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Objective: To examine the effects of a university's health vaccination initiative in increasing vaccination rates among international students/scholars in the United States. Methods: The vaccination initiative included: increasing vaccination opportunities by holding a pre-registration event, providing vaccine recommendations from healthcare professionals including a bilingual health interpreter, implementing campus-based marketing strategies, sending reminders using social media, and offering free and affordable vaccines. Results: Total 575 international students/scholars attended from 2016 to 2019 (N = 118, 163, 193, and 101, respectively), showing an increase compared to 2015. The most common vaccines administered were for influenza, human papillomavirus (HPV), tetanus, diphtheria, and acellular pertussis (Tdap), and Hepatitis A. Slightly less than one-quarter of participants received three or more vaccines. More women than men received HPV vaccine. Participants shared they would not have been vaccinated without this initiative and wished for more vaccination events. Conclusions: Future efforts are needed to implement this initiative across universities to further evaluate its effectiveness. [ABSTRACT FROM AUTHOR]

Introduction: This study characterized the population pharmacokinetics (PK) of vancomycin in patients treated with and without continuous renal replacement therapy (CRRT) or temporary mechanical circulatory support (tMCS), including extracorporeal membrane oxygenation or extracorporeal ventricular assist device. Methods: Critically ill adults with and without tMCS or CRRT prescribed vancomycin were enrolled for population PK modeling. Monte Carlo simulation provided dosing recommendations based on the probability of target attainment (PTA), achieving a 24-h area under curve (AUC24h) of 400–600 mg*h/L. Results: Twenty-five patients with 184 plasma samples were analyzed. The median age was 61.0 years. The final model was a two-compartment PK model. CRRT, serum creatinine, and body weight were significant predictors of clearance. CRRT was a covariate on the central volume of distribution. tMCS significantly decreased the intercompartmental clearance. The simulated mean trough levels at the 48th hour were lower in the tMCS group (13.4 versus 14.2 mg/dL in non-tMCS, p < 0.001) in a 70-kg subject with a creatinine of 1 mg/dL and a daily dose of 20 mg/kg, but the PTA was similar (61.8% versus 62.2%). A reduction of maintenance dose from 30 to 10 mg/kg/day with loading dose from 25 to 15 mg/kg is recommended while serum creatinine progresses from 0.5 to 4.0 mg/dL. For CRRT, the optimal regimen consists of 20–25 mg/kg loading and maintenance of 15 mg/kg/day. Conclusions: The dosing strategy of vancomycin can be based on body weight or renal function, regardless of tMCS. Intercompartmental clearance decreases under tMCS, which can mislead a dosing adjustment based on trough level. [ABSTRACT FROM AUTHOR]

The editorial in the Journal of Anesthesia discusses the concept of "fictitious weight" in pharmacokinetic simulations and target-controlled infusion (TCI) systems, focusing on propofol, remifentanil, and fentanyl. The study by Zhong and Xu aims to improve TCI performance by adjusting the input weight in the Marsh model to mimic the Eleveld model's behavior. Patient characteristics, such as body size and metabolic capacity, influence drug pharmacokinetics, requiring adjustments in PK models for accurate predictions in diverse patient populations. Efforts to enhance predictive accuracy by incorporating fictitious weight or height as covariates are ongoing, with validation from various facilities needed to confirm the effectiveness of new models. [Extracted from the article]

Background: Benzodiazepines are used in pediatric patients with congenital heart disease (CHD) because of their mild hemodynamic depressant effects. A novel short-acting benzodiazepine, remimazolam, is expected to be suitable for these patients. We examined the characteristics of remimazolam anesthesia in pediatric patients with CHD undergoing cardiac catheterization. Methods: This single-center retrospective study included pediatric patients undergoing cardiac catheterization for CHD. The primary outcome was the remimazolam dose for loss of consciousness. Secondary outcomes included the mean maintenance remimazolam dose, recovery time from anesthesia, predicted remimazolam concentration at emergence, decrease in blood pressure and heart rate, vasopressor administration during anesthesia, electroencephalogram index (bispectral index: BIS or patient state index: PSI), and life-threatening adverse events. Results: Thirty-nine patients, aged 2 months to 16 years, were included. Thirty-three patients received a median [interquartile] midazolam dose of 0.10 [0.10–0.10] mg.kg−1 in the pre-anesthesia room. The remimazolam dose for loss of consciousness was 0.34 [0.26–0.45] mg.kg−1. The mean maintenance dose was 1.0 [0.8–1.4] mg.kg−1.h−1. The recovery time was 15 [12–17] min. The predicted remimazolam concentration at emergence was 0.4–1.2 µg.ml−1 in 3–6-year-old patients. Blood pressure and heart rate decreased by 30% in 15 and 6 patients, respectively. Vasopressors were administered as a bolus in 8 patients. The BIS or PSI did not fall ≤ 60 or ≤ 50, respectively, in 51% of patients before tracheal intubation. No life-threatening adverse events were reported. Conclusions: Remimazolam is a good alternative anesthetic agent for pediatric patients undergoing cardiac catheterization for CHD. [ABSTRACT FROM AUTHOR]

Background: Inadvertent intra-arterial injection of sclerosants is an uncommon adverse event of both ultrasound-guided and direct vision sclerotherapy. This complication can result in significant tissue or limb loss and significant long-term morbidity. Objectives: To provide recommendations for diagnosis and immediate management of an unintentional intra-arterial injection of sclerosing agents. Methods: An international and multidisciplinary expert panel representing the endorsing societies and relevant specialities reviewed the published biomedical, scientific and legal literature and developed the consensus-based recommendations. Results: Actual and suspected cases of an intra-arterial sclerosant injection should be immediately transferred to a facility with a vascular/interventional unit. Digital Subtraction Angiography (DSA) is the key investigation to confirm the diagnosis and help select the appropriate intra-arterial therapy for tissue ischaemia. Emergency endovascular intervention will be required to manage the risk of major limb ischaemia. This includes intra-arterial administration of vasodilators to reduce vasospasm, and anticoagulants and thrombolytic agents to mitigate thrombosis. Mechanical thrombectomy, other endovascular interventions and even open surgery may be required. Lumbar sympathetic block may be considered but has a high risk of bleeding. Systemic anti-inflammatory agents, anticoagulants, and platelet inhibitors and modifiers would complement the intra-arterial endovascular procedures. For risk of minor ischaemia, systemic oral anti-inflammatory agents, anticoagulants, vasodilators and antiplatelet treatments are recommended. Conclusion: Inadvertent intra-arterial injection is an adverse event of both ultrasound-guided and direct vision sclerotherapy. Medical practitioners performing sclerotherapy must ensure completion of a course of formal training (specialty or subspecialty training, or equivalent recognition) in the management of venous and lymphatic disorders (phlebology), and be personally proficient in the use of duplex ultrasound in vascular (both arterial and venous) applications, to diagnose and provide image guidance to venous procedure. Expertise in diagnosis and immediate management of an intra-arterial injection is essential for all practitioners performing sclerotherapy. [ABSTRACT FROM AUTHOR]

Background: Research on the pharmacogenetic influence of hepatic CYP450 enzyme 2D6 (CYP2D6) on metabolism of drugs for psychosis and associated outcome has been inconclusive. Some results suggest increased risk of adverse reactions in poor and intermediate metabolizers, while others find no relationship. However, retrospective designs may fail to account for the long-term pharmacological treatment of patients. Previous studies found that clinicians adapted risperidone dose successfully without knowledge of patient CYP2D6 phenotype. Aim: Here, we aimed to replicate the results of those studies in a Dutch cohort of patients with psychosis (N = 418) on pharmacological treatment. Method: We compared chlorpromazine-equivalent dose between CYP2D6 metabolizer phenotypes and investigated which factors were associated with dosage. This was repeated in two smaller subsets; patients prescribed pharmacogenetics-actionable drugs according to published guidelines, and risperidone-only as done previously. Results: We found no relationship between chlorpromazine-equivalent dose and phenotype in any sample (complete sample: p = 0.3, actionable-subset: p = 0.82, risperidone-only: p = 0.34). Only clozapine dose was weakly associated with CYP2D6 phenotype (p = 0.03). Conclusion: Clinicians were thus not intuitively adapting dose to CYP2D6 activity in this sample, nor was CYP2D6 activity associated with prescribed dose. Although the previous studies could not be replicated, this study may provide support for existing and future pharmacogenetic research. [ABSTRACT FROM AUTHOR]

Population aging is a global reality driven by increased life expectancy. This demographic phenomenon is intrinsically linked to the epidemic of cognitive disorders such as dementia and Alzheimer's disease, posing challenges for elderly and their families. In this context, the search for new therapeutic strategies to prevent or minimize cognitive impairments becomes urgent, as these deficits are primarily associated with oxidative damage and increased neuroinflammation. Ferulic acid (FA), a natural and potent antioxidant compound, is proposed to be nanoencapsulated to target the central nervous system effectively with lower doses and an extended duration of action. Here, we evaluated the effects of the nanoencapsulated FA on d-galactose (d-Gal)- induced memory impairments. Male Wistar adult rats were treated with ferulic acid-loaded nanocapsules (FA-Nc) or non-encapsulated ferulic acid (D-FA) for 8 weeks concurrently with d-Gal (150 mg/kg s.c.) injection. As expected, our findings showed that d-Gal injection impaired memory processes and increased anxiety behavior, whereas FA-Nc treatment ameliorated these behavioral impairments associated with the aging process induced by d-Gal. At the molecular level, nanoencapsulated ferulic acid (FA-Nc) ameliorated the decrease in ACh and glutamate induced by d-galactose (d-Gal), and also increased GABA levels in the dorsal hippocampus, indicating its therapeutic superiority. Additional studies are needed to elucidate the mechanisms underlying our current promising outcomes. Nanoscience applied to pharmacology can reduce drug dosage, thereby minimizing adverse effects while enhancing therapeutic response, particularly in neurodegenerative diseases associated with aging. Therefore, the strategy of brain-targeted drug delivery through nanoencapsulation can be effective in mitigating aging-related factors that may lead to cognitive deficits. [ABSTRACT FROM AUTHOR]

