Hepatic sinusoidal obstruction syndrome after allogeneic hematopoietic stem cell transplantation in adult patients with idiopathic aplastic anemia

We retrospectively investigated the incidence, risk factors, and outcomes of SOS (sinusoidal obstruction syndrome; previously veno-occlusive disease [VOD]) after allogeneic hematopoietic stem cell transplantation (alloHSCT) in aplastic anemia. Two hundred and sixty patients were included in the analysis. SOS developed in 7.3% (n = 19/260) of patients. Classical Cy (200 mg/m²)-ATG was the most common conditioning regimen (84.2%) in the SOS group. The SOS mortality rate was 4/19 (21.1%). Univariate analyses revealed that Cy 200 mg/m² conditioning (p = 0.035), classical Cy-ATG conditioning (p = 0.007), and horse ATG conditioning (p < 0.001) were significant risk factors for developing SOS. Multivariate analysis revealed that only horse ATG conditioning was a poor prognostic factor (HR = 3.484; 95% CI 1.226–9.904; p = 0.002). Rabbit ATG (HR 12.719; 95% CI 2.332–69.373; p = 0.003) and weight gain > 10% (HR 35.655; 95% CI 2.208–575.805; p = 0.012) were risk factors in the overall SOS group. Both rabbit ATG conditioning and weight gain of more than 10% were associated with poor overall survival with a median of 1.2 months (5Y survival rate, any risk factor vs. none: 74.6% vs. 0.0%; p < 0.001; Fig. 2) in the SOS group.     

The association between the serum vitamin D levels and the stroke lesion size,functional ability,and cognition in elderly Korean ischemic stroke patients

The purpose of this study was to confirm the association between the serum vitamin D levels and ischemic stroke lesion size, functional ability, and cognitive function in elderly ischemic stroke patients. This study included Korean ischemic stroke patients aged 65 to 85 years. The size of the lesion was measured in brain images taken within 24 hours of hospitalization. The level of 25-(OH) Vitamin D (ng/mL), a metabolite of vitamin D, in the serum collected within 48 hours of hospitalization, and the modified Barthel index (MBI), gait performance, the muscle power of hip and knee extensors on the hemiplegic side, and mini-mental status examination (MMSE) were recorded within 1 week of the onset of the disease. Each factor was compared through correlation analysis, and the significance was confirmed using the Spearman correlation coefficient method. The association between the serum vitamin D levels and the size of the ischemic stroke lesion, the MBI, gait performance, the muscle power of hip and knee extensors on the hemiplegic side, and the MMSE were analyzed. It was confirmed that there was a significant correlation between all the factors (P < .005). In patients with serum vitamin D levels of ≥ 30 ng/mL, both the functional ability and cognitive functions were better than in patients lower than 30 ng/mL. We confirmed the lower the level of serum vitamin D levels, the larger the size of the ischemic stroke lesion when it occurred in elderly Koreans. And we confirmed that serum vitamin D levels affected the functional ability and cognitive function. And we recommend that elderly Koreans should maintain their blood vitamin D level above 30 ng/mL. We believe that this will help preserve the functional ability and cognitive function when ischemic stroke occurred.     

Effect of intraoperative intravenous ferric derisomaltose supplementation on reduction of postoperative anemia and transfusion in chronic kidney disease patients after total knee replacement

Total knee replacement (TKR) is associated with a large amount of bleeding; therefore, the prevalence of postoperative anemia is high. In particular, patients with chronic kidney disease (CKD) are more vulnerable to postoperative anemia than are healthy individuals. Accordingly, the effect of intraoperative intravenous ferric derisomaltose (FDI) supplementation on postoperative anemia and blood transfusion volume reduction in patients with CKD was studied. Patients who underwent unilateral TKR between January 2019 and December 2020 were retrospectively reviewed. In analyzing the data, the patients fell into the CKD group (n = 85) and the non-CKD group (n = 106). Each group was divided into a group using FDI and a non-FDI group, and classified into 4 groups. The postoperative hemoglobin level for each postoperative day (POD) was determined as the primary outcome. In addition, the patient transfusion rate, volume of transfusion, and length of hospital stay were set as secondary study outcomes during the period from surgery to discharge. There was no statistically significant difference in hemoglobin levels on PODs 0, 1, 2, 7, and 14 in the CKD group. In the CKD group, the transfusion volume of the FDI group was 0.58 ± 0.91 units per person, which was statistically significantly lower than 1.28 ± 1.28 units of the non-FDI group (P = .01). In the CKD group, the transfusion rate of the FDI group was 30.2%, which was statistically significantly lower than that of the non-FDI group, which was 56.3% (P = .02). This study showed that intravenous FDI supplementation after TKR in CKD patients did not reduce postoperative anemia but was an effective and safe treatment to reduce transfusion volume and transfusion rate. There was no statistically significant difference in hemoglobin levels on POD 0, 1, 2, 7, and 14 in the non-CKD group. In the non-CKD group, the transfusion volume of the FDI group was 0.46 ± 0.88 units per person, which was lower than the 0.56 ± 0.91 units of the non-FDI group, but it was not statistically significant (P = .59). In the non-CKD group, the transfusion rate of the FDI group was 23.0%, which was lower than that of the non-FDI group, which was 31.3%, but it was not statistically significant (P = .37).     

