Impact of pre-existing frailty on survival outcomes in solid-organ transplant candidates and recipients: A meta-analysis.

BACKGROUND: There is controversy surrounding the association between preexisting frailty and increased mortality in candidates and recipients of solid-organ transplants. This meta-analysis aimed to evaluate the impact of preexisting frailty on survival outcomes in solid-organ transplant candidates and recipients. METHODS: A systematic search was conducted in the PubMed, Web of Sciences, and Embase databases until October 2, 2023. Two reviewers independently selected the eligible studies according to the PECOS criteria: Participants (candidates and recipients of solid-organ transplants), Exposure (frailty), Comparison (no-frailty), Outcomes (waitlist or posttransplant mortality), and Study design (retrospective or prospective cohort studies). The pooled effects were summarized by pooling the adjusted hazard ratio (HR) with 95 % confidence intervals (CI) for the frail patients than those without frailty. RESULTS: Sixteen studies with 10091 patients met the eligibility criteria. Depending on the frailty tools used, the prevalence of frailty in solid-organ transplant candidates/recipients ranged from 4.6 % to 45.1 %. Frailty was significantly associated with an increased risk of waitlist mortality (HR 2.44; 95 % CI 1.84-3.24) and posttransplant mortality (HR 2.23; 95 % CI 1.61-3.09) in solid-organ transplant candidates and recipients, respectively. Subgroup analyses showed that the association of preexisting frailty with waitlist mortality and posttransplant mortality appeared to stronger in kidney transplant candidates (HR 2.70; 95 % CI 1.93-3.78) and lung transplantation recipients (HR 2.52; 95 % CI 1.23-5.15). CONCLUSION: Frailty is a significant predictor of reduced survival in solid-organ transplant candidates and recipients. Assessment of frailty has the potential to identify patients who are suitable for transplantation.

Effects of different early cardiac rehabilitation exercise treatments on the prognosis of acute myocardial infarction patients receiving percutaneous coronary intervention.

OBJECTIVES: Exercise rehabilitation is the core of Cardiac Rehabilitation (CR) and will improve the prognosis of patients receiving Percutaneous Coronary Intervention (PCI surgery). The current study retrospectively analyzed the effects of different exercise-based CR strategies on the prognosis of AMI patients receiving PCI treatment. METHODS: Clinicopathological information from 127 patients was collected and divided into different groups based on the exercise-based CR received, including Continuous Resistance Exercise (COR), Continuous Aerobic Exercise (COA), Interval Resistance Exercise (IVR), Interval Aerobic Exercise (IVA), Inspiratory Muscle Exercises (ITM), and Control. The differences regarding cardio-pulmonary function, hemodynamics, and life quality were analyzed against different CR strategies. RESULTS: All the exercise-based CR strategies showed improving effects compared with patients in the Control group regarding cardio-pulmonary parameters, with IVR showing the strongest improving effects (IVR > ITM > COR > IVA > COA) (p < 0.05) at the first recoding point. However, the improving effects of exercise-based CR declined with time. Regarding the effects on hemodynamics parameters, the improving effects of exercise-based CR were only observed regarding LVEF, and the effects of IVR were also the strongest (IVR > COR > ITM > COA > IVA) (p < 0.05). Similar improving effects were also observed for 6MWT and life quality (IVR showing the strongest improving effects) (p < 0.05), which all declined three months after the surgery. CONCLUSIONS: The current study showed that exercise-based CRs had better improving effects than the normal nursing strategy on the prognosis of AMI patients receiving PCI surgery.

Association of weight loss with cardiovascular or all-cause mortality in patients with heart failure: A meta-analysis.

