Implementing antimicrobial stewardship: lessons and perspectives from a university-affiliated tertiary hospital in Korea.

Antimicrobial stewardship programs (ASPs) can lower antibiotic use, decrease medical expenses, prevent the emergence of resistant bacteria, and enhance treatment for infectious diseases. This study summarizes the stepwise implementation and effects of ASPs in a single university-affiliated tertiary care hospital in Korea; it also presents future directions and challenges in resource-limited settings. At the study hospital, the core elements of the ASP such as leadership commitment, accountability, and operating system were established in 2000, then strengthened by the formation of the Antimicrobial Stewardship (AMS) Team in 2018. The actions of ASPs entail key components including a computerized restrictive antibiotic prescription system, prospective audit, post-prescription review through quantitative and qualitative intervention, and pharmacy-based interventions to optimize antibiotic usage. The AMS Team regularly tracked antibiotic use, the effects of interventions, and the resistance patterns of pathogens in the hospital. The reporting system was enhanced and standardized by participation in the Korea National Antimicrobial Use Analysis System, and educational efforts are ongoing. Stepwise implementation of the ASP and the efforts of the AMS Team have led to a substantial reduction in the overall consumption of antibiotics, particularly regarding injectables, and optimization of antibiotic use. Our experience highlights the importance of leadership, accountability, institution-specific interventions, and the AMS Team.

The impact of long working hours on daily sodium intake.

Background: Long working hours are associated with an increased risk of cardiovascular disease, yet the underlying mechanism(s) remain unclear. The study examines how occupational factors like working hours, shift work, and employment status correlate with dietary choices and sodium intake, impacting hypertension risk. Methods: This study used data from the Korea National Health and Nutrition Examination Survey conducted between 2013 and 2020. The dataset included 8,471 respondents, all of whom were wage workers aged 20 or older and reported working at least 36 hours per week. Individuals who have been previously diagnosed with or are currently diagnosed with hypertension, diabetes, or dyslipidemia were excluded. The average daily sodium intake was assessed via a 24-hour dietary recall method. Average weekly working hours were categorized into 3 groups: 36-40 hours, 41-52 hours, and over 52 hours. Multiple logistic regression models were used. Results: Study findings revealed that 83.7% of participants exceeded the recommended daily sodium intake of 2 g set by the World Health Organization. After adjusting for confounding factors, a positive correlation was observed between average working hours and daily sodium intake. Among males, statistical significance was found in the group with average weekly working hours of 41-52 hours (prevalence ratio [PR]: 1.17; 95% confidence interval [CI]: 1.05-1.30) and the group exceeding 52 hours (PR: 1.22; 95% CI: 1.09-1.38) when comparing the fourth quartile of daily sodium intake to the combined quartiles of Q1, Q2, and Q3. Among females, no significance was noted. Conclusions: Long working hours were associated with increased sodium intake, primarily among male workers. This connection is likely attributed to having less time for home-cooked meals, resulting in higher fast food consumption and dining out. A workplace intervention promoting healthy eating and reducing stress is essential to lower sodium consumption and mitigate hypertension risk.

Adverse effects of tamoxifen treatment on bone mineral density in premenopausal patients with breast cancer: a systematic review and meta-analysis.

