Diurnal Rhythms in the Red Seaweed Gracilariopsis chorda are Characterized by Unique Regulatory Networks of Carbon Metabolism.

Cellular and physiological cycles are driven by endogenous pacemakers, the diurnal and circadian rhythms. Key functions such as cell cycle progression and cellular metabolism are under rhythmic regulation, thereby maintaining physiological homeostasis. The photoreceptors phytochrome and cryptochrome, in response to light cues, are central input pathways for physiological cycles in most photosynthetic organisms. However, among Archaeplastida, red algae are the only taxa that lack phytochromes. Current knowledge about oscillatory rhythms is primarily derived from model species such as Arabidopsis thaliana and Chlamydomonas reinhardtii in the Viridiplantae, whereas little is known about these processes in other clades of the Archaeplastida, such as the red algae (Rhodophyta). We used genome-wide expression profiling of the red seaweed Gracilariopsis chorda and identified 3,098 rhythmic genes. Here, we characterized possible cryptochrome-based regulation and photosynthetic/cytosolic carbon metabolism in this species. We found a large family of cryptochrome genes in G. chorda that display rhythmic expression over the diurnal cycle and may compensate for the lack of phytochromes in this species. The input pathway gates regulatory networks of carbon metabolism which results in a compact and efficient energy metabolism during daylight hours. The system in G. chorda is distinct from energy metabolism in most plants, which activates in the dark. The green lineage, in particular, land plants, balance water loss and CO2 capture in terrestrial environments. In contrast, red seaweeds maintain a reduced set of photoreceptors and a compact cytosolic carbon metabolism to thrive in the harsh abiotic conditions typical of intertidal zones.

Origin of minicircular mitochondrial genomes in red algae.

Eukaryotic organelle genomes are generally of conserved size and gene content within phylogenetic groups. However, significant variation in genome structure may occur. Here, we report that the Stylonematophyceae red algae contain multipartite circular mitochondrial genomes (i.e., minicircles) which encode one or two genes bounded by a specific cassette and a conserved constant region. These minicircles are visualized using fluorescence microscope and scanning electron microscope, proving the circularity. Mitochondrial gene sets are reduced in these highly divergent mitogenomes. Newly generated chromosome-level nuclear genome assembly of Rhodosorus marinus reveals that most mitochondrial ribosomal subunit genes are transferred to the nuclear genome. Hetero-concatemers that resulted from recombination between minicircles and unique gene inventory that is responsible for mitochondrial genome stability may explain how the transition from typical mitochondrial genome to minicircles occurs. Our results offer inspiration on minicircular organelle genome formation and highlight an extreme case of mitochondrial gene inventory reduction.

Public perceptions and attitudes of the national project of bio-big data: A nationwide survey in the Republic of Korea.

Background: The National Project of Bio-Big Data (NPBBD) is a South Korean bio-big data collection project, expected to include health, genomic, and lifelog data of one million Koreans. The Ethical, Legal, and Social Implications study is a parallel study active since 2020. As part of the study, a public survey was conducted to evaluate public attitudes towards engagement schemes, such as public committees and web portals for communication between the public and researchers. Methods: An online survey was conducted from March 3-9, 2021, using structured questionnaires addressed to 1,000 adults aged 20-59 years. Results: Several respondents reported a positive attitude towards participation (43.6% "somewhat," 14.3% "definitely"), whereas approximately one-third (36.5%) reported a neutral attitude. Positive factors that may affect the willingness of the respondents to participate included receiving health information (25.1%), contributing to research on cancer and rare diseases (21.9%), and advancing personalized medicine (21.5%). Conversely, negative factors were mainly associated with concerns regarding the risk of data leakage (22.8%), discrimination (21.1%), lack of information (13.5%), possibility of knowing the risk of being diagnosed with an incurable diseases (12.5%), and possibility of using data in industry (11.3%). In terms of project governance, respondents tended to recognize the importance of public participation in incorporating public opinion into the project design. Conclusion: These results have implications for the participant recruitment process, public engagement strategies, and the scope of user (academics/industry, domestic/overseas) accessibility to the database.