BACKGROUND: A consensus has not been reached on the association between weight loss and survival outcomes in patients with heart failure (HF). This meta-analysis aimed to assess the association of weight loss with cardiovascular or all-cause mortality in patients with HF. METHODS: Two authors independently searched the articles indexed in the PubMed and Embase databases up to May 7, 2023. Post hoc analysis of randomized controlled trials or observational studies that reported the utility of weight loss in predicting cardiovascular or all-cause mortality in patients with HF were included. RESULTS: Thirteen studies reporting on 12 articles involving 26,164 patients with HF were included. A comparison of weight loss with stable weight showed that the pooled adjusted hazard ratio (HR) for all-cause mortality was 1.75 (95% confidence intervals [CI] 1.43-2.14). Subgroup analysis revealed that weight loss was associated with an increased risk of all-cause mortality, irrespective of whether patients were overweight/obese (HR 1.76; 95% CI 1.41-2.20) or not (HR 1.90; 95% CI 1.14-3.14). The pooled adjusted HR of cardiovascular mortality was 1.64 (95% CI 1.18-2.28) for patients with weight loss compared to those without. CONCLUSIONS: Weight loss is associated with an increased risk of cardiovascular and all-cause mortality in patients with HF. Assessing weight changes can provide prognostic information for patients with HF.

Rapid inverse radiative transfer solver for multiparameter spectrophotometry without integrating sphere.

Significance: Multiparameter spectrophotometry (MPS) provides a powerful tool for accurate characterization of turbid materials in applications such as analysis of material compositions, assay of biological tissues for clinical diagnosis and food safety monitoring. Aim: This work is aimed at development and validation of a rapid inverse solver based on a particle swarm optimization (PSO) algorithm to retrieve the radiative transfer (RT) parameters of absorption coefficient, scattering coefficient and anisotropy factor of a turbid sample. Approach: Monte Carlo (MC) simulations were performed to obtain calculated signals for comparison to the measured ones of diffuse reflectance, diffuse transmittance and forward transmittance. An objective function has been derived and combined with the PSO algorithm to iterate MC simulations for MPS. Results: We have shown that the objective function can significantly reduce the variance in calculated signals by local averaging of an inverse squared error sum function between measured and calculated signals in RT parameter space. For validation of the new objective function for PSO based inverse solver, the RT parameters of 20% Intralipid solutions have been determined from 520 to 1000 nm which took about 2.7 minutes on average to complete signal measurement and inverse calculation per wavelength. Conclusion: The rapid solver enables MPS to be translated into easy-to-use and cost-effective instruments without integrating sphere for material characterization by separating and revealing compositional profiles at the molecular and particulate scales.

Effects of different early cardiac rehabilitation exercise treatments on the prognosis of acute myocardial infarction patients receiving percutaneous coronary intervention

Abstract Objectives: Exercise rehabilitation is the core of Cardiac Rehabilitation (CR) and will improve the prognosis of patients receiving Percutaneous Coronary Intervention (PCI surgery). The current study retrospectively analyzed the effects of different exercise-based CR strategies on the prognosis of AMI patients receiving PCI treatment. Methods: Clinicopathological information from 127 patients was collected and divided into different groups based on the exercise-based CR received, including Continuous Resistance Exercise (COR), Continuous Aerobic Exercise (COA), Interval Resistance Exercise (IVR), Interval Aerobic Exercise (IVA), Inspiratory Muscle Exercises (ITM), and Control. The differences regarding cardio-pulmonary function, hemodynamics, and life quality were analyzed against different CR strategies. Results: All the exercise-based CR strategies showed improving effects compared with patients in the Control group regarding cardio-pulmonary parameters, with IVR showing the strongest improving effects (IVR > ITM > COR > IVA > COA) (p < 0.05) at the first recoding point. However, the improving effects of exercise-based CR declined with time. Regarding the effects on hemodynamics parameters, the improving effects of exercise-based CR were only observed regarding LVEF, and the effects of IVR were also the strongest (IVR > COR > ITM > COA > IVA) (p < 0.05). Similar improving effects were also observed for 6MWT and life quality (IVR showing the strongest improving effects) (p < 0.05), which all declined three months after the surgery. Conclusions: The current study showed that exercise-based CRs had better improving effects than the normal nursing strategy on the prognosis of AMI patients receiving PCI surgery.

The association between trimethylamine N-oxide levels and ischemic stroke occurrence: a meta-analysis and Mendelian randomization study.