BACKGROUND: It is well known that adjuvant tamoxifen treatment for breast cancer in postmenopausal women decreased bone loss. However, the effects of adjuvant tamoxifen therapy on bone mineral density (BMD) in premenopausal patients with breast cancer remains uncertain. Tamoxifen would have a potential impact of premenopausal BMD on health. The aim of this meta-analysis was to assess this in premenopausal women with primary breast cancer. METHODS: Through April 2020, studies reporting BMD changes of lumbar spine or hip in premenopausal women with primary breast cancer treated with adjuvant tamoxifen and tamoxifen plus chemotherapy or ovarian function suppression (OFS) were collected from EMBASE and PubMed. The meta-analysis was performed using random effects model of the standardized mean difference (SMD) of BMD in patients. RESULTS: A total of 1432 premenopausal patients were enrolled in eight studies, involving 198 patients treated with tamoxifen alone in three studies. After a 3-year median follow-up, adjuvant tamoxifen decreased the lumbar spinal and hip BMD by as much as an SMD of -1.17 [95% confidence interval (CI); -1.58 to -0.76)] and -0.66 (95% CI, -1.55 to 0.23), respectively. In subgroup analysis in patients treated adjuvant tamoxifen and tamoxifen plus chemotherapy or OFS according to follow-up duration, the bone change of < 3 years follow-up group was -0.03 SMD (95% CI, -0.47 to 0.41) and that of ≥ 3 years follow-up group was -1.06 SMD (95% CI, -1.48 to -0.64). Compared with patients who received tamoxifen alone, patients who received combination therapy with chemotherapy or OFS showed lesser bone loss at the lumbar spine. CONCLUSIONS: Our meta-analysis demonstrated that adjuvant tamoxifen therapy in premenopausal patients caused bone loss after 3 years of follow-up, especially at the lumbar spines. For a definite evaluation of the adverse effects of tamoxifen on bone, it is necessary to accumulate more relevant studies.

Differences of nutritional intake habits and Dietary Inflammatory Index score between occupational classifications in the Korean working population.

Background: Human nutrient intake is closely related to the conditions of their workplace. Methods: This study used data from the Korean National Health and Nutritional Examination Survey (KNHANES) conducted between 2016 and 2020. The study population comprised individuals aged 19 to 65 years who were engaged in paid work, excluding soldiers (total = 12,201, male = 5,872, female = 6,329). The primary outcome of interest was the Dietary Inflammatory Index (DII) score, which was calculated using dietary intake data. Generalized linear models were used for statistical analyses. Results: Pink-collar workers had higher DII scores, indicating a potentially higher inflammatory diet than white-collar workers (mean: 2.18 vs. 1.89, p < 0.001). Green and blue-collar workers displayed lower levels of dietary inflammation (green: 1.64 vs. 1.89, p = 0.019, blue: 1.79 vs. 1.89, p = 0.022). After adjusting for sex, age, income, education, and energy intake, the sole trend that persisted was the comparison between white-collar and pink-collar workers. Conclusions: DII scores and dietary patterns differed among occupational groups and genders.

EGF-conditioned M1 macrophages Convey reduced inflammation into corneal endothelial cells through exosomes.

Epidermal Growth Factor (EGF), a protein pivotal in cell proliferation and survival, has recently shown promise in alleviating inflammation. This study investigates EGF's impact on M1 macrophages, exploring its potential for anti-inflammatory and anti-vasculogenic interactions with corneal endothelial cells (CECs). Polarized M1 macrophages treated with EGF exhibited a suppression of gene expressions related to inflammatory and vasculogenic signals. The anti-inflammatory effects of EGF were observed in co-culture systems with human CECs (HCECs), showcasing its ability to alter macrophage phenotypes. Exosomes derived from EGF-treated M1 macrophages demonstrated enriched proteomic profiles related to immune system regulation and inflammation inhibition. When applied as eye drops in murine corneas, EGF-conditioned M1 macrophage-derived exosomes effectively reduced inflammation and increased M2-related ARG1 expression. This study highlights EGF's potential in mitigating inflammation in M1 macrophages and its delivery through exosomes to cultured HCECs and murine corneas, suggesting a novel therapeutic avenue for ocular surface anti-inflammatory treatments.

Predicting postoperative lung function using ventilation SPECT/CT in patients with lung cancer.

Background: Single-photon emission computed tomography/computed tomography (SPECT/CT) has the advantage of assessing regional lung function. We aimed to investigate the potential of ventilation (SPECT/CT) for predicting postoperative lung function in patients with lung cancer. Methods: This retrospective study included consecutive patients with lung cancer who underwent lobectomy, preoperative ventilation, and perfusion SPECT/CT between January 2020 and December 2021. The percentage of predicted postoperative forced expiratory volume in 1 s (ppoFEV1%) and the percentage of predicted postoperative diffusion capacity of the lung for carbon monoxide (ppoDLCO%) were calculated from the % counts of each scan based on anatomical segments for lobar function. Correlation tests were performed between the predicted lung function values and actual ppoFEV1% and ppoDLCO%. Results: Among the 47 patients, 29 men and 18 women aged 67.5±9.6 years were included. Moreover, 46 ventilation and 41 perfusion SPECT/CT scans were obtained. The pulmonary function on ventilation SPECT/CT strongly correlated with perfusion SPECT/CT (correlation coefficient r=0.939 for ppoFEV1%, P<0.001; r=0.938 for ppoDLCO%, P<0.001). Both ppoFEV1% and ppoDLCO% values obtained from the ventilation and perfusion scans strongly correlated with postoperative FEV1% and DLCO% (correlation coefficient, r=0.774 and r=0.768 for ventilation; r=0.795 and r=0.751 for perfusion, each P<0.001). Conclusions: Ventilation SPECT/CT was comparable to perfusion SPECT/CT in predicting postoperative lung function.

