Korea Nurses' Health Study and the health of reproductive-aged women: a cohort profile.

The Korea Nurses' Health Study (KNHS) is an ongoing, large-scale, prospective cohort study of female nurses, focusing on the effects of occupational, environmental, and lifestyle factors on the health of women. The first KNHS survey was performed in 2013-2014 (n=20,613). As of December 2023, 11 follow-up surveys have been conducted. Participants who were pregnant were asked to participate in the early pregnancy survey (n=2,179) and postpartum survey after giving birth (n=2,790). The main variables included sociodemographic, work-related, lifestyle, physical, mental, and women's health factors. Blood, urine, and toenail samples were collected from a participant subgroup of the first survey (n=1,983). The subgroups of the second survey completed a food frequency questionnaire in 2019 (n=300) and 2021 (n=871). In 2020, a subgroup of the first survey answered a coronavirus disease 2019 (COVID-19)-related survey (n=975). To examine various health-related factors in young adults, new participants were added to the KNHS cohort in the 11th (n=1,000) and 12th (n=1,002) surveys. The KNHS cohort will help identify health and illness determinants in Korean women. Data can be accessed at https://coda.nih.go.kr/frt/index.do.

Effects of Kt/Vurea on outcomes according to age in patients on maintenance hemodialysis.

Background: The guidelines recommended target and minimum single-pool Kt/Vurea are 1.4 and 1.2, respectively, in hemodialysis patients. However, the optimal hemodialysis dose remains controversial. We investigated the effects of Kt/Vurea on patient outcomes according to age, with a focus on older patients. Methods: This study used the hemodialysis quality assessment program and claims datasets. Patients were divided into four subgroups according to age (<65, 65-74, 75-84, and ≥85 years). Each group was divided into three subgroups according to Kt/Vurea : reference (ref) (1.2 ≤ Kt/Vurea ≤ 1.4), low (< 1.2), and high (> 1.4). Results: The low, ref, and high Kt/Vurea groups included 1668, 8156, and 16 546 (< 65 years); 474, 3058, and 7646 (65-74 years); 225, 1362, and 4194 (75-84 years); and 14, 126, and 455 (≥85 years) patients, respectively. The low Kt/Vurea group had higher mortality rates than the ref Kt/Vurea group irrespective of age [adjusted hazard ratio (aHR), 95% confidence interval (CI): 1.23, 1.11-1.36; 1.14, 1.00-1.30; 1.28, 1.09-1.52; and 2.10, 1.16-3.98, in patients aged <65, 65-74, 75-84, and ≥85 years, respectively]. The high Kt/Vurea group had lower mortality rates than the ref Kt/Vurea group in patients aged <65 and 65-74 years (aHR, 95% Cl: 0.87, 0.82-0.92 and 0.93, 0.87-0.99 in patients aged <65 and 65-74 years, respectively). Conclusions: These results support the current recommendations of a minimum Kt/Vurea of 1.2 even in patients age ≥85 years. In young patients, Kt/Vurea above the recommended threshold can be beneficial for survival.

Abnormally High Graphitic Crystallization of Cellulose Nanocrystals.

Cellulose nanocrystals (CNCs) are currently of great interest for many applications, such as energy storage and nanocomposites, because of their natural abundance. A number of carbonization studies have reported abnormal graphitization behavior of CNCs, although cellulose is generally known as a precursor for hard carbon (nongraphitizable carbon). Herein, we report a spray-freeze-drying (SFD) method for CNCs and a subsequent carbonization study to ascertain the difference in the structural development between the amorphous and crystalline phases. The morphological observation by high-resolution transmission electron microscopy of the carbonized SFD-CNC clearly shows that the amorphous and crystalline phases of CNC are attributed to the formation of hard and soft carbon, respectively. The results of a reactive molecular dynamics (RMD) study also show that the amorphous cellulose phase leads to the formation of fewer carbon ring structures, indicative of hard carbon. In contrast, the pristine crystalline cellulose phase has a higher density and thermal stability, resulting in limited molecular relaxation and the formation of a highly crystalline graphitic structure (soft carbon).

V advancement eversion flap for fingertip injury: Preventing ischemia and hook-nail deformity.

