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Frontiers in Medicine 2024Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes mellitus, often causing pain or numbness in the patient's limbs and even leading...
BACKGROUND
Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes mellitus, often causing pain or numbness in the patient's limbs and even leading to amputation and death. Elderly patients with DPN usually have higher morbidity and more severe results. Acupuncture has been widely used as an effective treatment for DPN in China. However, the efficacy of acupuncture in the treatment of DPN remains unclear. In this review, we aimed to explore the impact of acupuncture in alleviating symptoms of DPN.
METHOD AND ANALYSIS
Six databases were searched from inception to October 2023. We searched Medline, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and three Chinese databases, namely China National Knowledge Infrastructure (CNKI), SinoMed, and Wanfang. All randomized controlled trials related to the effect of acupuncture on DPN will be included. There was no restriction in language or publication year. The primary outcome is the response rate. The secondary outcomes are the Toronto clinical scoring system (TCSS), nerve conduction velocities (NCVs), and blood glucose before and after the treatment. Two researchers will be responsible for the selection of study, data extraction, and assessment of study quality independently. RevMan V5.1.0 software will be used to assess the risk of bias and generate data.
RESULTS
We searched 4518 studies, among which 9 RCTs were considered eligible. Overall, acupuncture treatment had a higher response rate than controls (relative risk (RR), -2.87 [95% confidence interval (CI), -5.27 to -0.48], = 0.02) and significantly alleviated the symptoms of DPN patients, reduced their blood glucose levels, and improved their NCVs compared to the control group. This study will provide a high-quality synthesis of current available evidence for the clinical treatment of DPN with this therapy.
CONCLUSION
The results suggested that acupuncture might be effective in improving symptoms of DPN in elderly patients. Owing to the overall low quality of the literature included, we need more large-sample, high-quality, and low-bias studies to prove it.
PubMed: 38947240
DOI: 10.3389/fmed.2024.1339747 -
Frontiers in Cardiovascular Medicine 2024Hypertrophic Cardiomyopathy (HCM), a widespread genetic heart disorder, is largely associated with sudden cardiac fatality. Necroptosis, an emerging type of programmed...
BACKGROUND
Hypertrophic Cardiomyopathy (HCM), a widespread genetic heart disorder, is largely associated with sudden cardiac fatality. Necroptosis, an emerging type of programmed cell death, plays a fundamental role in several cardiovascular diseases.
AIM
This research utilized bioinformatics analysis to investigate necroptosis's implication in HCM.
METHODS
The study retrieved RNA sequencing datasets GSE130036 and GSE141910 from the Gene Expression Omnibus (GEO) database. It detected necroptosis-linked differentially expressed genes (NRDEGs) by reviewing both the gene set for necroptosis and the differently expressed genes (DEGs). The enriched signaling pathway of HCM was assessed using GSEA, while common DEGs were studied through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Concurrently, the Protein-Protein Interaction network (PPI) proved useful for identifying central genes. CIBERSORT facilitated evaluating the correlation between distinct immune cell-type prevalence and NRDEGs by analyzing immune infiltration patterns. Lastly, GSE141910 dataset validated the expression ranks of NRDEGs and immune-cell penetration.
RESULTS
The investigation disclosed significant enrichment and activation of the necroptosis pathway in HCM specimens. Seventeen diverse genes, including CYBB, BCL2, and JAK2 among others, were identified in the process. PPI network scrutiny classified nine of these genes as central genes. Results from GO and KEGG enrichment analyses showed substantial connections of these genes to pathways pertaining to the HIF-1 signaling track, necroptosis, and NOD-like receptor signaling process. Moreover, an imbalance in M2 macrophage cells in HCM samples was observed. Finally, CYBB, BCL2, and JAK2 emerged as vital genes and were validated using the GSE141910 dataset.
CONCLUSION
These results indicate necroptosis as a probable underlying factor in HCM, with immune cell infiltration playing a part. Additionally, CYBB, BCL2, JAK2 could act as potential biomarkers for recognizing HCM. This information forms crucial insights into the basic mechanisms of HCM and could enhance its diagnosis and management.
