Is decreased psoas volume a risk factor for hip fracture? A comparative study of patients with and without hip fractures using the exact matching technique.

INTRODUCTION: Sarcopenia is linked to increased fall and hip fracture risk. However, studies often overlook comprehensively controlling for age, sex, bone mineral density (BMD), and body mass index (BMI). Our study aimed to determine if sarcopenia, determined by evaluating the psoas muscle volume, is an independent risk factor for hip fractures. We employed a methodological approach that includes the exact matching technique. METHODS: In this cross-sectional comparative study, we compared the data of patients who sustained hip fractures between 2015 and 2021 with those of a control group from a health screening center in a single center. The study included 545 patients with hip fractures and 1292 without fractures. We collected data on demographics, BMD determined using dual-energy X-ray absorptiometry, and abdominal and pelvic computed tomography (APCT) scans for psoas muscle volume analysis. RESULTS: The analysis after exact matching of 266 pairs revealed that psoas volume/height2 was the most significant and dominant risk factor among the evaluated indices. Multivariate logistic regression analysis, adjusting for age, sex, BMI, and BMD, identified height or height2-adjusted psoas muscle volume as an independent risk factor for hip fractures (p = 0.042 and p = 0.002, respectively). Age, female sex, lower BMI, and lower BMD were associated with an increased risk of hip fractures. CONCLUSION: Decreased psoas muscle volume adjusted for patient height independently predicts hip fracture risk. Psoas volume assessment via APCT is a practical tool for identifying at-risk individuals, emphasizing the necessity of including sarcopenia in hip fracture risk assessments.

Effect of various storage media on the physicochemical properties of plasma-treated dental zirconia.

This study investigated the effect of various storage media on the physicochemical properties of plasma-treated 3-mol% yttria-stabilized tetragonal zirconia: air, vacuum, deionized water (DIW), and plasma-activated water (PAW). Each group was divided into five subgroups based on storage periods: immediately after NTP irradiation (T0), and after 1 week (T1), 2 weeks (T2), 3 weeks (T3), and 4 weeks (T4). The control group (C) received no treatment. The storage groups were monitored weekly using various analytical techniques, including contact angle measurements, scanning electron microscopy (SEM), focused ion beam (FIB)-SEM, confocal laser scanning microscopy (CLSM), x-ray photoelectron spectroscopy (XPS), and x-ray diffraction (XRD). Our results demonstrate that plasma-treated zirconia surfaces stored in DIW retained or even increased their hydrophilicity due to the formation of hydrogen bonds and preservation of nitrogen functionalities. In contrast, surfaces stored in air exhibited significant hydrophobic recovery. FIB-SEM analysis showed no adverse internal structural changes regardless of storage medium. The roughness of the zirconia surface slightly increased after plasma treatment and was generally retained across all storage groups for 4 weeks, except for the air storage group. This study concludes that storage in DIW effectively preserves the enhanced surface properties of plasma-activated zirconia for up to 4 weeks.

Deep learning-based analysis of EGFR mutation prevalence in lung adenocarcinoma H&E whole slide images.

EGFR mutations are a major prognostic factor in lung adenocarcinoma. However, current detection methods require sufficient samples and are costly. Deep learning is promising for mutation prediction in histopathological image analysis but has limitations in that it does not sufficiently reflect tumor heterogeneity and lacks interpretability. In this study, we developed a deep learning model to predict the presence of EGFR mutations by analyzing histopathological patterns in whole slide images (WSIs). We also introduced the EGFR mutation prevalence (EMP) score, which quantifies EGFR prevalence in WSIs based on patch-level predictions, and evaluated its interpretability and utility. Our model estimates the probability of EGFR prevalence in each patch by partitioning the WSI based on multiple-instance learning and predicts the presence of EGFR mutations at the slide level. We utilized a patch-masking scheduler training strategy to enable the model to learn various histopathological patterns of EGFR. This study included 868 WSI samples from lung adenocarcinoma patients collected from three medical institutions: Hallym University Medical Center, Inha University Hospital, and Chungnam National University Hospital. For the test dataset, 197 WSIs were collected from Ajou University Medical Center to evaluate the presence of EGFR mutations. Our model demonstrated prediction performance with an area under the receiver operating characteristic curve of 0.7680 (0.7607-0.7720) and an area under the precision-recall curve of 0.8391 (0.8326-0.8430). The EMP score showed Spearman correlation coefficients of 0.4705 (p = 0.0087) for p.L858R and 0.5918 (p = 0.0037) for exon 19 deletions in 64 samples subjected to next-generation sequencing analysis. Additionally, high EMP scores were associated with papillary and acinar patterns (p = 0.0038 and p = 0.0255, respectively), whereas low EMP scores were associated with solid patterns (p = 0.0001). These results validate the reliability of our model and suggest that it can provide crucial information for rapid screening and treatment plans.