The cross-section of routine practice of echocardiographic diastolic evaluation in atrial fibrillation in a community hospital: A quality improvement project.

BACKGROUND: The echocardiographic assessment of diastolic function in the context of atrial fibrillation (AF) has been controversial and can be challenging and labor-intensive. We aimed to assess the actual practice of diastolic evaluation in AF in our community hospital echocardiography laboratory and to improve clinical performance by a quality improvement project. METHODS: We reviewed 244 echocardiograms in patients with AF at the time of echocardiography from November 2019 to November 2020 (pre-intervention phase). We classified cases into a complete versus incomplete evaluation group according to the completeness of diastolic parameter measurement. After an educational intervention, we reviewed 68 echocardiograms in patients with AF from August 2021 to October 2021 (post-intervention phase). RESULTS: Our results demonstrated an improvement in a complete diastolic assessment from 69% to 91% after intervention (p < .001). In the pre-intervention phase, the four parameters (mitral inflow pulsed wave Doppler image, left atrium volume index, mitral annular tissue Doppler image [TDI], and tricuspid regurgitation Vmax), mitral annular TDI was not acquired in 71 out of 244 cases (29.1%) and those cases were classified as incomplete evaluation group. Interestingly, in the pre-intervention phase, 57 out of 162 cases (35%) with preserved EF (≥50%) received significantly more incomplete diastolic evaluation than 14 out of 82 patients (17%) with reduced EF (<50%) (p = .004). There were no statistically significant differences in age, BMI, the reason for requesting echocardiography, and patient level of care between the complete and incomplete evaluation groups. In the post-intervention phase, completeness of diastolic measurement in AF was significantly improved compared to the pre-intervention phase (29% vs. 9%, p < .001, respectively). CONCLUSION: A quality improvement project effectively improved the clinical performance of diastolic evaluation in AF in our community echocardiography laboratory. After the intervention, we decreased an incomplete evaluation from 30% to 9%. More efforts should be needed to increase awareness and familiarity in evaluating diastolic function in AF.

Multimodal Data Collection System for Driver Emotion Recognition Based on Self-Reporting in Real-World Driving.

As vehicles provide various services to drivers, research on driver emotion recognition has been expanding. However, current driver emotion datasets are limited by inconsistencies in collected data and inferred emotional state annotations by others. To overcome this limitation, we propose a data collection system that collects multimodal datasets during real-world driving. The proposed system includes a self-reportable HMI application into which a driver directly inputs their current emotion state. Data collection was completed without any accidents for over 122 h of real-world driving using the system, which also considers the minimization of behavioral and cognitive disturbances. To demonstrate the validity of our collected dataset, we also provide case studies for statistical analysis, driver face detection, and personalized driver emotion recognition. The proposed data collection system enables the construction of reliable large-scale datasets on real-world driving and facilitates research on driver emotion recognition. The proposed system is avaliable on GitHub.

Implementing Perioperative Cardiac Risk Assessment in an Internal Medicine Residency Program: Experience from a Community Hospital.

Background: ACGME requires all Internal Medicine training programs to structure the curriculum to optimize resident educational experiences, including perioperative medicine. Teaching residents about perioperative risk management is challenging in a community hospital with limited resources and low surgical volume. Objective: Our goal was to introduce an interactive educational module on perioperative cardiac risk assessment and management in a community residency training program. Methods: The study was a single-center online education-based intervention from September 2020 to January 2021. 24 categorical internal medicine residents at MetroWest Medical center were included. A self-paced online education program followed by two sessions of a 30-minute, group modulated review and discussion were provided monthly. The pre- and post-evaluation with 20 questions were conducted to assess perioperative cardiac risk assessment and peri-operative cardiac risk management before and after education. Results: 20 out of 24 residents (83%) were included in the analysis. Medicine residents performed significantly better after involvement with the educational module by comparing the pre- and post-evaluation score (10.7 ± 2.7 vs. 13.8 ± 1.8, p < 0.001, respectively). The most significant improvement was noticed in postgraduate year PGY-1 residents (5.1 ± 2.5, p < 0.001), followed by PGY-2 (2.7 ± 1.6, p = 0.004), but not significant in PGY-3 residents (1.6 ± 2.3, p > 0.05). Conclusion: Implementing an interactive multi-modular curriculum in a community hospital increased residents' awareness and knowledge of perioperative cardiac risk assessment and management. We are confident that this will result in improved performance on the consult services.