Medical emergencies, though rare, may occur unpredictably in a dental office during or after dental procedures. It may occur accidentally or subsequent to systemic problems of patients. These series of clinical events entail instantaneous management to evade any potential consequences. Basic life support measures require sufficient knowledge, expertise, skills, and equipment. Several medications and equipment are necessary to be available for immediate reach in any dental office. Health authorities of different countries usually propose these lists to dental practitioners. However, the best emergency kit is the one, which is arranged and maintained by the dentists based on their needs and easily accessible for immediate use. Considering the importance of this subject and the results yielded from the regular visits of the Dental Supervision Department (Vice Chancellor for treatment of Shiraz University of Medical Sciences) to the dental centers of Shiraz in the spring and summer of 2023, we decided to recall the importance of emergency medicines and equipment through a brief communication. [ABSTRACT FROM AUTHOR]

Objective: To investigate the hemostatic effect of modified Sijunzi Granules (MSG) in primary immune thrombocytopenia (ITP) zebrafish model and explore the potential mechanism. Methods: AB strain wild type zebrafish were treated with simvastatin (6 µmol/L) for 24 h to establish the hemorrhage model (model control group). The zebrafish were treated with MSG at different doses (55.6, 167, and 500 µg/mL), respectively. The hemostatic effect was assessed by examining the intestinal bleeding and hemostatic rate. 5-Hydroxytryptamine (5-HT) content was determined using enzyme-linked immunosorbent assay (ELISA) assay. The expressions of 5-HT2aR, 5-HT2bR, and SERT genes were detected by quantitative real-time polymerase chain reaction(PCR). The protein expressions of protein kinase B (Akt), p-Akt, extracellular regulated protein kinases (Erk), and p-Erk were examined using Western blot analysis. Results: The intestinal bleeding rate was 37%, 40%, and 80% in the 55.6, 167, and 500 µg/mL dose of MSG, respectively, in which 55.6 and 167 µg/mL MSG dose groups were associated with significantly decreased intestinal bleeding rate when compared with the model control group (70%, P<0.05). Significantly higher hemostatic rates were also observed in the 55.6 (54%) and 167 (52%) µg/mL MSG dose groups (P<0.05). MSG increased the 5-HT content and mRNA expression levels of 5-HT2aR, 5-HT2bR, and SERT (P<0.05). In addition, caspase3/7 activity was inhibited (P<0.05). Significant increase in p-Akt and p-Erk was also detected after treatment with MSG (P<0.05). Conclusions: MSG could reduce the incidence and severity of intestinal bleeding in zebrafish by activating MAPK/Erk and PI3K/Akt signal pathways through regulating the levels of 5-HT and its receptors, which may provide evidence for the treatment of ITP. [ABSTRACT FROM AUTHOR]

Introduction: An inverse relationship has been identified between tacrolimus serum concentrations and donor-derived cell-free DNA (dd-cfDNA) levels after lung transplant, but limited data exists on this relationship in the kidney transplant population. Project Aim: The purpose of this evaluation was to examine the relationship between high tacrolimus variability and elevated dd-cfDNA levels in kidney and simultaneous pancreas-kidney transplant recipients at a single center. Design: Single-center, retrospective, descriptive comparative evaluation of kidney and pancreas-kidney transplant recipients who received longitudinal ddcfDNA surveillance. Intrapatient tacrolimus variability was assessed using the coefficient of variation (%CV) measured between 1 and 12 months posttransplant. Pediatrics, retransplant or multiorgan transplant recipients, and pregnant recipients were excluded. Results: One hundred fifteen recipients with 518 dd-cfDNA levels and 3028 tacrolimus troughs were assessed. Pancreas-kidney recipients had significantly higher median dd-cfDNA (0.29% vs. 0.18%, P =.034) and were excluded from analysis. Ninety-nine kidney transplant recipients were included for analysis. Recipients with tacrolimus %CV ≥30 (N = 66) had significantly higher median dd-cfDNA than %CV <30 (0.22% vs. 0.17%, P =.031). Tacrolimus %CV ≥30 demonstrated higher median peak dd-cfDNA than %CV <30, though this was not statistically significant (0.36% vs. 0.28%, P =.058). Conclusion: These data demonstrated that high intrapatient tacrolimus variability may be associated with elevated dd-cfDNA in the first year after kidney transplant. [ABSTRACT FROM AUTHOR]

As states legalize medical cannabis, school nurses face increased parent questions about administration at school. Although school nurses frequently collaborate on the development and implementation of medication administration policies, their perceptions of barriers to school-based medical cannabis administration are not well-documented. To explore these perceptions, we surveyed school nurses (n = 379) in sixteen states about their beliefs related to school-based medical cannabis administration policy development. Findings revealed school nurses from states completely legalizing cannabis expressed significantly fewer concerns about the safety, stigma, and federal status of medical cannabis than their peers in more restrictive states. Implications for practice include (a) education of key stakeholders, (b) collaboration with stakeholders to formulate medication administration policy; and (c) development of state-level guidance for school professionals. [ABSTRACT FROM AUTHOR]

Clinical experience shows an increased duration of labor in obese parturient women. It is unclear if this population should receive the same dose of vaginal misoprostol for induction of labor as non‐obese parturient women. We investigate the influence of obesity on the pharmacokinetics and placental transfer of the metabolite misoprostol acid in parturient women. Parturient women (n = 40) were enrolled and received misoprostol 25 µg/6 h vaginally and were allocated into two groups according to the pre‐pregnancy body mass index (BMI <30 kg/m2 non‐obese, n = 18 or BMI >30 kg/m2 obese, n = 22) or according to the labor induction outcome (failure [n = 10] or success [n = 30]). Blood collection for pharmacokinetic study occurred after the first misoprostol dose. The pharmacokinetic parameters obtained in non‐obese parturient women were not statistically different from those obtained in obese group (P Value >  .05). However, when the parturient women were grouped by the labor induction outcome, the failed labor induction group presented a higher (median [interquartile range]) BMI (44.4 [34.6‐47.9] vs 33.7 [28.9‐36.5] kg/m2) (P Value =  .0017), lower Cmax (11.5 [4.82‐22.2] vs 22.8 [14.2‐30.8] pg/mL) (P Value =  .0308) and not statistically different AUC0‐6 (31.8 [13.4‐61.5] vs 53.4 [35.4‐77.7]) pg·h/mL) (P Value =  .0580) and tmax (2.50 [1.19‐4.25] vs 3.00 (1.88‐5.00) h (P Value =  .3198) when compared with parturient women who presented successful labor induction. This data suggests a higher loading dose (higher volume of distribution) and unchanged maintenance dose (unchanged AUC0‐6) of misoprostol for this population. Further studies are required to investigate the efficacy and safety of higher misoprostol loading doses for this population. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia is the second leading cause of maternal death in Uganda. WHO recommends using magnesium sulphate (MgSO4) to prevent and treat preeclampsia with severe features (PEC) and eclampsia. MgSO4 is used to prevent eclampsia and treat women who experience an eclamptic convulsion to avoid severe maternal/infant illnesses and death. We set out to assess MgSO4 administration patterns in women with PEC or eclampsia and the immediate newborn outcomes of neonates. Methods: This was an analytical observational cohort study at Kawempe National Referral Hospital in Uganda. Two hundred ten pregnant mothers with PEC or eclampsia were recruited in the study after receiving the loading dose of MgSO4 and then followed through labour and delivery to observe MgSO4 administration patterns and immediate newborn outcomes using Apgar and Thompson scores. SPSS version 23 was used to analyse data, and both bivariate and multivariate logistic regressions were used to determine factors associated with the low Apgar score at five minutes. Results: Overall, majority of the patients received more than one dose with 33.3% received a sixth dose of MgSO4. The majority, 84.8%, of the mothers delivered live babies, 31.0% babies had complications, and were admitted to the neonatal intensive care unit (NICU). NICU admissions were mostly due to respiratory distress21.4%, preterm delivery21.0%, and 5.5% died within seven days. Majority 93.3% of the newborns had an Apgar score of seven and above at five minutes, of the newborns who were Thompson scored, 70.4% scored between 1 to 10 which is mild HIE. Initiation of MgSO4 treatment within one hour from prescription (AOR = 0.49, CI: 0.01–1.94), 4-hourly timing of the first maintenance dose (AOR = 0.22, CI: 0.06–0.79) and having complete doses of MgSO4 treatment (AOR = 0.89, CI: 0.03–3.05) decreased the likelihood of having low Apgar scores at five minutes. Conclusions: Timely administration of the first maintenance dose of MgSO4 decreases the likelihood of low Apgar score at 5 min and NICU admission in newborns, and most NICU admissions were due to respiratory distress and preterm delivery. [ABSTRACT FROM AUTHOR]

