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Frontiers in Endocrinology 2024The aim of this substudy (Eudra CT No:2019-001997-27)was to assess ATB availability in patients with infected diabetic foot ulcers(IDFUs)in the context of...
Does PAD and microcirculation status impact the tissue availability of intravenously administered antibiotics in patients with infected diabetic foot? Results of the DFIATIM substudy.
AIMS/HYPOTHESIS
The aim of this substudy (Eudra CT No:2019-001997-27)was to assess ATB availability in patients with infected diabetic foot ulcers(IDFUs)in the context of microcirculation and macrocirculation status.
METHODS
For this substudy, we enrolled 23 patients with IDFU. Patients were treated with boluses of amoxicillin/clavulanic acid(AMC)(12patients) or ceftazidime(CTZ)(11patients). After induction of a steady ATB state, microdialysis was performed near the IDFU. Tissue fluid samples from the foot and blood samples from peripheral blood were taken within 6 hours. ATB efficacy was the maximum serum and tissue ATB concentrations(C and C)and the percentage of time the unbound drug tissue concentration exceeds the minimum inhibitory concentration (MIC)(≥100% and ≥50%/60% fT>MIC). Vascular status was assessed by triplex ultrasound, ankle-brachial and toe-brachial index tests, occlusive plethysmography comprising two arterial flow phases, and transcutaneous oxygen pressure(TcPO).
RESULTS
Following bolus administration, the C of AMC was 91.8 ± 52.5 μgmL and the C of AMC was 7.25 ± 4.5 μgmL(<0.001). The C for CTZ was 186.8 ± 44.1 μgmL and the C of CTZ was 18.6 ± 7.4 μgmL(<0.0001). Additionally, 67% of patients treated with AMC and 55% of those treated with CTZ achieved tissue fT>MIC levels exceeding 50% and 60%, respectively. We observed positive correlations between both C and AUC and arterial flow. Specifically, the correlation coefficient for the first phase was 0.42; (=0.045), and for the second phase, it was =0.55(=0.01)and =0.5(=0.021).
CONCLUSIONS
Bactericidal activity proved satisfactory in only half to two-thirds of patients with IDFUs, an outcome that appears to correlate primarily with arterial flow.
Topics: Humans; Diabetic Foot; Microcirculation; Male; Female; Anti-Bacterial Agents; Middle Aged; Aged; Administration, Intravenous
PubMed: 38774229
DOI: 10.3389/fendo.2024.1326179 -
Journal of Diabetes Jun 2024Reportedly, the stress-hyperglycemia ratio (SHR) is closely associated with poor prognosis in patients with severe acute disease. However, the community-dwelling may...
Association between the stress-hyperglycemia ratio and all-cause mortality in community-dwelling populations: An analysis of the National Health and Nutrition Examination Survey (NHANES) 1999-2014.
BACKGROUND
Reportedly, the stress-hyperglycemia ratio (SHR) is closely associated with poor prognosis in patients with severe acute disease. However, the community-dwelling may also be in a state of stress due to environmental exposure. Our study aimed to explore the association between SHR and all-cause mortality in the community-dwelling population.
METHODS
A total of 18 480 participants were included out of 82 091 from the NHANES 1999-2014 survey. The Kaplan-Meier survival analyses were used to assess the disparities in survival rates based on SHR, and the log-rank test was employed to investigate the distinctions between groups. The multivariate Cox regression analysis and restricted cubic spline (RCS) analysis were performed to assess the association of SHR with all-cause mortality. A subgroup analysis was also conducted.
RESULTS
A total of 3188 deaths occurred during a median follow-up period of 11.0 (7.7; 15.4) years. The highest risk for all-cause mortality was observed when SHR≤ 0.843 or SHR ≥0.986 (log-rank p < .001). After adjusting for the confounding factors, compared with subjects in the second SHR quartile (Q2), participants in the highest (Q4, adjusted hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.28-1.73) and lowest quartiles (Q1, adjusted HR 1.37, 95% CI 1.16-1.60) have a higher probability of all-cause death. The RCS observed a dose-response U-shaped association between SHR and all-cause mortality. The U-shaped association between SHR and all-cause mortality was similar across subgroup analysis.
