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1.
Ann Oncol ; 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39241963

ABSTRACT

BACKGROUND: Epstein-Barr virus-specific cytotoxic T lymphocyte (EBV-CTL) is an autologous adoptive T cell immunotherapy generated from the blood of individuals and manufactured without genetic modification. In a previous Phase 2 trial of locally recurrent or metastatic nasopharyngeal cancer (R/M NPC) patients, first-line gemcitabine and carboplatin (GC) and EBV-CTL combination demonstrated objective anti-tumor EBV-CTL activity and a favorable safety profile. The present study explored whether this combined first-line chemo-immunotherapy strategy would produce superior clinical efficacy and better quality of life compared to conventional chemotherapy treatment. PATIENTS AND METHODS: This multicenter, randomized, Phase 3 trial evaluated the efficacy and safety of GC followed by EBV-CTL vs. GC alone as first-line treatment for R/M NPC patients. Thirty clinical sites in Singapore, Malaysia, Taiwan, Thailand, and the United States (US) were included. Subjects were randomized to first-line GC (4 cycles) and EBV-CTL (6 cycles) or GC (6 cycles) in a 1:1 ratio. The primary outcome was overall survival (OS) and secondary outcomes included progression-free survival, objective response rate, clinical benefit rate, quality of life, and safety. CLINICALTRIALS: gov identifier: NCT02578641. RESULTS: 330 subjects with NPC were enrolled. Most subjects in both treatment arms received ≥4 cycles of chemotherapy and most subjects in the GC+EBV-CTL group received ≥2 infusions of EBV-CTL. The central Good Manufacturing Practices (GMP) facility produced sufficient EBV-CTL for 94% of GC+EBV-CTL subjects. The median OS was 25.0 months in the GC+EBV-CTL group and 24.9 months in the GC group (hazard ratio = 1.19; 95% CI: 0.91, 1.56; P = 0.194). Only 1 subject experienced a Grade 2 serious adverse event related to EBV-CTL. CONCLUSION: GC+EBV-CTL in subjects with R/M NPC demonstrated a favorable safety profile but no overall improvement in OS vs. chemotherapy. This is the largest adoptive T cell therapy trial reported in solid tumors to date.

2.
Physiol Res ; 73(4): 665-670, 2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39264086

ABSTRACT

Genetic features are currently unknown in myelinated retinal nerve fibers (MRNF). For a 20-year-old asymptomatic female with unilateral MRNF, we performed whole genome sequencing (WGS) by standard workflow protocol to produce contiguous long-read sequences with Illumina DNA PCR-Free Prep. After tagmentation, libraries were sequenced on separate runs via NovaSeq 6000 platform at 2 x 150bp read length. Gene variants included rs2248799, rs2672589, rs7555070, rs247616_T and rs2043085_C all associated with an increased macular degeneration risk, and seven novel variants of uncertain significance. For optic disc enlargement, variants rs9988687_A, rs11079419_T, rs6787363 and rs10862708_A suggested an increased risk for this condition. In contrast, modeling revealed retinal detachment risk was reduced by variants identified at rs9651980_T, rs4373767_T, and rs7940691_T which were among five other previously unreported variants. WGS data placed proband at the 66th and 64th percentiles for disc anomaly and retinal detachment risk, respectively. Additionally, risk determined from 16 loci associated with age-related macular degeneration found the patient to be at the 18th percentile for this diagnosis (i.e., below average genetic predisposition). Fundoscopic findings showed mean RNFL thickness was lower with MRNF (77 OS vs. 96?m OD) and RNFL symmetry was impaired (43 %) but stable between 2020 and 2023. Rim area and cup volume were also substantially different (2.33 OS vs. 1.34mm2 OD, and 0.001 OS vs. 0.151mm3 OD, respectively). As the first known evaluation of MRNF via WGS, these data reveal a mixed picture with variants associated with different risks for potentially related ocular pathologies. In addition, we identify multiple new variants of unknown significance. Factors affecting gene expression in MRNF require further study. Key words: Whole genome sequencing, Retina, Myelination, Anatomy, Gene variants.


