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Background: Cumulative evidence has suggested that vitamin D deficiency is related with an increased susceptibility to various types of cancers. However, the association between vitamin D and thyroid cancer (TC) has remained to be unknown. Thus, there has been an urgent need for a meta-analysis to summarize existing evidence on vitamin D levels and the risk of TC. Objective: This meta-analysis aimed to figure out the association between vitamin D level and the risk of TC. Methods: A systematic search was performed for eligible articles on the association between vitamin D and TC based on PubMed, Embase, Web of Science, Cochrane, and ClinicalTrials.gov. Outcomes were the vitamin D level of cases with TC and the incidence of vitamin D deficiency in cases with TC comparing with the controls. The effect measures included standardized mean difference (SMD), ratio of means (RoM), and odds ratio (OR). A dose-response meta-analysis was performed to assess the correlation between vitamin D level and the risk of TC. Subgroup analyses and meta-regressions were conducted to explore the source of heterogeneity. And publication bias was evaluated through Begg's and Egger's tests. Results: Results of the meta-analysis revealed lower levels of vitamin D in TC cases comparing with those in control [SMD = -0.25, 95% CI: (-0.38, -0.12); RoM = 0.87, 95% CI: (0.81, 0.94)] and the levels of 1,25 (OH)D in cases with TC were also lower than controls [SMD = -0.49, 95% CI: (-0.80, -0.19); RoM = 0.90, 95% CI: (0.85, 0.96)]. And vitamin D deficiency was associated with the increased risk of TC [OR = 1.49, 95% CI: (1.23, 1.80)]. Additionally, results from the dose-response meta-analysis showed that there is a 6% increase in the risk of TC for each 10 ng/ml decrease in 25 (OH)D levels [OR = 0.94; 95% CI: (0.89, 0.99)]. Conclusions: Individuals with TC had lower levels of vitamin D compared to controls, and vitamin D deficiency was correlated with an increase risk of TC. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=504417, identifier: CRD42024504417.
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Diabetes is a widespread chronic disease that occurs mainly in the elderly population. Due to the difference in pathophysiology between elderly and young patients, the current clinical practice to treat elderly patients with anti-diabetes medications still faces some challenges and dilemmas, such as the urgent need for early diagnosis and prevention, and an imbalance between restricted dietary intake and the risk of undernutrition. Traditional Chinese medicine (TCM) offers various treatment regimens that are actively utilized in the field of diabetes management. Through multiple targets and multiple pathways, TCM formulas, medicinal herbs, and active natural products enhance the efficacy of diabetes prevention and diabetes control measures, simplify complex medication management, and improve common symptoms and common diabetic complications in elderly people. Historically, natural products have played a key role in material composition analysis of TCM and mechanism interpretation to enable drug discovery. However, there have been few conclusions on this topic. This review summarizes the development of TCM for the prevention and management of diabetes in elderly people, existing evidence-based clinical practices, and prospects for future development.
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Objective: To review studies on digital medicine in cardiovascular diseases (CVD), discuss its development process, knowledge structure and research hotspots, and provide a perspective for researchers in this field. Methods: The relevant literature in recent 20 years (January 2004 to October 2022) were retrieved from the Web of Science Core Collection (WoSCC). CiteSpace was used to demonstrate our knowledge of keywords, co-references and speculative frontiers. VOSviewer was used to chart the contributions of authors, institutions and countries and incorporates their link strength into the table. Results: A total of 5265 English articles in set timespan were included. The number of publications increased steadily annually. The United States (US) produced the highest number of publications, followed by England. Most publications were from Harvard Medicine School, followed by Massachusetts General Hospital and Brigham Women's Hospital. The most authoritative academic journal was JMIR mHealth and uHealth. Noseworthy PA may have the highest influence in this intersected field with the highest number of citations and total link strength. The utilization of wearable mobile devices in the context of CVD, encompassing the identification of risk factors, diagnosis and prevention of diseases, as well as early intervention and remote management of diseases, has been widely acknowledged as a knowledge base and an area of current interest. To investigate the impact of various digital medicine interventions on chronic care and assess their clinical effectiveness, examine the potential of machine learning (ML) in delivering clinical care for atrial fibrillation (AF) and identifying early disease risk factors, as well as explore the development of disease prediction models using neural networks (NNs), ML and unsupervised learning in CVD prognosis, may emerge as future trends and areas of focus. Conclusion: Recently, there has been a significant surge of interest in the investigation of digital medicine in CVD. This initial bibliometric study offers a comprehensive analysis of the research landscape pertaining to digital medicine in CVD, thereby furnishing related scholars with a dependable reference to facilitate further progress in this domain.
