Isobavachalcone enhances sensitivity of colistin-resistant Klebsiella pneumoniae: in vitro and in vivo proof-of-concept studies.

Antibiotic resistance poses a considerable worldwide concern, particularly in clinical environments where drug-resistant Gram-negative bacteria like Klebsiella pneumoniae present a major challenge. The objective of this research was to investigate the mechanisms by which isobavachalcone (IBC) restores the sensitivity of K. pneumoniae to colistin in vitro and to validate the synergistic therapeutic effect in vivo. The results indicate that the combined administration of colistin and IBC exhibits a potent antibacterial effect both in vitro and in vivo. The in vitro concurrent administration of colistin and IBC resulted in increased membrane permeability, compromised cell integrity, diminished membrane fluidity, and disrupted membrane homeostasis. Additionally, this combination reduced biofilm production, inhibited the synthesis of the AI-2 factor, altered membrane potential, and affected levels of reactive oxygen species and adenosine triphosphate synthesis, ultimately leading to bacterial death. In vivo experiments on Galleria mellonella and mice demonstrated that the co-administration of colistin and IBC increased the survival rate and significantly reduced pathological damage compared to colistin alone. These results suggested that IBC effectively restores the sensitivity of colistin by inducing physical disruption of bacterial membranes and oxidative stress. The combination therapy of colistin and IBC presents a viable and safe strategy to combat drug-resistant K. pneumoniae-associated infections.

Enhanced anti-inflammatory activity of chlorogenic acid via folic acid-TPGS-modified liposomes encapsulation: characterization and In vivo evaluation on colitis mice.

Introduction: Chlorogenic acid (CGA) has been identified to possess salient anti-inflammatory, antioxidant, and anticancer attributes. However, its application is limited by its instability and low bioavailability. Liposomes have been considered effective pharmaceutical delivery vehicles due to their ability to continuously release loaded drugs, improve drug stability, and display good biocompatibility. They can be easily modified by other small molecules to acquire additional biological functions. In this study, we developed and characterized folic acid-TPGS-modified chlorogenic acid liposome (FTCLP) and evaluated its anti-inflammatory activity. Methods: The successful encapsulation of CGA within FTCLP was confirmed through examination using electron microscopy, fourier-transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). The in vitro release characteristics of FTCLP were evaluated using the dialysis bag membrane method. Meanwhile, a dextran sulfate sodium (DSS) -induced colitis model was employed to investigate the anti-inflammatory effect of FTCLP and its mechanism. Results: The FTCLP exhibited an encapsulation efficiency (EE) of 84.85 ± 1.20% and a drug loading (DL) of 11.67 ± 0.04%. The particle size of FTCLP was determined to be 150.63 ± 0.71 nm, with a polydispersity index (PDI) of 0.198 ± 0.02 and a zeta potential of 2.61 ± 0.38 mV. The in vitro release profile followed the Higuchi model, indicating sustained-release characteristics. The in vivo study demonstrated that FTCLP treatment was effective in improving the symptoms of DSS-induced inflammatory response, as evidenced by mitigation of weight loss, reduction in the disease activity index (DAI) score, restoration of colon length, and attenuation of colon tissue damage. Furthermore, the levels of pro-inflammatory cytokines, including interferon-gamma (INF-γ), interleukin-1 beta (IL-1ß), and interleukin-6 (IL-6), were markedly diminished in both the serum and colon tissue. FTCLP was also observed to suppress the expression of INF-γ, IL-1ß, IL-6, tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κB) p65, while concomitantly upregulating the expression of Janus kinase (JAK) and signal transducer and activator of transcription 3 (STAT3). Besides, the administration of FTCLP was found to result in an increase in the abundance of Lactobacillaceae and Peptostreptococcaceae, while decreasing the abundance of Bacteroidaceae, Rikenellaceae, and Helicobacteraceae. Conclusion: Following encapsulation of CGA within liposomes, FTCLP revealed favorable stability and sustained release properties, and enhanced the anti-inflammatory effects by modulating multiple inflammation-related biomarkers. FTCLP has the potential to be a safe and effective drug for targeted therapy of colitis.

Fabrication and characterization of TPGS-modified chlorogenic acid liposomes and its bioavailability in rats.

