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Background Kimura's disease (KD) is a rare chronic inflammatory condition characterized by nodules and lymphadenopathy in the head and neck region, exhibiting type II inflammation. Dupilumab is commonly used against type II inflammation. Aim To evaluate the efficacy and safety of dupilumab in KD patients. Design The real-world study was conducted in a hospital in China. Methods Six male patients with a mean age of 24.50 ± 15.47 years were treated with dupilumab following the same protocol as that for atopic dermatitis (AD). Clinical and laboratory indicators, such as maximum nodule diameter, blood eosinophil count, eosinophil percentage, and total serum IgE levels were assessed at baseline, Week 12 and Week 24. Adverse events were documented. Paired t -tests and one-way ANOVA were used for statistical analysis. Results The results showed significant reductions in the longest nodule diameter at Week 12 (P  =   0.006) and Week 24 (P  =   0.017) compared to baseline. Blood eosinophil count decreased by 57.95% (P  =   0.024) at Week 12 and 90.59% (P  =   0.030) at Week 24. Eosinophil percentage decreased by 58.44% (P  =   0.026) at Week 12 and 89.37% (P  =   0.013) at Week 24. Total serum IgE levels decreased by 78.02% (P  =   0.040) at Week 12 and 89.55% (P  =   0.031) at Week 24. The presence of AD did not affect the results. One patient experienced temporary facial erythema after 32 weeks of treatment, which resolved with topical treatment. No other adverse events were reported. Conclusion Dupilumab demonstrated effectiveness in treating KD without severe adverse events. [ABSTRACT FROM AUTHOR]

Uncontrollable bleeding is recognized as the leading cause of preventable death among trauma patients. Early transfusion of blood products, especially plasma replacing crystalloid and colloid solutions, has been shown to increase survival of severely injured patients. However, the requirements for cold storage and thawing processes prior to transfusion present significant logistical challenges in prehospital and remote areas, resulting in a considerable delay in receiving thawed or liquid plasma, even in hospitals. In contrast, freeze- or spray-dried plasma, which can be massively produced, stockpiled, and stored at room temperature, is easily carried and can be reconstituted for transfusion in minutes, provides a promising alternative. Drawn from history, this paper provides a review of different forms of dried plasma with a focus on in vitro characterization of hemostatic properties, to assess the effects of the drying process, storage conditions in dry form and after reconstitution, their distinct safety and/or efficacy profiles currently in different phases of development, and to discuss the current expectations of these products in the context of recent preclinical and clinical trials. Future research directions are presented as well. [ABSTRACT FROM AUTHOR]

Summary: During World War II, Charles H. Best utilized Charles R. Drew's plasma isolation and drying technique to lead Canada's initiative to provide dried serum as a means of primary resuscitation for British casualties on the frontlines. Serum was likely utilized over plasma for its volume expansion properties without the risk of clotting during prolonged storage. We reconstituted dried serum from 1943 and discovered intact albumin, as well as anti‐thrombin, plasminogen, protein C and protein S activity. Proteomic analysis identified 71 proteins, most prominent being albumin, and positive for hepatitis B by serological testing. Transmission of blood‐borne diseases ended the programme, until modern advances in testing and pathogen reduction revived this technology. We tested the latest iteration of Canadian freeze‐dried plasma (FDP), which was stored for 4 years, and demonstrated that its clotting capacity remained equivalent to fresh frozen plasma. We recommend that FDP is a strong alternative to contemporary prehospital resuscitation fluids (e.g. normal saline/lactated Ringer's) in managing prehospital haemorrhage where whole blood is unavailable. [ABSTRACT FROM AUTHOR]