CONCLUSIONS
The SHR was significantly associated with all-cause mortality in the community-dwelling population, and the relationship was U-shaped.
Topics: Humans; Male; Female; Nutrition Surveys; Middle Aged; Independent Living; Hyperglycemia; Adult; Aged; Cause of Death; Risk Factors; Mortality; Stress, Physiological; United States; Prognosis; Kaplan-Meier Estimate
PubMed: 38769875
DOI: 10.1111/1753-0407.13567 -
World Journal of Diabetes May 2024Diabetes foot is one of the most serious complications of diabetes and an important cause of death and disability, traditional treatment has poor efficacy and there is... (Clinical Trial)
Clinical Trial
BACKGROUND
Diabetes foot is one of the most serious complications of diabetes and an important cause of death and disability, traditional treatment has poor efficacy and there is an urgent need to develop a practical treatment method.
AIM
To investigate whether Huangma Ding or autologous platelet-rich gel (APG) treatment would benefit diabetic lower extremity arterial disease (LEAD) patients with foot ulcers.
METHODS
A total of 155 diabetic LEAD patients with foot ulcers were enrolled and divided into three groups: Group A (62 patients; basal treatment), Group B (38 patients; basal treatment and APG), and Group C (55 patients; basal treatment and Huangma Ding). All patients underwent routine follow-up visits for six months. After follow-up, we calculated the changes in all variables from baseline and determined the differences between groups and the relationships between parameters.
RESULTS
The infection status of the three groups before treatment was the same. Procalcitonin (PCT) improved after APG and Huangma Ding treatment more than after traditional treatment and was significantly greater in Group C than in Group B. Logistic regression analysis revealed that PCT was positively correlated with total amputation, primary amputation, and minor amputation rates. The ankle-brachial pressure and the transcutaneous oxygen pressure in Groups B and C were greater than those in Group A. The major amputation rate, minor amputation rate, and total amputation times in Groups B and C were lower than those in Group A.
CONCLUSION
Our research indicated that diabetic foot ulcers (DFUs) lead to major amputation, minor amputation, and total amputation through local infection and poor microcirculation and macrocirculation. Huangma Ding and APG were effective attreating DFUs. The clinical efficacy of Huangma Ding was better than that of autologous platelet gel, which may be related to the better control of local infection by Huangma Ding. This finding suggested that in patients with DFUs combined with coinfection, controlling infection is as important as improving circulation.
PubMed: 38766441
DOI: 10.4239/wjd.v15.i5.923 -
Journal of Inflammation Research 2024Intervertebral disc degeneration (IDD) is the leading cause of low back pain (LBP). The mechanism of IDD development and progression is not fully understood. Peripheral...
BACKGROUND
Intervertebral disc degeneration (IDD) is the leading cause of low back pain (LBP). The mechanism of IDD development and progression is not fully understood. Peripheral biomarkers are increasingly vital non-radioactive methods in early detection and diagnosis for IDD. Nevertheless, less attention has been paid to the role of mitophagy genes in the progress of IDD. This study aimed to identify the mitophagy disease-causing genes in the process of IDD and mitophagy diagnostic biomarkers for IDD.
METHODS
Mitophagy-related differentially expressed genes (MRDEGs) related to IDD were investigated by analyzing the microarray datasets of IDD cases from GEO, PathCards and Molecular Signatures Databases. We used R software, WGCNA, PPI, mRNA-miRNA, mRNA-TF, GO, KEGG, GSEA, GSVA and Cytoscape to analyze and visualize the data. We further used ssGSEA for immunoinfiltration analysis to obtain different immune cell infiltration. LASSO model was developed to screen for genes that met the diagnostic gene model requirements. Finally, qRT-PCR, Western blotting and HE were used to verify hub genes and their expression from clinical IDD samples.