Chlorogenic acid (CGA), a polyphenol compound, exhibits excellent anti-oxidative, anti-hypoxic, antibacterial, antiviral, and anti-inflammatory activities, however the bioactivity of it has not been fully utilized in vivo due to its instability and low bioavailability. To address these issues, we prepared and characterized CGA-TPGS-LP, which is a TPGS-modified liposome loaded with CGA. The pharmacokinetics of CGA-TPGS-LP were studied in rats after oral administration. CGA-TPGS-LP was fabricated using a combination of thin film dispersion and ion-driven methods. The liposomes were observed to be uniformly small and spherical in shape. Their membranes were composed of lecithin, cholesterol, and TPGS lipophilic head with a TPGS hydrophilic tail chain coating on its surface. The loading efficiency and encapsulation efficiency were found to be 11.21% and 83.22%, respectively. The physicochemical characterisation demonstrated that the CGA was present in an amorphous form and retained its original structural state within the liposomal formulation. The stability of CGA was significantly improved by fabricating TPGS-LP. CGA-TPGS-LP exhibited good sustained-release properties in both simulated gastric and intestinal fluids. Following oral administration, ten metabolites were identified in rat plasma using UPLC-QTOF-MS. UPLC-QqQ-MS/MS quantitative analysis demonstrated that the oral bioavailability of CGA encapsulated in TPGS-modified liposomes was enhanced by 1.52 times. In addition, the three main metabolites of CGA had higher plasma concentrations and slower degradation rate. These results demonstrate that TPGS-modified liposomes could be a feasible strategy to further enhance the oral bioavailability of CGA, facilitating its clinical use.

Sample size calculation for mixture cure model with restricted mean survival time as a primary endpoint.

It is not uncommon for a substantial proportion of patients to be cured (or survive long-term) in clinical trials with time-to-event endpoints, such as the endometrial cancer trial. When designing a clinical trial, a mixture cure model should be used to fully consider the cure fraction. Previously, mixture cure model sample size calculations were based on the proportional hazards assumption of latency distribution between groups, and the log-rank test was used for deriving sample size formulas. In real studies, the latency distributions of the two groups often do not satisfy the proportional hazards assumptions. This article has derived a sample size calculation formula for a mixture cure model with restricted mean survival time as the primary endpoint, and did simulation and example studies. The restricted mean survival time test is not subject to proportional hazards assumptions, and the difference in treatment effect obtained can be quantified as the number of years (or months) increased or decreased in survival time, making it very convenient for clinical patient-physician communication. The simulation results showed that the sample sizes estimated by the restricted mean survival time test for the mixture cure model were accurate regardless of whether the proportional hazards assumptions were satisfied and were smaller than the sample sizes estimated by the log-rank test in most cases for the scenarios in which the proportional hazards assumptions were violated.

Time-varying effect in older patients with early-stage breast cancer: a model considering the competing risks based on a time scale.

Background: Patients with early-stage breast cancer may have a higher risk of dying from other diseases, making a competing risks model more appropriate. Considering subdistribution hazard ratio, which is used often, limited to model assumptions and clinical interpretation, we aimed to quantify the effects of prognostic factors by an absolute indicator, the difference in restricted mean time lost (RMTL), which is more intuitive. Additionally, prognostic factors of breast cancer may have dynamic effects (time-varying effects) in long-term follow-up. However, existing competing risks regression models only provide a static view of covariate effects, leading to a distorted assessment of the prognostic factor. Methods: To address this issue, we proposed a dynamic effect RMTL regression that can explore the between-group cumulative difference in mean life lost over a period of time and obtain the real-time effect by the speed of accumulation, as well as personalized predictions on a time scale. Results: A simulation validated the accuracy of the coefficient estimates in the proposed regression. Applying this model to an older early-stage breast cancer cohort, it was found that 1) the protective effects of positive estrogen receptor and chemotherapy decreased over time; 2) the protective effect of breast-conserving surgery increased over time; and 3) the deleterious effects of stage T2, stage N2, and histologic grade II cancer increased over time. Moreover, from the view of prediction, the mean C-index in external validation reached 0.78. Conclusion: Dynamic effect RMTL regression can analyze both dynamic cumulative effects and real-time effects of covariates, providing a more comprehensive prognosis and better prediction when competing risks exist.

Dynamic Microcirculation Characteristics of Plantar Skin Under Metatarsal Head of Human Foot in Response to Life-Like Pressure Stimulus.