Brachial-ankle pulse wave velocity as a predictor of long-term cardiovascular events in 2174 subjects with type 2 diabetes mellitus: A retrospective cohort study

The prognostic value of arterial stiffness in patients with diabetes mellitus (DM) remains unclear. The aim of this study was to investigate the association between brachial-ankle pulse wave velocity (baPWV) and the occurrence of cardiovascular events in people with DM. A total of 2714 subjects (mean age, 63.6 years; males, 59.3%) with type 2 DM and without documented cardiovascular disease and stroke were analyzed. The primary end-point of this study was composite cardiovascular events of cardiac death, non-fatal myocardial infarction, coronary revascularization and stroke. There were 118 composite events (4.3%) during a median follow-up period of 3.84 years (interquartile range, 1.60–5.52 years). In multivariable Cox regression analysis, higher baPWV (≥1672 cm/s) was associated with composite events even after controlling for potential confounders (hazard ratio [HR], 2.00; 95% confidence interval [CI], 1.31–3.07; P = .001). Compared to the lowest baPWV tertile, both middle (HR, 1.84; 95% CI, 1.03–3.27; P = .037) and the highest (HR, 2.97; 95% CI, 1.69–5.22; P < .001) tertile of baPWV were associated with increased risk of cardiovascular events in the same multivariable model. In conclusion, the baPWV was associated with cardiovascular events in people with type 2 DM. Considering the simplicity and convenience of baPWV measurement, baPWV may be useful for risk stratification of people with type 2 DM.     

Interkingdom assemblages in human saliva display group-level surface mobility and disease-promoting emergent functions

Fungi and bacteria often engage in complex interactions, such as the formation of multicellular biofilms within the human body. Knowledge about how interkingdom biofilms initiate and coalesce into higher-level communities and which functions the different species carry out during biofilm formation remain limited. We found native-state assemblages of Candida albicans (fungi) and Streptococcus mutans (bacteria) with highly structured arrangement in saliva from diseased patients with childhood tooth decay. Further analyses revealed that bacterial clusters are attached within a network of fungal yeasts, hyphae, and exopolysaccharides, which bind to surfaces as a preassembled cell group. The interkingdom assemblages exhibit emergent functions, including enhanced surface colonization and growth rate, stronger tolerance to antimicrobials, and improved shear resistance, compared to either species alone. Notably, we discovered that the interkingdom assemblages display a unique form of migratory spatial mobility that enables fast spreading of biofilms across surfaces and causes enhanced, more extensive tooth decay. Using mutants, selective inactivation of species, and selective matrix removal, we demonstrate that the enhanced stress resistance and surface mobility arise from the exopolymeric matrix and require the presence of both species in the assemblage. The mobility is directed by fungal filamentation as hyphae extend and contact the surface, lifting the assemblage with a “forward-leaping motion.” Bacterial cell clusters can “hitchhike” on this mobile unit while continuously growing, to spread across the surface three-dimensionally and merge with other assemblages, promoting community expansion. Together, our results reveal an interkingdom assemblage in human saliva that behaves like a supraorganism, with disease-causing emergent functionalities that cannot be achieved without coassembly.