Prognostic value of Dickkopf-1 and ß-catenin expression according to the antitumor immunity of CD8-positive tumor-infiltrating lymphocytes in biliary tract cancer.

The role of ß-catenin and Dickkopf-1 (DKK1) is dependent on the specific immunobiology of T cell inflammation in biliary tract cancer (BTC). We aimed to analyze the role of DKK1 or ß-catenin as a prognostic factor in BTC, and determine the clinical associations of ß-catenin and DKK1 with CD8+ tumor-infiltrating lymphocytes (TIL). We used data from The Cancer Genome Atlas Research Network and the clinicopathological data of 145 patients with BTC who had undergone primary radical resection between 2006 and 2016. CD8+ TIL expression was a significant predictor of favorable overall survival (OS) and relapse-free survival (RFS) (median OS, 34.9 months in high-TIL, 16.7 months in low-TIL, P < 0.0001 respectively; median RFS, 27.1 months in high-TIL, 10.0 months in low-TIL, P < 0.0001 respectively). In the high-CD8+ TIL BTC group, the tumor expression of ß-catenin and DKK1 had a significant negative impact on either OS or RFS. In the low-TIL BTC group, there were no differences according to ß-catenin and DKK1 expression. Cox regression multivariate analysis demonstrated that CD8+ TIL and ß-catenin retained significant association with OS. Among patients with resected BTC, the ß-catenin and DKK1 protein and high CD8+ TIL levels were associated with poor and good clinical outcomes, respectively.

Caring for a loved one with Parkinson's disease: the role of coping styles and relationship quality.

OBJECTIVE: Informal carers play an essential role in the care of individuals with Parkinson's disease (PD). This role, however, is often fraught with difficulties, including emotional, physical, and financial. Coping styles and relationship quality have been hypothesized to influence the impact of stressors. The aim of this study is to examine the relationship between carers' coping style, relationship quality, and carer burden. DESIGN: Cross-sectional. PARTICIPANTS: Thirty-nine PD patient carer dyads were included in the study. MEASUREMENTS: Participants completed self-rated questionnaires including the Dyadic Adjustment Scale, Zarit Burden Interview, and Brief Coping Orientation to Problems Experienced Inventory. RESULTS: Correlational analyses found significant and positive correlation between carer burden and all three coping styles (problem-focused, emotion-focused, and dysfunctional). There was also a moderate association between carers' perceived relationship quality and satisfaction and carer burden. Regression analyses found that carer's gender, severity of PD, relationship quality, emotion-focused, and dysfunctional coping styles did not predict carer burden. Conversely, problem-focused coping style predicted carer burden. CONCLUSION: The results highlight that there is no perfect way to react and care for a loved one and serves as important information for practitioners who design and implement interventions.

Anxiety disorders are associated with verbal memory impairment in patients with Parkinson's disease without dementia.

INTRODUCTION: Preliminary evidence has demonstrated a link between anxiety and memory impairment in Parkinson's disease (PD). This study further investigated this association using the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for anxiety disorders and a standardized cognitive test battery. METHODS: A convenience sample of 89 PD patients without dementia was recruited from neurology outpatient clinics. A cross-sectional design was applied. Participants completed two semi-structured interviews. The first interview diagnosed DSM-5 anxiety disorders, unspecified anxiety disorder, and no anxiety. The second interview applied a neurocognitive test battery comprising two tests for each domain. Logistic regression models compared cognitive characteristics associated with anxiety disorders to no anxiety. RESULTS: Clinically significant anxiety was associated with immediate verbal memory impairment compared to the no anxiety group (OR, 95% CI 0.52, 0.30-0.89; p = 0.018), controlling for sex and age. The anxiety disorders group demonstrated immediate (OR, 95% CI 0.46, 0.26-0.83; p = 0.010) and delayed (OR, 95% CI 0.63, 0.40-0.99; p = 0.047) verbal memory impairments compared to those without anxiety, controlling for sex and age. This association remained for immediate (OR, 95% CI 0.43, 0.22-0.84; p = 0.013), but not delayed verbal memory impairment (OR, 95% CI 0.65, 0.39-1.06; p = 0.081) when additionally controlling for disease severity, education and levodopa dose. CONCLUSION: These findings present first evidence that anxiety disorders are associated with verbal memory impairment in PD and have implications for the management and treatment of anxiety in PD.