Electrostatic attachment of exosome onto a 3D-fabricated calcium silicate/polycaprolactone for enhanced bone regeneration.

Exosomes have garnered attention for use in bone regeneration, but their low activity, rapid degradation, and inaccurate delivery have been obstacles to their use in clinical applications. As such, there exists a need for an exosome-integrated delivery platform. Calcium silicate (Ca-Si) is considered one of the most promising bioceramics for bone regeneration because of its remarkable ability to promote hydroxyapatite formation, osteoblast proliferation, and differentiation. However, Ca-Si has limitations, such as a high degradation rate leading to high pH values. Here, we propose a bone regeneration platform: three-dimensional-fabricated Ca-Si scaffolds immersed in polycaprolactone (PCL) coated with exosomes. This setup enhanced porosity, mechanical strength, and natural hydroxyapatite formation. Ca-Si incorporation increased the quantity of attached exosomes on the scaffold and enabled more sustainable control of their release compared to bare PCL. The exosome-coated scaffold exhibited excellent cell attachment and osteogenic differentiation, significantly increasing biocompatibility and the in situ recruitment of stem cells when transplanted into the subcutaneous tissue of mice. The bone regenerating efficacy of the exosome-attached scaffold was confirmed using a mouse calvarial bone defect animal model. These findings suggest a potential application of exosome-coated Ca-Si/PCL scaffolds as an osteogenic platform for critical bone defects.

A novel liquid plasma derivative inhibits melanogenesis through upregulation of Nrf2.

Non-thermal plasma (NTP) is an emerging technology with extensive applications in biomedicine, including treatment of abnormal pigmentation. However, very few studies have investigated how plasma induces anti-melanogenesis. Here, liquid plasma was prepared by treating an NTP jet with helium and oxygen (as carrier gases) for 15 min in serum-free culture media. In the zebrafish model, pigmentation ratio was observed with or without liquid plasma. The anti-melanogenic effect of liquid plasma was evaluated in human melanocytes by assessing the expression of melanogenesis-related genes using western blotting, RT-PCR, and immunohistochemistry. Liquid plasma reduced pigmentation in the zebrafish model and inhibited melanin synthesis in primary human melanocytes. Intracellular reactive oxygen species levels decreased and Nrf2 expression increased in liquid plasma-treated melanocytes. Liquid plasma affected microphthalmia-associated transcription factor (MITF) and tyrosinase mRNA and protein levels, tyrosinase activity, and melanin content. Considering the role of Wnt/ß-catenin and PI3K/Akt pathways in melanogenesis, the effect of liquid plasma on this pathway was determined; liquid plasma decreased active ß-catenin, LEF1/TCF4, MITF, and tyrosinase levels in a time-dependent manner and inhibited the nuclear translocation of ß-catenin. This inhibition subsequently suppressed melanogenesis by downregulating MITF and tyrosinase. These results suggest that liquid plasma may be used for treating pigmentary disorders.

Non-thermal atmospheric pressure plasma induces selective cancer cell apoptosis by modulating redox homeostasis.