BackgroundThe COVID-19 pandemic, caused by a novel coronavirus termed SARS-CoV-2, has spread quickly worldwide. Convalescent plasma (CP) obtained from patients following recovery from COVID-19 infection and development of antibodies against the virus is an attractive option for either prophylactic or therapeutic treatment, since antibodies may have direct or indirect antiviral activities and immunotherapy has proven effective in principle and in many clinical reports. ObjectiveWe seek to characterize the latest advances and evidence in the use of CP for COVID-19 through a systematic review and quantitative analysis, identify knowledge gaps in this setting, and offer recommendations and directives for future research. MethodsPubMed, Web of Science, and Embase were continuously searched for studies assessing the use of CP for COVID-19, including clinical studies, commentaries, reviews, guidelines or protocols, and in vitro testing of CP antibodies. The screening process and data extraction were performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Quality appraisal of all clinical studies was conducted using a universal tool independent of study designs. A meta-analysis of case-control and randomized controlled trials (RCTs) was conducted using a random-effects model. ResultsSubstantial literature has been published covering various aspects of CP therapy for COVID-19. Of the references included in this review, a total of 243 eligible studies including 64 clinical studies, 79 commentary articles, 46 reviews, 19 guidance and protocols, and 35 in vitro testing of CP antibodies matched the criteria. Positive results have been mostly observed so far when using CP for the treatment of COVID-19. There were remarkable heterogeneities in the CP therapy with respect to patient demographics, donor antibody titers, and time and dose of CP administration. The studies assessing the safety of CP treatment reported low incidence of adverse events. Most clinical studies, in particular case reports and case series, had poor quality. Only 1 RCT was of high quality. Randomized and nonrandomized data were found in 2 and 11 studies, respectively, and were included for meta-analysis, suggesting that CP could reduce mortality and increase viral clearance. Despite promising pilot studies, the benefits of CP treatment can only be clearly established through carefully designed RCTs. ConclusionsThere is developing support for CP therapy, particularly for patients who are critically ill or mechanically ventilated and resistant to antivirals and supportive care. These studies provide important lessons that should inform the planning of well-designed RCTs to generate more robust knowledge for the efficacy of CP in patients with COVID-19. Future research is necessary to fill the knowledge gap regarding prevention and treatment for patients with COVID-19 with CP while other therapeutics are being developed.

Despite the importance of the hemostatic properties of reconstituted freeze-dried plasma (FDP) for trauma resuscitation, few studies have been conducted to determine its post-reconstitution hemostatic stability. This study aimed to assess the short- (≤24 h) and long-term (≥168 h) hemostatic stabilities of Canadian and German freeze-dried plasma (CFDP and LyoPlas) after reconstitution and storage under different conditions. Post-reconstitution hemostatic profiles were determined using rotational thromboelastometry (ROTEM) and a Stago analyzer, as both are widely used as standard methods for assessing the quality of plasma. When compared to the initial reconstituted CFDP, there were no changes in ROTEM measurements for INTEM maximum clot firmness (MCF), EXTEM clotting time (CT) and MCF, and Stago measurements for prothrombin time (PT), partial thromboplastin time (PTT), D-dimer concentration, plasminogen, and protein C activities after storage at 4 °C for 24 h and room temperature (RT) (22–25 °C) for 4 h. However, an increase in INTEM CT and decreases in fibrinogen concentration, factors V and VIII, and protein S activities were observed after storage at 4 °C for 24 h, while an increase in factor V and decreases in antithrombin and protein S activities were seen after storage at RT for 4 h. Evaluation of the long-term stability of reconstituted LyoPlas showed decreased stability in both global and specific hemostatic profiles with increasing storage temperatures, particularly at 35 °C, where progressive changes in CT and MCF, PT, PTT, fibrinogen concentration, factor V, antithrombin, protein C, and protein S activities were seen even after storage for 4 h. We confirmed the short-term stability of CFDP in global hemostatic properties after reconstitution and storage at RT, consistent with the shelf life of reconstituted LyoPlas. The long-term stability analyses suggest that the post-reconstitution hemostatic stability of FDP products would decrease over time with increasing storage temperature, with a significant loss of hemostatic functions at 35 °C compared to 22 °C or below. Therefore, the shelf life of reconstituted FDP should be recommended according to the storage temperature. [ABSTRACT FROM AUTHOR]