Background: Acute lung injury (ALI) is the most lethal disease associated with sepsis, and there is a lack of effective drug treatment. As the major cells of sepsis-induced ALI, macrophages polarize toward the proinflammatory M1 phenotype and secrete multiple inflammatory cytokines to accelerate the disease process through nuclear factor kappa-B (NF-κB) and NLR family pyrin domain containing 3 (NLRP3) inflammasome signaling pathways. Taraxerone, the main component of the Chinese medicinal Sedum, possesses numerous biological activities. However, uncertainty remains regarding the potential of taraxerone to protect against sepsis-induced ALI. This study aimed to investigate the effects and mechanisms of taraxerone against ALI. Methods: An animal model for ALI was established by cecal ligation and puncture and treated with taraxerone via intraperitoneal administration. The protective effect of taraxerone on the lungs was analyzed using H&E staining, dihydroethidium staining, ELISA kits, cell counting, myeloperoxidase kit, malondialdehyde kit, glutathione kit, superoxide dismutase kit and flow cytometry. Western blotting, RT-PCR, flow cytometry, co-immunoprecipitation, and immunofluorescence were used to investigate the regulatory of taraxerone on SIRT1. Results: Our study demonstrates for the first time that taraxerone can activate SIRT1 in macrophages, promoting SIRT1 activity. This activation inhibited the NF-κB signaling pathway primarily through the dephosphorylation and deacetylation of p65. Simultaneously, taraxerone disrupted the NLRP3 inflammasome signaling pathway, thereby alleviating M1 polarization of macrophages and mitigating sepsis-induced pulmonary inflammation and oxidative stress. In vivo, EX527 was used to validate the anti-inflammatory and anti-oxidative stress effects of taraxerone mediated by SIRT1. Conclusion: SIRT1-mediated anti-inflammatory and anti-oxidative stress effects may be important targets for taraxerone in treating ALI. [ABSTRACT FROM AUTHOR]

Background Method Results Conclusion Allergen immunotherapy (AIT) aims at modulating the immune response by administration of allergen preparations at regular intervals over several years (1). For subcutaneous AIT (SCIT), the treatment is initiated with a dose escalation phase followed by a maintenance dose administration. Over the last decade, there has been a trend towards shortening dose escalation regimens to increase patient adherence. This open‐label, phase II trial aimed to investigate the safety and tolerability of a house dust mites (HDMs) SCIT product when used in a newly designed one‐strength dose escalation scheme.Patients, aged 12–65, suffering from HDM‐allergic rhinitis/rhinoconjunctivitis ± asthma were included. Patients were randomized to the one‐strength (6 injections from the highest strength 3) or the Standard dose escalation regimen (14 injections from strengths 1 to 3) using the HDMs‐SCIT product. All adverse events were reported. Tolerability was assessed on the Likert scale.One hundred and forty‐three patients were randomized, 79 adults and 64 adolescents. In total, the one‐strength regimen caused more adverse drug reactions (ADRs) than the Standard regimen (p = .0457). With both regimens most ADRs were local reactions which occurred more often in the one‐strength group (p = .0393). But there was no significant difference in the number of patients affected by systemic or serious ADRs between both regimens. No relevant differences occurred between the two age groups and no other risks were observed for adolescents compared to adults.The safety and tolerability of both regimens can be considered comparable, as most ADRs were local reactions, primarily rated as mild in intensity. Nevertheless, the one‐strength regimen caused more ADRs. Reducing the number of injections from 14 to 6 while using only one strength offers the potential to improve patient adherence which further might increase clinical efficacy. Future trials could confirm this hypothesis. [ABSTRACT FROM AUTHOR]

Pencil-beam scanning proton therapy has been considered a potential modality for the 3D form of spatially fractionated radiation therapy called lattice therapy. However, few practical solutions have been introduced in the clinic. Existing limitations include degradation in plan quality and robustness when using single-field versus multifield lattice plans, respectively. We propose a practical and robust proton lattice (RPL) planning method using multifield and evaluate its dosimetric characteristics compared to clinically acceptable photon lattice plans. Seven cases previously treated with photon lattice therapy were used to evaluate a novel RPL planning technique using 2-orthogonal beams: a primary beam (PB) and a robust complementary beam (RCB) that deliver 67% and 33%, respectively, of the prescribed dose to vertices inside the gross target volume (GTV). Only RCB is robustly optimized for setup and range uncertainties. The number and volume of vertices, peak-to-valley dose ratios (PVDRs), and volume of low dose to GTV of proton and photon plans were compared. The RPL technique was then used in the treatment of 2 patients and their dosimetric parameters were reported. The RPL strategy was able to achieve the clinical planning goals. Compared to previously treated photon plans, the average number of vertices increased by 30%, the average vertex volume by 49% (18.2 ± 25.9 cc vs 12.2 ± 14.5 cc, P =.21), and higher PVDR (10.5 ± 4.8 vs 2.5 ± 0.9, P <.005) was achieved. In addition, RPL plans show more conformal dose with less low dose to GTV (V30%, 60.9% ± 7.2% vs 81.6% ± 13.9% and V10%, 88.3% ± 4.5% vs 98.6% ± 3.6% [ P <.01]). The RPL plan for 2 treated patients showed PVDRs of 4.61 and 14.85 with vertices-to-GTV ratios of 1.52% and 1.30%, respectively. A novel RPL planning strategy using a pair of orthogonal beams was developed and successfully translated to the clinic. The proposed method can generate better quality plans, a higher number of vertices, and higher PVDRs than currently used photon lattice plans. [ABSTRACT FROM AUTHOR]

This systematic review explores the application of machine learning (ML) algorithms in sickle cell disease (SCD), focusing on diagnosis and several clinical characteristics, such as early detection of organ failure, identification of drug dosage, and classification of pain intensity. A comprehensive analysis of recent studies reveals promising results in using ML techniques for diagnosing and monitoring SCD. The review covers various ML algorithms, including Multilayer Perceptron, Support Vector Machine, Random Forest, Logistic Regression, Long short-term memory, Extreme Learning Machines, Convolutional Neural Networks, and Transfer Learning methods. Despite significant advances, challenges such as limited dataset sizes, interpretability concerns, and risks of overfitting are identified in studies. Future research directions entail addressing these limitations by harnessing larger and more representative datasets, enhancing model interpretability, and exploring advanced ML techniques like deep learning. Overall, this review underscores the transformative potential of ML in increasing the diagnosis, monitoring and define prognosis of sickle cell disease while also highlighting the need for further investigation in the field. [ABSTRACT FROM AUTHOR]

Background: Mycophenolate mofetil is used for the prevention of solid organ transplant rejection and for other indications, such as systemic lupus erythematosus (SLE). Objective: To determine the prescription patterns of mycophenolate mofetil in a group of Colombian patients. Methods: This was a cross-sectional study of patients receiving mycophenolate mofetil between 2021 and 2022. The data were obtained from a drug dispensing database. Sociodemographic, clinical (diagnostic), and pharmacological variables were identified. Results: A total of 979 patients who underwent treatment were identified; their mean age was 45.9 ± 17.1 years, and 87.4% were women. The main diagnosis associated with the use of mycophenolate mofetil was SLE (39.1%), followed by other rheumatic diseases (8.5%), nephrotic syndrome (7.5%), and solid organ transplantation (6.4%). The relationship between the mean dose and the defined daily dose was 0.75. Ten percent of patients received mycophenolate alone, whereas 32.9% received mycophenolate in combination therapy with conventional disease-modifying antirheumatic drugs and glucocorticoids. A total of 76.2% had polypharmacy (five or more drugs). Conclusions: Mycophenolate mofetil is used mainly in combination therapy for patients with SLE and other rheumatological diseases and for solid organ transplants at doses lower than those recommended. [ABSTRACT FROM AUTHOR]

A 51-year-old male patient presented with fever, myalgia, and bilateral thigh pain, followed by proximal weakness of limbs. Laboratory features were suggestive of inflammatory polymyositis (PM). He initially responded to steroids, but subsequently, the patient's clinical condition deteriorated. In the initial investigations, there was no evidence of any malignancy. Over the next 2 months, he had a catastrophic downhill course—progressive pancytopenia, acute abdominal pain, and features of mesenteric panniculitis and he eventually was diagnosed with acute myeloid leukemia (AML). This case underscores the high index of suspicion for underlying malignancy while managing cases of refractory PM and emphasizes the importance of comprehensive diagnostic evaluation and interdisciplinary collaboration in managing patients with complex autoimmune and hematological conditions. Jo-1 antibody, also known as anti-histidyl-tRNA synthetase antibody, is a specific type of autoantibody associated with a group of autoimmune diseases collectively known as idiopathic inflammatory myopathies (IIMs), particularly polymyositis (PM) and dermatomyositis (DM). Here, we present a case report highlighting the rare clinical association between Jo-1-positive PM and hematological malignancy. The presence of Jo-1 antibodies in this context may suggest potential immune dysregulation or paraneoplastic phenomena linking PM and AML. Accurate diagnosis and timely intervention are crucial for managing patients with complex autoimmune and hematological conditions, especially when they present with atypical clinical features and show poor response to treatment. [ABSTRACT FROM AUTHOR]

Background: Antiseizure medications (ASM) exhibit considerable interindividual variability in terms of efficacy and adverse events. Genetic variation is thought to contribute to these differences in clinical outcomes. Specifically, the response to valproic acid (VPA), a widely used ASM, is influenced by multiple pharmacogenetic factors. However, and in contrast to other ASMs such as phenytoin and carbamazepine, there is a paucity of data on the association between VPA and various gene variants. The aim of this study was hence to evaluate the influence of candidate pharmacogenetic variants on VPA efficacy, toxicity and serum concentrations in a homogeneous cohort of patients newly diagnosed with genetic generalized epilepsies (GGE). Methods: In this prospective cohort study, demographic, clinical and treatment outcomes of GGE patients were retrieved from their medical records. Whole exome sequencing was performed in collaboration with Epi25. Gene variants associated with VPA efficacy, metabolism and toxicities were retrieved from PharmGKB. An analysis was then conducted to explore potential associations between these gene variants and VPA clinical outcomes. Results: Of the 166 patients included, 60 (36.1%) experienced treatment failure while 106 (63.9%) achieved treatment success. After adjusting for VPA maintenance dose, carriers of the rs3892097 (CYP2D6) variant were 2.5 times more likely to experience treatment failure compared to wildtype (p = 0.026). The rs1057910 variant (CYP2C9*3) was associated with increased serum VPA concentrations (p = 0.034). Moreover, the rs1137101 variant (LEPR gene , a metabolism regulator) was significantly associated with a higher risk of weight gain (regression coefficient of 3.430 [0.674; 6.186], p = 0.015) and a higher frequency of hair loss (OR = 3.394 [1.157; 9.956], p = 0.026), while the rs4480 variant (SOD2 gene, encoding for a mitochondrial scavenging enzyme) was correlated with a lower frequency of hair loss (OR = 0.276 [0.089; 0.858], p = 0.026). Conclusion: These findings highlight the role of genetic factors in VPA treatment and underscore the potential for developing therapeutic strategies to enhance patient outcomes and minimize adverse effects. [ABSTRACT FROM AUTHOR]