Organelle Genome Variation in the Red Algal Genus Ahnfeltia (Florideophyceae).

The agarophyte Ahnfeltia (Ahnfeltiales, Rhodophyta) is a globally widespread genus with 11 accepted species names. Two of the most widespread species in this genus, A. plicata and A. fastigiata, may have diverged genetically due to past geographic changes and subsequent geographic isolation. To investigate this genomic and genetic diversity, we generated new plastid (ptDNAs) and mitochondrial genomes (mtDNAs) of these Ahnfeltia species from four different regions (A. plicata - Chile and UK and A. fastigiata - Korea and Oregon). Two architecture variations were found in the Ahnfeltia genomes: in ptDNA of A. fastigiata Oregon, the hypothetical pseudogene region was translocated, likely due to recombination with palindromic repeats or a gene transfer from a red algal plasmid. In mtDNA of A. fastigiata Korea, the composition of the group II intronic ORFs was distinct from others suggesting different scenarios of gain and loss of group II intronic ORFs. These features resulted in genome size differences between the two species. Overall gene contents of organelle genomes of Ahnfeltia were conserved. Phylogenetic analysis using concatenated genes from ptDNAs and mtDNAs supported the monophyly of the Ahnfeltiophycidae. The most probable individual gene trees showed that the Ahnfeltia populations were genetically diversified. These trees, the cox1 haplotype network, and a dN/dS analysis all supported the theory that these Ahnfeltia populations have diversified genetically in accordance with geographic distribution.

Increased risk of acute kidney injury in coronavirus disease patients with renin-angiotensin-aldosterone-system blockade use: a systematic review and meta-analysis.

Acute kidney injury (AKI) is a severe complication of coronavirus disease (COVID-19) that negatively affects its outcome. Concern had been raised about the potential effect of renin-angiotensin-aldosterone system (RAAS) blockades on renal outcomes in COVID-19 patients. However, the association between RAAS blockade use and incident AKI in COVID-19 patients has not been fully understood. We investigated the association between RAAS blockade exposure and COVID-19-related AKI in hospitalized patients through meta-analysis. Electronic databases were searched up to 24th December 2020. Summary estimates of pooled odds ratio (OR) of COVID-19-related AKI depending on RAAS blockade exposure were obtained through random-effects model. The random-effect meta-analysis on fourteen studies (17,876 patients) showed that RAAS blockade use was significantly associated with increased risk of incident AKI in hospitalized COVID-19 patients (OR 1.68; 95% confidence interval 1.19-2.36). Additional analysis showed that the association of RAAS blockade use on COVID-19-related AKI remains significant even after stratification by drug class and AKI severity. RAAS blockade use is significantly associated with the incident AKI in hospitalized COVID-19 patients. Therefore, careful monitoring of renal complications is recommended for COVID-19 patients with recent RAAS blockade use due to the potential risk of AKI.

Hippocampal correlates of episodic memory in Parkinson's disease: A systematic review of magnetic resonance imaging studies.

