Publications by authors named "P-L Lee"

The peri-operative management of non-small cell lung cancer (NSCLC) in earlier stage disease has seen significant advances in recent years with the incorporation of immune checkpoint inhibitors and targeted therapy. However, many unanswered questions and challenges remain, including the application of clinical trial data to routine clinical practice. Recognising the unique demographic profile of Asian patients with NSCLC and heterogeneous healthcare systems, the Asian Thoracic Oncology Research Group (ATORG) convened a consensus meeting in Singapore on 26 April 2024 to discuss relevant issues spanning diagnostic testing to post-neoadjuvant treatment considerations and future directions.

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Chimeric antigen receptor (CAR) T-cell therapy shows unprecedented efficacy for cancer treatment, particularly in treating patients with various blood cancers, most notably B-cell acute lymphoblastic leukemia. In recent years, CAR T-cell therapies have been investigated for treating other hematologic malignancies and solid tumors. Despite the remarkable success of CAR T-cell therapy, cytokine release syndrome (CRS) is an unexpected side effect that is potentially life-threatening.

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Background: Idiopathic interstitial pneumonias (IIPs), such as idiopathic pulmonary fibrosis and interstitial pneumonia with autoimmune features, present diagnostic and therapeutic challenges due to their heterogeneous nature. This study aimed to identify intrinsic molecular signatures within the lung microenvironment of these IIPs through proteomic analysis of bronchoalveolar lavage fluid (BALF).

Methods: Patients with IIP (n=23) underwent comprehensive clinical evaluation including pre-treatment bronchoscopy and were compared with controls without lung disease (n=5).

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Background And Purpose: Chronic diabetes is a prevalent systemic disease that impairs neuromotor functioning and often leads to increased risk of falls. Adopting an external focus of attention during motor skill practice has been shown to improve learning outcomes; however, it has not been examined in this population. We examined how attentional focus instructions (internal vs external) affect balance performance and learning in older adults with and without diabetes.

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  • Glioblastoma (GBM) is the deadliest brain tumor in adults, and current therapies are largely ineffective, which drives the need for new treatment strategies based on the tumor's metabolic needs, specifically glucose and glutamine.
  • A ketogenic metabolic therapy (KMT) approach targets these metabolic pathways by combining dietary changes with specific drugs to limit glycolysis and glutaminolysis, while promoting the use of non-fermentable fuels like ketones and fatty acids.
  • The glucose-ketone index (GKI) serves as a biomarker to monitor treatment effectiveness, aiming to create a more hostile environment for tumor growth and improve outcomes in GBM as well as potentially other cancer types reliant on similar metabolic pathways.
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While circadian disruption is recognized as a potential driver of depression, its real-world impact is poorly understood. A critical step to addressing this is the noninvasive collection of physiological time-series data outside laboratory settings in large populations. Digital tools offer promise in this endeavor.

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The majority of patients with kidney failure requiring replacement therapy will need the support of hemodialysis during their journey with kidney failure. A reliable functioning vascular access is required to provide hemodialysis. This Core Curriculum reviews the major forms of vascular access (arteriovenous fistula, arteriovenous graft, and central venous catheter) as well as the planning, preparation, creation, use, and maintenance of vascular access, requiring a P-L-A-N (Patient ESKD Life-Plan first then Access Needs) for each patient.

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With large wildfires becoming more frequent, we must rapidly learn how megafires impact biodiversity to prioritize mitigation and improve policy. A key challenge is to discover how interactions among fire-regime components, drought and land tenure shape wildfire impacts. The globally unprecedented 2019-2020 Australian megafires burnt more than 10 million hectares, prompting major investment in biodiversity monitoring.