Subject(s)
Nerve Fibers, Myelinated , Whole Genome Sequencing , Humans , Female , Young Adult , Nerve Fibers, Myelinated/pathology , Retina/pathology , Genetic Predisposition to Disease
3.
Am J Hematol ; 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39158218

ABSTRACT

Autologous hematopoietic cell transplantation (AHCT) is a commonly used treatment in multiple myeloma (MM). However, real-world global demographic and outcome data are scarce. We collected data on baseline characteristics and outcomes from 61 725 patients with newly diagnosed MM who underwent upfront AHCT between 2013 and 2017 from nine national/international registries. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), relapse incidence (RI) and non-relapse mortality (NRM). Median OS amounted to 90.2 months (95% CI 88.2-93.6) and median PFS 36.5 months (95% CI 36.1-37.0). At 24 months, cumulative RI was 33% (95% CI 32.5%-33.4%) and NRM was 2.5% (95% CI 2.3%-2.6%). In the multivariate analysis, superior outcomes were associated with younger age, IgG subtype, complete hematological response at auto-HCT, Karnofsky score of 100%, international staging scoring (ISS) stage 1, HCT-comorbidity index (CI) 0, standard cytogenetic risk, auto-HCT in recent years, and use of lenalidomide maintenance. There were differences in the baseline characteristics and outcomes between registries. While the NRM was 1%-3% at 12 months worldwide, the OS at 36 months was 69%-84%, RI at 12 months was 12%-24% and PFS at 36 months was 43%-63%. The variability in these outcomes is attributable to differences in patient and disease characteristics as well as the use of maintenance and macroeconomic factors. In conclusion, worldwide data indicate that AHCT in MM is a safe and effective therapy with an NRM of 1%-3% with considerable regional differences in OS, PFS, RI, and patient characteristics. Maintenance treatment post-AHCT had a beneficial effect on OS.

4.
Zhonghua Jie He He Hu Xi Za Zhi ; 47(7): 668-675, 2024 Jul 12.
Article in Chinese | MEDLINE | ID: mdl-38955754

ABSTRACT

Malignant pleural effusion (MPE) can be secondary to various advanced malignant tumors. Although systemic anti tumor therapy may be effective in primary tumors, it cannot reduce the accumulation of MPE in proportion of the patients. The interaction of tumor cells, immune cells, and mesenchymal cells, as well as the abnormal proliferation of tumor-associated blood vessels, together create an immunosuppressive microenvironment for MPE, which promotes the abnormal proliferation of tumor cells and the accumulation of MPE. With the in-depth study of the tumor microenvironment, the application of local systemic anti-tumor therapy with local intrathoracic application of immune checkpoint inhibitors, immune cells, cytokines, and gene-mediated cytotoxic immunotherapy are able to alleviate the immunosuppressive tumor microenvironment and inhibit the accumulation of MPE. This article aimed to describe the tumor microenvironment in MPE and provide clues for identifying novel therapeutic targets.


Subject(s)
Immunotherapy , Pleural Effusion, Malignant , Tumor Microenvironment , Humans , Pleural Effusion, Malignant/therapy , Immunotherapy/methods , Cytokines/metabolism , Immune Checkpoint Inhibitors/therapeutic use
5.
Public Health ; 233: 38-44, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38850601