PubMed: 38947229
DOI: 10.3389/fcvm.2024.1293786 -
Pulmonary Medicine 2024Bilothorax is defined as the presence of bile in the pleural space. It is a rare condition, and diagnosis is confirmed with a pleural fluid-to-serum bilirubin ratio of...
BACKGROUND
Bilothorax is defined as the presence of bile in the pleural space. It is a rare condition, and diagnosis is confirmed with a pleural fluid-to-serum bilirubin ratio of >1.
METHODS
The PubMed, Embase, Google Scholar, and CINAHL databases were searched using predetermined Boolean parameters. The systematic literature review was done per PRISMA guidelines. Retrospective studies, case series, case reports, and conference abstracts were included. The patients with reported pleural fluid analyses were pooled for fluid parameter data analysis.
RESULTS
Of 838 articles identified through the inclusion criteria and removing 105 duplicates, 732 articles were screened with abstracts, and 285 were screened for full article review. After this, 123 studies qualified for further detailed review, and of these, 115 were pooled for data analysis. The mean pleural fluid and serum bilirubin levels were 72 mg/dL and 61 mg/dL, respectively, with a mean pleural fluid-to-serum bilirubin ratio of 3.47. In most cases, the bilothorax was reported as a subacute or remote complication of hepatobiliary surgery or procedure, and traumatic injury to the chest or abdomen was the second most common cause. Tube thoracostomy was the main treatment modality (73.83%), followed by serial thoracentesis. Fifty-two patients (51.30%) had associated bronchopleural fistulas. The mortality was considerable, with 18/115 (15.65%) reported death. Most of the patients with mortality had advanced hepatobiliary cancer and were noted to die of complications not related to bilothorax.
CONCLUSION
Bilothorax should be suspected in patients presenting with pleural effusion following surgical manipulation of hepatobiliary structures or a traumatic injury to the chest. This review is registered with CRD42023438426.
Topics: Female; Humans; Bile; Bilirubin; Pleural Effusion; Thoracentesis; Thoracostomy; Aged
PubMed: 38947176
DOI: 10.1155/2024/3973056 -
Endoscopic Ultrasound 2024In portal hypertension, gastric varix-associated bleeding is known to have higher transfusion requirements, uncontrolled bleeding, rebleeding, intensive care unit...
BACKGROUND AND OBJECTIVES
In portal hypertension, gastric varix-associated bleeding is known to have higher transfusion requirements, uncontrolled bleeding, rebleeding, intensive care unit requirements, and death. EUS-guided coil insertion is now an acceptable modality for endoscopic management in cases of gastric varices. With this study, we discuss our large single-center experience in the use of EUS for coil and glue injection in gastric varices. We also look into adverse events associated with and possibilities of using this modality as both primary prophylaxis and a rescue therapy.
METHODS
The study was conducted in a tertiary care center in India. A total of 86 patients were included in the study. The indication for EUS-guided coil and glue was divided into 3 clinical situations, namely, rebleed, rescue, and primary. The technical success and clinical success, that is, control of bleed in patients, were confirmed by absence of Doppler signal on EUS, endoscopic view, and stabilized hemoglobin with no need of blood product transfusion to maintain hemoglobin.
RESULTS
The mean Child-Turcotte-Pugh score and Model for End-Stage Liver Disease-Na score were 9.2 and 14.6, respectively. The mean size of the gastric varices was 18.9 mm. The mean number of coils used was 2.9, and the average quantity of glue required was 1.6 mL. The technical success was 100% across the patient group. Clinical success was seen in 90% of the patient group. Mean follow-up was seen for 175.2 days.
CONCLUSIONS
EUS-guided coil and glue therapy has a role in different clinical settings, as primary therapy, rebleed, and rescue therapy. It has significant technical and clinical success. Its role in treatment algorithms needs to be further studied in prospective studies. It may offer a cost advantage in comparison to interventional radiology-led interventions.