The article provides guidance for insurance companies and payors on evaluating claims submitted using Current Procedural Terminology codes 95165, 95115, and 95117. It was jointly developed by the American Academy of Allergy Asthma and Immunology, the American Academy of Otolaryngic Allergy, and the American College of Allergy, Asthma and Immunology. The document outlines the services covered by these codes, the medical necessity of the procedures, and reasonable and unreasonable requests for documentation. The authors emphasize the importance of efficient, fair, and not unduly burdensome review processes for claims under these codes. [Extracted from the article]

Background/Aims: This study aimed to evaluate the safety and efficacy of continuous propofol infusion for anesthesia during endoscopic ultrasonography (EUS). Methods: A total of 427 consecutive patients who underwent EUS between May 2018 and February 2019 were enrolled in this study. The patients were divided into two propofol infusion groups: continuous (n=207) and intermittent (n=220). The following parameters were compared: (1) propofol dose, (2) respiratory and circulatory depression, (3) body movement requiring discontinuation of the examination, (4) awakening score, and (5) patient satisfaction. Results: The median total maintenance dose of propofol was significantly higher in the continuous group than in the intermittent group (160.0 mg vs. 130.0 mg, respectively); however, the reduction in SpO2 was significantly lower in the continuous group (2.9% vs. 13.2%). Body movements occurred less frequently in the continuous group than in the intermittent group (40.1% vs. 49.5%, respectively). The rate of complete awakening was significantly higher in the continuous group than in the intermittent group. Finally, there was a significant difference in the percentage of patients who answered "absolutely yes" when asked about receiving EUS again: 52.7% in the continuous group vs. 34.3% in the intermittent group. Conclusions: Continuous infusion resulted in stable sedation and reduced propofol-associated risks. [ABSTRACT FROM AUTHOR]

The article discusses a case of a 76-year-old male with relapsing polychondritis who developed immune reconstitution inflammatory syndrome (IRIS) associated with Pneumocystis jirovecii pneumonia (PCP) and otitis media. The patient's symptoms worsened while tapering glucocorticoids, leading to pneumonia and bilateral otitis media. The case highlights the challenges in diagnosing and managing non-HIV-associated IRIS in immunocompromised patients with connective tissue diseases. The study emphasizes the importance of understanding IRIS to improve monitoring and intervention strategies for similar cases. [Extracted from the article]

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome is a rare central nervous system inflammatory disorder with an unknown pathophysiology. We present the case of a 51‐year‐old female exhibiting clinical and radiological features consistent with CLIPPERS syndrome. She manifested diplopia, vertigo, gait ataxia, and lower limb asthenia, accompanied by impaired tandem gait, right sixth nerve palsy, and coarse horizontal nystagmus during the physical examination. Magnetic resonance imaging (MRI) revealed punctate and curvilinear lesions centered in the pons. Treatment with glucocorticoids resulted in significant clinical improvement, and the patient was discharged with a maintenance dose of prednisolone. Throughout a four‐year follow‐up period, the patient remained symptom‐free without any relapses using the low‐dose corticosteroid. The CLIPPERS syndrome diagnosis remains challenging, but recent evidence supports an autoimmune pathogenesis. Although corticosteroid treatment has shown significant clinical improvement, there are no established guidelines or clinical trials on the optimal therapeutic regimen. Despite its rarity, clinicians should consider CLIPPERS syndrome in patients with compatible clinical and radiological features to prevent irreversible neurological damage. [ABSTRACT FROM AUTHOR]

The study published in the Pediatric Allergy & Immunology journal explores the safety and effectiveness of early age peanut oral immunotherapy (epOIT) in 27 pediatric patients with peanut allergy. The study found that epOIT was successful in achieving desensitization in the majority of patients, with minimal adverse effects reported. The research suggests that epOIT could potentially modify the course of peanut allergy in young children, highlighting the need for further large-scale clinical trials in this area. [Extracted from the article]

Background: Steroids are widely used in maintenance immunosuppression treatment in kidney transplant recipients. Older individuals undergo age-related immunosenescence that consequently decreases their ability to process and evoke a response to foreign antigens. Thus, steroids may not be necessary in preventing allograft rejection and may consequently increase older recipients' risk of long-term steroid-related adverse effects. Objective: The objective of this study was to analyze the adverse outcomes of long-term steroid immunosuppression in older kidney transplant recipients using real-world electronic medical record data. Methods: The TriNetX database "US Collaborative Network" was utilized to perform a propensity score-matched case-control study comparing 1-year, 3-year, and 5-year adverse effects of steroid immunosuppression in older adults (aged ≥ 65 years) kidney transplant recipients who underwent either an early-steroid withdrawal (ESW) maintenance regimen or a steroid continuous immunosuppression (SCI) regimen between 31 December, 2010 and 31 December, 2020. Early-steroid withdrawal was defined as tacrolimus plus mycophenolate mofetil maintenance with no prednisone after the seventh day post-transplant. Steroid continuous immunosuppression was defined as tacrolimus plus mycophenolate mofetil plus prednisone maintenance. Cohorts were matched on age, race/ethnicity, and risk factors for adverse steroid-related outcomes and rejection. Outcomes included post-transplant diabetes mellitus, dyslipidemia osteoporosis/fractures, myocardial infarction, glaucoma/cataract, stroke, pulmonary embolism, and malignancy. Secondary outcomes analyzed incidences of infection-related outcomes, graft-related outcomes, and recipient mortality. Results: After matching, there were 304 recipients in each group (ESW, SCI). Mean age at the time of transplant was 69.2 ± 3.7 years (ESW) and 69.2 ± 3.4 years (SCI, p = 0.96). The Kaplan–Meier analysis showed recipients who underwent SCI had increased incidences of post-transplant diabetes mellitus at 1 year (22.36% vs 30.37%, p = 0.01) and 3 years (34.89% vs 44.29%, p = 0.01), but this became non-significant at 5 years post-transplant (41.97% vs 42.6%, p = 0.34). Incidences of acute pancreatitis were higher for the SCI cohort at 3 years (p = 0.02) as well as incidences of acute myocardial infarction at 5 years post-kidney transplant (6.75% vs 14.39%, p < 0.01). No difference was found for other adverse outcomes. Early-steroid withdrawal recipients experienced significantly fewer infection-related outcomes, such as cytomegalovirus, BK virus, sepsis/bacteremia, and fungal infections, compared with SCI recipients. Last, recipients who underwent ESW experienced fewer incidences of rejection and death-censored graft failure at 5 years post-transplant. Conclusions: There is currently no standard maintenance immunosuppression protocol for older kidney transplant recipients. Death-censored graft survival, rejection, and patient survival were improved with ESW. Steroid minimization may be beneficial in this population given that it lowers the risk of drug-induced adverse effects. [ABSTRACT FROM AUTHOR]

Background: Herniated intervertebral disc (HIVD) with radiculopathy is a common degenerative spine disorder. Transforaminal epidural steroid injection (TFESI) is one of the pain relief treatments for lumbar radiculopathy recommended by evidence‐based guidelines. Adequate contrast distribution is correlated with better pain control, but the best approach has not been confirmed yet. Aim: To confirm the distribution of contrast medium injected with a new approach of TFESI, that is, far lateral lateral recess approach (FLLR‐TFESI). Methods: Patients receiving TFESI due to HIVD with radiculopathy between 2010 January and 2020 August were retrospectively enrolled. While the FLLR‐TFESI was taken as the experimental group, the conventional approach was viewed as the control group. The baseline characteristics, the pattern of contrast enhancement under fluoroscopic guidance, and the complications of these patients were collected and analyzed. Results: A total of 380 patients were analyzed (143 in control group and 237 in experimental group). The two groups were balanced in most baseline characteristics, except disc extrusion (p = 0.01) and scoliosis (p = 0.04). The FLLR‐TFESI have a better contrast distribution (p < 0.01), even after adjustment (p < 0.001). No intrathecal injection was noted, but higher rate of intra‐disc injection was noted in FLLR‐TFESI group (10% vs. 3%, p = 0.008). Conclusion: The FLLR‐TFESI has a superior contrast enhancement and distribution in comparison to conventional approach. Prospective study to confirm the study result as well as the clinical benefits is suggested in the future. [ABSTRACT FROM AUTHOR]

Background: Nasal irrigation is among the most widely used treatment modalities for sinonasal diseases. The extent of irrigation is well studied in operated sinuses but not for non-operated sinuses. Moreover, the preferred head positioning during irrigation is not known. Herein, we studied the extent of nasal irrigation in cadaveric heads with non-operated sinuses. Methods: Nine cadaveric heads were used. Normal saline solution mixed with radiological contrast material was used to irrigate the nasal cavities with the heads in 2 different positions: standing-leaning-forward (SLF) and Head-down forward (HDF). After each irrigation, computed tomography images of the head were acquired. The extent of irrigation was assessed for each subunit of the sinonasal cavity. Results: Irrigation was performed twice on a total of 18 sides, each time in 1 position. Nine subunits were evaluated: inferior, middle, and superior meati; the olfactory cleft; and the frontal, maxillary, anterior, and posterior ethmoid and sphenoid sinuses. The extent of irrigation was significantly better in the HDF position for the olfactory cleft (100% vs 33%), P -value=.001, frontal sinus (33% vs 11%), P -value=.002, maxillary sinus (78% vs 17%), P -value=.001, and anterior ethmoid sinus (89% vs 17%), P -value=.001. There was no significant difference in the extent of irrigation between the 2 positions for the other evaluated subunits. The overall extent of irrigation was 70.37% of the subunits in HDF position and 45.06% of the subunits for SLF position, P -value=.001 Conclusions: Nasal irrigation reached the cavities of non-operated paranasal sinuses. However, while the extent of irrigation was limited in the SLF, it was well achieved in the HDF position. Studies on the clinical efficacy of irrigation in this position are recommended. [ABSTRACT FROM AUTHOR]