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Diabetic vascular complications (DVCs), including macro- and micro- angiopathy, account for a high percentage of mortality in patients with diabetes mellitus (DM). Endothelial dysfunction is the initial and role step for the pathogenesis of DVCs. Hyperglycemia and lipid metabolism disorders contribute to endothelial dysfunction via direct injury of metabolism products, crosstalk between immunity and inflammation, as well as related interaction network. Although physiological and phenotypic differences support their specified changes in different targeted organs, there are still several common mechanisms underlying DVCs. Also, inhibitors of these common mechanisms may decrease the incidence of DVCs effectively. Thus, this review may provide new insights into the possible measures for the secondary prevention of DM. And we discussed the current limitations of those present preventive measures in DVCs research. Video Abstract.
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Diabetes Mellitus , Angiopatías Diabéticas , Hiperglucemia , Humanos , Endotelio Vascular/metabolismo , Angiopatías Diabéticas/etiología , Angiopatías Diabéticas/metabolismo , Hiperglucemia/complicaciones , Inflamación/complicaciones , Inflamación/metabolismoRESUMEN
BACKGROUND: Immune checkpoint inhibitors (ICIs) with angiogenesis inhibitors have been used to treat advanced lung cancer. Their associated treatment-related adverse events (trAEs) are currently considered acceptable; however, no conclusion has been reached. We aimed to summarize the trAEs caused by ICIs combined with angiogenesis inhibitors in patients with advanced lung cancer. METHODS: Pulled studies met the following criteria: patients with advanced lung cancer who received treatment involving ICIs combined with angiogenesis inhibitors (with or without chemotherapy) in interventional or observational studies. Results included the type and number of trAEs or immune-related adverse events (irAEs), treatment-associated discontinuation and mortality, overall survival (OS), and progression-free survival (PFS). PROSPERO: CRD42022337656. RESULTS: The study enrolled 32 trials involving 2313 patients who had 7768 any-grade trAEs and 1078 grade ≥3 trAEs. The pooled incidences were 87.33% (95% confidence interval [CI]: 79.49-93.65; I2 = 94.04%) for any-grade trAEs, and 38.63% (95% CI: 28.28-49.50; I2 = 95.61%) for grade ≥3 trAEs. There were 132 kinds of any-grade trAEs involving 18 systems, and 99 kinds of grade ≥3 trAEs involving 16 systems. For all trAEs, we observed significant differences in the line of therapy, trial design, therapy combination, and types of angiogenesis inhibitors (all P < 0.05). The rate of trAEs increased with dosage and frequency of medication. Pooled incidences of discontinuation and mortality were 10.64% and 0.81%, respectively. Nearly 647 patients experienced irAEs, including 636 any-grade irAEs and 154 grade ≥3 irAEs. CONCLUSIONS: Overall, the incidence of trAEs caused by ICIs combined with angiogenesis inhibitors is generally acceptable. These trAEs have a wide spectrum nearly covering the full range of adverse events. Grade ≥3 trAEs are more closely associated with angiogenesis inhibitors than any grade. However, treatment-associated mortality remains concerning.