The present review asks whether magnetic resonance imaging (MRI) studies are able to define neural correlates of episodic memory within the hippocampus in Parkinson's disease (PD). Systematic searches were performed in PubMed, Web of Science, Medline, CINAHL, and EMBASE using search terms related to structural and functional MRI (fMRI), the hippocampus, episodic memory, and PD. Risk of bias was assessed for each study using the Newtown-Ottawa Scale. Thirty-nine studies met inclusion criteria; eight fMRI, seven diffusion MRI (dMRI), and 24 structural MRI (14 exploring whole hippocampus and 10 exploring hippocampal subfields). Critical analysis of the literature revealed mixed evidence from functional and dMRI, but stronger evidence from sMRI of the hippocampus as a biomarker for episodic memory impairment in PD. Hippocampal subfield studies most often implicated CA1, CA3/4, and subiculum volume in episodic memory and cognitive decline in PD. Despite differences in imaging methodology, study design, and sample characteristics, MRI studies have helped elucidate an important neural correlate of episodic memory impairment in PD with both clinical and theoretical implications. Natural progression of this work encourages future research on hippocampal subfield function as a potential biomarker of, or therapeutic target for, episodic memory dysfunction in PD.

Leriche Syndrome Misdiagnosed as Complex Regional Pain Syndrome in a Patient with Neuropathic Pain Caused by a Chip Fracture: A Case Report.

INTRODUCTION: Leriche syndrome is an aortoiliac occlusive disease caused by atherosclerotic occlusion. We report a case of Leriche syndrome with a fracture that was suspected as complex regional pain syndrome (CRPS), as the post-traumatic pain gradually worsened in the form of excruciating neuropathic pain. CASE REPORT: A 52-year-old woman with a history of hypertension was referred to the Department of Pain Medicine from a local orthopedic clinic because of suspected CRPS for excruciating neuropathic pain for one month. She complained of gait dysfunction and severe pain in the right foot following an incident of trauma with the right first toe. The average pain intensity assessed using the visual analog scale (VAS) was 90 (0: no pain, 100: the worst pain imaginable), and the neuropathic pain was evident as a score of 6/10 on Douleur neuropathique 4. Allodynia, hyperalgesia, blue discoloration of the skin, asymmetric temperature change (1.38 °C), and edematous soft tissue changes were observed. Ultrasonography showed a chip fracture in the first distal phalanx of the right first toe. The diagnosis was most probably CRPS type I according to the Budapest research criteria for CRPS. However, multiple pain management techniques were insufficient in controlling the symptoms. A month and a half later, an ankle-brachial index score of less than 0.4 suggested severe peripheral artery disease. Computed tomography angiography showed total occlusion between the infrarenal abdominal aorta and the bilateral common iliac arteries. Therefore, she underwent aortic-bifemoral bypass surgery with a diagnosis of Leriche syndrome. Three months after the surgery, the average pain intensity was graded as 10 on the VAS (0-100), the color of the skin of the right first toe improved and no gait dysfunction was observed. CONCLUSION: A chip fracture in a region with insufficient blood flow could manifest as excruciating neuropathic pain in Leriche syndrome.

DRER: Deep Learning-Based Driver's Real Emotion Recognizer.

In intelligent vehicles, it is essential to monitor the driver's condition; however, recognizing the driver's emotional state is one of the most challenging and important tasks. Most previous studies focused on facial expression recognition to monitor the driver's emotional state. However, while driving, many factors are preventing the drivers from revealing the emotions on their faces. To address this problem, we propose a deep learning-based driver's real emotion recognizer (DRER), which is a deep learning-based algorithm to recognize the drivers' real emotions that cannot be completely identified based on their facial expressions. The proposed algorithm comprises of two models: (i) facial expression recognition model, which refers to the state-of-the-art convolutional neural network structure; and (ii) sensor fusion emotion recognition model, which fuses the recognized state of facial expressions with electrodermal activity, a bio-physiological signal representing electrical characteristics of the skin, in recognizing even the driver's real emotional state. Hence, we categorized the driver's emotion and conducted human-in-the-loop experiments to acquire the data. Experimental results show that the proposed fusing approach achieves 114% increase in accuracy compared to using only the facial expressions and 146% increase in accuracy compare to using only the electrodermal activity. In conclusion, our proposed method achieves 86.8% recognition accuracy in recognizing the driver's induced emotion while driving situation.

The effect of baseline serum uric acid on chronic kidney disease in normotensive, normoglycemic, and non-obese individuals: A health checkup cohort study.