OBJECTIVE: Diabetic foot ulcer (DFU) is a severe complication with high mortality. High plantar pressure and poor microcirculation are considered main causes of DFU. The specific aims were to provide a novel technique for real-time measurement of plantar skin blood flow (SBF) under walking-like pressure stimulus and delineate the first plantar metatarsal head dynamic microcirculation characteristics because of life-like loading conditions in healthy individuals. METHODS: Twenty young healthy participants (14 male and 6 female) were recruited. The baseline (i.e., unloaded) SBF of soft tissue under the first metatarsal head were measured using laser Doppler flowmetry (LDF). A custom-made machine was utilized to replicate daily walking pressure exertion for 5 min. The exerted plantar force was adjusted from 10 N (127.3 kPa) to 40 N (509.3 kPa) at an increase of 5 N (63.7 kPa). Real-time SBF was acquired using the LDF. After each pressure exertion, postload SBF was measured for comparative purposes. Statistical analysis was performed using the R software. RESULTS: All levels of immediate-load and postload SBF increased significantly compared with baseline values. As the exerted load increased, the postload and immediate-load SBF tended to increase until the exerted load reached 35 N (445.6 kPa). However, in immediate-load data, the increasing trend tended to level off as the exerted pressure increased from 15 N (191.0 kPa) to 25 N (318.3 kPa). For postload and immediate-load SBF, they both peaked at 35 N (445.6 kPa). However, when the exerted force exceeds 35 N (445.6 kPa), both the immediate-load and postload SBF values started to decrease. CONCLUSIONS: Our study offered a novel real-time plantar soft tissue microcirculation measurement technique under dynamic conditions. For the first metatarsal head of healthy people, 20 N (254.6 kPa)-plantar pressure has a fair microcirculation stimulus compared with higher pressure. There might be a pressure threshold at 35 N (445.6 kPa) for the first metatarsal head, and soft tissue microcirculation may decrease when local pressure exceeds it.

Comparison of gasless transaxillary endoscopic thyroidectomy, endoscopic thyroidectomy via areola approach and conventional open thyroidectomy in patients with unilateral papillary thyroid carcinoma.

BACKGROUND: Gasless transaxillary endoscopic thyroidectomy (GTET) and endoscopic thyroidectomy via the areola approach (ETA) have emerged as minimally invasive surgical techniques for managing papillary thyroid carcinoma (PTC). This study aimed to assess the surgical efficacy of endoscopic thyroidectomy (ET) as compared to conventional open thyroidectomy (COT) in PTC patients. METHODS: Between 2020 and 2022, 571 PTC patients underwent unilateral thyroidectomy accompanied by ipsilateral central lymph node dissection. This cohort comprised 72 patients who underwent GTET, 105 ETA, and 394 COT. The analysis encompassed a comprehensive examination of patient clinicopathologic characteristics and postoperative complaints. Furthermore, the learning curve of GTET was evaluated using the cumulative summation (CUSUM) method. RESULTS: Patients in the ET group exhibited a lower mean age and a higher proportion of female individuals. Operation time in the ET group was significantly longer. No significant differences were observed in the incidence of postoperative complications among the three groups. With regard to postoperative complaints reported three months after surgery, GTET demonstrated superior alleviation of anterior chest discomfort and swallowing difficulties. Patients who underwent ET reported significantly higher cosmetic satisfaction levels. Additionally, the learning curve of GTET was 27 cases, and the operation time during the mature phase of the learning curve exhibited a significant reduction when compared to ETA. CONCLUSIONS: The findings of this study affirm the safety and feasibility of employing GTET and ETA for the surgical management of PTC. GTET presents an attractive surgical option, particularly for patients with unilateral PTC who place a premium on cosmetic outcomes.

Fingolimod synergizes and reverses K. pneumoniae resistance to colistin.