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Inhibidores de la Angiogénesis , Neoplasias Pulmonares , Humanos , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Supervivencia sin ProgresiónRESUMEN
Background: Immune checkpoint inhibitors (ICIs) have changed the situation of tumor therapy in recent years. However, for security reasons, those special populations are often excluded from clinical trials, such as infected hepatitis B or hepatitis C patients. ICIs are systematically reviewed and meta-analyzed for the first time in patients infected with hepatitis B or C in this paper. Methods: The relevant studies were searched in PubMed, EMBASE, Cochrane Library, and Web of Science until October 2022. Trials and observational studies meeting the inclusion criteria were included. The outcomes included the effectiveness of ICIs in patients with HBC/HCV (ORR, DCR, mOS, and mPFS), the incidence of adverse reactions, high-grade adverse reactions, and abnormal liver enzymes. At the same time, these indexes were compared with those of uninfected patients. Results: A total of 2,625 patients were enrolled, involving 1,179 patients with hepatitis (HBV or HCV). We found that ICIs showed higher ORR (25.80% vs. 18.10%) and DCR (66.22% vs. 58.74%) in patients with hepatitis B/C than those without infection. In terms of survival time, patients with hepatitis virus infection showed longer mOS (15.44 m vs. 13.30 m) but shorter mPFS (4.94 m vs. 5.01 m) than uninfected patients. As for safety data, patients with hepatitis showed a lower incidence of all-grade irAEs (68.02% vs. 70.43%) than uninfected patients, while that of 3-4 irAEs (21.27% vs. 21.79%) was similar in the two groups. However, hepatic dysfunction was more common and serious in hepatitis patients. Four HBVr and no HCVr were observed. Conclusion: According to this meta-analysis, ICIs are effective and safe for patients with hepatitis B or C, but basic liver enzymes have to be evaluated before treatment to avoid liver adverse events.
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Background: Radiomics have been increasingly used in the clinical management of hepatocellular carcinoma (HCC), such as markers prediction. Ki-67 and cytokeratin 19 (CK-19) are important prognostic markers of HCC. Radiomics has been introduced by many researchers in the prediction of these markers expression, but its diagnostic value remains controversial. Therefore, this review aims to assess the diagnostic value of radiomics in predicting Ki-67 and CK-19 expression in HCC. Methods: Original studies were systematically searched in PubMed, EMBASE, Cochrane Library, and Web of Science from inception to May 2023. All included studies were evaluated by the radiomics quality score. The C-index was used as the effect size of the performance of radiomics in predicting Ki-67and CK-19 expression, and the positive cutoff values of Ki-67 label index (LI) were determined by subgroup analysis and meta-regression. Results: We identified 34 eligible studies for Ki-67 (18 studies) and CK-19 (16 studies). The most common radiomics source was magnetic resonance imaging (MRI; 25/34). The pooled C-index of MRI-based models in predicting Ki-67 was 0.89 (95% CI:0.86-0.92) in the training set, and 0.87 (95% CI: 0.82-0.92) in the validation set. The pooled C-index of MRI-based models in predicting CK-19 was 0.86 (95% CI:0.81-0.90) in the training set, and 0.79 (95% CI: 0.73-0.84) in the validation set. Subgroup analysis suggested Ki-67 LI cutoff was a significant source of heterogeneity (I 2 = 0.0% P>0.05), and meta-regression showed that the C-index increased as Ki-67 LI increased. Conclusion: Radiomics shows promising diagnostic value in predicting positive Ki-67 or CK-19 expression. But lacks standardized guidelines, which makes the model and variables selection dependent on researcher experience, leading to study heterogeneity. Therefore, standardized guidelines are warranted for future research. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023427953.