ABSTRACT

OBJECTIVES: Socio-economic status (SES) disparities exist in the uptake of COVID-19 vaccination; however, most studies were conducted during the initial pandemic wave when vaccination was less discretionary, limiting generalizability. We aimed to determine whether differences in vaccination uptake across SES strata widened after the removal of vaccination-differentiated measures prior to the rollout of the second boosters, in a nationwide cohort of older Singaporeans at higher risk of severe-COVID-19. STUDY DESIGN: Retrospective population-based cohort study. METHODS: Retrospective population-based cohort study of all Singaporeans aged ≥60 years from 22nd February 2021-14th February 2023. Cox regression models controlling for demographics and comorbidities were used to estimate hazard-ratios (HRs) for the uptake of primary vaccination as well as first/second boosters, as recorded in the national vaccination registry, according to SES (housing type). RESULTS: 836,170 individuals were included for completion of a primary vaccine series; 784,938 individuals for completion of the first booster and 734,206 individuals for the completion of the second booster. Differences in vaccination uptake by SES strata were observed (e.g. vaccination uptake in lowest-SES [1-2 room public-housing] versus highest-SES [private housing]: second booster, 47.6% vs. 58.1%; first booster, 93.9% vs. 98.0%). However, relative differences did not markedly widen during second booster rollout when vaccination was more discretionary (e.g. amongst those aged 60-69 years: 0.75 [95% CI = 0.73-0.76] for the first booster; 0.81 [95% CI = 0.79-0.84] for the second booster). CONCLUSION: While differences in vaccination uptake across SES strata by housing type persisted during the rollout of primary vaccination and subsequent boosters in a nationwide cohort of older Singaporeans, differences did not widen substantially when vaccination was made more discretionary.


Subject(s)
COVID-19 Vaccines , COVID-19 , Social Class , Humans , Singapore , Aged , Female , Male , COVID-19/prevention & control , Middle Aged , Retrospective Studies , COVID-19 Vaccines/administration & dosage , Aged, 80 and over , Health Services Accessibility/statistics & numerical data , Vaccination/statistics & numerical data , Cohort Studies , SARS-CoV-2
6.
Zhonghua Gan Zang Bing Za Zhi ; 32(4): 332-339, 2024 Apr 20.
Article in Chinese | MEDLINE | ID: mdl-38733188

ABSTRACT

Objective: To evaluate the long-term efficacy of percutaneous microwave ablation (MWA) therapy for hepatocellular carcinoma. Methods: 2054 cases with Barcelona Clinic Liver Cancer (BCLC) stage 0~B at the Fifth Medical Center of the Chinese People's Liberation Army General Hospital from January 2006 to September 2020 were retrospectively collected. All patients were followed up for at least 2 years. The primary endpoint of overall survival and secondary endpoints (tumor-related survival, disease-free survival, and postoperative complications) of patients treated with ultrasound-guided percutaneous MWA were analyzed. Kaplan-Meier method was used for stratified survival rate analysis. Fine-and-Gray competing risk model was used to analyze overall survival. Results: A total of 5 503 HCC nodules [mean tumor diameter (2.6±1.6) cm] underwent 3 908 MWAs between January 2006 and September 2020, with a median follow-up time of 45.6 (24.0 -79.2) months.The technical effectiveness rate of 5 375 tumor nodules was 97.5%. The overall survival rates at 5, 10, and 15-years were 61.6%, 38.8%, and 27.0%, respectively. The tumor-specific survival rates were 67.1%, 47.2%, and 37.7%, respectively. The free tumor survival rates were 25.8%, 15.7%, and 9.9%, respectively. The incidence rate of severe complications was 2.8% (108/3 908). Further analysis showed that the technical effectiveness and survival rate over the passing three time periods from January 2006-2010, 2011-2015, and 2016-September 2020 were significantly increased, with P < 0.001, especially for liver cancer 3.1~5.0 cm (P < 0.001). Conclusion: Microwave ablation therapy is a safe and effective method for BCLC stage 0-B, with significantly enhanced technical efficacy and survival rate over time.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Microwaves , Humans , Liver Neoplasms/surgery , Liver Neoplasms/therapy , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/surgery , Microwaves/therapeutic use , Retrospective Studies , Survival Rate , Treatment Outcome , Disease-Free Survival , Catheter Ablation/methods , Female , Postoperative Complications/epidemiology , Male , Middle Aged
7.
Clin Neurophysiol ; 164: 1-18, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38805900

ABSTRACT

Conventional electrophysiological methods, i.e. nerve conduction studies and electromyography are suitable methods for the diagnosis of neuromuscular disorders, however, they provide limited information about muscle fibre membrane properties and underlying disease mechanisms. Muscle excitability testing is a technique that provides in vivo information about muscle fibre membrane properties such as membrane potential and ion channel function. Since the 1960s, various methodologies have been suggested to examine muscle membrane properties but technical difficulties have limited its use. In 2009, an automated, fast and simple application, the so-called multi-fibre muscle velocity recovery cycles (MVRC) has accelerated the use of muscle excitability testing. Later, frequency ramp and repetitive stimulation protocols have been developed. Though this method has been used mainly in research for revealing disease mechanisms across a broad range of neuromuscular disorders, it may have additional diagnostic uses; value has been shown particularly in muscle channelopathies. This review will provide a description of the state-of-the art of methodological and clinical studies for muscle excitability testing.