Background: Thiopurine co‐therapy with anti‐tumour necrosis factor‐alpha (anti‐TNFα) agents is associated with higher anti‐TNFα drug levels and reduced immunogenicity in inflammatory bowel disease (IBD). Aims: We aimed to evaluate the association between 6‐thioguanine nucleotide (6‐TGN) and anti‐TNFα levels and the optimal 6‐TGN threshold level associated with higher anti‐TNFα levels in combination therapy. Methods: We performed a retrospective cross‐sectional multicentre study of patients with IBD on combination anti‐TNFα and thiopurine maintenance therapy between January 2015 and August 2021. Primary outcomes were infliximab and adalimumab levels. Secondary outcomes were antibodies to infliximab (ATI) or adalimumab (ATA). Univariable and multivariable linear regression were performed to identify variables associated with anti‐TNFα levels. Receiver operator characteristic curves were used to define the optimal 6‐TGN cut‐off levels associated with therapeutic anti‐TNFα levels. Results: The study included 743 paired 6‐TGN and anti‐TNFα levels (640 infliximab and 103 adalimumab). 6‐TGN levels were associated with infliximab levels, but not adalimumab levels, on univariable and multivariable regression. The optimal 6‐TGN cut‐off associated with therapeutic infliximab levels (≥5 mcg/mL) was 261 pmol/8 × 108 red blood cell (RBC) (area under the curve (AUC) = 0.57) for standard infliximab dosing and 227.5 pmol/8 × 108 RBC (AUC = 0.58) for escalated dosing. For therapeutic adalimumab levels (≥7.5 mcg/mL), the 6‐TGN cut‐off was 218.5 pmol/8 × 108 RBC (AUC = 0.59) for standard adalimumab dosing and 237.5 pmol/8 × 108 RBC (AUC = 0.63) for escalated dosing. Conclusion: 6‐TGN levels were weakly associated with infliximab but not adalimumab levels in combination therapy. 6‐TGN levels in the lower end of the therapeutic range (230–260 pmol/8 × 108 RBC) may be adequate to maintain higher infliximab levels, particularly with escalated infliximab dosing. [ABSTRACT FROM AUTHOR]

Background: Delivery variations during radiotherapy can cause discrepancies between planned and delivered dose distribution. These variations could arise from random and systematic offsets in certain machine parameters or systematic offsets related to the calibration process of the treatment unit. Purpose: The aim of this study was to present a novel simulation‐based methodology to evaluate realistic delivery variations in three dimensions (3D). Additionally, we investigated the dosimetric impact of delivery variations for volumetric modulated arc therapy (VMAT) plans for different treatment sites and complexities. Methods: Twelve VMAT plans for different treatment sites (prostate‐, head & neck‐, lung‐, and gynecological cancer) were selected. The clinical plan used for the treatment of each patient was reoptimized to create one plan with reduced complexity (i.e., simple plan) and one of higher complexity (i.e., complex plan). This resulted in a total of 36 plans. Delivery variations were simulated by randomly introducing offsets in multi‐leaf collimator position, jaw position, gantry angle and collimator angle simultaneously. Twenty simulations were carried out for each of the 36 plans, yielding 720 simulated deliveries. To explore the impact of individual offsets, additional simulations were conducted for each type of offset separately. A 3D dose calculation was performed for each simulation using the same calculation engine as for the clinical plan. Two standard deviations (2SD) of dose were determined for every voxel for 3D‐spatial evaluations. The dose variation in certain DVH metrics, that is, D2% and D98% for the clinical target volume and five different DVH metrics for selected organs at risk, was calculated for the twenty simulated deliveries of each plan. For comparison, the effect of delivery variations was assessed by conducting measurements with the Delta4 phantom. Results: The volume of voxels with 2SD above 1% of the prescribed dose was consistently larger for the complex plans in comparison to their corresponding simple and clinical plans. 2SDs larger than 1% were in many cases, found to accumulate outside the planning target volume. For complex plans, regions with 2SDs larger than 1% were detected also inside the high dose region, exhibiting, on average, a size six times larger volume, than those observed in simple plans. Similar results were found for all treatment sites. Variation in the selected DVH metrics for the simulated deliveries was generally largest for the complex plans with few exceptions. When comparing the 2SD distribution of the measurements with the 2SD distribution from the simulations, the spatial information showed deviations outside the PTV in both simulations and measurements. However, the measured values were, on average, 35% higher for the prostate plans and 10% higher for the head & neck plans compared to the simulated values. Conclusions: The presented methodology effectively quantified and localized dose deviations due to delivery offsets. The 3D analysis provided information that was undetectable using the analysis based on DVH metrics. Dosimetric uncertainties due to delivery variations were prominent at the edge of the high‐dose region irrespective of treatment site and plan complexity. Dosimetric uncertainties inside the high‐dose region was more profound for plans of higher complexity. [ABSTRACT FROM AUTHOR]

Background: Huashi Baidu Formula (HBF) is a clinical formula known for its efficacy against coronavirus disease 2019 (COVID-19). HBF may reduce the number of patients with abnormal serum creatinine while improving respiratory symptoms, suggesting that this formula may have potential for treating acute kidney injury (AKI). However, the protective effect of HBF on AKI has not been definitively confirmed, and the mechanism remains unclear. Therefore, the present study explored the renoprotective effects and molecular mechanisms of HBF and screened for its active ingredients to identify new potential applications of renoprotection by HBF. Methods: The present study first assessed the protective effects of HBF on AKI in a DOX-induced mouse model. Then, RNA-seq and bioinformatics analyses were used to explore the related pathological processes and potential molecular mechanisms, which were subsequently validated using qRT-PCR and Western blotting. Furthermore, candidate compounds with potential binding affinity to two pivotal targets, sphingosine kinase 1 (SphK1) and plasminogen activator inhibitor-1 (PAI-1), were screened from the 29 constituents present in the blood using Microscale Thermophoresis (MST). Finally, to identify the active ingredients, the candidate components were re-screened using the SphK1 kinase activity detection system or the uPA/PAI-1 substrate colorimetric assay system. Results: In the DOX-induced AKI mouse model, therapeutic administration of HBF significantly reduced the levels of CRE, BUN, TNF-α, IL-1β, IL-6, and UA in plasma and the levels of MDA, T-CHO, and TG in kidney tissue. Additionally, the levels of TP and Alb in plasma and SOD and CAT in the kidney tissue were significantly increased. Histopathological assessment revealed that HBF reduced tubular vacuolation, renal interstitial inflammatory cell infiltration, tubular atrophy, and positive staining of renal interstitial collagen. RNA-seq and bioinformatics analyses showed that oxidative stress, the immune-inflammatory response, and extracellular matrix (ECM) formation could be the pathological processes that HBF targets to exerts its renoprotective effects. Furthermore, HBF regulated the APJ/SPHK1/NF-κB and APJ/PAI-1/TGFβ signaling axes and reduced the phosphorylation levels of NF-κB p65 and SMAD2 and the expression of cytokines and the ECM downstream of the axis. Finally, six SphK1 inhibitors (paeoniflorin, astragalin, emodin, glycyrrhisoflavone, quercetin, and liquiritigenin) and three PAI-1 inhibitors (glycyrrhisoflavone, licochalcone B, and isoliquiritigenin) were identified as potentially active ingredients in HBF. Conclusion: In brief, our investigation underscores the renoprotective effect of HBF in a DOX-induced AKI model mice, elucidating its mechanisms through distinct pathological processes and identifying key bioactive compounds. These findings offer new insights for broadening the clinical applications of HBF and unravelling its molecular mode of action. [ABSTRACT FROM AUTHOR]

Trastuzumab is a potent targeted therapy drug for HER2-positive cancer patients. A comprehensive understanding of trastuzumab's mechanism of action, pharmacokinetic (PK) parameters, and steady-state exposure in different treatment regimens and administration routes is essential for a thorough evaluation of the drug's safety and effectiveness. Due to the distinctive pharmacokinetics, indications, and administration methods of trastuzumab, this understanding becomes crucial. Drug exposure can be assessed by measuring trastuzumab's peak concentration, trough concentration, or area under the curve through assays like enzyme-linked immunosorbent assay (ELISA) or liquid chromatography-tandem mass spectrometry (LC-MS/MS). The dose-response (D-R) and exposure-response (E-R) relationships establish the correlation between drug dosage/exposure and the therapeutic effect and safety. Additionally, various covariates such as body weight, aspartate transaminase, and albumin levels can influence drug exposure. This review provides a comprehensive overview of trastuzumab's mechanism of action, data on steady-state concentration and PK parameters under multiple administration routes and indications, discussions on factors influencing PK parameters, and evaluations of the effectiveness and safety of E-R and D-R in diverse HER2-positive cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to develop and evaluate a population PK model of mycophenolic acid (MPA) in pediatric kidney transplant patients to aid MPA dose optimization. Methods: Data were collected from pediatric kidney transplant recipients from a Dutch academic hospital (Radboudumc, the Netherlands). Pharmacokinetic model-building and model-validation analyses were performed using NONMEM. Subsequently, we externally evaluated the final model using data from another academic hospital. The final model was used to develop an optimized dosing regimen. Results: Thirty pediatric patients were included of whom 266 measured MPA plasma concentrations, including 20 full pharmacokinetic (PK) curves and 24 limited sampling curves, were available. A two-compartment model with a transition compartment for Erlang-type absorption best described the data. The final population PK parameter estimates were Ktr (1.48 h−1; 95% CI, 1.15–1.84), CL/F (16.0 L h−1; 95% CI, 10.3–20.4), Vc/F (24.9 L; 95% CI, 93.0–6.71E25), Vp/F (1590 L; 95% CI, 651–2994), and Q/F (36.2 L h−1; 95% CI, 9.63–74.7). The performance of the PK model in the external population was adequate. An optimized initial dose scheme based on bodyweight was developed. With the licensed initial dose, 35% of patients were predicted to achieve the target AUC, compared to 42% using the optimized scheme. Conclusion: We have successfully developed a pharmacokinetic model for MPA in pediatric renal transplant patients. The optimized dosing regimen is expected to result in better target attainment early in treatment. It can be used in combination with model-informed follow-up dosing to further individualize the dose when PK samples become available. [ABSTRACT FROM AUTHOR]