Klebsiella pneumoniae (K. pneumoniae) infection and the rapid spread of multi-drug resistant (MDR) bacteria pose a serious threat to global healthcare. Polymyxin E (colistin), a group of cationic antimicrobial polypeptides, is currently one of the last resort treatment options against carbapenem-resistant Gram-negative pathogens. The effectiveness of colistin has been compromised due to its intensive use. This study found that fingolimod (FLD), a natural product derivative, exhibited a significant synergistic bactericidal effect on K. pneumoniae when combined with colistin, both in vitro and in vivo. The checkerboard method was employed to assess the in vitro synergistic effect of FLD with colistin. FLD enhanced the susceptibility of bacteria to colistin and lowered effectively minimum inhibitory concentrations (MIC) when compared to colistin MIC, and the fractional inhibitory concentrations (FIC) value was less than 0.3. The time-kill curve demonstrated that the combination treatment of FLD and colistin had significant bactericidal efficacy. The in vitro concurrent administration of colistin and FLD resulted in heightening membrane permeability, compromising cell integrity, diminishing membrane fluidity, and perturbing membrane homeostasis. They also induced alterations in membrane potential, levels of reactive oxygen species, and adenosine triphosphate synthesis, ultimately culminating in bacterial death. Moreover, the combination of FLD with colistin significantly influenced fatty acid metabolism. In the mouse infection model, the survival rate of mice injected with K. pneumoniae was significantly improved to 67% and pathological damage was significantly relieved with combination treatment of FLD and colistin when compared with colistin treatment. This study highlights the potential of FLD in combining with colistin for treating infections caused by MDR isolates of K. pneumoniae.

Wearable laser Doppler flowmetry for non-invasive assessment of diabetic foot microcirculation: methodological considerations and clinical implications.

Significance: Type 2 diabetes mellitus (T2DM) is a global health concern with significant implications for vascular health. The current evaluation methods cannot achieve effective, portable, and quantitative evaluation of foot microcirculation. Aim: We aim to use a wearable device laser Doppler flowmetry (LDF) to evaluate the foot microcirculation of T2DM patients at rest. Approach: Eleven T2DM patients and twelve healthy subjects participated in this study. The wearable LDF was used to measure the blood flows (BFs) for regions of the first metatarsal head (M1), fifth metatarsal head (M5), heel, and dorsal foot. Typical wavelet analysis was used to decompose the five individual control mechanisms: endothelial, neurogenic, myogenic, respiratory, and heart components. The mean BF and sample entropy (SE) were calculated, and the differences between diabetic patients and healthy adults and among the four regions were compared. Results: Diabetic patients showed significantly reduced mean BF in the neurogenic (p=0.044) and heart (p=0.001) components at the M1 and M5 regions (p=0.025) compared with healthy adults. Diabetic patients had significantly lower SE in the neurogenic (p=0.049) and myogenic (p=0.032) components at the M1 region, as well as in the endothelial (p<0.001) component at the M5 region and in the myogenic component at the dorsal foot (p=0.007), compared with healthy adults. The SE in the myogenic component at the dorsal foot was lower than at the M5 region (p=0.050) and heel area (p=0.041). Similarly, the SE in the heart component at the dorsal foot was lower than at the M5 region (p=0.017) and heel area (p=0.028) in diabetic patients. Conclusions: This study indicated the potential of using the novel wearable LDF device for tracking vascular complications and implementing targeted interventions in T2DM patients.

A Joy-Stick Assistant Three-Dimensional Modified Technique of Minimally Invasive Surgery for Mild or Moderate Hallux Valgus.

BACKGROUND: Minimally invasive surgery (MIS) such as minimally invasive chevron osteotomy and Akin osteotomy (MICA) has become popular in the treatment of hallux valgus. However, how to correct three-dimensional deformities in hallux valgus effectively and simply in MICA is still difficult. Special equipment is required in MICA as has been reported before. It is meaningful and necessary to reduce the reliance on special equipment in MICA. METHODS: From January 2021 to July 2022, patients with mild or moderate hallux valgus were treated with a joy-stick assistant three-dimensional modified technique (Joy-stick 3D technique) of MIS. VAS, AOFAS Hallux MTP-IP scores, hallux valgus angle (HVA), intermetatarsal angle (IMA), and distal metatarsal articular angle (DMAA) were measured pre- and postoperatively at the last follow-up of at least 6 months. Scores and radiologic angles were compared using paired sample t-test. RESULTS: A total of 36 cases were included. HVA, IMA, and DMAA were (22.3 ± 6.1)°, (14.0 ± 3.2)°, and (8.9 ± 3.2)° preoperatively, and decreased to (7.0 ± 1.8)°, (3.7 ± 1.0)°, and (3.3 ± 1.1)° postoperatively. VAS decreased from 4.3 ± 1.7 to 0.7 ± 0.7. AOFAS Hallux MTP-IP scores improved from 68.6 ± 7.6 to 92.9 ± 6.1. Comparing mild and moderate cases, though HVA, IMA, and DMAA were significantly different preoperatively, the angles became statistically similar after surgery. CONCLUSIONS: A joy-stick assistant three-dimensional modified technique is proposed to control the three-dimensional position of the metatarsal head and to reduce dependence on special tools. Mild and moderate hallux valgus deformities are effectively corrected using Joy-stick 3D technique.