Subject(s)
Electromyography , Muscle, Skeletal , Neuromuscular Diseases , Humans , Electromyography/methods , Muscle, Skeletal/physiology , Muscle, Skeletal/physiopathology , Neuromuscular Diseases/physiopathology , Neuromuscular Diseases/diagnosis , Electric Stimulation/methods , Membrane Potentials/physiology , Neural Conduction/physiology
8.
Biochim Biophys Acta Mol Basis Dis ; 1870(6): 167216, 2024 08.
Article in English | MEDLINE | ID: mdl-38718843

ABSTRACT

Studies have highlighted an upregulation of PD-1 expression in CD4+ T cells, which accelerates lung fibrosis by activating the IL-17/STAT3 pathway, leading to IL-17A and TGF-ß1 secretion. However, the relation with traumatic tracheal stenosis (TS) remains unexplored. Our analysis found significant increases in PD-1+CD4+ T cells, IL-17A, and TGF-ß1 in the TS patients (n = 10). The cellular model used CD4+ T cells co-cultured with bronchial fibroblasts while the animal model used a nylon brush to scrape the damaged tracheal mucosa. Interventions with PD-1 and STAT3 inhibitors both in vitro (n = 5) and in vivo (n = 6) showed decreased expression of TGF-ß1 and IL-17A in CD4+ T cells, decreased collagen I synthesis in vitro, and reduced tractal fibrosis in vivo. Furthermore, PD-1's modulation of the STAT3 was evident. This research unveils PD-1+CD4+ T cells' role in TS, thus suggesting a novel immunotherapeutic strategy to counteract tracheal fibrosis.


Subject(s)
CD4-Positive T-Lymphocytes , Interleukin-17 , Programmed Cell Death 1 Receptor , STAT3 Transcription Factor , Signal Transduction , Tracheal Stenosis , STAT3 Transcription Factor/metabolism , Programmed Cell Death 1 Receptor/metabolism , Programmed Cell Death 1 Receptor/genetics , Interleukin-17/metabolism , Interleukin-17/immunology , Humans , Animals , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Tracheal Stenosis/pathology , Tracheal Stenosis/metabolism , Tracheal Stenosis/immunology , Male , Female , Adult , Middle Aged , Transforming Growth Factor beta1/metabolism , Mice , Fibrosis , Disease Models, Animal , Trachea/pathology , Trachea/metabolism , Trachea/immunology
9.
Hepatol Int ; 18(3): 833-869, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38578541

ABSTRACT

Acute-on-chronic liver failure (ACLF) is a syndrome that is characterized by the rapid development of organ failures predisposing these patients to a high risk of short-term early death. The main causes of organ failure in these patients are bacterial infections and systemic inflammation, both of which can be severe. For the majority of these patients, a prompt liver transplant is still the only effective course of treatment. Kidneys are one of the most frequent extrahepatic organs that are affected in patients with ACLF, since acute kidney injury (AKI) is reported in 22.8-34% of patients with ACLF. Approach and management of kidney injury could improve overall outcomes in these patients. Importantly, patients with ACLF more frequently have stage 3 AKI with a low rate of response to the current treatment modalities. The objective of the present position paper is to critically review and analyze the published data on AKI in ACLF, evolve a consensus, and provide recommendations for early diagnosis, pathophysiology, prevention, and management of AKI in patients with ACLF. In the absence of direct evidence, we propose expert opinions for guidance in managing AKI in this very challenging group of patients and focus on areas of future research. This consensus will be of major importance to all hepatologists, liver transplant surgeons, and intensivists across the globe.