BACKGROUND: Trimethylamine-N-oxide (TMAO), an intestinal microbiota-derived choline metabolite, has been found to be associated with ischemic stroke (IS) in more and more studies. However, the causal role of TMAO on IS occurrence remains perplexing. METHODS: We comprehensively screened the related clinical studies on PubMed, Web of Science, and Embase. Case-control and cohort studies that reported the TMAO levels of both IS patients and healthy controls were included, and the risk of bias was assessed according to the criteria by the Centre for Evidence-Based Medicine in Oxford, UK. A meta-analysis of the retrieved publications was performed with a random-effect model to analyze the connection between TMAO levels and IS events. Besides, a Mendelian randomization (MR) analysis was performed to study the causal effect of TMAO on IS, with pooled data of TMAO and IS obtained from genome-wide association studies (GWAS). The following methods were used: MR-Egger, weighted median, inverse-variance weighted, simple mode, and weighted mode. The study has been registered in INPLASY (Registration number: INPLASY2023100027). RESULTS: Eight cohort or case-control studies covering 2444 cases and 1707 controls were identified. The pooled data indicated that the IS patients tended to have higher TMAO levels compared with the controls (mean difference: 1.97 µM; 95% confidence interval [CI]: 0.87, 3.07; P = 0.0005), while distinctive heterogeneity (I2 = 96%, P < 0.00001) was observed. Sub-group analysis revealed that the heterogeneity of the studies might be derived from the studies themselves. However, no causal effect of TMAO on IS was observed (P > 0.05) in the Mendelian randomization analysis of this study. CONCLUSION: We confirmed that IS patients tend to have higher TMAO levels than healthy individuals, while our findings of MR analysis did not support the causal role of TMAO in IS occurrence. Therefore, more studies are required for a better understanding of the relationship between TMAO levels and IS onset.

Smurf1 polyubiquitinates on K285/K282 of the kinases Mst1/2 to attenuate their tumor-suppressor functions.

Sterile 20-like kinases Mst1 and Mst2 (Mst1/2) and large tumor suppressor 1/2 are core kinases to mediate Hippo signaling in maintaining tissue homeostasis. We have previously demonstrated that Smad ubiquitin (Ub) regulatory factor 1 (Smurf1), a HECT-type E3 ligase, ubiquitinates and in turn destabilizes large tumor suppressor 1/2 to induce the transcriptional output of Hippo signaling. Here, we unexpectedly find that Smurf1 interacts with and polyubiquitinates Mst1/2 by virtue of K27- and K29-linked Ub chains, resulting in the proteasomal degradation of Mst1/2 and attenuation of their tumor-suppressor functions. Among the potential Ub acceptor sites on Mst1/2, K285/K282 are conserved and essential for Smurf1-induced polyubiquitination and degradation of Mst1/2 as well as transcriptional output of Hippo signaling. As a result, K285R/K282R mutation of Mst1/2 not only negates the transcriptional output of Hippo signaling but enhances the tumor-suppressor functions of Mst1/2. Together, we demonstrate that Smurf1-mediated polyubiquitination on K285/K282 of Mst1/2 destabilizes Mst1/2 to attenuate their tumor-suppressor functions. Thus, the present study identifies Smurf1-mediated ubiquitination of Mst1/2 as a hitherto uncharacterized mechanism fine-tuning the Hippo signaling pathway and may provide additional targets for therapeutic intervention of diseases associated with this important pathway.

A primary Rosai-Dorfman-Destombes disease of the scalp: case report and literature review.

Background: Rosai-Dorfman-Destombes disease (RDD) was first described in 1965 as a benign histiocytic proliferative disorder of unknown cause. Cases of RDD limited to cutaneous tissue have been reported over the past few decades, but single cutaneous RDD of the scalp is rare. Case presentation: We report a 31-year-old male with a lump on the parietal scalp without extranodal lesion lasting 1 month with gradual enlargement. The surgical incision ruptured with purulent after the first resection. Then the patient was treated with plastic surgery after disinfection and antibiotic treatment. Finally, he recovered well and discharged after 20 days. Conclusions: RDD of the scalp is rare. Surgical incision can cure the lesion but it may become infected because of increased lymphocytic infiltration. Early diagnosis and differential diagnosis of RDD are necessary. For treatment, individualized therapy is critical to patient prognosis.

Sarcopenia defined by the psoas muscle mass or quality is associated with poor survival in patients with aortic aneurysm undergoing surgery: A meta-analysis.