Background: To describe the occurrence, rate of geographic atrophy (GA) expansion, and changes in visual acuity (VA) after reabsorption of subfoveal pigment epithelial detachments (PED). Methods: Included patients had reabsorption of a PED followed by GA. Patients underwent clinical examination with SD-OCT. Images were classified by size with grading occurring post reabsorption. VA was recorded pre-reabsorption, post-reabsorption, and over time. Results: The average age of the cohort, consisting of 22 eyes from 19 participants, was 86.9 years at reabsorption. Prior to reabsorption, the VA was 20/80 and then declined to 20/200 (p = 0.001) with an average follow-up time of 30.2 months. There was no significant VA change after the initial loss with reabsorption. The average initial lesion size of GA was 0.987 mm2 with an average growth rate of 0.274 mm/year. Conclusions: This study longitudinally examined GA growth rate in patients with reabsorbed PEDs. These patients started with a drusenoid or serous PED, had a dramatic reduction in vision and GA that occurred in place of the PED. These GA lesions have a slower growth rate and a smaller area of onset compared to rates previously reported in the literature. They do not show significant VA change after reabsorption. As we have entered the era of GA therapy, these patients may not benefit from current treatments. [ABSTRACT FROM AUTHOR]

Larvae of black carp (Mylopharyngodon piceus), grass carp (Ctenopharyngodon idella), silver carp (Hypophthalmichthys molitrix), and bighead carp (Hypophthalmichthys nobilis) were collected at a stationary location in the Changsha section of the Xiangjiang River from May, 2011 to July, 2020, and the relationships between abundance of the larvae and hydrological indices were analysed. Our results showed that the first appearance time of the larvae exhibited obvious annual differences, most of which were concentrated in mid-to-late May and early June, whereas 2016 was advanced to early May, which was the earliest year in the investigated 10 years. Moreover, the larval emergence was concentrated in mid-to-late May from 2017 to 2020, which was significantly earlier than those in early June of 2011-2013. Larval compositions of the four major carp species were significantly different between different years. Only water temperature significantly correlated with the compositions of the four major carp larvae. Water temperature significantly correlated with the catch-per-unit-of-effort of C. idella larvae, and rainfall for 3 consecutive days significantly correlated with the catch-per-unit-of-effort of H. nobilis larvae. [ABSTRACT FROM AUTHOR]