Subject(s)
Acute Kidney Injury , Acute-On-Chronic Liver Failure , Acute-On-Chronic Liver Failure/therapy , Acute-On-Chronic Liver Failure/diagnosis , Acute-On-Chronic Liver Failure/complications , Acute-On-Chronic Liver Failure/etiology , Humans , Acute Kidney Injury/therapy , Acute Kidney Injury/etiology , Acute Kidney Injury/diagnosis , Liver Transplantation
10.
Med J Malaysia ; 79(2): 170-175, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38553922

ABSTRACT

INTRODUCTION: Haemophilia is one of the commonest inherited bleeding disorders which may lead to long term disabilities if not treated properly. Our aim of study is to understand the clinical characteristic, treatment and complications of adult haemophilia patients in our centre. MATERIALS AND METHODS: A retrospective cross-sectional review of all adult haemophilia A (HA) or haemophilia B (HB) patients who received treatment in Hospital Pulau Pinang from January 2021 to December 2022 was conducted. Data was retrieved from patients' medical records. RESULTS: A total of 75 haemophilia patients (64 HA and 11 HB) were included in this study with median age of 37 years (range 19 70). 42 of them had severe haemophilia (50% of HA, 91% of HB). All HB and 93.8% of severe HA patients were on prophylaxis. Six severe and one mild HA patients developed inhibitor with four of them currently on non-factor prophylaxis. 24 patients (32%) had prior hepatitis C infection and all of them have been successfully treated. The mean annual bleeding rate for severe haemophilia patients were 1.77 (SD ±3.6). Target joints were observed in 9.3% of patients with ankle joint (71.4%) being the most affected joint. More than one quarter (26.7%) of our patients have comorbidities with majority of them having hypertension (17/20), followed by diabetes mellitus (5/20) and ischemic heart disease (5/20). CONCLUSION: Our study showed that a significant number of adult patients with haemophilia have comorbidities. Apart from optimising factor replacement therapy, future planning should include improvement in screening, risk modification and prevention of cardiovascular disease.


Subject(s)
Hemophilia A , Hemophilia B , Adult , Humans , Hemophilia A/therapy , Hemophilia A/drug therapy , Cross-Sectional Studies , Retrospective Studies , Malaysia/epidemiology , Hemophilia B/complications , Hemophilia B/drug therapy
11.
Med J Malaysia ; 79(2): 206-211, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38553928

ABSTRACT

INTRODUCTION: Numerous tonometers are available to measure intraocular pressure (IOP) in children with glaucoma. This review aims to discuss IOP measurement techniques and principles and compare the accuracy, tolerability and ease of use of available tonometers in measuring IOP in paediatric glaucoma patients. MATERIALS AND METHODS: A review of observational studies was conducted to discuss the accuracy, tolerability and ease of use of tonometers in measuring IOP in children with glaucoma. RESULTS: Goldmann applanation tonometry (GAT) and its portable handheld versions remain the gold standard in measuring IOP. Tono-Pen (Reichert Ophthalmic Instruments, Depew, New York, USA) and rebound tonometer (RBT) both correlate well with GAT. Although both tonometers tend to overestimate IOP, Tono-Pen overestimates more than RBT. Overestimation is more remarkable in higher IOP and corneal pathologies (such as but not limited to scarred cornea and denser corneal opacity). RBT was better tolerated than other tonometers in children and was easier to use in children of all ages. CONCLUSIONS: RBT is the preferred tonometer for measuring IOP in children with glaucoma, as it is less traumatic, time efficient and does not require fluorescein dye or anaesthesia. However, examiners should use a second tonometer to confirm elevated IOP readings from the RBT.