BACKGROUND: The impact of sarcopenia estimated by the skeletal muscle mass or quality on survival remains controversial in patients with aortic aneurysm. This meta-analysis aimed to assess the association between sarcopenia defined by the psoas muscle mass or quality and all-cause mortality in patients with aortic aneurysm. METHODS: We comprehensively searched PubMed, Web of Science, and Embase databases until December 31, 2022. Studies investigating the association of CT-derived psoas muscle mass (psoas muscle area [PSA] and psoas muscle index [PMI]) or quality (lean PSA [LPSA]) with all-cause mortality in patients with aortic aneurysm undergoing surgery were included. RESULTS: Eighteen studies reporting on 19 articles, enrolling 4767 patients were identified. A comparison of the bottom with the top psoas muscle mass, the pooled adjusted hazard ratios (HR) of all-cause mortality was 2.34 (95% confidence intervals [CI] 1.58-3.47). Low psoas muscle mass was associated with an increased risk of all-cause mortality when defined by the PSA (HR 2.01; 95% CI 1.42-2.75) or PMI (HR 2.37; 95% CI 1.24-4.55). Per 1 cm2 PMA increase conferred a 10% reduction in all-cause mortality. Patients with bottom LPMA had an increased risk of all-cause mortality (HR 3.27; 95% CI 1.90-5.60). Each 100 cm2 × HU LPMA increase conferred a 15% reduction in all-cause mortality. CONCLUSIONS: Sarcopenia defined by the low psoas muscle mass or quality independently predicts all-cause mortality in patients with aortic aneurysm. However, the overall certainty of evidence for the categorical analysis of psoas muscle mass was downgraded by the presence of publication bias and significant heterogeneity.

Trigeminal Nerve Isolation Application in Microvascular Decompression for Treating Trigeminal Neuralgia: A Retrospective Study.

This study aimed to compare the outcomes of trigeminal nerve isolation (TNI) with conventional microvascular decompression (CMVD) in cases of trigeminal neuralgia (TN). We retrospectively reviewed 143 TN cases who underwent microvascular decompression from January 2017 to January 2020. The surgical management of TNI or CMVD in all patients was randomized. The cases were divided into two groups, one group underwent a TNI and the other one received CMVD. The general data, postoperative outcomes, and complications were reviewed retrospectively. Cases with a narrow cistern of cerebellopontine, short trigeminal nerve root, and arachnoid adhesion were defined as difficult cases. All of the cases were followed up for at least 1 year. Surgical outcomes were assessed and compared between the two groups. In results, we found no significant differences in the general data, duration of hospitalization and blood loss between the two procedures. However, of the 143 cases, 12 cases (17.1%) recurred after surgery in the CMVD group, and four cases (5.5%) recurred after TNI operation. The rates of pain relief were 69 (94.5%) in the CMVD group, and 58 (82.9%) for TNI ( P =0.027). In the TNI group, there was only one difficult case among four no pain-relief cases, while in the CMVD group, 10 difficult cases were found among the 12 no pain-relief cases ( P =0.008). In conclusion, the TNI technique is more effective than the CMVD procedure and could also be performed on patients with classical TN. Future double-blind and randomized controlled trials are necessary to confirm this result.

Structural plasticity of the contralesional hippocampus and its subfields in patients with glioma.