Fingolimod Inhibits Exopolysaccharide Production and Regulates Relevant Genes to Eliminate the Biofilm of K. pneumoniae.

Klebsiella pneumoniae (K. pneumoniae) exhibits the ability to form biofilms as a means of adapting to its adverse surroundings. K. pneumoniae in this biofilm state demonstrates remarkable resistance, evades immune system attacks, and poses challenges for complete eradication, thereby complicating clinical anti-infection efforts. Moreover, the precise mechanisms governing biofilm formation and disruption remain elusive. Recent studies have discovered that fingolimod (FLD) exhibits biofilm properties against Gram-positive bacteria. Therefore, the antibiofilm properties of FLD were evaluated against multidrug-resistant (MDR) K. pneumoniae in this study. The antibiofilm activity of FLD against K. pneumoniae was assessed utilizing the Alamar Blue assay along with confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), and crystal violet (CV) staining. The results showed that FLD effectively reduced biofilm formation, exopolysaccharide (EPS), motility, and bacterial abundance within K. pneumoniae biofilms without impeding its growth and metabolic activity. Furthermore, the inhibitory impact of FLD on the production of autoinducer-2 (AI-2) signaling molecules was identified, thereby demonstrating its notable anti-quorum sensing (QS) properties. The results of qRT-PCR analysis demonstrated that FLD significantly decreased the expression of genes associated with the efflux pump gene (AcrB, kexD, ketM, kdeA, and kpnE), outer membrane (OM) porin proteins (OmpK35, OmpK36), the quorum-sensing (QS) system (luxS), lipopolysaccharide (LPS) production (wzm), and EPS production (pgaA). Simultaneously, FLD exhibited evident antibacterial synergism, leading to an increased survival rate of G. mellonella infected with MDR K. pneumoniae. These findings suggested that FLD has substantial antibiofilm properties and synergistic antibacterial potential for colistin in treating K. pneumoniae infections.

MicroRNA-181b-5p Facilitates Thyroid Cancer Growth via Targeting Programmed Cell Death 4.

To explore the potential mechanism of microRNA (miR)-181b-5p promoting the progression of thyroid cancer (TC) by targeting programmed cell death 4 (PDCD4). Analysis of miR-181b-5p and PDCD4 expression in TC was performed. The impact of miR-181b-5p and PDCD4 on proliferation, migration, invasion, and apoptosis of TC cells was examined. The binding relationship between miR-181b-5p and PDCD4 was predicted and verified. miR-181b-5p was up-regulated in TC, while PDCD4 was down-regulated. Down-regulating miR-181b-5p or up-regulating PDCD4 inhibited the proliferation, migration, and invasion of TC cells, and promoted cell apoptosis. PDCD4 was the downstream target of miR-181b-5p, and down-regulation of PDCD4 counteracted the inhibitory effect of down-regulation of miR-181b-5p on the proliferation, migration, and invasion of TC cells and the promoting effect on apoptosis. miR-181b-5p inhibits the proliferation, migration, and invasion of TC cells and promotes cell apoptosis by targeting PDCD4.

The important role of whole-process computed tomography guidance for percutaneous gastrostomy in esophageal cancer patients who are unsuitable for or have had unsuccessful attempts with endoscopic and fluoroscopic gastrostomy.