Under extreme conditions of heat exposure and exercise stress, the human body undergoes major physiological changes. Perturbations in organ blood flows, gastrointestinal properties, and vascular physiology may impact the body's ability to absorb, distribute, and eliminate drugs. Clinical studies on the effect of these stressors on drug pharmacokinetics demonstrate that the likelihood of pharmacokinetic alteration is dependent on drug properties and the intensity of the stressor. The objectives of this study were to use literature data to quantify the correlation between exercise and heat exposure intensity to changing physiological parameters and further, to use this information for the parameterization of a whole-body, physiologically based pharmacokinetic model for the purposes of determining those drug properties most likely to demonstrate altered drug pharmacokinetics under stress. Cardiac output and most organ blood flows were correlated with heart rate using regression analysis. Other altered parameters included hematocrit and intravascular albumin concentration. Pharmacokinetic simulations of intravenous and oral administration of hypothetical drugs with either a low or high value of lipophilicity, unbound fraction in plasma, and unbound intrinsic hepatic clearance demonstrated that the area under the curve of those drugs with a high unbound intrinsic clearance was most affected (up to a 130% increase) following intravenous administration, whereas following oral administration, pharmacokinetic changes were smaller ( Key words: physiologically based pharmacokinetic model, physiology, heat exposure, exercise stress, drug pharmacokinetics. Resume : Dans des conditions extremes de stress lie a l'effort et a la chaleur, le corps humain subit des modifications physiologiques majeures. Des perturbations dans les debits sanguins organiques, les proprietes gastroinstestinales et la physiologie vasculaire pourraient influer sur la capacite du corps a absorber, distribuer et eliminer les medicaments. Des etudes cliniques sur l'effet de ces facteurs stressants sur la pharmacocinetique des medicaments demontrent que la probabilite de modification de la pharmacocinetique est dependante des proprietes medicamenteuses et de l'intensite de l'agent stressant. La presente etude a eu comme objectifs d'utiliser les donnees de la litterature pour quantifier la correlation entre l'intensite de l'effort et de l'exposition a la chaleur et les modifications des parametres physiologiques, puis d'utiliser cette information pour la parametrisation d'un modele pharmacocinetique a base physiologique corps entier afin de determiner les proprietes medicamenteuses les plus susceptibles de demontrer les modifications de la pharmacocinetique des medicaments dans des conditions de stress. Le debit cardiaque et les debit sanguins de la plupart des organes ont ete correles avec la frequence cardiaque a l' aide de l' analyse de regression. L' hematocrite et la concentration d'albumine intravasculaire ont fait partie des parametres modifies. Les simulations pharmacocinetiques de l'administration intraveineuse et orale de medicaments hypothetiques ayant une lipophilicite faible ou elevee, une fraction non liee dans le plasma et une clairance hepatique intrinseque non liee ont demontre que la surface sous la courbe des medicaments ayant une forte clairance intrinseque non liee a ete fortement modifiee (jusqu'a une augmentation de 130 %) apres l'administration i.v., alors qu'apres l'administration orale, les modifications pharmacocinetiques ont ete plus faibles (augmentation Mots-cles : modele pharmacocinetique a base physiologique, physiologie, exposition a la chaleur, stress lie a l'effort, pharmacocinetique de medicaments. [Traduit par la Redaction], Introduction Pharmacokinetics is the area of pharmacology that deals with drug absorption, distribution, metabolism, and excretion (Benet et al. 1996). Dosing regimens are based on the unique pharmacokinetic profile inherent [...]

Background: Freeze‐dried plasma (FDP) is a promising blood component for prehospital resuscitation given its logistic advantages over fresh frozen plasma (FFP). COVID‐19 convalescent (CC) plasma has been used to treat coronavirus disease 2019 (COVID‐19) patients, and its corresponding FDP has potential use during future pandemics. Therefore, we conducted the study to determine if the hemostatic and immunological properties of plasma can be retained after lyophilization. Study design and methods: Hemostatic tests were conducted with Rotational Thromboelastometry (ROTEM) and a Stago analyzer. Anti‐severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) IgG (Immunoglobulin G) and neutralizing activity were analyzed using Meso Scale Diagnostics immunoassay kits. Results: There were no differences in ROTEM parameters and Stago measurements for prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen and D‐dimer concentrations, and antithrombin, factor V, VIII, and protein S activities between FFP and FDP for either pre‐COVID‐19 or CC samples. Differences were observed in INTEM clotting time and PT and PTT when comparing reconstituted FDP stored at 4°C for 24 h or room temperature for 4 h to healthy control. Both CC‐FFP and CC‐FDP showed two orders of magnitude higher concentrations of IgG antibodies against SARS‐CoV‐2 antigens than pre‐COVID‐19‐FFP and pre‐COVID‐19‐FDP and healthy control. Similarly, the CC samples showed approximately 4‐fold higher %‐inhibition of receptor binding than the pre‐COVID‐19 samples. There were no differences in either the antibody levels or neutralization activity between CC‐FFP and CC‐FDP. Discussion: We demonstrated that FDP and CC‐FDP retained the same hemostatic and antibody functional activities relative to their initial plasma sources, supporting clinical evaluation of their benefits in severe trauma and COVID‐19 patients. [ABSTRACT FROM AUTHOR]