Subject(s)
Glaucoma , Intraocular Pressure , Child , Humans , Glaucoma/diagnosis , Tonometry, Ocular/methods , Cornea , Manometry , Reproducibility of Results
12.
Med J Malaysia ; 79(2): 237-239, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38553932

ABSTRACT

A prescribing policy for SGLT2-inhibitors was implemented in a local public tertiary cardiology centre in Sabah to improve access for heart failure (HF) patients. The study evaluated 169 HF patients with reduced ejection fraction (HFrEF) who met the policy criteria. After starting SGLT2- inhibitors, a significant proportion of patients experienced decreased NTproBNP levels, indicating a positive response. HF hospitalisation rates within 1 year were lower compared to the previous year. No adverse events were reported, suggesting that the treatment is safe. Findings demonstrates the benefits of implementing prescribing policies to enhance treatment accessibility and generate valuable real-world data at the local healthcare level..


Subject(s)
Heart Failure , Sodium-Glucose Transporter 2 Inhibitors , Humans , Heart Failure/drug therapy , Stroke Volume/physiology , Sodium-Glucose Transporter 2 , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Hospitalization
13.
Indian J Thorac Cardiovasc Surg ; 40(2): 213-218, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38389783

ABSTRACT

Objective: A quarter of all cardiac tumors are malignant, and most (~ 95%) are sarcomas. It is the most aggressive malignant cardiac tumor carrying the worst prognosis. Tumor involvement with the vital intracardiac structures makes it difficult for complete surgical resection. We aimed to study the role of complete surgical resection and its importance in long-term outcomes. Methods: We analyzed published literature from 2002 to 2022 using PubMed. Cases reported adult, intracardiac sarcomas, and received surgical resections were included. We reviewed 132 published case reports, including and analyzed the following variables: demographics, clinical presentations, diagnostic imaging modality, the extent of surgical resection, pathological diagnosis, tumor location, postoperative chemo-radiation therapy, and follow-up (including re-operation, local and distant recurrence). Results: A total of 135 patients are included from 132 articles. The mean age was 46.69 (18-86) and 76 patients were females. The main complaints were dyspnea (70%) and chest pain (32%). Performed investigations were transthoracic echocardiography (TTE) in 114/135 (84%), computer tomography (CT) scan 89/135 (66%), trans-esophageal echocardiography (TOE) 22%, and cardiac magnetic resonance imaging (MRI) 29%. The most common location was the atrium (left 46%, right 30%). Complete surgical resection was performed in 91 cases (67%), and frozen section was performed in 62 patients (43 positives). Incomplete resections were in 42 cases. Patients who underwent complete surgical resection had mean survival of 14.58 months and median of 10.5 months, compared to incomplete resection patients with 9.12 months and 6.5 months respectively. Conclusion: Our review shows complete surgical resection results in better short- and long-term outcomes in intracardiac sarcoma patients. Furthermore, combining chemo-radiotherapy has additional benefits towards long-term survival.

14.
Zhonghua Liu Xing Bing Xue Za Zhi ; 45(1): 123-127, 2024 Jan 10.
Article in Chinese | MEDLINE | ID: mdl-38228534

ABSTRACT

Objective: To analyze the use of medicare antiviral drugs (ART) and related factors among HIV-infected people in Ningbo City. Methods: The retrospective data was collected related to infection and treatment of HIV-infected people in ART in Ningbo up to February 2023 through the National Infectious Disease Surveillance System. Binary logistic regression was used to analyze the factors related to medicare antiviral drug use in HIV-infected people. R 4.2.2 software was used for statistical analysis. Results: A total of 6 433 HIV-infected people with ART records were collected, among which 5 783 were in ART. The prevalence of medicare drugs use among people in ART was 24.8% (1 435/5 783, 95%CI: 23.7%-25.9%). Beilun District (8.7%, 43/497) and Fenghua District (5.7%, 14/247) had the lowest level in medicare drugs use. Among people in ART using medicare or out-of-pocket drugs, the prevalence of those who had at least one viral load test in the last year (84.9%, 1 352/1 593) was significantly lower than that of those using free drugs (91.4%, 3 829/4 190) (χ2=52.50, P<0.001). The results of multivariate logistic analysis showed that the factors influencing medicare drug use included low educational level (junior high school and below: aOR=0.24, 95%CI:0.17-0.34), farmer or worker (farmer: aOR=0.60, 95%CI: 0.39-0.91; worker: aOR=0.42, 95%CI: 0.27-0.64), low monthly income (<3 000 Yuan: aOR=0.29, 95%CI: 0.18-0.45), the longer interval time between diagnosis and treatment (≥21 days: aOR=0.47, 95%CI: 0.30-0.74). Conclusions: Significant regional differences on the prevalence of medicare antiviral drugs use in HIV-infected people exist in Ningbo City. Follow-up management program of patients should be improved to strengthen patient compliance to mobilize medicare drug promotion. Meanwhile, publicity of medicare drugs should be strengthened for farmers or workers with low education level and patients with delayed treatment.