BACKGROUND: Anticancer treatments aim to selectively target cancer cells without harming normal cells. While non-thermal atmospheric pressure plasma (NTAPP) has shown anticancer potential across various studies, the mechanisms behind its selective action on cancer cells remain inadequately understood. This study explores the mechanism of NTAPP-induced selective cell death and assesses its application in cancer therapy. METHODS: We treated HT1080 fibrosarcoma cells with NTAPP and assessed the intracellular levels of mitochondria-derived reactive oxygen species (ROS), mitochondrial function, and cell death mechanisms. We employed N-acetylcysteine to investigate ROS's role in NTAPP-induced cell death. Additionally, single-cell RNA sequencing was used to compare gene expression in NTAPP-treated HT1080 cells and human normal fibroblasts (NF). Western blotting and immunofluorescence staining examined the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2), a key antioxidant gene transcription factor. We also evaluated autophagy activity through fluorescence staining and transmission electron microscopy. RESULTS: NTAPP treatment increased ROS levels and induced mitochondrial dysfunction, leading to apoptosis in HT1080 cells. The involvement of ROS in selective cancer cell death was confirmed by N-acetylcysteine treatment. Distinct gene expression patterns were observed between NTAPP-treated NF and HT1080 cells, with NF showing upregulated antioxidant gene expression. Notably, NRF2 expression and nuclear translocation increased in NF but not in HT1080 cells. Furthermore, autophagy activity was significantly higher in normal cells compared to cancer cells. CONCLUSIONS: Our study demonstrates that NTAPP induces selective cell death in fibrosarcoma cells through the downregulation of the NRF2-induced ROS scavenger system and inhibition of autophagy. These findings suggest NTAPP's potential as a cancer therapy that minimizes damage to normal cells while effectively targeting cancer cells.

Development of a multi-modal learning-based lymph node metastasis prediction model for lung cancer.

PURPOSE: This study proposed a three-dimensional (3D) multi-modal learning-based model for the automated prediction and classification of lymph node metastasis in patients with non-small cell lung cancer (NSCLC) using computed tomography (CT) images and clinical information. METHODS: We utilized clinical information and CT image data from 4239 patients with NSCLC across multiple institutions. Four deep learning algorithm-based multi-modal models were constructed and evaluated for lymph node classification. To further enhance classification performance, a soft-voting ensemble technique was applied to integrate the outcomes of multiple multi-modal models. RESULTS: A comparison of the classification performance revealed that the multi-modal model, which integrated CT images and clinical information, outperformed the single-modal models. Among the four multi-modal models, the Xception model demonstrated the highest classification performance, with an area under the curve (AUC) of 0.756 for the internal test dataset and 0.736 for the external validation dataset. The ensemble model (SEResNet50_DenseNet121_Xception) exhibited even better performance, with an AUC of 0.762 for the internal test dataset and 0.751 for the external validation dataset, surpassing the multi-modal model's performance. CONCLUSIONS: Integrating CT images and clinical information improved the performance of the lymph node metastasis prediction models in patients with NSCLC. The proposed 3D multi-modal lymph node prediction model can serve as an auxiliary tool for evaluating lymph node metastasis in patients with non-pretreated NSCLC, aiding in patient screening and treatment planning.

Comparison of bone turnover suppression in atypical femoral fractures and osteoporotic hip fractures.