The microbial life on Earth often resides on surfaces, where cells form multicellular structures known as biofilms (1). Extensive efforts have been devoted to understanding the biofilm formation process and the mechanisms underlying the biofilm lifestyle (1–3). While most studies have focused on bacteria, eukaryotic microbes also frequently form biofilms. Furthermore, previous studies have revealed that biofilms composed of bacteria and fungi are highly abundant in nature, establishing complex interkingdom interactions (4–7). Such bacterial–fungal biofilms can display enhanced virulence and survival, which is achieved through tight cell–cell cohesion, metabolite exchange, and extracellular polymeric matrices within established communities (4–6). How interkingdom biofilms initiate and develop on the surface, and which functions the different species carry out during this process, remains unclear.In the human oral cavity, biofilms formed by bacteria and fungi have a major impact on health (7, 8). For example, patients affected by severe childhood caries (tooth decay), a widespread and costly infectious disease affecting toddlers worldwide (9), display high carriage of the bacterium Streptococcus mutans and the fungus Candida albicans, both in saliva and in biofilms formed on teeth (dental plaque) (10). Previous studies have shown that these distinct microbes form interkingdom biofilms with enhanced virulence under sugar-rich conditions (11, 12). However, interactions of these two species in saliva have not been characterized, and the extent to which the interactions between S. mutans and C. albicans influence the dynamics of biofilm formation and its functional properties is unknown.In this study, we investigated the interactions between S. mutans and C. albicans during colonization and biofilm formation in human saliva, and made several unexpected discoveries with implications for disease. We observed that in saliva of toddlers affected by severe tooth decay, S. mutans and C. albicans formed highly structured interkingdom assemblages. Using real-time multiscale imaging and computational analysis, we studied the organization of such interkingdom assemblages and assessed their role during biofilm formation spatiotemporally. These experiments showed that bacterial clusters attached to yeast and hyphal complexes to form assemblages that display emergent properties, including enhanced surface colonization, a higher growth rate, and a stronger tolerance to shear stress and antimicrobials, which are not observed in either bacteria or fungi alone. Surprisingly, when individually tracked, these interkingdom assemblages display a unique mode of migratory group-level mobility, enabled by fungal filamentation across surfaces, which is used by the attached bacterial clusters for “hitchhiking.” Through this mobility, the interkingdom assemblages rapidly proliferate across the surface and expand three-dimensionally, leading to biofilm superstructures and extensive enamel decay on ex vivo tooth surfaces that cannot be achieved by each species alone. Hence, our data reveal an interkingdom assemblage found in human saliva that efficiently colonizes, displays emergent properties, and enhances surface spreading through a group-level mobility mechanism that propels clusters of otherwise nonmotile bacteria and fungi across the surface, to ultimately promote community spatial expansion and disease-causing activity.     

Optimizing Heat Treatment Conditions for Measuring CFRP and GFRP Resin Impregnation

As the use of carbon-fiber-reinforced plastic (CFRP) and glass-fiber-reinforced plastic is frequent in the field of construction, a method for measuring FRP resin content is needed. Herein, thermal gravimetric analysis (TGA) was employed to optimize the heat treatment conditions (temperature and time) for determining the resin content in which only the resin was removed without fiber heat loss. Accordingly, the measurement was performed in 100 °C increments at a resin pyrolysis temperature up to 800 °C with a heat treatment time of 4 h to continuously observe the degree of thermal decomposition of the resin. The thermal decomposition of unsaturated polyester was confirmed at the melting point (350 ℃) regardless of the type of fibers used as reinforcement. In the case of CFRP, most of the resin decomposition occurred at 300 °C. Notably, the resin was removed at a pyrolysis temperature of 400 ℃ and almost no change in weight was observed. However, at a pyrolysis temperature of 500 °C or higher, the thermal decomposition of the fibers occurred partially. The results show that the composite resin was removed within 10 min at a pyrolysis temperature of 400 °C in an air atmosphere when using TGA.     

Intramuscular [18F]F-FDG Administration for Successful PET Imaging of Golden Hamsters in a Maximum Containment Laboratory Setting

Positron emission tomography (PET) is becoming an important tool for the investigation of emerging infectious diseases in animal models. Usually, PET imaging is performed after intravenous (IV) radiotracer administration. However, IV injections are difficult to perform in some small animals, such as golden hamsters. This challenge is particularly evident in longitudinal imaging studies, and even more so in maximum containment settings used to study high-consequence pathogens. We propose the use of intramuscular (IM) administration of 2-deoxy-2[¹⁸F]fluoro-D-glucose ([¹⁸F]F-FDG) for PET imaging of hamsters in a biosafety level 4 (BSL-4) laboratory setting. After [¹⁸F]F-FDG administration via IM or IV (through surgically implanted vascular access ports), eight hamsters underwent static or dynamic PET scans. Time–activity curves (TACs) and standardized uptake values (SUVs) in major regions of interest (ROIs) were used to compare the two injection routes. Immediately after injection, TACs differed between the two routes. At 60 min post-injection, [¹⁸F]F-FDG activity for both routes reached a plateau in most ROIs except the brain, with higher accumulation in the liver, lungs, brain, and nasal cavities observed in the IM group. IM delivery of [¹⁸F]F-FDG is an easy, safe, and reliable alternative for longitudinal PET imaging of hamsters in a BSL-4 laboratory setting.