Keratinocyte-derived circulating microRNAs in extracellular vesicles: a novel biomarker of psoriasis severity and potential therapeutic target.

BACKGROUND: Psoriasis is a chronic inflammatory disorder characterized by pathogenic hyperproliferation of keratinocytes and immune dysregulation. Currently, objective evaluation tools reflecting the severity of psoriasis are insufficient. MicroRNAs in extracellular vesicles (EV miRNAs) have been shown to be potential biomarkers for various inflammatory diseases. Our objective was to investigate the possibility of plasma-derived EV miRNAs as a marker for the psoriasis disease severity. METHODS: EVs were extracted from the plasma of 63 patients with psoriasis and 12 with Behçet's disease. We performed next-generation sequencing of the plasma-derived EV miRNAs from the psoriasis patients. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the level of EV miRNA expression. In situ hybridization was used to discern the anatomical location of miRNAs. qRT-PCR, western blotting, and cell counting kits (CCKs) were used to investigate IGF-1 signaling in cells transfected with miRNA mimics. RESULTS: We identified 19 differentially expressed EV miRNAs and validated the top three up-and down-regulated EV miRNAs. Among these, miR-625-3p was significantly increased in patients with severe psoriasis in both plasma and skin and most accurately distinguished moderate-to-severe psoriasis from mild-to-moderate psoriasis. It was produced and secreted by keratinocytes upon stimulation. We also observed a significant intensification of IGF-1 signalling and increased cell numbers in the miR-625-3p mimic transfected cells. CONCLUSIONS: We propose keratinocyte-derived EV miR-625-3p as a novel and reliable biomarker for estimating the severity of psoriasis. This biomarker could objectively evaluate the severity of psoriasis in the clinical setting and might serve as a potential therapeutic target. Trial registration None.

HDAC11 Regulates Palmitate-induced NLRP3 Inflammasome Activation by Inducing YAP Expression in THP-1 Cells and PBMCs.

Histone deacetylase 11 (HDAC11) has been implicated in the pathogenesis of metabolic diseases characterized by chronic low-grade inflammation, such as obesity. However, the influence of HDAC11 on inflammation and the specific effect of HDAC11 on the palmitic acid (PA)-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation are poorly understood. The effect of PA treatment on HDAC11 activity and the NLRP3 inflammasome was investigated in human peripheral blood mononuclear cells and THP-1 cells. The PA-induced responses of key markers of NLRP3 inflammasome activation, including NLRP3 gene expression, caspase-1 p10 activation, cleaved IL-1ß production, and extracellular IL-1ß release, were assessed as well. The role of HDAC11 was explored using a specific inhibitor of HDAC11 and by knockdown using small interfering (si)HDAC11 RNA. The relationship between HDAC11 and yes-associated protein (YAP) in the PA-induced NLRP3 inflammasome was investigated in THP-1 cells with HDAC11 or YAP knockdown. Following PA treatment, HDAC11 activity and protein levels increased significantly, concomitant with activation of the NLRP3 inflammasome. Notably, PA-induced the upregulation of NLRP3, caspase-1 p10 activation, the production of cleaved IL-1ß, and the release of IL-1ß into the extracellular space, all of which were attenuated by FT895 treatment and by HDAC11 knockdown. In THP-1 cells, PA induced the expression of YAP and its interaction with NLRP3, resulting in NLRP3 inflammasome activation, whereas both were inhibited by FT895 and siHDAC11 RNA. These findings demonstrate a pivotal role for HDAC11 in the PA-induced activation of the NLRP3 inflammasome. HDAC11 inhibition thus represents a promising therapeutic strategy for mitigating NLRP3 inflammasome-related inflammation in the context of obesity.

