Application of metabolic phase-specific modified nutrition risk in critically ill score: a prospective observational study in critically ill patients.

Background and aims: The prevalence of malnutrition in intensive care units (ICU) is high and can be caused by poor intake or absorption of nutrients in the digestive track, as well as disease-related inflammation. As strong catabolism restricts nutrient supply and potentially leads to subsequent malnutrition, appropriate nutrition should be provided based on the metabolic status. However, nutritional support strategies for considering the metabolic phase are not well established. Therefore, this study aimed to establish a strategy for nutritional support in each phase by implementing a phase-specific modified Nutrition Risk in Critically Ill (mNUTRIC) score. Methods: This prospective observational study was conducted on all adult patients admitted to the medical ICU for at least 36 h at Seoul National University Bundang Hospital between September 2020 and September 2022. Patient nutrition assessment (mNUTRIC score), clinical information, and nutritional supply (calories and proteins) were measured twice, in the acute phase (measured at 2 days) and late phase (measured at 7 days). The relationship between nutritional supply and 28-day mortality was analyzed using multiple logistic regression according to the mNUTRIC score in the acute and late phases. Risk factors related to 28-day mortality were analyzed using univariate and multivariate Cox proportional hazards regressions. Results: Of the 631 patients admitted to the ICU during the study period, 613 were included in the acute phase and 361 patients were included in the late phase. Nutritional supply was associated with 28-day mortality, with high mNUTRIC scores in both the acute and late phases. Cox proportional hazards regression analysis demonstrated that a high mNUTRIC score [hazard ratio (HR) 3.20 and 2.52, respectively], lactate >2.5 mg/dL were independent risk factors in both the acute and late phases. In addition, Albumin <2.5 mg/dL, the presence of neoplasm, and the need for dialysis in the acute phase, calorie adequacy <0.7 in the late phase (HR, 2.19) were identified as additional risk factors. Conclusion: The mNUTRIC score is a suitable tool for identifying critically ill patients who benefit from nutritional support. Nutritional supply should be considered for patients with high mNUTRIC scores in both the acute and late phases; however, careful supply should be provided in the acute phase and sufficient supply should be provided in the late phase.

Synthesis and evaluation of antibody-drug conjugates with high drug-to-antibody ratio using dimaleimide-DM1 as a linker- payload.

The notable characteristics of recently emerged Antibody-Drug Conjugates (ADCs) encompass the targeting of Human Epidermal growth factor Receptor 2 (HER2) through monoclonal antibodies (mAbs) and a high ratio of drug to antibody (DAR). The achievements of Kadcyla® (T-DM1) and Enhertu® (T-Dxd) have demonstrated that HER2-targeting antibodies, such as trastuzumab, have shown to be competitive in terms of efficacy and price for development. Furthermore, with the arrival of T-Dxd and Trodelvy®, high-DAR (7-8) ADCs, which differ from the moderate DAR (3-4) ADCs that were formerly regarded as conventional, are being acknowledged for their worth. Following this trend of drug development, we endeavored to develop a high-DAR ADC using a straightforward approach involving the utilization of DM1, a highly potent substance, in combination with the widely recognized trastuzumab. To achieve a high DAR, DM1 was conjugated to reduced cysteine through the simple design and synthesis of various dimaleimide linkers with differing lengths. Using LC and MS analysis, we have demonstrated that our synthesis methodology is uncomplicated and efficacious, yielding trastuzumab-based ADCs that exhibit a remarkable degree of uniformity. These ADCs have been experimentally substantiated to exert an inhibitory effect on cancer cells in vitro, thus affirming their value as noteworthy additions to the realm of ADCs.

Lysophosphatidic Acid Promotes Epithelial-Mesenchymal Transition in Kidney Epithelial Cells via the LPAR1/MAPK-AKT/KLF5 Signaling Pathway in Diabetic Nephropathy.