PURPOSE: To explore the value of clinical application with the whole process computed tomography (CT) guided percutaneous gastrostomy in esophageal tumor patients. MATERIALS AND METHODS: A consecutive series of 32 esophageal tumor patients in whom endoscopic gastrostomy or fluoroscopy guided gastrostomy were considered too dangerous or impossible due to the esophagus complete obstruction, complicate esophageal mediastinal fistula, esophageal trachea fistula or severe heart disease. All of the 32 patients were included in this study from 2 medical center and underwent the gastrostomy under whole process CT guided. RESULTS: All of the gastrostomy procedure was finished successfully under whole process CT guided and the technical success rate was 100%. The average time for each operation was 27 min. No serious complications occurred and the minor complications occurred in 3 patients, including local infection, severe hyperplasia of granulation tissue and tube dislodgment. There were no procedure related deaths. CONCLUSION: The technical success rate of whole process CT guided percutaneous gastrostomy is high and the complication is low. This technique can be used feasible and effectively in some special patients.

The potentially dangerous zone of the dorsomedial cutaneous nerve in minimally invasive surgery for hallux valgus: a cadaveric study.

BACKGROUND: This study aims to describe the distribution of the dorsomedial cutaneous nerve (DMCN) in the middle and proximal parts of the metatarsal from a lateral view. The purpose is to provide guidance to surgeons in protecting the nerve during the 3rd and 4th generation minimally invasive surgery (MIS) for hallux valgus (HV). METHODS: A total of 20 cadaveric feet were dissected to expose the course of the DMCN and sentinel vein. Measurements of the distances between the nerve/vein and the upper border of the metatarsal, as well as the height of the metatarsal, were taken from a lateral view. The distribution area was then described in proportion. RESULTS: At the base of the metatarsal, the DMCN was distributed in the upper 25.7% of the area. When it reached the middle of the metatarsal, the DMCN was distributed in the upper 13.2-47.2% of the area. As for the sentinel vein, it was distributed in the upper 23.5-71.9% and upper 4.1-52.7%, respectively, at these two positions. CONCLUSIONS: The area, which is above the line connecting the upper 1/4 point at the base of the first metatarsal and the 1/2 point at the middle of the first metatarsal, is a dangerous zone for the DMCN. Avoiding the zone is recommended during MIS for HV.

SERS combined with QuEChERS using NBC and Fe3O4 MNPs as cleanup agents to rapidly and reliably detect chlorpyrifos pesticide in citrus.

The surface-enhanced Raman spectroscopy (SERS) technique is being increasingly used for the detection of pesticide residues in agricultural products. However, there are large amounts of fluorescence-producing substances in agricultural products, which seriously affect the Raman signal of the analyte. In this paper, the QuEChERS method was used to remove interfering fluorescent substances in the analyte, and the purification effects of different doses of nano bamboo charcoal (NBC) and Fe3O4 magnetic nanoparticle (Fe3O4 MNP) adsorbents were studied. Meanwhile, the Raman spectral acquisition conditions (AuNPs, test solution, and NaCl) were optimized based on the orthogonal test method. The results showed that 300 µL AuNPs, 40 µL test solution, and 100 µL 1.5% NaCl gave the best SERS response effect. 12.5 mg NBC combined with 10 mg Fe3O4 MNPs could effectively remove the interfering substances from citrus. The Raman spectra of chlorpyrifos molecules were theoretically modeled using density-functional theory (DFT). By comparing the DFT results with the actual tests, five feature peaks, at 338, 522, 558, 672, and 1600 cm-1, were obtained for the detection of chlorpyrifos pesticide residues in citrus. Based on the Raman feature peak intensity at 672 cm-1, the concentration of chlorpyrifos in citrus showed a good linear relationship (R2 = 0.9979) in the concentration range of 3-20 mg kg-1. The recovery rate was 92.12% to 98.38%, and the relative standard deviation (RSD) was 1.77% to 5.29%. The lowest detection concentration was about 3 mg kg-1, and the detection time of a single sample could be completed within 15 min. This study showed that the combination of SERS and QuEChERS preprocessing methods could achieve rapid detection of chlorpyrifos pesticide residues in citrus.

Mid-term assessment of subtalar arthroereisis with Talar-Fit implant in pediatric patients with flexible flatfoot and comparing the difference between different sizes and exploring the position of the inserted implant.