Epimedium is a Chinese herb known as "yin and yang fire," first mentioned in the Compendium of Materia Medica. Many of the proprietary Chinese medicines used in clinical practice contain Epimedium as an ingredient, and its main active constituents include icariin, icaritin, and icariside II, among others. In addition to its traditional use in treating fatigue and sexual problems, modern research has confirmed that the main bioactive compounds in Epimedium have pharmacological effects such as antidepressant, antibacterial, antiviral, antioxidant, and anti-inflammatory properties, as well as inhibiting bone destruction, promoting bone growth, improving immune regulation and protecting the cardio-cerebral vascular system. With the continuous development of extraction and purification techniques, the development and use of bioactive compounds in Epimedium have significantly progressed, and the anticancer effect has received widespread attention. Since natural herbs have few side effects on the human body and do not easily develop drug resistance, they have long been the direction of research in cancer treatment. This review summarizes the latest research on the anticancer effects of Epimedium and its extracts, describes the bioactive compounds, pharmacological efficacy, and antitumor mechanism of Epimedium, and gives a new view on the administration and development of Epimedium. [ABSTRACT FROM AUTHOR]

Background: Between 5 and 50% of atypical hemolytic uremic syndrome (aHUS) cases in children are caused by autoantibodies against complement factor H (CFH). Given the acquired autoimmune nature of the disease, plasma exchange (PE) and various immunosuppressive treatments have been used. More recently, eculizumab has been proposed. Methods: In this multicenter, retrospective study, we report outcomes of 12 children with anti-FH antibody-associated HUS treated with eculizumab associated with various immunosuppressive regimens. Results: Patients were treated with eculizumab for 15.5 [9.5;23.0] months and 3 received PE or IgG adsorption. Three patients received mycophenolate mofetil (MMF) alone, 1 patient received MMF and steroids, 1 patient received MMF and rituximab, 3 patients received MMF/steroids and rituximab, and 4 patients did not receive any immunosuppression. Anti-FH antibody levels significantly decreased but no difference was observed based on the immunosuppressive regimen. Eculizumab was discontinued in 7/10 patients after 11 [7.5;15.5] months and MMF in 6/8 patients after 36 [35;40] months. Anti-FH titers at MMF discontinuation ranged from 257 to 3425 UI/L. None of these patients relapsed and eGFR at last follow-up was above 70 mL/min/1.73 m2 in all patients. Conclusions: Eculizumab is effective and safe in inducing and maintaining remission in aHUS secondary to anti-FH antibodies and renders reduction of anti-FH titers less urgent. Anti-FH antibody titers decreased in most patients irrespective of the immunosuppressive treatment chosen, so that a strategy consisting of combining eculizumab with MMF monotherapy seems sufficient at least in non-Indian or less severe forms of anti-FH antibody-associated HUS. [ABSTRACT FROM AUTHOR]

A 14-year-old patient presents with hematuria and proteinuria. Clinical evaluation reveals a positive anti-nuclear antibody titer, positive anti-double stranded DNA antibody and hypocomplementemia. Systemic lupus erythematosus (SLE) is diagnosed based on the 2019 EULAR/ACR (European League Against Rheumatism/American College of Rheumatology) classification criteria (Aringer et al. Arthritis Rheumatol 71:1400–1412, 2019). A kidney biopsy is performed that confirms the presence of immune complex glomerulonephritis, ISN-RPS (International Society of Nephrology/Renal Pathology Society) class IV (Bajema et al. Kidney Int 93:789–796, 2018). According to the latest clinical practice guidelines (Rovin et al. Kidney Int 100:753–779, 2021; Fanouriakis et al. Ann Rheum Dis 83:15–29, 2023), there are alternatives to treating this patient with cyclophosphamide. But what if this patient also presented with oliguria and volume overload requiring intensive care and dialysis? What if this patient also presented with altered mental status and seizures, and was diagnosed with neuropsychiatric lupus? What if this patient was also diagnosed with a pulmonary hemorrhage and respiratory failure? The clinical practice guidelines do not address these scenarios that are not uncommon in patients with SLE. Moreover, in some countries worldwide, patients do not have the privilege of access to biologics or more expensive alternatives. The purpose of this review is to evaluate the contemporary options for initial treatment of nephritis in patients with SLE. [ABSTRACT FROM AUTHOR]

During discussions at the Data Science Roundtable meeting in Japan, there were instances where the adoption of the BOIN design was declined, attributed to the extension of study duration and increased sample size in comparison to the 3 + 3 design. We introduce an accelerated BOIN design aimed at completing a clinical phase I trial at a pace comparable to the 3 + 3 design. Additionally, we introduce how we could have applied the BOIN design within our company, which predominantly utilized the 3 + 3 design for most of its clinical oncology dose escalation trials. The accelerated BOIN design is adaptable by using efficiently designated stopping criterion for the existing BOIN framework. Our approach is to terminate the dose escalation study if the number of evaluable patients treated at the current dose reaches 6 and the decision is to stay at the current dose for the next cohort of patients. In addition, for lower dosage levels, considering a cohort size smaller than 3 may be feasible when there are no safety concerns from non-clinical studies. We demonstrate the accelerated BOIN design using a case study and subsequently evaluate the performance of our proposed design through a simulation study. In the simulation study, the average difference in the percentage of correct MTD selection between the accelerated BOIN design and the standard BOIN design was − 2.43%, the average study duration and the average sample size of the accelerated BOIN design was reduced by 14.8 months and 9.22, respectively, compared with the standard BOIN design. Key Objective: Can a clinical trial designer suggest a BOIN design to clinicians who only have experience with the 3 + 3 design that would complete the study as quickly as the 3 + 3 design while increasing the accuracy of correct maximum tolerated dose (MTD) selection? Knowledge Generated: We propose an accelerated BOIN design to be completed in a phase I trial as quickly as the 3 + 3 design. We also introduce how we were the first to apply the BOIN design where our company applied the 3 + 3 design for most of the clinical oncology dose-escalation trials. Relevance: The information we present is useful for those who want to finish an accelerated BOIN design as quickly as a 3 + 3 design or who are having trouble applying a BOIN design. [ABSTRACT FROM AUTHOR]

(1) Background and Objectives: Vitamin D is implicated in the pathogenesis of Chronic Kidney Disease—Mineral and Bone Disorder (CKD-MBD) in hemodialysis (HD) patients, including the development of secondary hyperparathyroidism (SHP). While cholecalciferol supplementation is recommended for vitamin D deficiency correction, its impact on CKD-MBD remains inconsistent. The aim of this observational prospective study was to assess the effect of cholecalciferol in achieving high–normal serum 25-hydroxycholecalciferol (25(OH)D > 75 ng/mL) levels and its impact on CKD-MBD biochemical markers, including 1,25-dihydroxycholecalciferol (1,25(OH)2D) and parathormone (PTH) in HD patients. The study also evaluated the maintenance dosage required to sustain 25(OH)D levels within the 50–75 ng/mL range. (2) Materials and Methods: A total of 22 HD patients with baseline 25(OH)D levels 30–50 ng/mL received cholecalciferol (70,000 IU/week) to achieve the target serum 25(OH)D > 75 ng/mL. Baseline data on calcium, phosphate, 1–84 PTH, 25(OH)D, and 1,25(OH)2D serum levels were compared with the data when 25(OH)D > 75 ng/mL was targeted or when the highest 25(OH)D levels were noted. (3) Results: Cholecalciferol significantly improved vitamin D status in HD patients, with 73% reaching the target 25(OH)D level >75 ng/mL in a median time of 7.5 weeks, with a median total dose of 525,000 IU. This was associated with a significant rise in 1,25(OH)2D, decrease in 1–84 PTH, and no significant effect on calcium and phosphate levels. The median maintenance dose of cholecalciferol was established at 30,000 IU/week. (4) Conclusions: The findings support the use of cholecalciferol targeting high normal 25(OH)D levels to improve biochemical markers of CKD-MBD in HD patients. [ABSTRACT FROM AUTHOR]