The epithelial-mesenchymal transition (EMT) is a differentiation process associated with fibrogenesis in diabetic nephropathy (DN). Lysophosphatidic acid (LPA) is a small, naturally occurring glycerophospholipid implicated in the pathogenesis of DN. In this study, we investigated the role of LPA/LPAR1 signaling in the EMT of tubular cells as well as the underlying mechanisms. We observed a decrease in E-cadherin and an increase in vimentin expression levels in the kidney tubules of diabetic db/db mice, and treatment with ki16425 (LPAR1/3 inhibitor) inhibited the expression of these EMT markers. Ki16425 treatment also decreased the expression levels of the fibrotic factors fibronectin and alpha-smooth muscle actin (α-SMA) in db/db mice. Similarly, we found that LPA decreased E-cadherin expression and increased vimentin expression in HK-2 cells, which was reversed by treatment with ki16425 or AM095 (LPAR1 inhibitor). In addition, the expression levels of fibronectin and α-SMA were increased by LPA, and this effect was reversed by treatment with ki16425 and AM095 or by LPAR1 knockdown. Moreover, LPA induced the expression of the transcription factor, Krüppel-like factor 5 (KLF5), which was decreased by AM095 treatment or LPAR1 knockdown. The expression levels of EMT markers and fibrotic factors induced by LPA were decreased upon KLF5 knockdown in HK-2 cells. Inhibition of the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and serine-threonine kinase (AKT) pathways decreased LPA-induced expression of KLF5 and EMT markers. In conclusion, these data suggest that LPA contributes to the pathogenesis of diabetic nephropathy by inducing EMT and renal tubular fibrosis via regulation of KLF5 through the LPAR1.

Association of Handgrip Strength in Various Disabilities in Korean Adults over 50 Years Old: A Nationwide Cross-Sectional Study.

Several studies have shown an association between low hand grip strength (HGS) and functional limitations. This study aims to elucidate the association between HGS and functional limitations. We used the nationwide health examination data and included 13,517 Korean adults that were aged ≥ 50 years. We measured HGS using digital dynamometer and the maximum value of the dominant hand was divided into quartiles for the analysis. Functional limitations were assessed by using self-administered questionnaires. We categorized the 24 reported causes of functional limitations into musculoskeletal, cardiometabolic, neuropsychiatric, cancers, and others. In multiple regression analysis, the functional limitations tended to increase as HGS was lowered in both sexes. When analyzing according to the reasons of functional limitations, the ORs for functional limitations due to cardiometabolic problem tended to increase as the HGS decreased in men (p for trend = 0.039). Similar trends were observed in neuropsychiatric problem in women (p for trend = 0.002) and other problems in both men and women (p for trend = 0.014 in men, p for trend = 0.004 in women). No significant trends were observed for musculoskeletal problems and cancer in both men and women. The functional limitations were inversely associated with HGS, which were inconsistent according to different etiologies of functional limitations.

Effects of N-acetylcysteine inhalation therapy on the quality of life of patients with head and neck cancer who are receiving radiation therapy: a prospective non-randomized controlled multi-center study.

BACKGROUNDS AND PURPOSE: Radiation therapy is an important mode of treatment for patients with head and neck cancers, but some associated complications can reduce the quality of life. We investigated whether N-acetylcysteine inhalation therapy improved the quality of life of such patients. MATERIALS AND METHODS: We designed a prospective, non-randomized controlled multi-center study involving 10 institutions. We enrolled 120 patients (80 in the experimental group and 40 in the control group). Patients in the experimental group inhaled nebulized liquid N-acetylcysteine (2400 mg daily) for 8 weeks from the start of radiation therapy. Quality of life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire H&N 35. RESULTS: N-acetylcysteine inhalation was not associated with any side effect or discomfort. The reduction in painkiller use from the end of N-acetylcysteine inhalation therapy to the 1-month follow-up was greater in the experimental group than in the control group (P = 0.014). Dry mouth symptoms also improved significantly in the experimental group (P = 0.019). CONCLUSION: N-acetylcysteine inhalation improves the quality of life of patients with head and neck cancers who are receiving radiation therapy, without any specific side effect.

Socioeconomic Vulnerability, Mental Health, and Their Combined Effects on All-Cause Mortality in Koreans, over 45 Years: Analysis of Korean Longitudinal Study of Aging from 2006 to 2014.