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  • A clinical trial was conducted with 400 patients suffering from severe tricuspid regurgitation, comparing outcomes between those who received transcatheter tricuspid-valve replacement alongside medical therapy and those who received medical therapy alone.
  • The primary outcome measured included death rates, hospitalizations due to heart failure, and improvements in quality of life and functional capacity, showing a significant advantage for the valve-replacement group.
  • After one year, the valve-replacement group demonstrated better overall health outcomes, although there was a higher incidence of severe bleeding compared to the control group.
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  • The study investigates how AI-generated measurements of intraprostatic tumor volume from MRI scans can predict the risk of metastasis in prostate cancer patients treated with either radiation therapy or radical prostatectomy.
  • A total of 732 patients were involved, with findings indicating that a larger tumor volume significantly correlated with increased rates of metastasis during the follow-up periods, which averaged 6.9 years for radiation therapy and 5.5 years for surgery.
  • The research highlighted that the AI-based volume measurements provided independent prognostic information, outperforming traditional risk categorization methods in predicting long-term metastasis.
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Malformations of cortical development (MCD) are structural anomalies that disrupt the normal process of cortical development. Patients with these anomalies frequently present with seizures, developmental delay, neurologic deficits, and cognitive impairment, resulting in a wide spectrum of neurologic outcomes. The severity and type of malformation, in addition to the genetic pathways of brain development involved, contribute to the observed variability.

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Fast, nondestructive three-dimensional (3D) imaging of live suspension cells remains challenging without substrate treatment or fixation, precluding scalable single-cell morphometry with minimal alterations. While optical sectioning techniques achieve 3D live cell imaging, lateral versus depth resolution differences further complicate analysis. We present a scalable microfluidic method capable of 3D fluorescent isotropic imaging of live, nonadherent cells suspended inside picoliter droplets with high-speed single-cell volumetric readout (800 to 1,200 slices in 5 to 8 s) and near-diffraction limit resolution (~216 nm).

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Human microglia play a pivotal role in neurological diseases, but we still have an incomplete understanding of microglial heterogeneity, which limits the development of targeted therapies directly modulating their state or function. Here, we use single-cell RNA sequencing to profile 215,680 live human microglia from 74 donors across diverse neurological diseases and CNS regions. We observe a central divide between oxidative and heterocyclic metabolism and identify microglial subsets associated with antigen presentation, motility and proliferation.

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Introduction: Stroke burden is largely due to long-term impairments requiring prolonged care and loss of productivity. We aim to identify and assess studies of different registered pharmacological therapies as treatments for improving post-stroke impairments and/or disabilities.

Methods: In a systematic search and review (PROSPERO registration: CRD42022376973), studies of treatments that have been investigated as recovery-enhancing or recovery-promoting treatments in adult patients who had suffered a stroke will be searched for, screened, and reviewed based on the following: participants (P): adult humans, aged 18 years or older, diagnosed with stroke; interventions (I): registered or marketed pharmacological therapies that have been investigated as recovery-enhancing or recovery-promoting treatments in stroke; comparators (C): active or placebo or no comparator; outcomes (O): stroke-related neurological impairments and functional/disability assessments.

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  • Steroidal mineralocorticoid receptor antagonists help patients with heart failure and reduced ejection fraction, but their effectiveness in those with mildly reduced or preserved ejection fraction is unclear, indicating a need for further research on finerenone.
  • In a double-blind study, patients with heart failure (ejection fraction 40% or greater) were assigned to receive either finerenone or a placebo to assess its impact on heart failure events and cardiovascular death.
  • Results showed that finerenone led to fewer worsening heart failure events and a lower overall rate of primary outcome events compared to placebo, although it also carried a higher risk of hyperkalemia.
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  • Renal dysfunction is common in heart failure patients and linked to poor outcomes, but how cardiac structure and function impact kidney health remains unclear.
  • This study analyzed data from the PARAGON-HF trial to explore the relationship between echocardiographic measurements of heart structure/function and changes in kidney function over time.
  • Results showed that higher left ventricular mass and certain heart parameters are associated with greater declines in kidney function and an increased risk of serious kidney-related events, suggesting that cardiac health plays a crucial role in renal outcomes for these patients.
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  • This study investigates genetic variants linked to outer retinal tubulation (ORT) by analyzing the prevalence and clinical consequences of ORT in patients with inherited retinal diseases (IRDs).
  • A cohort of 565 IRD patients underwent SD-OCT imaging, revealing that 104 exhibited ORT, primarily associated with specific genetic variants, especially in RPE-specific and some non-RPE-specific genes.
  • The findings show a strong correlation between ORT presence and IRDs caused by RPE-specific and non-RPE-specific genes, while no cases of ORT were found in patients with photoreceptor-specific gene variants.
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Background It is unclear whether breast US screening outcomes for women with dense breasts vary with levels of breast cancer risk. Purpose To evaluate US screening outcomes for female patients with dense breasts and different estimated breast cancer risk levels. Materials and Methods This retrospective observational study used data from US screening examinations in female patients with heterogeneously or extremely dense breasts conducted from January 2014 to October 2020 at 24 radiology facilities within three Breast Cancer Surveillance Consortium (BCSC) registries.