INTRODUCTION: The independent role of serum uric acid (SUA) on kidney disease is controversial due to its association with metabolic syndrome. The objective of this study was to investigate the association of baseline SUA with development of chronic kidney disease and eGFR decline in normotensive, normoglycemic and non-obese individuals during follow up period. MATERIALS AND METHODS: We included non-hypertensitive, non-diabetic, and non-obese 13,133 adults with estimated glomerular filtration rate (eGFR) ≥ 60ml/min/1.73m2 who had a voluntary health check-up during 2004-2017. RESULTS: SUA was positively related to adjusted means of systolic blood pressure (SBP), triglyceride, body mass index, and body fat percent. SUA was inversely associated with high density lipoprotein HDL (P for trend ≤0.001). SUA was an independent risk factor for the development of diabetes, hypertension, and obesity. During 45.0 [24.0-76.0] months of median follow up, the highest quartiles of SUA showed significant risks of 30% eGFR decline compared than the lowest quartile (RR:3.701; 95% CI: 1.504-9.108). The highest quartile had a 2.2 fold (95% CI: 1.182-4.177) increase in risk for incident chronic kidney disease (CKD). CONCLUSIONS: SUA is an independent risk factor for the development of diabetes, hypertension, and obesity in the healthy population. High SUA is associated with increased risk of CKD development and eGFR decline in participants with intact renal function.

A genome-wide investigation of the effect of farming and human-mediated introduction on the ubiquitous seaweed Undaria pinnatifida.

Human activity is an important driver of ecological and evolutionary change on our planet. In particular, domestication and biological introductions have important and long-lasting effects on species' genomic architecture and diversity. However, genome-wide analysis of independent domestication and introduction events within a single species has not previously been performed. The Pacific kelp Undaria pinnatifida provides such an opportunity because it has been cultivated in its native range in Northeast Asia but also introduced to four other continents in the past 50 years. Here we present the results of a genome-wide analysis of natural, cultivated and introduced populations of U. pinnatifida to elucidate human-driven evolutionary change. We demonstrate that these three categories of origin can be distinguished at the genome level, reflecting the combined influence of neutral (demography and migration) and non-neutral (selection) processes.

Maintenance chemotherapy after 6 cycles of platinum-doublet regimen in anthracycline-and taxane-pretreated metastatic breast cancer.

BACKGROUND/AIMS: Sequential monotherapy is recommended for anthracycline-and taxane-resistant metastatic breast cancer (MBC), but combination chemotherapy is considered in patients with visceral crisis. Cisplatin-doublet chemotherapy is a combination regimen for MBC, but prolonged treatment is challenging because of toxicity. We analyzed the role of single-agent maintenance chemotherapy after cisplatin-doublet chemotherapy for MBC. METHODS: From January 2011 to December 2017, 96 anthracycline- and taxane- resistant MBC patients were retrospectively reviewed, and 49 patients with a sustained clinical benefit during the initial 6 cycles of cisplatin-doublet chemotherapy were enrolled for study. Patients were treated with gemcitabine-cisplatin (gemcitabine, 1,250 mg/m2, intravenously [IV], days 1 to 8; cisplatin 60 mg/m2, IV, day 1) or capecitabine-cisplatin (capecitabine 2,500 mg/m2, orally, days 1 to 14; cisplatin 60 mg/m2, IV, day 1) during the induction period. After 6 cycles, 16 patients were switched to single-maintenance treatment (gemcitabine or capecitabine) and the doublet regimen was continued in 24 patients. Survival outcomes (progression- free survival [PFS] and overall survival [OS]) were analyzed. RESULTS: Among the 49 patients who showed a clinical benefit during cisplatin- doublet therapy, 24 were maintained on the doublet regimen, 16 were switched to single-maintenance treatment, and chemotherapy was suspended until disease progression in nine patients. The single-maintenance chemotherapy group showed superior survival than the chemotherapy holiday and doublet regimen groups (median PFS 15.43 months vs. 8.37 and 10.67 months, respectively, p = 0.008; median OS 43.67 months vs. 22.17 and 22.33 months, respectively, p = 0.014). CONCLUSION: Patients showing a clinical benefit during 6 cisplatin-doublet chemotherapy cycles may have a sustained survival benefit from single-maintenance chemotherapy.

