS, effectiveness of treatment with desmopressin was assessed. The patients' mean age was 53 years (range, 23-73), 70% were male, and all had various comorbidities. Following markedly elevated vwf antigen (vWF: Ag; mean, 546% ( sd , 282]), vWF collagen binding capacity (mean, 469% [ sd , 271]), vWF activity (vWF:A; mean, 383% [ sd , 132]), and factor VIII activity (mean, 302% [ sd , 106]), and only borderline decreases in high-molecular-weight (HMW) vWF multimers before vvECMO, all of these variables decreased and HMW vWF multimers became undetectable within hours following initiation of vvECMO. All variables fully recovered within 3-38 hours after discontinuation of vvECMO. During vvECMO, decreases in the vWF:A/vWF:Ag ratio correlated with absent HMW vWF multimers. Desmopressin did not affect vWF parameters. CONCLUSIONS: In patients with COVID-19-associated ARDS, AVWS developed soon after initiation of vvECMO. The vWF:A/vWF:Ag ratio was a suitable screening test for AVWS. As desmopressin was ineffective, bleeding during vvECMO-associated AVWS should preferably be treated with concentrates containing vWF.

Hypernatremia-A Manifestation of COVID-19: A Case Series.

We report for the first time therapy-resistant hypernatremia (plasma sodium concentration ≥150 mmol per liter) developing in 6 of 12 critically ill coronavirus disease 2019 (COVID-19) patients age 57-84 years requiring mechanical ventilation. There was no correlation between plasma sodium concentrations and sodium input. Plasma concentrations of chloride were elevated, those of potassium decreased. These findings are consistent with abnormally increased renal sodium reabsorption, possibly caused by increased angiotensin II activity secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced downregulation of angiotensin-converting enzyme 2 (ACE2) receptors. As hypernatremia was associated with increased length of intensive care unit stay, special attention should be paid to the electrolyte status of COVID-19 patients.

Problems of subgroup analysis in randomized controlled trial.

Multiple subgroup analyses of the same data increase the risk of generating false positive findings. All outcomes and planned subgroup analyses should thus be prespecified and described in the original trial registry. When outcome changes during an ongoing trial seem justifiable, publications must disclose and explain such changes.

Optical clearing: impact of optical and dielectric properties of clearing solutions on pulmonary tissue mechanics.

Optical clearing allows tissue visualization under preservation of organ integrity. Optical clearing of organs with a physiological change in three-dimensional geometry (such as the lung) would additionally allow visualization of macroscopic and microscopic tissue geometry. A prerequisite, however, is the preservation of the native tissue mechanics of the optically cleared lung tissue. We investigated the impact of optical and dielectric properties of clearing solutions on biomechanics and clearing potency in porcine tissue strips of healthy lungs. After fixation, bleaching, and rehydration, four methods of optical clearing were investigated using eight different protocols. The mechanical and optical properties of the cleared lung tissue strips were investigated by uniaxial tensile testing and by analyzing optical transparency and translucency for red, green, and blue light before, during, and after the biochemical optical clearing process. Fresh tissue strips were used as controls. Best balance between efficient clearing and preserved mechanics was found for clearing with a 1:1 mixture of dimethyl sulfoxide (DMSO) and aniline. Our findings show that 1) the degree of tissue transparency and translucency correlated with the refractive index of the clearing solution index (r = 0.976, P = 0.0004; and r = 0.91, P = 0.0046, respectively), 2) tissue mechanics were affected by dehydration and the type of clearing solution, and 3) tissue biomechanics and geometry correlated with the dielectric constant of the clearing solution (r = -0.98, P < 0.00001; and r = 0.69, P = 0.013, respectively). We show that the lower the dielectric constant of the clearing solutions, the larger the effect on tissue stiffness. This suggests that the dielectric constant is an important measure in determining the effect of a clearing solution on lung tissue biomechanics. Optimal tissue transparency requires complete tissue dehydration and a refractive index of 1.55 of the clearing solution.NEW & NOTEWORTHY Investigating optical clearing in porcine lung tissue strips, we found that refractive index and dielectric constant of the clearing solution affected tissue clearing and biomechanics. By documenting the impact of the composition of the clearing solution on clearing potency and preservation of tissue mechanics, our results help to compose optimal clearing solutions. In addition, the results allow conclusions on the molecular interaction of solvents with collagen fibers in tissue, thereby consolidating existing theories about the functionality of collagen.