RESULTS
We identified 14 MRDEGs and 12 hub genes. GO, KEGG, GSEA and GSVA analyses demonstrated that hub genes were critical for the development of IDD. LASSO diagnostic model consisted of six hub genes, among which SQSTM1, ATG7 and OPTN were significantly different between the two IDD disease subtypes. At the same time, SQSTM1 also had a high correlation with immune characteristic subtypes. The results of qRT-PCR and Western blotting also indicated that these genes were significantly differentially expressed in nucleus pulposus cells (NPCs) of the IDD group.
CONCLUSION
We explored an association between MRDEGs-associated signature in IDD and validated that hub genes like SQSTM1 might serve as biomarkers for diagnostic and therapeutic targets for IDD. Meanwhile, this study can provide new insights into the functional characteristics and mechanism of mitophagy in the development of IDD.
PubMed: 38764497
DOI: 10.2147/JIR.S461668 -
International Journal of Hyperthermia :... 2024Psoriasis is characterized by an increase in the proliferation of keratinocytes and nerve fiber activity, contributing to the typical skin lesions. Pulsed Dye Laser...
INTRODUCTION
Psoriasis is characterized by an increase in the proliferation of keratinocytes and nerve fiber activity, contributing to the typical skin lesions. Pulsed Dye Laser (PDL) treatment is effective for the treatment of psoriatic lesions but its mechanism remains unclear. One hypothesis is that PDL causes thermal damage by the diffusion of heat to neighboring structures in lesional skin. There is limited information on the thermal sensitivity of these neighboring skin cells when exposed to hyperthermia for durations lasting less than a minute. Our study aimed to investigate the cell-specific responses to heat using sub-minute exposure times and moderate to ablative hyperthermia.
MATERIALS AND METHODS
Cultured human endothelial cells, smooth muscle cells, neuronal cells, and keratinocytes were exposed to various time (2-20 sec) and temperature (45-70 °C) combinations. Cell viability was assessed by measuring intracellular ATP content 24 h after thermal exposure and this data was used to calculate fit parameters for the Arrhenius model and CEM43 calculations.
RESULTS
Our results show significant differences in cell survival between cell types ( < 0.0001). Especially within the range of 50-60 °C, survival of neuronal cells and keratinocytes was significantly less than that of endothelial and smooth muscle cells. No statistically significant difference was found in the lethal dose (LT50) of thermal energy between neuronal cells and keratinocytes. However, CEM43 calculations showed significant differences between all four cell types.
CONCLUSION
The results imply that there is a cell-type-dependent sensitivity to thermal damage which suggests that neuronal cells and keratinocytes are particularly susceptible to diffusing heat from laser treatment. Damage to these cells may aid in modulating the neuro-inflammatory pathways in psoriasis. These data provide insight into the potential mechanisms of PDL therapy for psoriasis and advance our understanding of how thermal effects may play a role in its effectiveness.
Topics: Humans; Skin; Keratinocytes; Cell Survival
PubMed: 38754976
DOI: 10.1080/02656736.2024.2354435 -
Journal of Inflammation Research 2024Acupoint autohemotherapy (A-AHT) has been proposed as an alternative and complementary treatment for atopic dermatitis (AD), yet the exact role of its blood component in...
PURPOSE
Acupoint autohemotherapy (A-AHT) has been proposed as an alternative and complementary treatment for atopic dermatitis (AD), yet the exact role of its blood component in terms of therapeutic efficacy and mechanism of action is still largely unknown.
METHODS
This study aimed to evaluate the therapeutic efficacies and action mechanisms of intramuscular injections of autologous whole blood (AWB) and mouse immunoglobulin G (IgG) (autologous or heterologous) at acupoints on 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse models. Serum levels of total immunoglobulin E (IgE), IgG, interleukin-10 (IL-10), and interferon-gamma (IFN-γ) were measured, as well as mRNA expression levels of Forkhead box P3 (FoxP3), IL-10 and IFN-γ in dorsal skin lesions, and IL-10, IFN-γ and FoxP3CD4T cells in murine spleen.