BACKGROUND: We evaluated the effects of socioeconomic factors and psychosocial factors, both individually and combined, on all-cause mortality risk (mortality risk). METHODS: We conducted an 8-year (2006-2014) longitudinal analysis of 10,247 individuals who took part in the Korean Longitudinal Study of Aging, a nationwide survey of people aged 45-79 years. Socioeconomic vulnerability (SEV) was assessed with factors such as education, household income, commercial health insurance, and residential area. Mental health (MH) was assessed with factors such as depression, social engagement, and life satisfaction. The covariates were age, gender, marital status, cohabiting, number of chronic diseases, and health behaviors such as regular exercise, smoking, and alcohol intake. We used a Cox proportional hazard analysis to investigate the effects of SEV and MH on mortality risk and also to analyze the superimposed effects of SEV-MH on mortality risk. RESULTS: After the controlling for the covariates, high SEV and negative MH were found to be strong predictors of all-cause mortality. The highest quartile of SEV (vs. lowest) had a 1.70 times greater mortality risk (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.24-2.33) and the highest quartile of MH (vs. lowest) had a 2.13 times greater mortality risk (HR, 2.13; 95% CI, 1.72-2.64). Being in the highest quartile for both SEV and MH (vs. lowest) increased mortality risk more than 3 times (HR, 3.11; 95% CI, 2.20-4.40). CONCLUSION: High SEV and negative MH were independently associated with increased mortality risk, and their superimposed effects were associated with an increased risk of mortality.

Dietary magnesium intake and risk of cancer: a meta-analysis of epidemiologic studies.

The aim of this study was to investigate the association between dietary magnesium and the risk of overall cancer using a meta-analysis. We searched PubMed, SCOPUS, and the Cochrane Review through November 2012. All the articles searched were independently reviewed by 3 authors based on predetermined selection criterion. A total of 13 epidemiologic studies, 6 case-control studies, and 7 prospective cohort studies involving 1,236,004 participants were included in the final analysis. When all studies were pooled, the relative risk (RR) of overall cancer for the highest level of dietary magnesium intake was 0.801 [95% confidence interval (CI): 0.664-0.966) compared with the lowest level of dietary magnesium intake. In subgroup meta-analyses by study design, there was a significant inverse association between dietary magnesium and the risk of cancer in case-control studies (RR = 0.663, 95% CI: 0.475-0.925), whereas there was no significant association in prospective cohort studies (RR = 0.888, 95% CI: 0.745-1.060). Furthermore, there was a significant preventive effect of dietary magnesium for colorectal cancer (RR = 0.775, 95% CI: 0.655-0.919), but not for other cancer. Our meta-analysis showed that higher dietary magnesium intake seems to have a protective effect for cancer, especially colorectal cancer and in females.

Disappearance of an adnexal mass with Saam acupuncture: a case report.

We report the case of a 30-year-old woman with a right adnexal mass resembling an ovarian cyst who declined diagnostic laparoscopy and requested treatment with acupuncture. The patient was treated with Saam acupuncture for 14 weeks. After treatment, transvaginal sonography revealed disappearance of the right adnexal mass. No adverse effects of the Saam acupuncture treatment were reported.

Gastric cancer detection using gastric juice pepsinogen and melanoma-associated gene RNA.

OBJECTIVES: To develop a new method for gastric cancer detection with gastric juice using melanoma-associated gene (MAGE) RNA and pepsinogen (PG). METHODS: In total, 183 gastric juice and paired serum specimens were obtained from 134 patients with gastric cancer and 49 healthy individuals. The gastric juice specimens were analyzed with MAGE A1 to A6 nested reverse transcription-polymerase chain reaction. The serum and gastric juice PG were measured with a PG I and II immunoassay. RESULTS: The gastric juice PG I and PG I/II ratios were more accurate than those of serum. The combination test using the gastric PG I/II ratio and MAGE was the most accurate, with a sensitivity of 77.6% and a specificity of 87.8%. The sensitivity was 78.8% for stage I gastric cancer and not influenced by cancer location or pathologic type. CONCLUSIONS: The combination test is potentially an additional tool for gastric cancer detection.

γδ T cells are increased in the peripheral blood of patients with gastric cancer.