OBJECTIVES: To characterize the structural plasticity of the contralesional hippocampus and its subfields in patients with unilateral glioma. METHODS: 3D T1-weighted MRI images were collected from 55 patients with tumors infiltrating the left (HipL, n = 27) or right (HipR, n = 28) hippocampus, along with 30 age- and sex-matched healthy controls (HC). Gray matter volume differences of the contralesional hippocampal regions and three control regions (superior frontal gyrus, caudate nucleus, and superior occipital gyrus) were evaluated using voxel-based morphometry (VBM) analyses. Volumetric differences in the hippocampus and its subregional volume were measured using the FreeSurfer software. RESULTS: Compared with HC, patients with unilateral hippocampal glioma exhibited significantly larger gray matter volume in the contralesional hippocampus and parahippocampal regions (cluster = 571 voxels for HipL; cluster 1 = 538 voxels and cluster 2 = 88 voxels for HipR; family-wise error corrected p < 0.05). No significant alterations were found in control regions. Volumetric analyses showed the same trend in the contralesional hippocampal subregions for both patient groups, including the CA1 head, CA3 head, hippocampus amygdala transition area (HATA), fimbria, and the granule cell molecular layer of the dentate gyrus head (GC-ML-DG head). Notably, the differences of the contralesional HATA (HipL: η2 = 0.418, corrected p = 0.002; HipR: η2 = 0.313, corrected p = 0.052) and fimbria (HipL: η2 = 0.450, corrected p < 0.001; HipR: η2 = 0.358, corrected p = 0.012) still held after the Bonferroni correction. CONCLUSIONS: Our findings provide evidence for macrostructural plasticity of the contralateral hippocampus in patients with unilateral hippocampal glioma. Specifically, HATA and fimbria exhibit great potential in this process. KEY POINTS: • Glioma infiltration of the hippocampal regions induces a significant increase in gray matter volume on the contralateral side. • Specifically, the HATA and fimbria regions exhibit favorable plastic potential in the process of lesion-induced structural remolding.

Synergistic structural and functional alterations in the medial prefrontal cortex of patients with high-grade gliomas infiltrating the thalamus and the basal ganglia.

Background: High-grade gliomas (HGGs) are characterized by a high degree of tissue invasion and uncontrolled cell proliferation, inevitably damaging the thalamus and the basal ganglia. The thalamus exhibits a high level of structural and functional connectivity with the default mode network (DMN). The present study investigated the structural and functional compensation within the DMN in HGGs invading the thalamus along with the basal ganglia (HITBG). Methods: A total of 32 and 22 healthy controls were enrolled, and their demographics and neurocognition (digit span test, DST) were assessed. Of the 32 patients, 18 patients were involved only on the left side, while 15 of them were involved on the right side. This study assessed the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), gray matter (GM) volume, and functional connectivity (FC) within the DMN and compared these measures between patients with left and right HITBG and healthy controls (HCs). Result: The medial prefrontal cortex (mPFC) region existed in synchrony with the significant increase in ALFF and GM volume in patients with left and right HITBG compared with HCs. In addition, patients with left HITBG exhibited elevated ReHo and GM precuneus volumes, which did not overlap with the findings in patients with right HITBG. The patients with left and right HITBG showed decreased GM volume in the contralateral hippocampus without any functional variation. However, no significant difference in FC values was observed in the regions within the DMN. Additionally, the DST scores were significantly lower in patients with HITBG, but there was no significant correlation with functional or GM volume measurements. Conclusion: The observed pattern of synchrony between structure and function was present in the neuroplasticity of the mPFC and the precuneus. However, patients with HITBG may have a limited capacity to affect the connectivity within the regions of the DMN. Furthermore, the contralateral hippocampus in patients with HITBG exhibited atrophy. Thus, preventing damage to these regions may potentially delay the progression of neurological function impairment in patients with HGG.

Radiogenomics to characterize the immune-related prognostic signature associated with biological functions in glioblastoma.

OBJECTIVES: The tumor microenvironment and immune cell infiltration (ICI) associated with glioblastoma (GBM) play a vital role in cancer development, progression, and prognosis. This study aimed to establish an ICI-related prognostic biomarker and explore the associations between ICI signatures and radiomic features in patients with GBM. METHODS: The gene expression and survival data of patients with GBM were obtained from three databases. Based on the ICI pattern, an individualized ICI score for each GBM patient was developed in the discovery set (n = 400) and independently verified in the validation set (n = 374). A total of 5915 radiomic features were extracted from the intratumoral and peritumoral regions. Recursive feature elimination and support vector machine methods were performed to select the key features and generate a model predictive of low- or high- ICI scores. The prognostic value of the identified radio genomic model was examined in an independent dataset (n = 149) using imaging and survival data. RESULTS: We found that higher ICI scores often indicated worse patient prognosis (multivariable hazard ratio: 0.48 and 0.63 in discovery and validation set, respectively) and higher expression levels of immune checkpoint-related genes. A model that combined 11 radiomic features could well distinguish tumors with different ICI scores (AUC = 0.96, accuracy = 94%). This model was proven to be helpful for noninvasive prognostic stratification in an independent validation cohort. CONCLUSIONS: ICI scores may serve as an effective prognostic biomarker to characterize potential biological processes in patients with GBM. This ICI signature can be evaluated noninvasively through radiogenomic analysis. KEY POINTS: • Immune cell infiltration (ICI) scores can serve as an effective prognostic biomarker in patients with glioblastoma. • The ICI signature can be evaluated noninvasively through radiomic features derived from the intratumoral and peritumoral regions. • The prognostic value of the radiogenomic model can be verified by independent survival and MRI data.