Breast cancer poses a significant health risk and remains the most prevalent cancer among women. The side effects associated with traditional chemotherapy, such as neurotoxicity, liver or kidney dysfunction, highlight the urgent need for novel breast cancer therapies. In this regard, local delivery of chemotherapeutics has been emerged to be one of the efficient methods to eradicate the tumor cells. Injectable hydrogels were developed as drug delivery systems for localized drug accumulation and controlled drug release at the tumor site. Hydrogels are 3D network of polymeric structures with notable biocompatibility, swelling properties and mechanical strength. In fact, an injectable hydrogel enhances drug delivery efficiency, reduces systemic drug cytotoxicity, minimizes the essential drug dosage and frequency of drug administration. The studies based on injectable hydrogels for specific cancer therapy showed that such platforms are more effective and durable methods than traditional chemotherapy. Additionally, they are vastly used in inhibiting postsurgical tumor recurrence. These hydrogel platforms can integrate multiple breast cancer therapies into a single structure to improve the treatment efficacy. In this review, a variety of injectable hydrogel drug delivery platforms were discussed for several types of applications, such as gene therapy, drug delivery, immunotherapy, photothermal therapy, photodynamic therapy, and combined therapies with synergistic effects against breast cancer. Moreover, we provided a brief summary of the recent advances in the application of such hydrogels for breast cancer treatment. This review provides insight into the recent advancements in injectable hydrogels and discusses the potential future applications and challenges associated with this drug delivery technology toward cancer therapy. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether the combination of chemotherapy with staged Chinese herbal medicine (CHM) therapy could enhance health-related quality of life (QoL) in non-small-cell lung cancer (NSCLC) patients and prolong the time before deterioration of lung cancer symptoms, in comparison to chemotherapy alone. Methods: A prospective, double-blind, randomized, controlled trial was conducted from December 14, 2017 to August 28, 2020. A total of 180 patients with stage I B–IIIA NSCLC from 5 hospitals in Shanghai were randomly divided into chemotherapy combined with CHM (chemo+CHM) group (120 cases) or chemotherapy combined with placebo (chemo+placebo) group (60 cases) using stratified blocking randomization. The European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life-Core 30 Scale (QLQ-C30) was used to evaluate the patient-reported outcomes (PROs) during postoperative adjuvant chemotherapy in patients with early-stage NSCLC. Adverse events (AEs) were assessed in the safety analysis. Results: Out of the total 180 patients, 173 patients (116 in the chemo+CHM group and 57 in the chemo+placebo group) were included in the PRO analyses. The initial mean QLQ-C30 Global Health Status (GHS)/QoL scores at baseline were 57.16 ± 1.64 and 57.67 ± 2.25 for the two respective groups (P>0.05). Compared with baseline, the chemo+CHM group had an improvement in EORTC QLQ-C30 GHS/QoL score at week 18 [least squares mean (LSM) change 17.83, 95% confidence interval (CI) 14.29 to 21.38]. Conversely, the chemo+placebo group had a decrease in the score (LSM change −13.67, 95% CI −22.70 to −4.63). A significant between-group difference in the LSM GHS/QoL score was observed, amounting to 31.63 points (95% CI 25.61 to 37.64, P<0.001). The similar trends were observed in physical functioning, fatigue and appetite loss. At week 18, patients in the chemo+CHM group had a higher proportion of improvement or stabilization in GHS/QoL functional and symptom scores compared to chemo+placebo group (P<0.001). The median time to deterioration was longer in the chemo+CHM group for GHS/QoL score [hazard ratio (HR)=0.33, 95% CI 0.23 to 0.48, P<0.0010], physical functioning (HR=0.43, 95% CI 0.25 to 0.75, P=0.0005), fatigue (HR=0.47, 95% CI 0.30 to 0.72, P<0.0001) and appetite loss (HR=0.65, 95% CI 0.42 to 1.00, P=0.0215). The incidence of AEs was lower in the chemo+CHM group than in the chemo+placebo group (9.83% vs. 15.79%, P=0.52). Conclusion: The staged CHM therapy could help improve the PROs of postoperative patients with early-stage NSCLC during adjuvant chemotherapy, which is worthy of further clinical research. (Registry No. NCT03372694) [ABSTRACT FROM AUTHOR]

Background: Peanut allergy is a common food allergy with potentially life-threatening implications. Early oral immunotherapy for peanut allergy (P-EOIT) has been shown to be effective and safe in research and specialty clinic settings. Provision of P-EOIT in primary care would make it available to more patients. We sought to assess the safety of P-EOIT in a primary care setting by documenting the rates of peanut-related allergic reactions leading to emergency department (ED) visits and use of epinephrine. We also examined adherence by assessing the percentage of patients reaching maintenance phase and continuing ingestion after one year of P-EOIT. Methods: This retrospective study included all patients aged less than 36 months who started P-EOIT at a primary care allergy clinic in New Brunswick, Canada, from 2016 to 2020. The population included patients who (1) had a history of an allergic reaction to peanuts with a positive skin prick test or positive peanut specific IgE level (ps-IgE) or (2) no history of ingestion and a baseline ps-IgE ≥5 kU/L. Patients had biweekly clinic visits with graded increases in peanut protein up to a maintenance dose of 300 mg of peanut protein daily. A blinded retrospective review of paper charts and electronic medical records was conducted along with phone interviews regarding ED visits and epinephrine use. Results: All 69 consented patients reached maintenance dose over a median of 29 weeks, and 66 patients (95.7%) were still regularly consuming peanut protein after 1 year of maintenance. One patient had a peanut ingestion-related ED visit requiring epinephrine during the escalation phase of peanut protein dosing (1.4%). During the first year of maintenance phase, no patients had peanut ingestion-related ED visits nor required epinephrine. Conclusion: Early oral immunotherapy for peanut allergy in a primary care setting appears to be safe and our findings suggest that it does not lead to an increased burden of emergency department visits. Our population had high adherence rates, with the majority achieving maintenance dose and staying on this dose for one year. [ABSTRACT FROM AUTHOR]

Introduction: Quinidine (QND) sulfate is an effective treatment for atrial fibrillation (AF) in horses, and several dosage regimens have been proposed to address its wide variability in response and potential adverse effects. The purpose of this study was to analyze the variability in plasma quinidine concentrations using population pharmacokinetics to determine an effective and safe dosage regimen for Thoroughbred horses. Methods: Six healthy Thoroughbred horses were treated with 20mg/kg quinidine sulfate dihydrate (16.58mg/kg QND base) administered PO or 5mg/kg quinidine hydrochloride monohydrate (4.28mg/kg QND base) administered IV (single administration), and blood samples were taken regularly. Four healthy horses were treated with 20mg/kg quinidine sulfate dihydrate administered twice (every 6h) via PO route. For the other 19 Thoroughbred racehorses that developed AF, blood samples were taken during quinidine therapy. Quinidine concentrations were measured in all plasma samples using liquid chromatography with tandem mass spectrometry, and the data from 29 horses were modeled using a nonlinear mixed-effects model, followed by Monte Carlo simulations (MCS). Results: The median quinidine concentration for successful sinus rhythm conversion was 2.0 µg/mL (range: 0.5-2.7 µg/mL) in AF horses, while a median concentration of 3.8 µg/mL (range: 1.6-5.1 µg/mL) showed adverse effects. MCS predicted that plasma quinidine concentrations for quinidine sulfate dihydrate PO administration (loading dose: 30 mg/kg, maintenance dose: 6.5 mg/kg q 2 h) reached 1.4, 2.0 and 2.7 µg/mL in 90, 50 and 10% of the horse populations, respectively. Increasing the loading dose to 45 mg/kg and the maintenance dose to 9 mg/kg q 2 h, the plasma concentrations achieved were 1.9, 2.8, and 3.8 µg/mL in 90, 50, and 10% of horse populations, respectively. Discussion: Using simulations, different empirical dosing regimens were proposed to achieve plasma quinidine concentrations immediately or progressively, representing a tradeoff between optimizing therapeutic effects and minimizing adverse effects. A combination of these dosing regimens is recommended to gradually increase the therapeutic concentration levels of quinidine for safe and effective treatment of AF in racehorses. [ABSTRACT FROM AUTHOR]

Background: Intra- and postoperative hemorrhage is a relevant problem in major abdominal surgery, leading to acute anemia and necessitating transfusion of packed red blood cells. It is estimated that in 30% of abdominal surgeries, intra- or postoperative transfusion is required. Transfusion potentially has detrimental health effects and poses a considerable socioeconomic burden. Tranexamic acid, a lysine analog inhibiting plasminogen activation and providing clot stability, has been used to reduce hemorrhage. While there is ample evidence in other surgical disciplines, it is almost completely lacking in abdominal surgery. Methods: This multicenter double-blind parallel group randomized superiority trial will compare tranexamic acid (loading dose 1000 mg over 10 min prior to skin incision, maintenance dose 125 mg/h continuously until skin closure or until 1000 mg have been administered) to placebo in patients ≥ 18 years undergoing elective esophagectomy, gastrectomy, colectomy, rectal resection, pancreatic resection, or hepatectomy. The primary efficacy endpoint is the intra- or postoperative transfusion of at least one unit of packed red blood cells. Key secondary endpoints are the number of transfused units per patient, estimated intraoperative blood loss, postoperative complications/mortality, length of hospital stay, operation/anesthesia time, D-dimer levels, and quality of life. Sample size calculation is based on the assumption that in the control group, 30% of patients require transfusion while the intervention achieves a risk reduction of 33%, reducing the probability to 20%. With a type one error of 5% and a power of 90%, using a two-sided χ2 test, this results in 412 patients per group. Accounting for non-compliance, 425 patients are to be randomized per group. The total trial duration will be 30 months with a recruitment period of 18 months. Discussion: If the proposed trial yielded positive results, the routine use of tranexamic acid in major abdominal surgery would be supported. This would avoid acute anemia with detrimental effects such as tissue hypoxia and organ injury, as well as the negative immediate and delayed effects of transfusions. Trial registration: EU CT Nr: 2023–509970-43–01, NCT06414031. Registered on 10 May 2024. [ABSTRACT FROM AUTHOR]