Pulsed-dye laser as an effective treatment for recalcitrant granulomatous rosacea and a potential regulator of CXCL9 expression.

Granulomatous rosacea (GR) is a rare and distinct variant of rosacea. We report three cases of recalcitrant GR successfully treated with pulsed-dye laser (PDL) and provide experimental evidence supporting its potential as a treatment option. PDL treatment demonstrated remarkable efficacy in the three clinical cases, despite their resistance to conventional therapies. Chemokine ligand 9 (CXCL9), a key chemokine involved in inflammation and granuloma formation, was found to be increased in skin sections from all three patients. In vitro experiments using human monocytes and dermal fibroblasts demonstrated that PDL treatment significantly reduced CXCL9 expression in fibroblasts. These findings suggest that PDL may modulate CXCL9 secretion in fibroblasts, potentially limiting the recruitment of immune cells to the lesion. Although further research is needed to fully understand the precise mechanisms underlying the role of CXCL9 in GR, PDL may be a promising therapeutic approach for refractory GR.

Obstructive Uropathy Caused by Massive Fecal Impaction in a Patient With Congenital Anorectal Malformation and Neurogenic Bladder.

Anorectal malformations (ARMs) comprise a broad spectrum of congenital anomalies involving both anorectal and urogenital tracts. After diagnosis, urological problems should be evaluated in addition to surgical correction of ARMs. Commonly encountered urological problems in patients with ARMs are recurrent urinary tract infections, vesicoureteral reflux, and chronic kidney disease. Therefore, the proper timing of urination and appropriate defecation habits are essential for preserving renal function in patients with ARMs. Here, we report a case of acute hydronephrosis by severe stool impaction in a patient with a history of congenital ARMs and neurogenic bladder. In this case, the physicians should consider properly managing chronic constipation and urination in patients with ARMs despite successful surgical corrections.

Transglutaminase 2 Prevents Premature Senescence and Promotes Osteoblastic Differentiation of Mesenchymal Stem Cells through NRF2 Activation.

Transglutaminase 2 (TG2) is a multifunctional enzyme that exhibits transamidase, GTPase, kinase, and protein disulfide isomerase (PDI) activities. Of these, transamidase-mediated modification of proteins regulates apoptosis, differentiation, inflammation, and fibrosis. TG2 is highly expressed in mesenchymal stem cells (MSCs) compared with differentiated cells, suggesting a role of TG2 specific for MSC characteristics. In this study, we report a new function of TG2 in the regulation of MSC redox homeostasis. During in vitro MSC expansion, TG2 is required for cell proliferation and self-renewal by preventing premature senescence but has no effect on the expression of surface antigens and oxidative stress-induced cell death. Moreover, induction of differentiation upregulates TG2 that promotes osteoblastic differentiation. Molecular analyses revealed that TG2 mediates tert-butylhydroquinone, but not sulforaphane, -induced nuclear factor erythroid 2-related factor 2 (NRF2) activation in a transamidase activity-independent manner. Differences in the mechanism of action between two NRF2 activators suggest that PDI activity of TG2 may be implicated in the stabilization of NRF2. The role of TG2 in the regulation of antioxidant response was further supported by transcriptomic analysis of MSC. These results indicate that TG2 is a critical enzyme in eliciting antioxidant response in MSC through NRF2 activation, providing a target for optimizing MSC manufacturing processes to prevent premature senescence.

The moderating and mediating effects of personality on the association between morningness and well-being.

