A Cellular Model of Shear‐Induced Hemolysis

A novel model is presented to study red blood cell (RBC) hemolysis at cellular level. Under high shear rates, pores form on RBC membranes through which hemoglobin (Hb) leaks out and increases free Hb content of plasma leading to hemolysis. By coupling lattice Boltzmann and spring connected network models through immersed boundary method, we estimate hemolysis of a single RBC under various shear rates. First, we use adaptive meshing to find local strain distribution and critical sites on RBC membranes, and then we apply underlying molecular dynamics simulations to evaluate damage. Our approach comprises three sub‐models: defining criteria of pore formation, calculating pore size, and measuring Hb diffusive flux out of pores. Our damage model uses information of different scales to predict cellular level hemolysis. Results are compared with experimental studies and other models in literature. The developed cellular damage model can be used as a predictive tool for hydrodynamic and hematologic design optimization of blood‐wetting medical devices.     

Three‐dimensional parametric modeling of bicuspid aortopathy and comparison with computational flow predictions

Bicuspid aortic valve (BAV)‐associated ascending aneurysmal aortopathy (namely “bicuspid aortopathy”) is a heterogeneous disease making surgeon predictions particularly challenging. Computational flow analysis can be used to evaluate the BAV‐related hemodynamic disturbances, which likely lead to aneurysm enlargement and progression. However, the anatomic reconstruction process is time consuming so that predicting hemodynamic and structural evolution by computational modeling is unfeasible in routine clinical practice. The aim of the study was to design and develop a parametric program for three‐dimensional (3D) representations of aneurysmal aorta and different BAV phenotypes starting from several measures derived by computed‐tomography angiography (CTA). Assuming that wall shear stress (WSS) has an important implication on bicuspid aortopathy, computational flow analyses were then performed to estimate how different would such an important parameter be, if a parametric aortic geometry was used as compared to standard geometric reconstructions obtained by CTA scans. Morphologic parameters here documented can be used to rapidly model the aorta and any phenotypes of BAV. t‐test and Bland–Altman plot demonstrated that WSS obtained by flow analysis of parametric aortic geometries was in good agreement with that obtained from the flow analysis of CTA‐related geometries. The proposed program offers a rapid and automated tool for 3D anatomic representations of bicuspid aortopathy with promising application in routine clinical practice by reducing the amount of time for anatomic reconstructions.     

No effect of HLA‐C mismatch after allogeneic hematopoietic stem cell transplantation with unrelated donors and T‐cell depletion in patients with hematological malignancies

HLA‐C mismatch in unrelated donor's hematopoietic stem cell transplantation (HSCT) has been associated with poor patient outcome. However, the impact of HLA‐C mismatch in the context of HSCT combined with in vivo T‐cell depletion remains unclear. We therefore performed a single‐center, retrospective analysis of the clinical outcome on patients with hematological malignancies treated with allo‐HSCT, who underwent T‐cell depletion. The majority of the patients (n=276) received a HLA‐A, HLA‐B, HLA‐DRB1‐matched graft that were either also HLA‐C matched (n=260), or patients with the permissive HLA‐C*03:03/03:04 mismatch (n=16), while the remaining patients (n=95) received a HLA‐C‐mismatched graft (excluding HLA‐C*03:03/03:04 mismatches). We did not observe any significant differences between the HLA‐C‐matched patients (including the permissive HLA‐C*03:03/03:04 mismatch) and the HLA‐C‐mismatched patients regarding cumulative proportion surviving, graft failure, relapse‐free survival, relapse, or acute graft‐versus‐host disease. Our data suggest that in the context of high dose T lymphocyte‐depleting agents, HLA‐C matching is not essential for patients with hematological malignancies.     

The role of procalcitonin as a marker of diabetic foot ulcer infection

Foot ulcers are frequent in diabetic patients and are responsible for 85% of amputations, especially in the presence of infection. The diagnosis of diabetic foot ulcer infection is essentially based on clinical evaluation, but laboratory parameters such as erythrocyte sedimentation rate (ESR), white blood count (WBC), C‐reactive protein (CRP) and, more recently, procalcitonin (PCT) could aid the diagnosis, especially when clinical signs are misleading. Fifteen diabetic patients with infected foot ulcers were admitted to our department and were compared with an additional group of patients with non‐infected diabetic foot ulcers (NIDFUs). Blood samples were collected from all patients in order to evaluate laboratory markers. In the current study, the diagnostic accuracy of PCT serum levels was evaluated in comparison with other inflammatory markers such as CRP, ESR and WBC as an indicator to make the distinction between infected diabetic foot ulcers (IDFUs) and NIDFUs. CRP, WBC, ESR and especially PCT measurements represent effective biomarkers in the diagnosis of foot infections in diabetic patients particularly when clinical signs are misleading.     

Mesenchymal stem cell‐conditioned medium accelerates wound healing with fewer scars

Mesenchymal stem cells (MSCs) derived from umbilical cord s (UC‐MSCs) have been shown to enhance cutaneous wound healing by means of the paracrine activity. Fibroblasts are the primary cells involved in wound repair. The paracrine effects of UC‐MSCs on dermal fibroblasts have not been fully explored in vitro or in vivo. Dermal fibroblasts were treated with conditioned media from UC‐MSCs (UC‐MSC‐CM). In this model, UC‐MSC‐CM increased the proliferation and migration of dermal fibroblasts. Moreover, adult dermal fibroblasts transitioned into a phenotype with a low myofibroblast formation capacity, a decreased ratio of transforming growth factor‐β1,3 (TGF‐β1/3) and an increased ratio of matrix metalloproteinase/tissue inhibitor of metalloproteinases (MMP/TIMP). Additionally, UC‐MSC‐CM‐treated wounds showed accelerated healing with fewer scars compared with control groups. These observations suggest that UC‐MSC‐CM may be a feasible strategy to promote cutaneous repair and a potential means to realise scarless healing.     

Measurement of morphological and physiological skin properties in aged care residents: a test–retest reliability pilot study

This test–retest pilot study investigated the intra‐rater reliability and reproducibility of non‐invasive technologies to objectively quantify morphological (colour, thickness and elasticity) and physiological (transepidermal water loss (TEWL), hydration, sebum and pH) skin properties in an aged care population. Three consecutive measurements were taken from five anatomical skin sites, with the mean of each measurement calculated. The intra‐class correlation coefficient (ICC) and the standard error of measurement (SEM) were used to examine the intra‐rater reliability and reproducibility of measurements. Non‐invasive technologies in this study showed almost perfect reliability for ultrasound measurements of the subepidermal low echogenicity band (SLEB) (ρ = 0·95–0·99) and skin thickness (ρ = 0·95–0·99) across all sites. The ICC was substantial to almost perfect for pH (ρ = 0·76–0·88) and viscoelasticity (ρ = 0·67–0·91) across all sites. Hydration (ρ = 0·53–0·85) and skin retraction (ρ = 0·57–0·99) measurements ranged from moderate to almost perfect across all sites. TEWL and elasticity were substantial to almost perfect across four sites. Casual sebum levels and most colour parameters showed poor ICC. The use of non‐invasive technologies in this study provided an objective and reliable means for quantifying ageing skin and may offer future studies a valuable option for assessing skin tear risk.