We aimed to compare the extent of bone turnover suppression between patients with atypical femoral fractures (AFFs) and osteoporotic hip fractures (typical femur fractures, TFFs) using a one-to-one matching strategy. A single-center retrospective comparison of females aged ≥ 60 years who underwent operative treatment for AFFs and TFFs between January 2010 and March 2021 was conducted. Demographic characteristics and clinical data including fracture site, past medical history, bone mineral density (BMD), bisphosphonate (BP) medication history, and serum bone turnover marker (BTM) levels were examined. Moreover, we performed a logistic regression analysis to determine the risk factors for AFFs and a one-to-one matched-pair analysis to compare various BTMs. Overall, 336 consecutive females were included: 113 with AFFs and 213 with TFFs. The mean age, BMI, and lowest BMD T-score were 78.6 years, 22.8 kg/m2, and -3.3, respectively. Patients with AFF were younger, had lower BMD, higher BMI, higher prevalence of rheumatoid arthritis, a greater proportion with previous steroid or BP use, and a longer history of BP use than patients with TFF. The 48:48 matched-pair analysis revealed higher serum 25(OH) vitamin-D (30.5 vs 18.2 ng/mL, P < 0.001) and calcium levels (8.8 vs 8.3 ng/dL, P = 0.009) and lower serum CTX levels (0.33 vs 0.54 ng/mL, P = 0.010) in the AFF group than in the TFF group, suggesting a more suppressed bone remodeling. No differences in the other BTM levels were found. Despite identical histories and durations of BP use, the AFF group exhibited lower CTX levels, suggesting more suppressed bone remodeling. This observation leads us to infer that more suppressed bone remodeling, indicated by lower CTX levels, could be linked to the occurrence of AFFs.

Clinical application of whole-genome sequencing of solid tumors for precision oncology.

Genomic alterations in tumors play a pivotal role in determining their clinical trajectory and responsiveness to treatment. Targeted panel sequencing (TPS) has served as a key clinical tool over the past decade, but advancements in sequencing costs and bioinformatics have now made whole-genome sequencing (WGS) a feasible single-assay approach for almost all cancer genomes in clinical settings. This paper reports on the findings of a prospective, single-center study exploring the real-world clinical utility of WGS (tumor and matched normal tissues) and has two primary objectives: (1) assessing actionability for therapeutic options and (2) providing clarity for clinical questions. Of the 120 patients with various solid cancers who were enrolled, 95 (79%) successfully received genomic reports within a median of 11 working days from sampling to reporting. Analysis of these 95 WGS reports revealed that 72% (68/95) yielded clinically relevant insights, with 69% (55/79) pertaining to therapeutic actionability and 81% (13/16) pertaining to clinical clarity. These benefits include the selection of informed therapeutics and/or active clinical trials based on the identification of driver mutations, tumor mutational burden (TMB) and mutational signatures, pathogenic germline variants that warrant genetic counseling, and information helpful for inferring cancer origin. Our findings highlight the potential of WGS as a comprehensive tool in precision oncology and suggests that it should be integrated into routine clinical practice to provide a complete image of the genomic landscape to enable tailored cancer management.

A recent update on the fixation techniques for femoral neck fractures: A narrative review.

Femoral neck fractures present significant challenges in orthopedic surgery, particularly due to technical difficulties and a high complication rate. Surgical intervention is generally recommended, with osteosynthesis and arthroplasty being the main treatment options. Osteosynthesis techniques, including dynamic hip screw (DHS), multiple cannulated screws (MCS), and the femoral neck system (FNS), aim to achieve stable fixation and facilitate fracture healing. Factors influencing the choice of osteosynthesis include fracture displacement, bone quality, patient age, and the presence of posterior tilt. While DHS offers high stability, MCS is preferred in stable type fractures with minimal invasive procedures. FNS, a newer technique, combines the advantages of DHS and MCS, providing strong fixation with minimal soft tissue damage. Considering the comprehensive findings of biomechanical and clinical studies to date, when performing osteosynthesis for unstable femoral neck fractures, caution should be exercised with MCS as it may have slightly inadequate fixation strength compared to DHS and FNS. FNS, being the newest technique, demonstrates superior fixation strength comparable to DHS and is as minimally invasive as MCS. However, it is essential to remember that long-term follow-up results are lacking for FNS.

An epidermal growth factor receptor-targeting immunotoxin based on IgG shows potent antitumor activity against head and neck cancer.