Background: Morningness (morning-eveningness preference or chronotypes) and personality can be both associated with well-being, but few studies have directly compared these two constructs as correlates of well-being. Thus, the first purpose of this study was to test the effects of interactions between stable personality traits (temperaments) and morningness on well-being. Furthermore, personality factors are often composed of both stable biological factors (temperament) and socio-cultural factors (character), and little is known about personality interplay of temperament and character factors with respect to morningness and well-being. The second purpose of this study was therefore to examine the sequential mediating effects of temperament and character factors on the relationship between morningness and well-being. Methods: The Composite Scale of Morningness, the Korean version of the Temperament and Character Inventory-Revised Short Version (TCI-RS), and the Satisfaction with Life Scale were used to measure morningness, personality dimensions, and well-being, respectively, in 287 Korean university students. Moderating and sequentially mediating effects of temperament and character traits were determined using Hayes' PROCESS macro in SPSS after controlling for sex and age. Results: First, novelty-seeking (NS) and persistence (PS) temperaments have demonstrated the moderating effect in the association between morningness and well-being. The positive effects of morningness on life satisfaction increased with lower NS and PS, respectively. However, other temperaments such as harm avoidance (HA) and reward dependence (RD) have not shown the moderation in the relationship between morningness on well-being. Second, HA temperament and self-directedness (SD) character sequentially mediated the relationship between morningness and well-being. The combination of low scores of HA and high scores of SD have shown the positive effect on the relationship between morningness and well-being. Discussion: This study demonstrated that both the interactions between temperaments and morningness, and combination of specific TCI-RS temperament and character traits play important roles in influencing the association between morningness and well-being. The significance of the mature SD character and its implications for well-being are discussed with limitation of the present study.

CD38 Inhibition Protects Fructose-Induced Toxicity in Primary Hepatocytes.

A fructose-enriched diet is thought to contribute to hepatic injury in developing non-alcoholic steatohepatitis (NASH). However, the cellular mechanism of fructose-induced hepatic damage remains poorly understood. This study aimed to determine whether fructose induces cell death in primary hepatocytes, and if so, to establish the underlying cellular mechanisms. Our results revealed that treatment with high fructose concentrations for 48 h induced mitochondria-mediated apoptotic death in mouse primary hepatocytes (MPHs). Endoplasmic reticulum stress responses were involved in fructose-induced death as the levels of phosho-eIF2α, phospho-C-Jun-N-terminal kinase (JNK), and C/EBP homologous protein (CHOP) increased, and a chemical chaperone tauroursodeoxycholic acid (TUDCA) prevented cell death. The impaired oxidation metabolism of fatty acids was also possibly involved in the fructose-induced toxicity as treatment with an AMP-activated kinase (AMPK) activator and a PPAR-α agonist significantly protected against fructose-induced death, while carnitine palmitoyl transferase I inhibitor exacerbated the toxicity. However, uric acid-mediated toxicity was not involved in fructose-induced death as uric acid was not toxic to MPHs, and the inhibition of xanthine oxidase (a key enzyme in uric acid synthesis) did not affect cell death. On the other hand, treatment with inhibitors of the nicotinamide adenine dinucleotide (NAD)+-consuming enzyme CD38 or CD38 gene knockdown significantly protected against fructose-induced toxicity in MPHs, and fructose treatment increased CD38 levels. These data suggest that CD38 upregulation plays a role in hepatic injury in the fructose-enriched diet-mediated NASH. Thus, CD38 inhibition may be a promising therapeutic strategy to prevent fructose-enriched diet-mediated NASH.

Similarity-Driven Fine-Tuning Methods for Regularization Parameter Optimization in PET Image Reconstruction.

We present an adaptive method for fine-tuning hyperparameters in edge-preserving regularization for PET image reconstruction. For edge-preserving regularization, in addition to the smoothing parameter that balances data fidelity and regularization, one or more control parameters are typically incorporated to adjust the sensitivity of edge preservation by modifying the shape of the penalty function. Although there have been efforts to develop automated methods for tuning the hyperparameters in regularized PET reconstruction, the majority of these methods primarily focus on the smoothing parameter. However, it is challenging to obtain high-quality images without appropriately selecting the control parameters that adjust the edge preservation sensitivity. In this work, we propose a method to precisely tune the hyperparameters, which are initially set with a fixed value for the entire image, either manually or using an automated approach. Our core strategy involves adaptively adjusting the control parameter at each pixel, taking into account the degree of patch similarities calculated from the previous iteration within the pixel's neighborhood that is being updated. This approach allows our new method to integrate with a wide range of existing parameter-tuning techniques for edge-preserving regularization. Experimental results demonstrate that our proposed method effectively enhances the overall reconstruction accuracy across multiple image quality metrics, including peak signal-to-noise ratio, structural similarity, visual information fidelity, mean absolute error, root-mean-square error, and mean percentage error.