Real-World Clinical Data of Palbociclib in Asian Metastatic Breast Cancer Patients: Experiences from Eight Institutions.

PURPOSE: Use of cyclin-dependent kinase 4/6 inhibitors improved survival outcome of hormone receptor (HR) positive metastatic breast cancer (MBC) patients, including Asian population. However, Asian real-world data of palbociclib is limited. We analyzed the real-world clinical practice patterns and outcome in HR-positive, MBC Asian patients treated with palbociclib. MATERIALS AND METHODS: Between April 2017 to November 2019, 169 HR-positive, human epidermal growth factor-2-negative MBC patients treated with letrozole or fulvestrant plus palbocilib were enrolled from eight institutions. Survival outcome (progression-free survival [PFS]), treatment response and toxicity profiles were analyzed. RESULTS: Median age of letrozole plus palbociclib (145 patients, 85.8%) and fulvestrant plus palbociclib (24 patients, 14.2%) was 58 and 53.5 years, with median follow-up duration of 14.63 months (range 0.2 to 33.9 months). Median PFS (mPFS) of letrozole plus palbociclib and fulvestrant plus palbociclib was 25.6 (95% confidence interval [CI], 19.1 to not reached) and 6.37 months (95% CI, 5.33 to not reached), comparable to previous phase 3 trials. In letrozole plus palbociclib arm, luminal A (hazard ratio, 2.86; 95% CI, 1.20 to 6.80; p=0.017) and patients with good performance (Eastern Cooperative Oncology Group 0-1 [hazard ratio, 3.68; 95% CI, 1.70 to 7.96]) showed better mPFS. In fulvestrant plus palbociclib group, chemotherapy naïve patients showed better mPFS (hazard ratio, 12.51, 95% CI, 1.59 to 99.17; p=0.017). The most common grade 3 or 4 adverse event was neutropenia (letrozole 86.3%, fulvestrant 88.3%). CONCLUSION: To our knowledge, this is the first real-world data of palbociclib reported in Asia. Palbociclib showed comparable benefit to previous phase 3 trials in Asian patients during daily clinical practice.

Renal hyperfiltration as a risk factor for chronic kidney disease: A health checkup cohort study.

INTRODUCTION: Renal hyperfiltration (RHF) has been found to be an independent predictor of adverse cardiovascular outcome. However, it remains uncertain whether it is precursor of chronic kidney disease (CKD) in a healthy population. MATERIALS AND METHODS: To determine relative risks and identify the predictor of incident proteinuria and decline of estimated glomerular filtration rate (eGFR) in subjects with RHF. A total of 55,992 subjects aged ≥20 years who underwent health check-up during 2004-2017 were included. Among them, 16,946 subjects who completed at least two health checkups were analyzed. RESULTS: A total of 949 (5.6%) subjects developed proteinuria and 98 (0.6%) subjects showed ≥ 30% of eGFR decline. The risk of incident proteinuria was significantly higher in those with RHF (RR: 1.644; 95% CI: 1.064-2.541). Those with RHF showed 8.720 fold (95% CI: 4.205-18.081) increased risk for ≥30% decline. ESR, CRP, and monocyte count showed reversed J shaped curve according to the increase of eGFR. The adjusted mean of monocyte count was significantly higher in participants with eGFR ≥90ml/min/1.73m2 or < 60ml/min/1.73m2 compared to that in patients with eGFR 75-89ml/min/1.73m2. Compared to subjects with the lowest tertile of monocyte and no RHF, those with the highest tertile of monocyte count in the RHF group had 3.314-fold (95% CI: 1.893-5.802) higher risk of incident proteinuria and 3.822-fold (95% CI, 1.327-11.006) risk of 30% eGFR decline. CONCLUSIONS: RHF had significantly increased risk of developing proteinuria and CKD in healthy subjects. Higher monocyte count might be used as a predictor of CKD in subjects with RHF.