Subject(s)
HIV Infections , Substance-Related Disorders , Aged , United States/epidemiology , Humans , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/diagnosis , Retrospective Studies , Prevalence , Medicare , Antiviral Agents/therapeutic use
16.
Injury ; 55(2): 111037, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38142626

ABSTRACT

BACKGROUND: Patient factors are known to contribute to decision making and treatment of ankle fractures. The presence of poor baseline mobility, diabetes, neuropathy, alcoholism, cognitive impairment, inflammatory arthritis or polytrauma can result in a higher risk of failure or complications. Limited evidence is available on the optimum management for this challenging cohort of patients herein described as complex ankle fractures. This UK multicentre study assessed and evaluated the epidemiology of ankle fractures complicated by significant comorbidity and patient factors and use of specialist surgical techniques such as hindfoot nails (HFN) / tibiotalarcalcaneal (TCC) nails and enhanced open reduction and internal fixation (ORIF). PATIENTS AND METHODS: A UK-wide collaborative study was performed of adult distal AO43/AO44 fractures, associated with 1 or more of the patient factors listed above. Primary outcomes included patient demographics, comorbidities, surgical technique and implants. Secondary outcomes included surgical complications and early post-operative weight bearing instructions. Statistical analysis was performed to assess patient and fracture characteristics on outcome, including propensity matching. RESULTS: One-thousand three hundred and sixty patients, with at least one of the above complex factors, from 56 centres were included with a mean age of 53.1 years. 90.2% (1227) patients underwent primary fixation which included 78.9% (1073) standard open reduction internal fixations (ORIF), 3.25% (43) extended ORIF and 8.1% (111) primary HFN / TCC. Overall wound complications and thromboembolic events were similar in the hindfoot nail group and the ORIF group (11.7% vs 10.7%). Wound complications were greater in diabetic patients versus non-diabetic patients independent of fixation method (15.8% vs 9.0%). After propensity matching for comorbidities and fracture type, overall complications were lower in the hindfoot nail (11.8%) and extended ORIF groups (16.7%), than the standard ORIF group (18.6%). CONCLUSION: Only a minority of complex ankle fractures are treated with specialised techniques (HFN/TCC or extended ORIF). Though more commonly used in older and frail patients their perceived advantages are often negated by a reluctance to bear weight early. These techniques demonstrated a better complication profile to standard ORIF but hindfoot nail with joint preparation for fusion was associated with more complications than hindfoot nail for fixation. LEVEL OF EVIDENCE: III.


Subject(s)
Ankle Fractures , Adult , Humans , Aged , Middle Aged , Ankle Fractures/epidemiology , Ankle Fractures/surgery , Fracture Fixation, Internal/methods , Ankle Joint/surgery , Open Fracture Reduction/methods , Cohort Studies , Treatment Outcome , Retrospective Studies
17.
Trends Neurosci Educ ; 33: 100215, 2023 12.
Article in English | MEDLINE | ID: mdl-38049294

ABSTRACT

BACKGROUND: Exercise has transient effects on cognition and mood, however the impact of Physical Education (PE) on cognitive and affective processes across the school day has not been examined. METHOD: This study used wearables and questionnaires to track student arousal, engagement, and emotion across school days/periods following PE. Skin conductance, heart rate, heart rate variability, and self-reported engagement, arousal, and valence were analyzed for 23 students (age 15-17 years) on days with and without PE. RESULTS: Sympathetic arousal was significantly higher for two hours following PE and there were stronger decreases in arousal across other classes relative to days without PE. On days with PE, engagement decreased, whereas valence increased from morning to afternoon. CONCLUSION: These findings highlight the importance of considering acute effects of PE on learning across the entire school day, and demonstrates the feasibility of wearables to clarify how the timing of PE could positively or negatively affect self-regulation and learning.