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Background: The Gender, Age and Physiology (GAP) model is a simple mortality prediction tool in patients with idiopathic pulmonary fibrosis that uses demographic and physiological variables available at initial evaluation. White blood cell variables may have associations with idiopathic pulmonary fibrosis outcomes. We evaluated whether incorporating blood cell counts in modified GAP (cGAP) models would improve outcome prediction in patients with idiopathic pulmonary fibrosis.

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Purpose: To describe the optical coherence tomography (OCT) features that can differentiate eyes with fovea-off exudative retinal detachment (ERD) vs rhegmatogenous retinal detachment (RRD), with particular attention to outer retinal corrugations (ORCs).

Design: Multicenter, retrospective cross-sectional study.

Methods: Multicenter, retrospective cross-sectional study of patients diagnosed with unilateral or bilateral fovea-off ERD or primary, acute, fovea-off RRD between 2016 and 2021.

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  • - CDD is a rare neurodevelopmental disorder linked to mutations in the CDKL5 gene, leading to symptoms like epilepsy, muscle weakness, and developmental delays.
  • - Researchers created a gene therapy vector, AAV9.Syn.hCDKL5, to deliver the CDKL5 gene to the brain, using a specific promoter to enhance gene expression.
  • - Studies in mice showed that injecting the vector directly into the cerebrospinal fluid improved distribution and resulted in biological activity, with successful functional improvements observed at higher doses.
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  • The study investigates the relationship between body mass index (BMI) and Parkinson's disease (PD) using a method called Mendelian randomization to determine if higher genetically predicted BMI is linked to a lower incidence of PD.
  • Researchers analyzed genetic data from large groups of individuals, including over 800,000 for BMI and nearly 29,000 for PD, focusing on factors like age, disease duration, and gender to examine the associations.
  • Results indicated an inverse relationship between genetically predicted BMI and PD, particularly among younger participants and women, suggesting that lower BMI may be associated with a higher risk of developing Parkinson's disease.
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  • Dilated cardiomyopathy is a rare genetic heart condition, and the study focused on the drug ARRY-371797, showing initial promise in improving walking distance after 12 weeks and maintaining benefits over 144 weeks.
  • The REALM-DCM trial was a phase 3 study involving patients with specific genetic traits and heart failure symptoms, comparing ARRY-371797 against a placebo over 24 weeks with multiple outcomes of interest.
  • The trial was stopped early due to an interim analysis showing that ARRY-371797 did not significantly improve key measures like walking distance or overall heart function compared to placebo, indicating futility in continuing.
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Supplementation with CBM588, a bifidogenic live bacterial product, has been associated with improved clinical outcomes in persons with metastatic renal cell carcinoma (mRCC) receiving nivolumab and ipilimumab. However, its effect on those receiving tyrosine kinase inhibitor-based combinations is unknown. In this open-label, randomized, investigator-initiated, phase 1 study, 30 participants with locally advanced or mRCC with histological confirmation of clear cell, papillary or sarcomatoid component were randomized in a 2:1 fashion to receive cabozantinib (an inhibitor of vascular endothelial growth factor receptor, MET and AXL) and nivolumab (anti-programmed cell death protein 1) with or without CBM588 as first-line treatment.

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