A real-time, personalized sleep intervention using mathematical modeling and wearable devices.

The prevalence of artificial light exposure has enabled us to be active any time of the day or night, leading to the need for high alertness outside of traditional daytime hours. To address this need, we developed a personalized sleep intervention framework that analyzes real-world sleep-wake patterns obtained from wearable devices to maximize alertness during specific target periods. Our framework utilizes a mathematical model that tracks the dynamic sleep pressure and circadian rhythm based on the user's sleep history. In this way, the model accurately predicts real-time alertness, even for shift workers with complex sleep and work schedules (N = 71, t = 13~21 days). This allowed us to discover a new sleep-wake pattern called the adaptive circadian split sleep, which incorporates a main sleep period and a late nap to enable high alertness during both work and non-work periods of shift workers. We further developed a mobile application that integrates this framework to recommend practical, personalized sleep schedules for individual users to maximize their alertness during a targeted activity time based on their desired sleep onset and available sleep duration. This can reduce the risk of errors for those who require high alertness during nontraditional activity times and improve the health and quality of life for those leading shift work-like lifestyles.

Evaluation of a New Monofocal Intraocular Lens in Patients Undergoing Cataract and Vitrectomy Surgery for Idiopathic Macular Hole.

PURPOSE: To evaluate the usefulness of a newly generated monofocal intraocular lens (IOL) in patients who underwent combined cataract and pars plana vitrectomy (PPV) surgery for idiopathic macular hole (MH). METHODS: A prospective study was conducted on 89 eyes of 89 patients who underwent combined cataract and PPV surgery for MH. The patients were divided into two groups: Eyhance ICB00 and Tecnis ZCB00. Pre-operative characteristics, post-operative visual outcomes, contrast sensitivity, and complications were compared between the two groups. A univariate regression analysis was performed to identify the factors that may affect the postoperative visual outcomes. RESULTS: Both groups showed significant improvement in mean corrected distance visual acuity (CDVA) six months post-operation (p < 0.001). There was no significant difference in pre-operative characteristics or complications between the two groups. However, the Eyhance ICB00 group showed a significantly higher uncorrected intermediate visual acuity (UCIVA) value at 6 months after surgery than the Tecnis ZCB00 group (p = 0.014). Contrast sensitivity values were not significantly different between the two groups. The univariate regression analysis revealed a significant correlation between preoperative CDVA and minimum linear diameter of MH with postoperative UCIVA in the Eyhance ICB00 group. CONCLUSIONS: The newly generated Eyhance ICB00 IOL showed promising results in terms of post-operative UCIVA, with no significant difference in complications or contrast sensitivity values compared to the Tecnis ZCB00 IOL. These findings suggest that the Eyhance ICB00 IOL may be a useful option for patients who undergo combined cataract and PPV surgery for idiopathic MH, particularly for those who require intermediate visual acuity.

Chemical Knockdown of Phosphorylated p38 Mitogen-Activated Protein Kinase (MAPK) as a Novel Approach for the Treatment of Alzheimer's Disease.

Targeted protein degradation (TPD) provides unique advantages over gene knockdown in that it can induce selective degradation of disease-associated proteins attributed to pathological mutations or aberrant post-translational modifications (PTMs). Herein, we report a protein degrader, PRZ-18002, that selectively binds to an active form of p38 MAPK. PRZ-18002 induces degradation of phosphorylated p38 MAPK (p-p38) and a phosphomimetic mutant of p38 MAPK in a proteasome-dependent manner. Given that the activation of p38 MAPK plays pivotal roles in the pathophysiology of Alzheimer's disease (AD), selective degradation of p-p38 may provide an attractive therapeutic option for the treatment of AD. In the 5xFAD transgenic mice model of AD, intranasal treatment of PRZ-18002 reduces p-p38 levels and alleviates microglia activation and amyloid beta (Aß) deposition, leading to subsequent improvement of spatial learning and memory. Collectively, our findings suggest that PRZ-18002 ameliorates AD pathophysiology via selective degradation of p-p38, highlighting a novel therapeutic TPD modality that targets a specific PTM to induce selective degradation of neurodegenerative disease-associated protein.