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Diabetes mellitus has become a major public health issue globally, putting an enormous burden on global health systems and people. Among all diseased groups, a considerable part of patients are elderly, while their clinical features, pathogenic processes, and medication regimens are different from patients of other ages. Despite the availability of multiple therapies and techniques, there are still numerous elderly diabetes patients suffering from poor blood glucose control, severe complications, and drug adverse effects, which negatively affect the quality of life in their golden years. Traditional Chinese Medicine (TCM) has been widely used in the treatment of diabetes for several decades, and its relevant clinical practice has confirmed that it has a satisfactory effect on alleviating clinical symptoms and mitigating the progression of complications. Chinese herbal medicine and its active components were used widely with obvious clinical advantages by multiple targets and signaling pathways. However, due to the particular features of elderly diabetes, few studies were conducted to explore Traditional Chinese Medicine intervention on elderly diabetic patients. This study reviews the research on clinical features, pathogenic processes, treatment principles, and TCM treatments, hoping to provide fresh perspectives on the prevention and management strategies for elderly diabetes.
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Background: Extensive-stage small-cell lung cancer (ES-SCLC) is highly malignant, is highly prone to recurrence, and has a short survival period. It is very difficult to achieve long-term survival in ES-SCLC, which has not been significantly improved in the last 20 years. For a long time, platinum-based chemotherapy has occupied the core position in the treatment of small-cell lung cancer (SCLC), but there are few options for treatment drugs or regimens, and if disease progression occurs, the options for follow-up regimens are obviously limited. The advent of immunotherapy has changed this situation to some extent, and immunotherapy has shown some effects in improving efficiency and prolonging survival, whether in first- or third-line therapy, but it is still unsatisfactory. Case presentation: A 57-year-old patient with ES-SCLC experienced disease progression after four lines of treatment including synchronous radiotherapy, chemotherapy, and antiangiogenesis. However, the patient still benefited when switching to the programmed cell death receptor-1 (PD-1) inhibitor toripalimab in combination with chemotherapy in the fifth line. Even after the development of immune resistance, the patient still benefited after switching to tislelizumab in combination with different chemotherapy regimens or alone in the sixth and seventh lines. Following the progression of tislelizumab in combination with chemotherapy, the patient again profited after switching to durvalumab in combination with anlotinib and again achieved a progressive-free survival (PFS) of 11 months. Overall, the patient achieved a total of 45 months of PFS and 50 months of overall survival (OS), with a shocking and exciting 30 months of PFS achieved in the immune combination phase alone. Conclusion: We report a patient with ES-SCLC who achieved long-term survival after at least eight lines of therapy including chemotherapy, antiangiogenesis, and different immune checkpoint inhibitors (ICIs). This suggests that long-term survival in SCLC is possible with aggressive, combined, and standardized treatment. Otherwise, immunotherapy postline enablement can still benefit patients, rechallenge after immune resistance is also possible in SCLC, and combination with chemotherapy or antiangiogenic therapy can improve the efficacy and prolong the survival. This will provide new ideas and options for the selection of treatment options for SCLC.
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Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Persona de Mediana Edad , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/patología , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/patología , Inmunoterapia , Progresión de la EnfermedadRESUMEN
Lung cancer is the leading cause of cancer-related death worldwide. A meta-analysis was conducted to assess the benefits and risks of neoadjuvant immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). Online databases, including PubMed, Embase, Web of Science, Cochrane Library, and clinicaltrials.gov, were retrospectively and systematically searched for eligible trials from database inception to May 2021. A total of 792 patients from 21 clinical trials were included. For surgical data, the pooled operation rate and R0 resection rate were 92% (95% CI 87-96%) and 97% (95% CI 94-99%). Additionally, neoadjuvant ICIs achieved a major pathological response (MPR) of 39% (95% CI 25-53%), including 25% (95% CI 16-36%) pathological complete response (pCR). With radiological response assessment, the pooled objective response rate (ORR) and disease control rate (DCR) were 44% (95% CI 21-68%) and 88% (95% CI 75-98%), respectively. In terms of safety, the pooled rate of any-grade and grade 3-5 treatment-related adverse effects (TRAEs) were 57% (95% CI 38-76%) and 15% (95% CI 6-28%). Eventually, the study concludes that neoadjuvant ICIs are effective and safe for patients with early-stage NSCLC. Key Words: Neoadjuvant therapy, Immune checkpoint inhibitors, Non-small cell lung cancer, Meta-analysis.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Terapia Neoadyuvante , Estudios RetrospectivosRESUMEN