RESULTS
It showed that repeated acupoint injection of AWB, autologous total IgG (purified from autologous blood in AD mice) or heterologous total IgG (purified from healthy blood in normal mice) effectively reduced the severity of AD symptoms and decreased epidermal and dermal thickness as well as mast cells in skin lesions. Additionally, AWB acupoint injection was found to upregulate FoxP3, IL-10 and IFN-γ CD4T cells in murine spleen, suppressing the production of IgE antibodies and increasing that of IgG antibodies in the serum. Furthermore, both AWB and autologous total IgG administrations significantly elevated FoxP3 expression, mRNA levels of IL-10 and IFN-γ in dorsal skin lesions. However, acupoint injection of heterologous total IgG had no effect on regulatory T (Treg) and Th1 cells modulation.
CONCLUSION
These findings suggest that the therapeutic effects of A-AHT on AD are mediated by IgG-induced activation of Treg cells.
PubMed: 38751687
DOI: 10.2147/JIR.S454325 -
International Heart Journal May 2024Treatment with enhanced external counterpulsation (EECP) or cardiac rehabilitation (CR) benefits patients with coronary heart disease; this paper intends to explore the... (Randomized Controlled Trial)
Randomized Controlled Trial
A Randomized Controlled Study of Enhanced External Counterpulsation with Cardiac Rehabilitation in Patients with Nonobstructive Coronary Artery Disease and Coronary Microvascular Dysfunction.
Treatment with enhanced external counterpulsation (EECP) or cardiac rehabilitation (CR) benefits patients with coronary heart disease; this paper intends to explore the feasibility of EECP combined with CR in patients with nonobstructive coronary heart disease (NOCAD) and coronary microcirculation disorders (CMD).In January 2021-2022 month June our income NOCAD patients as the research object, the line of cardiac magnetic resonance (CMR), myocardial perfusion reserve (MPR) < 2.0 coronary microcirculation disorders (CMD, 80 cases). Random indicator method 80 CMD patients divided into two groups, 40 cases in each. Usual treatment group: conventional drugs and CR therapy. EECP treatment group: on the basis of standard treatment group, employ EECP therapy. Comparing the two groups before and after the treatment curative effect cardiac function index, endothelial unction index, adverse cardiovascular events, etc.After EECP treatment, the treatment group showed a higher effective rate compared to the usual treatment group (P < 0.05). EECP group curative effect, left ventricular ejection fraction,plasma NO and vascular endothelial growth factor levels higher than the usual group, the incidence of adverse cardiovascular events is lower than the usual group. The difference was statistically significant (P < 0.05).EECP combined with cardiac rehabilitation in patients with CMD symptoms has better effect and safety and provides reference for treatment of CMD patients.
Topics: Humans; Male; Cardiac Rehabilitation; Counterpulsation; Coronary Artery Disease; Female; Middle Aged; Microcirculation; Aged; Coronary Circulation; Treatment Outcome
PubMed: 38749752
DOI: 10.1536/ihj.23-454 -
PloS One 2024Microphysiological models (MPS) are increasingly getting recognized as in vitro preclinical systems of pathophysiology and drug discovery. However, there is also a...
Microphysiological models (MPS) are increasingly getting recognized as in vitro preclinical systems of pathophysiology and drug discovery. However, there is also a growing need to adapt and advance MPS to include the physiological contributions of the capillary vascular dynamics, because they undergo angiogenesis or vasculogenesis to deliver soluble oxygen and nutrients to its organs. Currently, the process of formation of microvessels in MPS is measured arbitrarily, and vascularized MPS do not include oxygen measurements in their analysis. Sensing and measuring tissue oxygen delivery is extremely difficult because it requires access to opaque and deep tissue, and/or requires extensive integration of biosensors that makes such systems impractical to use in the real world. Here, a finite element method-based oxygen transport program, called AngioMT, is built in MATLAB. AngioMT processes the routinely acquired 2D confocal images of microvascular networks in vitro and solves physical equations of diffusion-reaction dominated oxygen transport phenomena. This user-friendly image-to-physics transition in AngioMT is an enabling tool of MPS analysis because unlike the averaged morphological measures of vessels, it provides information of the spatial transport of oxygen both within the microvessels and the surrounding tissue regions. Further, it solves the more complex higher order reaction mechanisms which also improve the physiological relevance of this tool when compared directly against in vivo measurements. Finally, the program is applied in a multicellular vascularized MPS by including the ability to define additional organ/tissue subtypes in complex co-cultured systems. Therefore, AngioMT serves as an analytical tool to enhance the predictive power and performance of MPS that incorporate microcirculation.