Radiomics-Based Machine Learning to Predict Recurrence in Glioma Patients Using Magnetic Resonance Imaging.

OBJECTIVE: Recurrence is a major factor in the poor prognosis of patients with glioma. The aim of this study was to predict glioma recurrence using machine learning based on radiomic features. METHODS: We recruited 77 glioma patients, consisting of 57 newly diagnosed patients and 20 patients with recurrence. After extracting the radiomic features from T2-weighted images, the data set was randomly divided into training (58 patients) and testing (19 patients) cohorts. An automated machine learning method (the Tree-based Pipeline Optimization Tool) was applied to generate 10 independent recurrence prediction models. The final model was determined based on the area under the curve (AUC) and average specificity. Moreover, an independent validation set of 20 patients with glioma was used to verify the model performance. RESULTS: Recurrence in glioma patients was successfully predicting by machine learning using radiomic features. Among the 10 recurrence prediction models, the best model achieved an accuracy of 0.81, an AUC value of 0.85, and a specificity of 0.69 in the testing cohort, but an accuracy of 0.75 and an AUC value of 0.87 in the independent validation set. CONCLUSIONS: Our algorithm that is generated by machine learning exhibits promising power and may predict recurrence noninvasively, thereby offering potential value for the early development of interventions to delay or prevent recurrence in glioma patients.

Case report: Significance of the large rhomboid lip in microvascular decompression: insights from two clinical cases.

The rhomboid lip (RL) is a layer of neural tissue that extends outside the fourth ventricle and is connected to the lateral recess of the fourth ventricle. Although this anatomical structure has been rigorously studied, it is often overlooked in microvascular decompression (MVD) surgery. In this report, we present two cases, one of hemifacial spasm (HFS) and one of glossopharyngeal neuralgia (GPN), in which a large RL was observed during surgery. We found that a large RL is easily confused with arachnoid cysts, and accurate identification and dissection are important to protect the lower cranial nerves.

First-in-human study to investigate the safety and pharmacokinetics of salvianolic acid A and pharmacokinetic simulation using a physiologically based pharmacokinetic model.

Salvianolic acid A (SAA) is a water-soluble phenolic acid component from Salvia miltiorrhiza Bunge currently under development for myocardial protection treatment for coronary heart disease (CHD). We investigated the safety, tolerability, and pharmacokinetics of single and multiple ascending doses of SAA. Additionally, a physiologically based pharmacokinetic (PBPK) model was developed to simulate the pharmacokinetics of SAA. This was a first-in-human (FIH), randomized, double-blind, placebo-controlled, single, and multiple-dose study in 116 healthy Chinese subjects with the range of 10-300 mg and 60-200 mg SAA, respectively. SAA was well tolerated at all dose levels, following both single and multiple doses, with a low overall incidence of treatment-emergent adverse events (TEAEs) which appeared to be no dose-related. The main pharmacokinetic parameter of SAA, assessed by the power model, was the lack of proportionality with the dose range after single dosing. The 90% CIs of the slope ß of Cmax (1.214 [1.150-1.278]) and AUC0-t (1.222 [1.156-1.288]) were not within the predefined acceptance range, and the direction of the deviation was higher than expected. PBPK modeling suggested the transfer ability saturation of hepatic organic anion-transporting polypeptide 1B1 (OATP1B1) and P-glycoprotein (P-gp) might result in a relatively low distribution rate at higher doses. Clinical plasma concentrations observed were in good agreement with PBPK prediction. SAA showed well-characterized pharmacokinetics and was generally well tolerated in the dose range investigated. The PBPK model provides valuable pharmacokinetic knowledge for further clinical development.