Introduction: Traumatic fingertip amputation is the most common type of upper extremity injuries. The V-Y advancement flap is a reliable method for reconstructing fingertip defects, but it is associated with complications such as hook-nail deformity and suture site ischemia. Here, we describe our modifications to V-Y advancement flap technique, termed as "V advancement eversion flap" and review the outcomes of this procedure in 21 patients with fingertip amputation. Methods: This was a retrospective review of 21 consecutive patients with fingertip injury who were treated surgically using the V advancement eversion flap technique at a single trauma center between 2006 and 2019. We analyzed the age, injury location and mechanism, Allen classification, injury geometry, and objective and subjective clinical outcomes. Results: Twenty-three fingertip amputations with defect sizes greater than 1.0 cm2 from the tip to lunula were included in this study. The mean age of the patients was 43.6 years (range, 24-65 years). The average follow-up period was 20 months (range, 12-37 months). The average wound healing time (apparent epithelization) was 29.4 days (range, 14-41 days). At the final follow-up, all flaps had healed uneventfully without noticeable hook-nail deformity. In the static two-point discrimination test, the mean value was 4.61 mm in the injured finger. Patient ratings of the outcomes were "excellent" in 18 and "good" in 5 cases. Conclusion: The V advancement eversion flap technique, when properly designed and executed in fingertip amputation cases, can minimize morbidity and result in successful wound healing without flap necrosis and hook-nail deformity.

Association of physical activity with fractures in kidney transplant recipients: A Korean nationwide cohort study.

Kidney transplant recipients are at high risk for fractures, primarily due to post-transplant bone disease. This retrospective cohort study analyzed data from the Korean National Health Insurance Service, including 10 083 kidney transplant recipients examined from 2009 to 2017. We assessed fracture incidence, emphasizing vertebral and hip fractures, and the association of physical activity and traditional risk factors with fracture risk. Kidney transplant recipients were categorized into three groups according to physical activity levels: non-activity, metabolic equivalent of task (MET) 1-499, and MET ≥500. Physical activity was associated with a decreased risk of all types of fractures: any (MET 1-499: adjusted hazard ratio (aHR) .75; 95% confidence interval (CI) .62-.92, MET ≥500: aHR .84; 95% CI .70-1.00), vertebral (MET 1-499: aHR .69; 95% CI .49-.98, MET ≥500: aHR .67; 95% CI .49-.91), and hip (MET 1-499: aHR .43; 95% CI .23-.81) fractures. Additionally, older age, female sex, and diabetes were associated with an increased fracture risk. The assessment of physical activity and traditional risk factors could improve fracture risk prediction. Our findings emphasize the need for further research to establish optimal physical activity recommendations for fracture prevention in kidney transplant recipients.

Scalable Design of Ru-Embedded Carbon Fabric Using Conventional Carbon Fiber Processing for Robust Electrocatalysts.

Metal-carbon composites are extensively utilized as electrochemical catalysts but face critical challenges in mass production and stability. We report a scalable manufacturing process for ruthenium surface-embedded fabric electrocatalysts (Ru-SFECs) via conventional fiber/fabric manufacturing. Ru-SFECs have excellent catalytic activity and stability toward the hydrogen evolution reaction, exhibiting a low overpotential of 11.9 mV at a current density of 10 mA cm-2 in an alkaline solution (1.0 M aq KOH solution) with only a slight overpotential increment (6.5%) after 10,000 cycles, whereas under identical conditions, that of commercial Pt/C increases 6-fold (from 1.3 to 7.8 mV). Using semipilot-scale equipment, a protocol is optimized for fabricating continuous self-supported electrocatalytic electrodes. Tailoring the fiber processing parameters (tension and temperature) can optimize the structural development, thereby achieving good catalytic performance and mechanical integrity. These findings underscore the significance of self-supporting catalysts, offering a general framework for stable, binder-free electrocatalytic electrode design.

A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma.

PURPOSE: Clinical implications of neoadjuvant immunotherapy in patients with locally advanced but resectable head and neck squamous cell carcinoma (HNSCC) remain largely unexplored. PATIENTS AND METHODS: Patients with resectable HNSCC were randomized to receive a single dose of preoperative durvalumab (D) with or without tremelimumab (T) before resection, followed by postoperative (chemo)radiotherapy based on multidisciplinary discretion and 1-year D treatment. Artificial intelligence (AI)-powered spatial distribution analysis of tumor-infiltrating lymphocytes and high-dimensional profiling of circulating immune cells tracked dynamic intratumoral and systemic immune responses. RESULTS: Of the 48 patients enrolled (D, 24 patients; D+T, 24 patients), 45 underwent surgical resection per protocol (D, 21 patients; D+T, 24 patients). D±T had a favorable safety profile and did not delay surgery. Distant recurrence-free survival (DRFS) was significantly better in patients treated with D+T than in those treated with D monotherapy. AI-powered whole-slide image analysis demonstrated that D+T significantly reshaped the tumor microenvironment toward immune-inflamed phenotypes, in contrast with the D monotherapy or cytotoxic chemotherapy. High-dimensional profiling of circulating immune cells revealed a significant expansion of T-cell subsets characterized by proliferation and activation in response to D+T therapy, which was rare following D monotherapy. Importantly, expansion of specific clusters in CD8+ T cells and non-regulatory CD4+ T cells with activation and exhaustion programs was associated with prolonged DRFS in patients treated with D+T. CONCLUSIONS: Preoperative D±T is feasible and may benefit patients with resectable HNSCC. Distinct changes in the tumor microenvironment and circulating immune cells were induced by each treatment regimen, warranting further investigation.