The epidermal growth factor receptor (EGFR) is an important target for cancer therapies. Many head and neck cancer (HNC) cells have been reported to overexpress EGFR; therefore, anti-EGFR therapies have been attempted in patients with HNC. However, its clinical efficacy is limited owing to the development of drug resistance. In this study, we developed an EGFR-targeting immunotoxin consisting of a clinically proven anti-EGFR IgG (cetuximab; CTX) and a toxin fragment (LR-LO10) derived from Pseudomonas exotoxin A (PE) using a novel site-specific conjugation technology (peptide-directed photo-crosslinking reaction), as an alternative option. The immunotoxin (CTX-LR-LO10) showed specific binding to EGFR and properties of a typical IgG, such as stability, interactions with receptors of immune cells, and pharmacokinetics, and inhibited protein synthesis via modification of elongation factor-2. Treatment of EGFR-positive HNC cells with the immunotoxin resulted in apoptotic cell death and the inhibition of cell migration and invasion. The efficacy of CTX-LR-LO10 was evaluated in xenograft mouse models, and the immunotoxin exhibited much stronger tumor suppression than CTX or LR-LO10. Transcriptome analyses revealed that the immunotoxins elicited immune responses and altered the expression of genes related to its mechanisms of action. These results support the notion that CTX-LR-LO10 may serve as a new therapeutic agent targeting EGFR-positive cancers.

Which interbody device minimized nonunion, subsidence, and reoperation after anterior cervical discectomy and fusion? A systematic review and meta-analysis comparing allograft versus polyetheretherketone cage.

OBJECTIVE: Nonunion and significant subsidence after anterior cervical discectomy and fusion (ACDF) are associated with poor clinical outcomes, which occasionally lead to revision surgery. Allograft and polyetheretherketone (PEEK) cages are the two most commonly used interbody spacer devices for ACDF. Although studies have been conducted to compare the efficacies of these two interbody materials, the question remains regarding the superiority of one over the other. Therefore, the authors conducted a systematic review and meta-analysis to compare nonunion, subsidence, and reoperation rates after ACDF using allograft and PEEK cages as interbody devices. METHODS: In this systematic review and meta-analysis, the authors systematically searched the MEDLINE, EMBASE, and Cochrane Library databases for studies published prior to November 2023 that compared the efficacy and safety of allograft and PEEK cages for ACDF. A pooled analysis was designed to identify differences in nonunion, subsidence, and reoperation rates between the two interbody devices. RESULTS: Ten studies involving 1462 patients (allograft, 852 patients; PEEK cage, 610 patients) were included. The pooled analysis demonstrated that allograft had a significantly lower rate of nonunion compared to that of PEEK cages (OR 0.33, 95% CI 0.14-0.79; p = 0.01). Furthermore, the reoperation rate due to nonunion was significantly higher with PEEK cages compared to that with allograft (OR 0.28, 95% CI 0.11-0.71; p < 0.01), whereas the reoperation rate due to overall causes did not display significant results (OR 0.38, 95% CI 0.11-1.29; p = 0.12). The incidence of significant subsidence (OR 0.66, 95% CI 0.28-1.55; p = 0.34) and the mean amount of subsidence (standard mean difference 0.03, 95% CI -0.42 to 0.47; p = 0.90) did not demonstrate significant differences between allograft and PEEK cages. CONCLUSIONS: Overall, the current meta-analysis suggests the advantages of allograft over PEEK cages used for ACDF, due to an enhanced fusion rate and minimized revision risk, with no increase in the risk of subsidence.

Hearing impairment increases the risk of hip fracture-related mortality and recurrent hip fractures: A propensity score matching analysis.