Subject(s)
Physical Education and Training , Schools , Humans , Adolescent , Students/psychology , Affect , Arousal
18.
Cell Mol Life Sci ; 81(1): 7, 2023 Dec 13.
Article in English | MEDLINE | ID: mdl-38092984

ABSTRACT

Cancer cells are exposed to major compressive and shearing forces during invasion and metastasis, leading to extensive plasma membrane damage. To survive this mechanical stress, they need to repair membrane injury efficiently. Targeting the membrane repair machinery is thus potentially a new way to prevent invasion and metastasis. We show here that annexin-A2 (ANXA2) is required for membrane repair in invasive breast and pancreatic cancer cells. Mechanistically, we show by fluorescence and electron microscopy that cells fail to reseal shear-stress damaged membrane when ANXA2 is silenced or the protein is inhibited with neutralizing antibody. Silencing of ANXA2 has no effect on proliferation in vitro, and may even accelerate migration in wound healing assays, but reduces tumor cell dissemination in both mice and zebrafish. We expect that inhibiting membrane repair will be particularly effective in aggressive, poor prognosis tumors because they rely on the membrane repair machinery to survive membrane damage during tumor invasion and metastasis. This could be achieved either with anti-ANXA2 antibodies, which have been shown to inhibit metastasis of breast and pancreatic cancer cells, or with small molecule drugs.


Subject(s)
Membrane Proteins , Pancreatic Neoplasms , Animals , Mice , Cell Line, Tumor , Cell Membrane/metabolism , Membrane Proteins/metabolism , Pancreatic Neoplasms/pathology , Zebrafish
19.
Zhonghua Yu Fang Yi Xue Za Zhi ; 57(10): 1704-1710, 2023 Oct 06.
Article in Chinese | MEDLINE | ID: mdl-37859392

ABSTRACT

Schizophrenia is a severe psychiatric disorder with an unclear etiology and various clinical manifestations. The diagnosis and consequent treatment of schizophrenia mainly rely on clinical symptoms. Multiple risk sites associated with schizophrenia have been identified, yet objective indicators have not been found to facilitate clinical diagnosis and treatment of schizophrenia. The development of omics technology provides different perspectives on the etiology of schizophrenia and make the early identification, diagnosis and treatment of the disorder possible. This article summarizes the prevalence of schizophrenia, reviews the research results and shortcomings of transcriptomics and proteomics, as well as the latest achievements and prospects of multi-omics, aiming to reveal the use of omics in SZ, provide more comprehensive biological evidence to reveal the complex pathogenesis of schizophrenia and provide a theoretical basis for the early identification, accurate diagnosis, disease progression control, and prognosis improvement of schizophrenia.


Subject(s)
Proteomics , Schizophrenia , Humans , Proteomics/methods , Transcriptome , Schizophrenia/genetics
20.
Neuroimage ; 281: 120367, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37689175

ABSTRACT

Whether education research can be informed by findings from neuroscience studies has been hotly debated since Bruer's (1997) famous claim that neuroscience and education are "a bridge too far". However, this claim came before recent advancements in portable electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) technologies, and second-person neuroscience techniques that brought about significant headway in understanding instructor-learner interactions in the classroom. To explore whether neuroscience and education are still two very separate fields, we systematically review 15 hyperscanning studies that were conducted in real-world classrooms or that implemented a teaching-learning task to investigate instructor-learner dynamics. Findings from this investigation illustrate that inter-brain synchrony between instructor and learner is an additional and valuable dimension to understand the complex web of instructor- and learner-related variables that influence learning. Importantly, these findings demonstrate the possibility of conducting real-world classroom studies with portable neuroimaging techniques and highlight the potential of such studies in providing translatable real-world implications. Once thought of as incompatible, a successful coupling between neuroscience and education is now within sight.

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