Background: Immune checkpoint inhibitors (ICIs) emerge as the first-line treatment of lung adenocarcinoma (LUAD); selection of subpopulations acquiring clinical benefit is required. Associations between epigenetic modulation of tumor microenvironment (TME) and clinical outcome are far from clear. We focused on immune-related genes closely regulated by DNA methylation to identify the potential clinical outcome indicators. Methods: We systematically calculated immunophenotype score (IMpS) and classified immunophenotypes based on seven TME features in three independent cohorts. The overlapping of differential expressed genes and methylated probes targeted genes was regarded as genes closely regulated by DNA methylation. Then, probe/gene pairs which highly correlated with each other and IMpS were identified and named as immune-related probe/gene pairs (mIMg). Prognostic mIMg were selected and verified in seven independent validation cohorts. Results: Three immune phenotypes were clustered, and similar results were obtained in the three independent training cohorts. C2 displayed as an immunologically hot phenotype, whereas C3 corresponded with immunologically cold phenotype. Average methylation level was decreased from C2 to C3 (C2 > C1 > C3). Similarly, ICIs nonresponders showed global hypo-methylation compared with responders. Genes in mIMg were mainly enriched, especially in T-cell receptor activation, and repressed in noninflamed TME by hyper-methylation. Among mIMg, low expression and hyper-methylation of CD247, LCK, and PSTPIP1 were risk factors of overall survival (OS). ICIs nonresponders were more likely to be hyper-methylated in the three genes. By integrating with the oncogenes status, we demonstrated that EGFR wt and SRGN overexpressed patients were associated with chronic inflammation and immune evasion, showing an immunologically hot phenotype, which might lead to the short OS but derive clinical benefit from ICIs. Conclusions: This study identifies hyper-methylation and concurrent repression of CD247, LCK, PSTPIP1 as immune negative indicators and risk factors for prognosis in LUAD. Moreover, EGFR/SRGN axis may participate in immune modification to influence ICIs response and clinical outcome in LUAD.
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BACKGROUND: Mounting randomized clinical trials have proved that immune checkpoint inhibitors (ICIs) achieved better overall survival (OS) and progression-free survival (PFS) than chemotherapy drugs for advanced non-small cell lung cancer (NSCLC) patients. However, some literatures have indicated that different sexes might not have equal immune response. Also, no agreement reached on the issue whether therapeutic benefit of ICIs is related to sex. OBJECTIVES: To explore the association between efficacy of ICIs for NSCLC patients and their sexes and summarize overall treatment-related adverse events (TRAEs) in an exploratory manner. METHODS: We performed this systematic review and meta-analysis of all potentially relevant studies retrieved from PubMed, EMBASE, and the Cochrane Library until June 2021, for eligible randomized controlled trials (RCTs) comparing immunotherapy with chemotherapy in advanced NSCLC patients. Literature screening, summary data extraction was performed independently and in duplicate. The pooled hazard ratio (HR) and 95% confidence interval (CI) of OS, PFS and TRAEs were calculated, applying STATA software and random-effects models. This study was registered in international prospective register of systematic reviews (PROSPERO), number CRD42020210797. RESULTS: Twenty-one trials involving 12,675 NSCLC patients were included. For patients with advanced NSCLC, ICIs significantly prolonged the OS (males: HR 0.73, 95%CI 0.67-0.79; females: HR 0.73, 95%CI 0.61-0.85) and PFS (males: HR 0.62, 95%CI 0.55-0.70; females: HR 0.68, 95%CI 0.55-0.81) versus chemotherapy. Overall, there was no statistical difference between their sexes (OS: P = 0.97; PFS: P = 0.43), respectively. Owing to insufficient TRAEs data of different sexes, we only found immunotherapy for NSCLC patients had more all-grades (RR 0.88; 95%CI 0.82-0.95) and 3-5 grades (RR 0.60; 95%CI 0.47-0.75) AEs compared with chemotherapy. CONCLUSION: Our findings indicated that the interaction between immunotherapy efficacy and different sexes was equally evident. Overall, patients with NSCLC could obtain more benefits from ICIs than chemotherapy regimen regardless of their sexes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (https://www.crd.york.ac.uk/prospero/), identifier CRD42020210797.