Background: Subtalar arthroereisis (STA) has gained growing acceptance as a viable approach solution for the management of pediatric flexible flatfoot. However, STA still remains controversial. The purpose of this study is to assess the effect of STA using the Talar-Fit implant for treating pediatric flexible flatfoot. Specifically, the aims of the study are as follows: first, to present the mid-term outcomes of STA using the Talar-Fit implant; second, to compare the radiographic and clinical outcomes associated with varying sizes of Talar-Fit implant; and third, to analyze the optimal position of the inserted implants. Methods: A retrospective analysis was conducted on a cohort of 57 pediatric patients diagnosed with flexible flatfoot (77 feet) who underwent STA utilizing Talar-Fit between January 2014 and December 2021. The participants were categorized into five groups according to the size of the implant: Group 8, Group 9, Group 10, Group 11, and Group 12. The evaluation included the assessment of clinical function using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hind foot score, as well as the assessment of radiographic data such as the calcaneal pitch angle (CPA), lateral Meary angle (LMA), talar declination angle (TDA), and medial longitudinal arch angle (MLAA) were evaluated. Furthermore, the position of the inserted implants was also recorded, including angle, depth, and distance. The comparison of pre- and postoperation was conducted using the paired Student's t-test, whereas the analysis of differences among subgroups was performed using the Wilcoxon rank-sum test. A P-value < 0.05 is considered statistically significant. Results: In total, 57 pediatric patients (77 feet) were successfully followed-up for an average period of 26.8 months. The overall AOFAS score significantly improved from 58.6 ± 10.9 to 85.2 ± 8.6 (P < 0.001). Furthermore, the LMA decreased from 20.3° ± 3.6° to 4.5° ± 1.3°, the CPA increased from 14.8° ± 1.6° to 23.6° ± 2.7°(P < 0.05), the TDA decreased from 40.2° ± 2.3° to 25.5° ± 3.2°(P < 0.05), and the MLAA decreased from 140.1° ± 2.8° to 121.4° ± 3.9°(P < 0.05). No statistically significant differences were observed among subgroups regarding the final outcomes. The improvements of CPA, TDA, and MLAA among different groups were significantly different; however, the adjusted P-values were all greater than 0.05. The implant were inserted at a mean angle of 89.5° ± 2.4°, a mean depth of 0.9 mm ± 2.1 mm, and a mean distance of 9.9 mm ± 0.9 mm. Eight patients experienced complications, including six cases of pain occurrence and two cases of implant dislocation. Conclusion: STA with Talar-Fit has demonstrated satisfactory mid-term outcomes. A Talar-Fit with a larger size may demonstrate a superior effect when compared with that of a smaller size. The implants were inserted in a similar position, indicating that the medial edge of the implant may be possible to transcend the midline of the talus neck.

The influence of diabetes and age-related degeneration on body balance control during static standing: a study based on plantar center-of-pressure trajectories and principal component analysis.

BACKGROUND: Aging and diabetes can impair the balance function of the elderly and diabetic patients and increase their fall risk. This study aimed to assess the shaking amplitude of the center-of-pressure (CoP) during static standing, to analyze the effects of aging and diabetes on the balance control. MATERIALS AND METHODS: This cross-sectional observational study, compared the balance performance of 20 healthy younger adults (27.65 ± 5.60 years), 16 healthy older adults (58.88 ± 3.54 years) and 15 diabetic patients (58.33 ± 5.33 years) in four static standing conditions on a force plate: horizontal, anteroposterior (AP), left and right slope planes (5° angles on AP, left and right directions, respectively). The trajectory coordinates of the CoP over time were recorded and analyzed by principal components analysis to obtain the 95% confidence ellipse and its parameters: angle, major and minor axes lengths, and area. The balance indicators were compared among the three groups using one-way analysis of variance (ANOVA), Brown-Forsythe test or Kruskal-Wallis H test, depending on the normality and homogeneity of variance assumptions. RESULTS: The diabetic group had a significantly larger confidence ellipse area than the healthy younger adults on the horizontal plane (P = 0.032) and than the healthy older adults on the horizontal (P = 0.036), AP slope (P = 0.023), and right ML slope (P = 0.037) planes. There were no significant differences in the major axis length of the confidence ellipse among the three groups. The diabetic group had a significantly longer minor axis length than the healthy younger adults on the AP slope (P = 0.039), left ML slope (P = 0.045) and right ML slope (P = 0.016) planes and than the healthy older adults on the AP slope (P = 0.007), left ML slope (P = 0.035) and right ML slope (P = 0.012) planes. CONCLUSIONS: The balance control of diabetic patients is decreased compared with healthy younger and older people, and the body swing amplitude increases mainly in the direction of minor axis of confidence ellipse during static standing, while the swing amplitude in the direction of the major axis has no significant change. Evaluating the balance function of diabetic patients can help clinicians identify people with fall risk early and intervene early, thereby reducing the occurrence of fall events in this population.