Sarcopenia assessed with DXA and CT increases the risk of perioperative complications in patients with gastrectomy.

OBJECTIVES: We investigated sarcopenia prevalence using various diagnostic criteria based on dual-energy X-ray absorptiometry (DXA) and computed tomography (CT) in gastric cancer patients who underwent gastrectomy, and evaluated the association between sarcopenia and perioperative complications. METHODS: This retrospective study included consecutive patients with gastric cancer who underwent gastrectomy, and preoperative DXA and CT from January 2013 to November 2020. Body composition was measured using DXA and CT. Height-adjusted DXA-based Appendicular Skeletal Muscle Mass Index (ASMI) and CT-based skeletal muscle cross-sectional area at the L3 level (SMI) were measured. Sarcopenia and sarcopenic obesity were defined using reported cutoff values. The chi-square test and univariate analysis were performed to determine risk factors for significant and severe perioperative complications (Clavien-Dindo Grades ≥ 2 and ≥ 3, respectively). RESULTS: In total, 77 males and 43 females aged 61.4 ± 11.0 years were included. ASMI and SMI were correlated (r = 0.819), but sarcopenia prevalence varied (20.0-63.3%), depending on the criteria applied. Univariate analysis revealed sarcopenia defined using the Asian Working Group on Sarcopenia (AWGS) criteria and sarcopenic obesity as risk factors for significant (odds ratio [OR] 2.76, p = 0.030 vs. OR 4.31, p = 0.002) and severe perioperative complications (OR 3.77, p = 0.036 vs. OR 4.78, p = 0.010). In subgroup analyses, sarcopenia and sarcopenic obesity were significantly associated with perioperative complications only in males. CONCLUSION: Perioperative complication risk can be predicted from sarcopenia defined using the AWGS criteria and sarcopenic obesity measured using DXA and CT, particularly in males. KEY POINTS: • The prevalence of sarcopenia varies due to definition differences. • Sarcopenia and sarcopenic obesity are risk factors for significant and severe perioperative complications, particularly in males. • Our results suggest that physicians need to pay attention to perioperative complications after surgical treatment of male patients with sarcopenia and sarcopenic obesity.

Gut bacteria-derived 3-phenylpropionylglycine mitigates adipocyte differentiation of 3T3-L1 cells by inhibiting adiponectin-PPAR pathway.

BACKGROUND: Gut microbiota provide numerous types of metabolites that humans cannot produce and have a huge influence on the host metabolism. Accordingly, gut bacteria-derived metabolites can be employed as a resource to develop anti-obesity and metabolism-modulating drugs. OBJECTIVE: This study aimed to examine the anti-adipogenic effect of 3-phenylpropionylglycine (PPG), which is a glycine conjugate of bacteria-derived 3-phenylpropionic acid (PPA). METHODS: The effect of PPG on preadipocyte-to-adipocyte differentiation was evaluated in 3T3-L1 differentiation models and the degree of the differentiation was estimated by Oil red O staining. The molecular mechanisms of the PPG effect were investigated with transcriptome analyses using RNA-sequencing and quantitative real-time PCR. RESULTS: PPG suppressed lipid droplet accumulation during the adipogenic differentiation of 3T3-L1 cells, which is attributed to down-regulation of lipogenic genes such as acetyl CoA carboxylase 1 (Acc1) and fatty acid synthase (Fasn). However, other chemicals with chemical structures similar to PPG, including cinnamoylglycine and hippuric acid, had little effect on the lipid accumulation of 3T3-L1 cells. In transcriptomic analysis, PPG suppressed the expression of adipogenesis and metabolism-related gene sets, which is highly associated with downregulation of the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Protein-protein association network analysis suggested adiponectin as a hub gene in the network of genes that were differentially expressed genes in response to PPG treatment. CONCLUSION: PPG inhibits preadipocyte-to-adipocyte differentiation by suppressing the adiponectin-PPAR pathway. These data provide a potential candidate from bacteria-derived metabolites with anti-adipogenic effects.