Association Between Psychosocial Acuity and Glycemic Control in a Pediatric Type 1 Diabetes Clinic.

PURPOSE: The purpose of this study was to describe the frequency of psychosocial risk and its associations with glycemic levels in youth with type 1 diabetes (T1D) seen by social work staff during regular clinical care. METHODS: A retrospective longitudinal analysis of observational clinical data was conducted. Individuals (1-26 years) with known T1D who were seen at a pediatric diabetes clinic in a US academic medical center between 2014 and 2021 were included. Variables included psychosocial acuity, A1C, and demographic characteristics. Chi-square tests, Wilcoxon rank sum tests, and mixed linear regressions were used to examine associations between demographic variables, psychosocial acuity, and A1C. RESULTS: Of 966 patients, 513 (53.1%) were male, 76 (7.9%) were non-Hispanic Black, and 804 (83.2%) were non-Hispanic White. There was a mean of 6.9 annual social work encounters per patient, with 3 psychosocial domains measured at each visit. Results showed that as psychosocial acuity level increased, glycemic control decreased. There were significant differences in A1C according to race/ethnicity, insurance, age, and psychosocial acuity. CONCLUSIONS: In a real-world clinical population, psychosocial acuity was associated with glycemic control. Presenting for psychosocial issues in their diabetes clinic was associated with reduced glycemic control among youth with T1D. There is an opportunity to connect pediatric patients with appropriate mental health services and psychosocial supports.

NJK14047 inhibition of p38 MAPK ameliorates inflammatory immune diseases by suppressing T cell differentiation.

p38 MAPK has been implicated in the pathogenesis of rheumatoid arthritis and psoriasis. To assess the therapeutic efficacy of the p38 MAPK inhibitor NJK14047 in the treatment of rheumatoid arthritis and psoriasis, we developed mouse models of collagen-induced rheumatoid arthritis (CIA) and imiquimod-induced psoriasis (IIP). NJK14047 was found to suppress arthritis development and psoriasis symptoms and also suppressed histopathological changes induced by CIA and IIP. Furthermore, we established that CIA and IIP evoked increases in the mRNA expression levels of Th1/Th17 inflammatory cytokines in the joints and skin, which was again suppressed by NJK14047. NJK14047 reversed the enlargement of spleens induced by CIA and IIP as well as increases in the levels of inflammatory cytokine in spleens following induction by CIA and IIP. In human SW982 synovial cells, NJK14047 was found to suppress lipopolysaccharide-induced increases in the mRNA expression of proinflammatory cytokines. NJK14047 inhibition of p38 MAPK suppressed the differentiation of naïve T cells to Th17 and Th1 cells. Our findings in this study provide convincing evidence indicating the therapeutic efficacy of the p38 MAPK inhibitor NJK14047 against CIA and IIP, which we speculate could be associated with the suppression on T-cell differentiation.

Impact of anemia requiring transfusion or erythropoiesis-stimulating agents on new-onset cardiovascular events and mortality after continuous renal replacement therapy.

Anemia is common in critically ill patients undergoing continuous renal replacement therapy (CRRT). We investigated the impact of anemia requiring red blood cell (RBC) transfusion or erythropoiesis-stimulating agents (ESAs) on patient outcomes after hospital discharge in critically ill patients with acute kidney injury (AKI) requiring CRRT. In this retrospective cohort study using the Health Insurance Review and Assessment database of South Korea, 10,923 adult patients who received CRRT for 3 days or more between 2010 and 2019 and discharged alive were included. Anemia was defined as the need for RBC transfusion or ESAs. Outcomes included cardiovascular events (CVEs) and all-cause mortality after discharge. The anemia group showed a tendency to be older with more females and had more comorbidities compared to the control group. Anemia was not associated with an increased risk of CVEs (adjusted hazard ratio [aHR]: 1.05; 95% confidence interval [CI]: 0.85-1.29), but was associated with an increased risk of all-cause mortality (aHR: 1.41; 95% CI 1.30-1.53). For critically ill patients with AKI requiring CRRT, anemia, defined as requirement for RBC transfusion or ESAs, may increase the long-term risk of all-cause mortality.