Is a Preoperative MRI Scan Necessary for Acute Achilles Tendon Rupture?

BACKGROUND: Different treatment methods have been developed for acute Achilles tendon rupture (ATR), including conservative treatment, minimally invasive or transdermal surgery, and open surgery, and there is no consensus about which method is superior. It is important to clarify the presence of Achilles tendon (AT) degeneration, the rupture site, and the rupture shape before surgery to determine whether minimally invasive or open surgery should be selected, thereby reducing the re-rupture rate following acute ATR. The aim of this study was to investigate the diagnostic value of MRI in identifying the presence of AT degeneration, the rupture site, and the rupture shape for acute closed ATR. METHODS: From January 2016 to December 2019, patients with acute closed ATR who had undergone repair surgery were retrospectively enrolled. All patients received MRI examination, and the distance between the insertion site and broken end and the rupture shape (types I, II, and III) were independently determined by two observers. Then, the stump of the AT was exposed during the operation. The rupture site and rupture shape were recorded and compared and analyzed with the MRI results. Consistency analyses (using Cohen's kappa coefficient or intraclass correlation coefficient-ICC) and calculation of diagnostic performance indexes were, respectively, conducted to evaluate the diagnostic value of the MRI. RESULTS: This study included 47 consecutive patients with acute ATR, with an average age of 38.4 years. Among them, 40 were male, and seven were female. The intraoperative exploration demonstrated a total of 34 (72.3%), 10 (21.3%), and three (6.4%) patients with type I, II, and III ruptures, respectively. The average distance between the insertion site and the proximal broken end measured intraoperatively was 4.07 ± 1.57 cm. High or excellent consistencies were found for ATR classifications (kappa: 0.739-0.770, p < 0.001) and rupture sites (ICC: 0.962-0.979, p < 0.001) between two observers and between observers 1 and 2 and intraoperative findings. Tendinopathy was identified in 22 patients by MRI and confirmed during surgery. CONCLUSIONS: MRI scanning of acute closed ATR can help determine whether there is degeneration of the AT, as well as the location and shape of the rupture, which can guide the selection of the optimal operation method for orthopedic surgeons. Therefore, it is necessary to take preoperative MRI scans for patients with acute Achilles tendon ruptures.

Endovascular treatment for massive haemoptysis due to pulmonary pseudoaneurysm: report of 23 cases.

PURPOSE: To evaluate the safety and effectiveness of endovascular treatment for massive haemoptysis caused by pulmonary pseudoaneurysm (PAP). METHODS: The clinical data, imaging data, and endovascular treatment protocol of 23 patients with massive haemoptysis caused by continuous PAP were retrospectively analysed. The success, complications, postoperative recurrence rate, and influence of the treatment on pulmonary artery pressure were also evaluated. RESULTS: Nineteen patients with a bronchial artery-pulmonary artery (BA-PA) and/or nonbronchial systemic artery-pulmonary artery (NBSA-PA) fistula underwent bronchial artery embolization (BAE) and/or nonbronchial systemic artery embolization (NBSAE) + pulmonary artery embolization (PAE). The pulmonary artery (PA) pressures before and after embolization were 52.11 ± 2.12 (35-69 cmH2O) and 33.58 ± 1.63 (22-44 cmH2O), respectively (P = 0.001). Four patients did not have a BA-PA and/or NBSA-PA fistula. Embolization was performed in two patients with a distal PAP of the pulmonalis lobar arteria. Bare stent-assisted microcoils embolization was performed in the other two patients with a PAP of the main pulmonary lobar arteries. The PA pressures of the four patients before and after treatment were 24.50 ± 1.32 (22-28 cmH2O) and 24.75 ± 1.70 (22-29 cmH2O), respectively (P = 0.850). The technique had a 100% success rate with no serious complications and a postoperative recurrence rate of 30%. CONCLUSION: Endovascular treatment is safe and effective for massive haemoptysis caused by PAP. BAE and/or NBSAE can effectively reduce pulmonary hypertension in patients with a BA-PA and/or NBSA-PA fistula.