PubMed: 38947113
DOI: 10.1097/eus.0000000000000038 -
Research Square Jun 2024Static cold storage of donor livers at 4°C incompletely arrests metabolism, ultimately leading to decreases in ATP levels, oxidative stress, cell death, and organ...
Static cold storage of donor livers at 4°C incompletely arrests metabolism, ultimately leading to decreases in ATP levels, oxidative stress, cell death, and organ failure. Hydrogen Sulfide (H S) is an endogenously produced gas, previously demonstrated to reduce oxidative stress, reduce ATP depletion, and protect from ischemia and reperfusion injury. H S is difficult to administer due to its rapid release curve, resulting in cellular death at high concentrations. AP39, a mitochondrially targeted, slow-release H S donor, has been shown to reduce ischemia-reperfusion injury in hearts and kidneys. Thus, we investigated whether the addition of AP39 during 3-day static cold storage can improve liver graft viability. At the end of storage, livers underwent six hours of acellular normothermic machine perfusion, a model of transplantation. During simulated transplantation, livers stored with AP39 showed reduced resistance, reduced cellular damage (ALT and AST), and reduced apoptosis. Additionally, bile production and glucose, as well as energy charge were improved by the addition of AP39. These results indicate that AP39 supplementation improves liver viability during static cold storage.
PubMed: 38947096
DOI: 10.21203/rs.3.rs-4487319/v1 -
Research Square Jun 2024Background The demand for genetic services has outpaced the availability of resources, challenging clinicians untrained in genetic integration into clinical...
Background The demand for genetic services has outpaced the availability of resources, challenging clinicians untrained in genetic integration into clinical decision-making. The UTHealth Adult Cardiovascular Genomics Certificate (CGC) program trains non-genetic healthcare professionals to recognize, assess, and refer patients with heritable cardiovascular diseases. This asynchronous online course includes 24 modules in three tiers of increasing complexity, using realistic clinical scenarios, interactive dialogues, quizzes, and tests to reinforce learning. We hypothesized that the CGC will increase genomic competencies in this underserved audience and encourage applying genomic concepts in clinical practice. Methods Required course evaluations include pre- and post- assessments, knowledge checks in each module, and surveys for module-specific feedback. After 6 months, longitudinal feedback surveys gathered data on the long-term impact of the course on clinical practice and conducted focused interviews with learners. Results The CGC was accredited in September 2022. Principal learners were nurses (24%), nurse practitioners (21%), physicians (16%), and physician assistants. Scores of 283 learners in paired pre- and post-assessments increased specific skills related to recognizing heritable diseases, understanding inheritance patterns, and interpreting genetic tests. Interviews highlighted the CGC's modular structure and linked resources as key strengths. Learners endorsed confidence to use genetic information in clinical practice, such as discussing genetic concepts and risks with patients and referring patients for genetic testing. Learners were highly likely to recommend the CGC to colleagues, citing its role in enhancing heritable disease awareness. Conclusions The CGC program effectively empowers non-genetic clinicians to master genomic competencies, fostering collaboration to prevent deaths from heritable cardiovascular diseases, and potentially transforming healthcare education and clinical practice.
PubMed: 38947076
DOI: 10.21203/rs.3.rs-4469272/v1 -
Research Square Jun 2024Coronary artery calcium (CAC) scans contain valuable information beyond the Agatston Score which is currently reported for predicting coronary heart disease (CHD) only....
AI-enabled Cardiac Chambers Volumetry and Calcified Plaque Characterization in Coronary Artery Calcium (CAC) Scans (AI-CAC) Significantly Improves on Agatston CAC Score for Predicting All Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis.