PURPOSE: Despite the ongoing rise in hip fractures and the adverse effects of hearing impairment (HI) on increased mortality and morbidity, research addressing the influence of HI on mortality risk or complications in patients with hip fractures remains absent. This study aimed to analyze the effects of HI on mortality and treatment outcomes among patients with hip fracture. METHODS: We retrospectively collected data from consecutive patients diagnosed with hip fractures between January 2007 and March 2022 who had auditory examination records. From the initially enrolled 265 patients, data for 58 with HI and 58 without HI (control group) were extracted using a 1:1 propensity score matching. The primary outcome included comparison of mortality rates, and the secondary outcome encompassed the comparison of postoperative medical and surgical complications. RESULTS: The 1-year cumulative mortality rate was not significantly different between the HI and control groups, but the overall cumulative mortality rate was significantly higher in the HI than in the control group (63.0 % and 48.6, respectively; P = 0.046) in a follow-up period of up to 16 years. The HI group had a significantly higher incidence of "second hip fractures due to falls" than the control group (P = 0.016), although no differences in other medical and surgical complications were revealed. CONCLUSIONS: Awareness of the long-term risk of higher mortality when managing patients with hip fracture and HI is important. To reduce the risk of second hip fractures, paying more attention to fall prevention education and taking a more proactive approach, especially for those with HI.

What is the Optimal Nail Length to Treat Osteoporotic Subtrochanteric Fractures? A Finite Element Analysis.

Background: Operative management with intramedullary nail fixation remains the definitive treatment of choice for osteoporotic subtrochanteric (ST) fractures; however, there remains no consensus regarding the proper nail length. We aimed to use 3-dimensional finite element (FE) analysis to determine the optimal nail length for the safe fixation of osteoporotic ST fractures. Methods: Nine modes of FE models were constructed using 9 different lengths of cephalomedullary nails (short nails: 170, 180, and 200 mm; long nails: 280, 300, 320, 340, 360, and 380 mm) from the same company. The interfragmentary motion was analyzed. Additionally, the peak von Mises stress (PVMS) in the cortical bone, cancellous bone of the femoral head, and the nail were measured, and the yielding risk for each subject was investigated. Results: Long nails were associated with less interfragmentary motion. In the cortical bone, the PVMS of short nails was observed at the distal locking screw holes of the femoral medial cortex; however, in long nails, the PVMS was observed at the lag screw holes on the lateral cortex. The mean yielding risk of long nails was 40.1% lower than that of short nails. For the cancellous bone of the femoral head, the PVMS in all 9 FE models was in the same area: at the apex of the femoral head. There was no difference in the yielding risk between short and long nails. For implants, the PVMS was at the distal locking screw hole of the nail body in the short nails and the nail body at the fracture level in the long nails. The mean yielding risk was 74.9% lower for long nails than that for short nails. Conclusions: Compared to short nails, long nails with a length of 320 mm or more showed less interfragmentary motion and lower yielding risk in low-level osteoporotic ST fractures. The FE analysis supports long nails as a safer option than short nails, especially for treating transverse-type low-level osteoporotic ST fractures.

Clinical and Radiological Outcomes of Computer-Assisted Navigation in Primary Total Knee Arthroplasty for Patients with Extra-articular Deformity: Systematic Review and Meta-Analysis.

Background: Computer-assisted navigation surgery (CAS) during primary total knee arthroplasty (TKA) may help improve outcomes for patients with extra-articular deformity (EAD); however, this has not been extensively studied. Therefore, we aimed to investigate the clinical and radiological outcomes following primary TKA using CAS in patients with EAD. Methods: We searched Medline, Embase, and the Cochrane Library up to March 3, 2023 for studies investigating surgical outcomes of using the navigation system for TKA to treat patients with EAD. From 14 studies, 539 knees with EAD that underwent navigation TKA were enrolled. We investigated the knee range of motion (ROM), outcome scores at final follow-up (Knee Society Score [KSS] and Knee Functional Score [KFS]), and pre- and postoperative mechanical hip-knee-ankle (mHKA) angle using lower extremity scanogram. The meta-analysis was based on the single-arm method, and all data were pooled using a random-effects model. Results: Following our meta-analyses, the mean knee ROM changed from 87.0° (95% confidence interval [CI], 75.9°-98.1°) preoperatively to 109.4° (95% CI, 97.9°-120.8°) postoperatively. The adjusted KSS was 93.45 points (95% CI, 88.36-98.54 points), and the adjusted KFS was 91.57 points (95% CI, 86.80-96.33 points) in knees with EAD that underwent CAS-TKA. As a radiological outcome, the mHKA angle changed from 169.53° (95% CI, 166.90°-172.16°) preoperatively to 178.81° (95% CI, 178.31°-179.30°) postoperatively. Conclusions: CAS-TKA yielded positive clinical results and demonstrated a satisfactory alignment of the lower limb's mechanical axis. CAS-TKA showed promise for primary TKA procedures, demonstrating favorable clinical and radiological outcomes even in complex cases involving EAD.