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BACKGROUND: The method to evaluate the efficacy of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors has become a big concern for researchers with its widely application. Pseudoprogressive disease (PPD) makes this process more difficult, which means that the tumor progressed at the initial evaluation, but re-evaluation after continued treatment suggested that the treatment was effective. However, PPD has not attracted enough attention of clinical doctors. This article is to systematically evaluate the incidence of PPD associated with PD-1/PD-L1 inhibitors with meta-analysis, to provide guidance for the recognition and management of PPD. METHODS: The databases of PubMed, EMBase, Cochrane Library were retrieved from the earliest collection date of the databases until Dec 5, 2019. The search terms of "pseudoprogressive disease, anti-PD-1, anti-PD-L1, PD-1/PD-L1 inhibitor, etc" were used for logistic combination search. Published studies on PPD caused by PD-1/PD-L1 inhibitors were included. Meta-analysis was performed with Stata 15.1. Subgroup analysis was performed according to the study population, tumor type, and evaluation criteria for efficacy. RESULTS: Seven researches, including 1458 patients were taken into the study. Meta-analysis showed that the overall incidence of PPD was 3.70% (95% confidence interval [CI]: 2.70%, 4.90%). Subgroup analysis showed that the incidence of PPD was 3.30% (95% CI: 1.90%, 5.90%) in non-small cell lung cancer patients and 5.10% (95% CI: 2.30%, 11.6%) in melanoma patients. There was no statistically significant difference between East and West populations and among various efficacy evaluation criteria. CONCLUSION: The incidence of PPD related to PD-1/PD-L1 inhibitors is not high, but the evaluation criteria has not yet been unified. Close monitoring, careful identification and proper application should be carried out in the clinic, and full management of the treatment with PD-1/PD-L1 inhibitors should be well done.
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Antígeno B7-H1/antagonistas & inhibidores , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Ensayos Clínicos como Asunto , Progresión de la Enfermedad , Humanos , Carga TumoralRESUMEN
Objective. In China, the method of clearing heat and removing dampness medicine of Chinese traditional medicine has been widely used on gout. However, the clinical effects are various and not summarized systematically. Methods. In this study, a large number of randomized controlled clinical trials were reviewed and analyzed and the clinical efficacy and adverse reactions of traditional Chinese medicine with clearing heat and removing dampness effects for the treatment of gout were systematically evaluated. A comprehensive search of databases including pubMed, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database, Wanfang Data, and SinoMed was performed. Results. There are 69 randomized controlled trials with 5915 sample sizes meeting the criteria in the study. The results of the meta-analysis indicate that the effects of clearing heat and removing dampness medicine were slightly better than western medicine in the treatment of gout based on the following parameters: serum uric acid (standardized mean difference (SMD):-62.14, 95% confidence interval (CI): -78.12 to-46.15), C reactive protein (SMD: -4.21, 95% CI: -6.19 to -2.23), erythrocyte sedimentation rate (SMD: -6.23, 95% CI: -8.39 to-4.06), and overall clinical response (relative risk (RR): 1.11, 95% CI: 1.08 to 1.15) and, in the profile of adverse drug reactions, the clearing heat and removing dampness medicine showed less adverse reactions than traditional Western medicine (RR: 0.18, 95% CI: 0.10 to 0.32). Conclusions. Through a systemic evaluation of the clinical efficacy of the clearing heat and removing dampness medicine of traditional Chinese medicine and western medicine on gout, the clearing heat and removing dampness medicine and western medicine possessed similar clinical efficacy, but traditional Chinese medicine treatments are superior to western medicine in controlling adverse reactions.