BACKGROUND: γδ T cells are implicated in immunoregulation. However, little is known about the characteristics of γδ T cells in gastric cancer. In this study, we assessed the incidence of γδ T cells and lymphocyte subsets in the peripheral blood of gastric cancer patients. METHODS: We enrolled 48 patients and 49 healthy controls. The γδ T cells, lymphocyte subsets were analyzed with flow cytometry. RESULTS: The mean percentage of γδ T cells in patients with gastric cancer was 5.0±3.4% and for controls 2.3±1.6%. Twenty (41.7%) of the 48 patients with gastric cancer had a high percentage (more than 5%) of peripheral blood γδ T cells, while 4 (8.2%) of the 49 controls did. The percentage of CD3⁺ T cells were elevated in gastric cancer compared to controls (P=0.007). The CD4/CD8 ratio increased in gastric cancer (P=0.311). The percentage of CD3⁺CD4⁻CD8⁻ T cells increased in gastric cancer compared to controls (P=0.004). CONCLUSION: The proportion of γδ T cells in the peripheral blood of gastric cancer patients was significantly higher in comparison to that in the healthy controls. Our findings suggest that increased proportion of peripheral γδ T cells may explain anti-tumor immunity against gastric cancer partly.

Radiographic bone damage in chronic gout is negatively associated with the inflammatory cytokines soluble interleukin 6 receptor and osteoprotegerin.

OBJECTIVE: We investigated the risk factors for radiographic bone damage to foot joints in patients with chronic gout among various patient characteristics and serum inflammatory cytokines such as interleukin 1ß (IL-1ß), IL-6, soluble IL-6 receptor (sIL-6R), osteoprotegerin (OPG), and receptor activator of nuclear factor-κB ligand (RANKL). METHODS: Fifty consecutive male patients with gout and 54 age-matched healthy male controls were enrolled. Serum levels of cytokines including IL-1ß, IL-6, sIL-6R, OPG, and RANKL were measured using ELISA. Radiographic damage indices including erosion scores, narrowing scores, and total scores for foot joints were assessed according to a modified Sharp-van der Heijde system. RESULTS: There were significant differences in serum IL-1ß, IL-6, sIL-6R, OPG, and RANKL levels between patients with gout and the controls, after adjustment for confounding factors such as age, body mass index, blood urea nitrogen, creatinine, triglyceride, and fasting blood glucose (p = 0.034 for IL-1ß, p < 0.001 for IL-6, p = 0.040 for sIL-6R, p = 0.002 for OPG, and p = 0.018 for RANKL). Radiographic damage indices (erosion, narrowing, and total scores) were negatively associated with serum sIL-6R and OPG levels in multivariable-adjusted regression analysis. Serum sIL-6R levels in patients without radiographic damage were higher than in those with damage (p = 0.006). CONCLUSION: Radiographic damage in patients with chronic gouty arthritis was negatively associated with serum sIL-6R and OPG. Further study on the role of inflammatory cytokines in the pathogenesis of radiographic damage in gout is needed.

Increased insulin resistance and serum resistin in Korean patients with Behçet's disease.

BACKGROUND AND AIMS: This study was designed to identify susceptibility to insulin resistance and the association of serum resistin and adiponectin with insulin resistance in patients with Behçet's disease (BD). Also, we identify risk determinants for insulin resistance in BD patients. METHODS: The study population consisted of 82 BD patients (n = 26 males) and 89 healthy controls (n = 40 males). Clinical data were collected at the time of enrollment, and serum resistin and adiponectin levels were measured using enzyme-linked immunosorbent assays. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated by measuring fasting plasma glucose and insulin levels. RESULTS: BD patients and healthy controls differed significantly in insulin resistance (HOMA-IR) (1.3 +/- 1.1 vs. 0.7 +/- 0.5, p<0.001) and serum resistin level (7901.7 +/- 1314.9 vs. 7444.2 +/- 1841.6, p = 0.001) but not in serum adiponectin level (p = 0.223). No differences in HOMA-IR, serum adiponectin, and serum resistin were found between patients with active and inactive BD. It is determined that plasma glucose, plasma insulin, and serum resistin may be determinant for the HOMA-IR. The number of metabolic syndrome components is closely correlated with HOMA-IR in BD patients (r = 0.245, p = 0.029). CONCLUSION: This study demonstrates that there is an increased susceptibility to insulin resistance in patients with BD as compared to healthy controls. Serum resistin level may be an independent determinant for insulin resistance in BD patients.