Simple Summary: In this article, the authors introduce a new metric called the modified Fragility Index (mFI) to assess the accuracy of determining the maximum tolerated dose (MTD) in early oncology clinical trials. The mFI measures how sensitive the MTD decision is to the inclusion of a few more participants in the trial. The authors analyzed three published cancer trials and found that two trials were robust to adding more participants, indicating that the MTD estimate remained stable. However, in the other trial, the MTD estimate was more fragile and could have changed with just one or two more participants. The mFI metric helps researchers make more reliable decisions about the appropriate MTD. By considering the potential impact of additional participants, researchers can improve accuracy and confidence in dose determination, leading to better treatment outcomes for patients. Objectives: The sample sizes of phase I trials are typically small; some designs may lead to inaccurate estimation of the maximum tolerated dose (MTD). The objective of this study was to propose a metric assessing whether the MTD decision is sensitive to enrolling a few additional subjects in a phase I dose-finding trial. Methods: Numerous model-based and model-assisted designs have been proposed to improve the efficiency and accuracy of finding the MTD. The Fragility Index (FI) is a widely used metric quantifying the statistical robustness of randomized controlled trials by estimating the number of events needed to change a statistically significant result to non-significant (or vice versa). We propose a modified Fragility Index (mFI), defined as the minimum number of additional participants required to potentially change the estimated MTD, to supplement existing designs identifying fragile phase I trial results. Findings: Three oncology trials were used to illustrate how to evaluate the fragility of phase I trials using mFI. The results showed that two of the trials were not sensitive to additional subjects' participation while the third trial was quite fragile to one or two additional subjects. Conclusions: The mFI can be a useful metric assessing the fragility of phase I trials and facilitating robust identification of MTD. [ABSTRACT FROM AUTHOR]

Background: the role of the R202Q (c.605G>A, p.Arg202Gln) missense variant of the MEFV gene has been debated as either a benign polymorphism or a potentially pathogenic mutation. We report and discuss here the case of a young female with corticosteroid-dependent recurrent pericarditis carrying the homozygous R202Q variant, exhibiting distinctive clinical features possibly influenced by this genetic variant. Methods: a 30-year-old woman with a previous diagnosis of cancer and recent respiratory infection presented with severe pleuritic chest pain, hypotension, tachycardia, and fever. Initial diagnostic evaluation indicated cardiac tamponade, and emergent pericardiocentesis was performed. Despite initial treatment with NSAIDs, colchicine, and corticosteroids, the patient experienced multiple recurrences. Genetic testing identified homozygous R202Q variant in the MEFV gene. Given the corticosteroid dependency and recurrent nature of her condition, IL-1 inhibitor anakinra was introduced, leading to significant improvement, although tapering below 150 mg per week failed to prevent recurrences. Results: the introduction of anakinra resulted in rapid symptom relief and resolution of pericardial effusion. However, attempts to taper or discontinue anakinra led to pericarditis recurrences. Ultimately, a maintenance dose of 50 mg every three days was established, which maintained remission for 18 months without recurrence. Despite multiple tapering attempts, further reduction in anakinra dosage was unsuccessful without triggering relapses. Conclusions: the R202Q variant, although typically considered benign, may contribute to an autoinflammatory phenotype resembling familial Mediterranean fever. This case underscores the potential pathogenicity of the homozygous R202Q variant in recurrent pericarditis and its responsiveness to IL-1 inhibition. In patients with corticosteroid-dependent recurrent pericarditis, genetic testing for the R202Q variant should be considered when anti-IL-1 drugs cannot be withdrawn. Further studies are warranted to elucidate the variant's role in pericardial inflammation and guide personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Intraoperative nerve monitoring (INM) to assess for recurrent laryngeal nerve dysfunction during thyroid surgery is becoming the standard of care in many institutions. Successful provision of data analysis with the help of IONM requires complete relaxation of the larynx and suppression of the reflex. We investigated the role of intravenous lidocaine in providing such working conditions to ensure the least impact on hemodynamic changes and obtain better conditions for working with IONM. The study aims to evaluate the effect of lidocaine, administered intravenously in estimated doses, on the IONM and laryngotracheal reflexes during surgical interventions on the thyroid and parathyroid glands. Methods: Forty-six patients were randomly assigned to Group 1 where lidocaine was administered and Group 2 where no lidocaine was administered. All patients were anaesthetized with a narcotic analgesic and inhalation anaesthetic. The loading dose of lidocaine was administered at the rate of 1 mg/kg intravenously, and the maintenance dose was calculated at 1.5 mg/kg/hour. For IONM, a Dragonfly single-channel laryngeal surface electrode (C2 NerveMonitor; 8 channel system for intraoperative Neurophysiological Monitoring, GERMANY) attached to a cuffed ETT #7 (MEDICARE, China) was used during surgery the same to the manufacturer's instructions. Results: The number of patients who required StMC strength at 0.5 mA (the manufacturer's recommended strength is 1.5 mA) was significantly higher in the lidocaine group (P=0.001) than in the no lidocaine group (P=0, 00006). The same number of patients with < 50% DAIL at the end of surgery was significantly higher in group 1 than in group 2. In addition, the proportion of patients with hypotensive episodes and blood pressure medication requirements more than twice during surgery was significantly lower in group 1 than in group 2 (P < 0.05). Conclusions: Patients who were prescribed lidocaine intravenously were more resistant to laryngotracheal irritation during surgery, and this made it possible to maintain such a condition of the larynx, which was necessary to ensure increased relaxation of the larynx and suppression of reflexes when using IONM. Our ability to elicit a positive signal with StMC 0.5 mA intraoperatively and provide a DAIL < 50% before the end of surgery was statistically significant in the IV lidocaine group (group 1). [ABSTRACT FROM AUTHOR]

Background: Slow transit constipation (STC) is highly prevalent and has rising incidence. Shouhui Tongbian capsule (SHTB) is a traditional Chinese Medicine formula with extensive and highly efficacious usage in STC treatment, however, its mechanism of action, especially the regulation of microbiome and lipid metabolites, remains unclear. Methods: After quality control of SHTB using LC‒MS to obtain its material basis, we tried to elucidate the cohesive modulatory network of SHTB against STC using hyphenated methods from microbiomics, lipidomics, mass spectrometry imaging (MSI) and molecular methods. Results: SHTB could repair intestinal barrier damage, reduce systemic inflammation and increase intestinal motility in a diphenoxylate-induced STC rat model. Based on 16S rDNA sequencing results, SHTB rehabilitated the abnormal changes in Alloprevotella, Coprococcus, Marvinbryantia, etc., which were associated with STC symptoms. Meanwhile, microbial functional prediction showed that lipid metabolism was improved with SHTB administration. The differential lipids, including fatty acids, lysophosphatidylcholine, phosphatidylcholine, sphingomyelin triglyceride and ceramide, that are closely related to STC disease and SHTB efficacy. Furthermore, SHTB significantly reversed the abnormal expression of these key target enzymes in colon samples, including CTP-phosphocholine cytidylyltransferase, CTP-phosphoethanolamine cytidylyltransferase, phosphatidic acid phosphatase, acid sphingomyelinase etc. Conclusions: Combined analysis demonstrated that SHTB reducing lipid accumulation and recovery of intestinal microbial homeostasis was the critical mechanism by which SHTB treats STC. [ABSTRACT FROM AUTHOR]

Background: Astragali radix (AR) is one of the most widely used traditional Chinese herbal medicines. It exhibits diverse biological activities, including immunomodulatory and anti-inflammatory properties; however, some of its activities have only been demonstrated in vitro. Objective: To examine the effects of orally administered AR extract on immune cells and the intestine under physiological conditions, which bridges the gap between previously observed in vitro outcomes and in vivo results. Methods: AR extract was prepared by hot water extraction. Three separate animal experiments were conducted to isolate macrophages, splenocytes, and the small intestine epithelium. For the macrophage preparation experiment, an intraperitoneal injection of sterile thioglycolate was administered. The mice received oral AR extract at doses of 0.1, 0.5, or 2.5 g/kg for ten days. At the end of each experiment, cells or tissues were isolated. A portion of macrophages and splenocytes were analyzed for the phenotypic changes. The remaining cells were cultured and stimulated with lipopolysaccharide (LPS) or mitogen ex vivo to assess activation status, proliferation, and cytokine production. Samples of the intestine were subjected to real-time RT-PCR. Results: Peritoneal macrophages from AR-treated mice exhibited increased expression of scavenger receptors, including SRA and CD36. Stimulation of these macrophages ex vivo with LPS selectively modulated the inflammatory response, including reduced expression of the costimulatory molecules CD40 and CD86, which are important for T cell responses, without affecting TNF-α and IL-6 production. Splenocytes from AR-treated mice exhibited a dose-dependent increase in CD4 and CD8 T cells; however, stimulation with mitogen decreased T cell proliferation and reduced IFN-γ production, which is essential for macrophage activation. An analysis of the small intestinal epithelium revealed an attenuated antimicrobial response, including reduced IgA content in the lumen and decreased expression of mucin-2 and polymeric Ig receptor genes. Conclusion: The response of immune cells following oral treatment with AR extract did not replicate the previously documented in vitro findings. Immune cells and intestinal epithelium from mice administered oral AR extract exhibited a selective anti-inflammatory phenotype. The overall findings indicate that the systemic effects after oral administration of AR extract include reduced sensitivity to inflammatory insults. [ABSTRACT FROM AUTHOR]

Background: This study aims to investigate the short-term effects and safety of adjunct Suxiao Jiuxin Pills (SJPs) on conventional therapy in chronic coronary syndrome (CCS) patients who are intolerant to the adverse effects of long-acting nitrates. Methods: This was a multicenter, randomized, double-blind, placebo-controlled trial. A total of 174 CCS participants from eight clinical study centers in China were included in the modified intention-to-treat analyses. Participants with CCS and intolerance to the adverse effects of long-acting nitrates were recruited and randomized to either the SJPs or the placebo group for a duration of 4 weeks. Results: Compared to the placebo group, the SJPs group showed a significant improvement in the efficacy rate after 4 weeks (OR = 2.43, 95% CI = 1.32 to 4.47, P = 0.004). Besides, individuals without a history of alcohol consumption showed a greater improvement in the SAQ summary score compared to those with a history of alcohol consumption. Conclusion: Adjunctive SJPs enhance the effectiveness of short-term conventional anti-angina treatment for patients with CCS who experience intolerance to long-acting nitrates, without significant adverse effects during application. Trial registration: Chinese Clinical Trials Registry Platform, ChiCTR2100050066. Registered 16 August 2021, https://www.chictr.org.cn/showproj.html?proj=131470. [ABSTRACT FROM AUTHOR]