Coronary artery calcium (CAC) scans contain valuable information beyond the Agatston Score which is currently reported for predicting coronary heart disease (CHD) only. We examined whether new artificial intelligence (AI) algorithms applied to CAC scans may provide significant improvement in prediction of all cardiovascular disease (CVD) events in addition to CHD, including heart failure, atrial fibrillation, stroke, resuscitated cardiac arrest, and all CVD-related deaths. We applied AI-enabled automated cardiac chambers volumetry and automated calcified plaque characterization to CAC scans (AI-CAC) of 5830 individuals (52.2% women, age 61.7±10.2 years) without known CVD that were previously obtained for CAC scoring at the baseline examination of the Multi-Ethnic Study of Atherosclerosis (MESA). We used 15-year outcomes data and assessed discrimination using the time-dependent area under the curve (AUC) for AI-CAC versus the Agatston Score. During 15 years of follow-up, 1773 CVD events accrued. The AUC at 1-, 5-, 10-, and 15-year follow up for AI-CAC vs Agatston Score was (0.784 vs 0.701), (0.771 vs. 0.709), (0.789 vs.0.712) and (0.816 vs. 0.729) (p<0.0001 for all), respectively. The category-free Net Reclassification Index of AI-CAC vs. Agatston Score at 1-, 5-, 10-, and 15-year follow up was 0.31, 0.24, 0.29 and 0.29 (p<.0001 for all), respectively. AI-CAC plaque characteristics including number, location, and density of plaque plus number of vessels significantly improved NRI for CAC 1-100 cohort vs. Agatston Score (0.342). In this multi-ethnic longitudinal population study, AI-CAC significantly and consistently improved the prediction of all CVD events over 15 years compared with the Agatston score.
PubMed: 38947043
DOI: 10.21203/rs.3.rs-4433105/v1 -
Research Square Jun 2024Background - Glaucoma is a complex multifactorial disease where apoptosis and inflammation represent two key pathogenic mechanisms. However, the relative contribution of...
Background - Glaucoma is a complex multifactorial disease where apoptosis and inflammation represent two key pathogenic mechanisms. However, the relative contribution of apoptosis versus inflammation in axon degeneration and death of retinal ganglion cells (RGCs) is not well understood. In glaucoma, caspase-8 is linked to RGC apoptosis, as well as glial activation and neuroinflammation. To uncouple these two pathways and determine the extent to which caspase-8-mediated inflammation and/or apoptosis contributes to the death of RGCs, we used the caspase-8 D387A mutant mouse ( ) in which a point mutation in the auto-cleavage site blocks caspase-8-mediated apoptosis but does not block caspase-8-mediated inflammation. Methods- Intracameral injection of magnetic microbeads was used to elevate the intraocular pressure (IOP) in wild-type, Fas deficient Fas , and mice. IOP was monitored by rebound tonometry. Two weeks post microbead injection, retinas were collected for microglia activation analysis. Five weeks post microbead injection, visual acuity and RGC function were assessed by optometer reflex (OMR) and pattern electroretinogram (pERG), respectively. Retina and optic nerves were processed for RGC and axon quantification. Two- and five-weeks post microbead injection, expression of the necrosis marker, RIPK3, was assessed by qPCR. Results- Wild-type, Fas , and mice showed similar IOP elevation as compared to saline controls. A significant reduction in both visual acuity and pERG that correlated with a significant loss of RGCs and axons was observed in wild-type but not in Fas mice. The mice displayed a significant reduction in visual acuity and pERG amplitude and loss of RGCs and axons similar to that in wild-type mice. Immunostaining revealed equal numbers of activated microglia, double positive for P2ry12 and IB4, in the retinas from microbead-injected wild-type and mutant mice. qPCR analysis revealed no induction of RIPK3 in wild-type or mice at two- or five-weeks post microbead injection. Conclusions- Our results demonstrate that caspase-8-mediated extrinsic apoptosis is not involved in the death of RGCs in the microbead-induced mouse model of glaucoma implicating caspase-8-mediated inflammation, but not apoptosis, as the driving force in glaucoma progression. Taken together, these results identify the caspase-8-mediated inflammatory pathway as a potential target for neuroprotection in glaucoma.