Topics: Oxygen; Humans; Animals; Biological Transport; Neovascularization, Physiologic; Microvessels; Microcirculation; Models, Biological; Microphysiological Systems
PubMed: 38748761
DOI: 10.1371/journal.pone.0299160 -
Ear, Nose, & Throat Journal May 2024The aim of this study is to investigate the effectiveness of combining hyperbaric oxygen therapy (HBOT) with conventional pharmacological interventions in the...
Clinical Observations on the Combined Use of Hyperbaric Oxygenation and Conventional Medications in the Management of Type 2 Diabetes Mellitus Concurrent With Sudden Deafness.
The aim of this study is to investigate the effectiveness of combining hyperbaric oxygen therapy (HBOT) with conventional pharmacological interventions in the management of type 2 diabetes mellitus concurrent with sudden deafness. A cohort of 96 patients diagnosed with sudden deafness was enrolled and subsequently randomized into 2 groups: a treatment group (n = 50) and a control group (n = 46). The control group received standard conventional treatment aimed at enhancing microcirculation and nutritional support for nerves, while the treatment group underwent conventional symptomatic treatment coupled with HBOT. The evaluation encompassed the monitoring of blood glucose and blood lipid levels, clinical efficacy, and absolute hearing threshold improvement in both groups. Following the intervention, noteworthy reductions in blood glucose and blood lipid levels were observed in both groups compared to their respective pretreatment values. Furthermore, posttreatment values in the treatment group exhibited a statistically significant decrease in comparison to those in the control group ( < .05). On assessing clinical efficacy posttreatment, the treatment group demonstrated a significantly higher efficacy than the control group ( < .05). In addition, the absolute hearing thresholds in both groups exhibited a significant decrease posttreatment compared to baseline values. Notably, the treatment group displayed a statistically significant reduction in absolute hearing thresholds compared to the control group posttreatment ( < .05). The combined therapeutic approach utilizing hyperbaric oxygen exhibits effectiveness in mitigating auditory impairment among individuals manifesting sudden deafness concomitant with type 2 diabetes mellitus. Furthermore, this treatment approach is associated with a concurrent reduction in blood glucose and blood lipid levels.
PubMed: 38747325
DOI: 10.1177/01455613241254433 -
Journal of Alzheimer's Disease Reports 2024Alzheimer's disease may be effectively treated with acupoint-based acupuncture, which is acknowledged globally. However, more research is needed to understand the...
BACKGROUND
Alzheimer's disease may be effectively treated with acupoint-based acupuncture, which is acknowledged globally. However, more research is needed to understand the alterations in acupoints that occur throughout the illness and acupuncture treatment.
OBJECTIVE
This research investigated the differences in acupoint microcirculation between normal mice and AD animals . This research also examined how acupuncture affected AD animal models and acupoint microcirculation.
METHODS
6-month-old SAMP8 mice were divided into two groups: the AD group and the acupuncture group. Additionally, SAMR1 mice of the same month were included as the normal group. The study involved subjecting a group of mice to 28 consecutive days of acupuncture at the ST36 () and CV12 () acupoints. Following this treatment, the Morris water maze test was conducted to assess the mice's learning and memory abilities; the acoustic-resolution photoacoustic microscope (AR-PAM) imaging system was utilized to observe the microcirculation in CV12 acupoint region and head-specific region of each group of mice.
RESULTS
In comparison to the control group, the mice in the AD group exhibited a considerable decline in their learning and memory capabilities ( < 0.01). In comparison to the control group, the vascular in the CV12 region and head-specific region in mice from the AD group exhibited a considerable reduction in length, distance, and diameter r ( < 0.01). The implementation of acupuncture treatment had the potential to enhance the aforementioned condition to a certain degree.
CONCLUSIONS
These findings offered tangible visual evidence that supports the ongoing investigation into the underlying mechanisms of acupuncture's therapeutic effects.
PubMed: 38746630
DOI: 10.3233/ADR-230193