Development and validation of a reliable method for automated measurements of psoas muscle volume in CT scans using deep learning-based segmentation: a cross-sectional study.

OBJECTIVES: We aimed to develop an automated method for measuring the volume of the psoas muscle using CT to aid sarcopenia research efficiently. METHODS: We used a data set comprising the CT scans of 520 participants who underwent health check-ups at a health promotion centre. We developed a psoas muscle segmentation model using deep learning in a three-step process based on the nnU-Net method. The automated segmentation method was evaluated for accuracy, reliability, and time required for the measurement. RESULTS: The Dice similarity coefficient was used to compare the manual segmentation with automated segmentation; an average Dice score of 0.927 ± 0.019 was obtained, with no critical outliers. Our automated segmentation system had an average measurement time of 2 min 20 s ± 20 s, which was 48 times shorter than that of the manual measurement method (111 min 6 s ± 25 min 25 s). CONCLUSION: We have successfully developed an automated segmentation method to measure the psoas muscle volume that ensures consistent and unbiased estimates across a wide range of CT images.

The Impact of Polymers on Enzalutamide Solid Self-Nanoemulsifying Drug Delivery System and Improved Bioavailability.

Enzalutamide (ENZ), marketed under the brand name Xtandi® as a soft capsule, is an androgen receptor signaling inhibitor drug actively used in clinical settings for treating prostate cancer. However, ENZ's low solubility and bioavailability significantly hinder the achievement of optimal therapeutic outcomes. In previous studies, a liquid self-nanoemulsifying drug delivery system (L-SNEDDS) containing ENZ was developed among various solubilization technologies. However, powder formulations that included colloidal silica rapidly formed crystal nuclei in aqueous solutions, leading to a significant decrease in dissolution. Consequently, this study evaluated the efficacy of adding a polymer as a recrystallization inhibitor to a solid SNEDDS (S-SNEDDS) to maintain the drug in a stable, amorphous state in aqueous environments. Polymers were selected based on solubility tests, and the S-SNEDDS formulation was successfully produced via spray drying. The optimized S-SNEDDS formulation demonstrated through X-ray diffraction and differential scanning calorimetry data that it significantly reduced drug crystallinity and enhanced its dissolution rate in simulated gastric and intestinal fluid conditions. In an in vivo study, the bioavailability of orally administered formulations was increased compared to the free drug. Our results highlight the effectiveness of solid-SNEDDS formulations in enhancing the bioavailability of ENZ and outline the potential translational directions for oral drug development.

Blunted cardiovascular responses to exercise by inhibiting afferent feedback via spinal cord stimulation in heart failure.

This case study investigated the impact of SCS on alterations in blood pressure during constant-load exercise in a female patient with heart failure. Three different SCS frequencies [No SCS (~0 Hz), Low SCS (~100 Hz), and High SCS (~1000 Hz)] with and without ischaemic stimulation of the legs (cuffs) were randomly applied during constant-load exercise. To determine cardiovascular and ventilatory responses to exercise following SCS frequencies, BP, heart rate (HR), and respiratory gas exchange were measured. This experiment was duplicated in visit 1 and visit 2 with a random application of SCS frequency order and the data were averaged. There were no significant differences among three frequencies with no leg ischaemia. However, High SCS demonstrated lower BP, HR, and respiratory gas exchange relative to No SCS and Low SCS. SCS may be effective in improving cardiovascular and ventilatory responses in HF and high-frequency stimulation provides more clinical benefit; however, further studies are needed.