PubMed: 38947028
DOI: 10.21203/rs.3.rs-4409426/v1 -
Research Square Jun 2024Paxlovid has been approved for use in patients who are at high risk for severe acute COVID-19 illness. Evidence regarding whether Paxlovid protects against Post-Acute...
Paxlovid has been approved for use in patients who are at high risk for severe acute COVID-19 illness. Evidence regarding whether Paxlovid protects against Post-Acute Sequelae of SARS-CoV-2 infection (PASC), or Long COVID, is mixed in high-risk patients and lacking in low-risk patients. With a target trial emulation framework, we evaluated the association of Paxlovid treatment within 5 days of SARS-CoV-2 infection with incident Long COVID and hospitalization or death from any cause in the post-acute period (30-180 days after infection) using electronic health records from the Patient-Centered Clinical Research Networks (PCORnet) RECOVER repository. The study population included 497,499 SARS-CoV-2 positive patients between March 1, 2022, to February 1, 2023, and among which 165,256 were treated with Paxlovid within 5 days since infection and 307,922 were not treated with Paxlovid or other COVID-19 treatments. Compared with the non-treated group, Paxlovid treatment was associated with reduced risk of Long COVID with a Hazard Ratio (HR) of 0.88 (95% CI, 0.87 to 0.89) and absolute risk reduction of 2.99 events per 100 persons (95% CI, 2.65 to 3.32). Paxlovid treatment was associated with reduced risk of all-cause death (HR, 0.53, 95% CI 0.46 to 0.60; risk reduction 0.23 events per 100 persons, 95% CI 0.19 to 0.28) and hospitalization (HR, 0.70, 95% CI 0.68 to 0.73; risk reduction 2.37 events per 100 persons, 95% CI 2.19 to 2.56) in the post-acute phase. For those without documented risk factors, the associations (HR, 1.03, 95% CI 0.95 to 1.11; risk increase 0.80 events per 100 persons, 95% CI -0.84 to 2.45) were inconclusive. Overall, high-risk, nonhospitalized adult patients with COVID-19 who were treated with Paxlovid within 5 days of SARS-CoV-2 infection had a lower risk of Long COVID and all-cause hospitalization or death in the post-acute period. However, Long COVID risk reduction with Paxlovid was not observed in low-risk patients.
PubMed: 38947026
DOI: 10.21203/rs.3.rs-4536807/v1 -
MedRxiv : the Preprint Server For... Jun 2024Heart disease is the leading cause of death worldwide, and cardiac function as measured by ejection fraction (EF) is an important determinant of outcomes, making...
Heart disease is the leading cause of death worldwide, and cardiac function as measured by ejection fraction (EF) is an important determinant of outcomes, making accurate measurement a critical parameter in PT evaluation. Echocardiograms are commonly used for measuring EF, but human interpretation has limitations in terms of intra- and inter-observer (or reader) variance. Deep learning (DL) has driven a resurgence in machine learning, leading to advancements in medical applications. We introduce the ViViEchoformer DL approach, which uses a video vision transformer to directly regress the left ventricular function (LVEF) from echocardiogram videos. The study used a dataset of 10,030 apical-4-chamber echocardiography videos from patients at Stanford University Hospital. The model accurately captures spatial information and preserves inter-frame relationships by extracting spatiotemporal tokens from video input, allowing for accurate, fully automatic EF predictions that aid human assessment and analysis. The ViViEchoformer's prediction of ejection fraction has a mean absolute error of 6.14%, a root mean squared error of 8.4%, a mean squared log error of 0.04, and an of 0.55. ViViEchoformer predicted heart failure with reduced ejection fraction (HFrEF) with an area under the curve of 0.83 and a classification accuracy of 87 using a standard threshold of less than 50% ejection fraction. Our video-based method provides precise left ventricular function quantification, offering a reliable alternative to human evaluation and establishing a fundamental basis for echocardiogram interpretation.
PubMed: 38947006
DOI: 10.1101/2024.06.21.24309327