Social Determinants of Health and Multimorbidity Among Adults 50 Years and Older in the United States.

BACKGROUND: Living with two or more chronic conditions simultaneously-known as multimorbidity-has become increasingly prevalent as the aging population continues to grow. However, the factors that influence the development of multimorbidity are still not fully understood. OBJECTIVES: The purpose of this study was to investigate the prevalence of multimorbidity among U.S. adults 50 years and older and identify associated factors with multimorbidity. METHODS: We used data from four cycles from the National Health and Nutrition Examination Survey (2011-2018) to examine the associations between social determinants of health and multimorbidity among American adults aged 50 years and older. A set of variables on socioeconomic status and health behaviors was chosen based on the social determinants of health conceptual framework developed by the World Health Organization. In our study, 4,552 participants were included. All analyses were accounted for a complex survey design and the use of survey weights. Multiple logistic regression analyses were performed to examine the associated factors with multimorbidity. RESULTS: The average age was 63.1 years, and 52.9% were female. The average number of chronic conditions was 2.27. The prevalence of multimorbidity was 63.8%, with high cholesterol and hypertension being the most prevalent conditions. In the adjusted model, age, gender, household income, citizenship status, health insurance, healthcare access, body mass index, and smoking status were found to be associated with living with multimorbidity. DISCUSSION: Our results indicate that continued efforts aimed at promoting smoking cessation and maintaining a healthy weight will be beneficial in preventing the onset of chronic conditions. Additional research is warranted to gain a deeper understanding of the interrelationships between gender, race/ethnicity, household income, citizenship status, health insurance, and healthcare access as social determinants of health in the context of multimorbidity. Further research will help us develop targeted interventions and policies to address disparities and improve health outcomes for individuals with multimorbidity.

Adherence to the American Cancer Society guidelines on nutrition and physical activity for cancer survivors and biomarkers of inflammation among breast cancer survivors.

OBJECTIVES: This study investigated whether adherence to the overall lifestyle recommendations in the American Cancer Society (ACS) guidelines on nutrition and physical activity for cancer survivors was associated with inflammation in breast cancer survivors. METHODS: The study included 409 women who had undergone breast cancer surgery at least 1 year before enrollment. A generalized linear model was used to estimate the least square means and 95% confidence intervals of plasma levels of inflammatory markers according to lifestyle factors defined in terms of adherence to the ACS guidelines. RESULTS: Higher overall adherence scores were associated with lower levels of high-sensitivity C-reactive protein (hs-CRP) (p for trend=0.015) and higher levels of adiponectin (p for trend=0.009). Similar significant associations of hs-CRP (p for trend= 0.004) and adiponectin (p for trend=0.010) levels were observed with the score for the body mass index (BMI) component of the adherence score. A higher diet component score was associated with a higher adiponectin level (p for trend=0.020), but there was no significant association for the physical activity component score. CONCLUSIONS: The present study's findings suggest that maintaining a healthy lifestyle according to the ACS guidelines was associated with beneficial effects on inflammatory marker levels, especially hs-CRP and adiponectin, among breast cancer survivors. Among the 3 components of lifestyle guidelines, the BMI component exhibited the most similar tendency to the overall adherence score in relation to inflammatory indicators. Further prospective and intervention studies are needed to investigate longitudinal associations between lifestyle factors and inflammatory markers among breast cancer survivors.

Dietary intake is associated with the prevalence of uterine leiomyoma in Korean women: A retrospective cohort study.

OBJECTIVE: Uterine leiomyoma (UL), the most prevalent benign gynecologic tumor among reproductive-aged women, lacks sufficient research on the potential association between dietary intake and its occurrence in Korean women. Addressing this research gap, this study aims to evaluate the potential link between dietary intake and the prevalence of UL in Korean women. METHODS: In this cross-sectional study, a cohort of 672 women, aged 23 to 73, were enrolled, with 383 (57%) being premenopausal. Dietary intake was assessed using a validated food frequency questionnaire (FFQ), and UL presence was determined through ultrasonography. The analysis focused exclusively on items within ten categories, including vegetables/fruit, vegetables, fruits, red meat, processed meat, poultry, fish, dairy product, milk, and alcohol. Multiple logistic regression models were employed to explore the relationship between dietary intake and the prevalence of UL, calculating odds ratios (ORs) and 95% confidence intervals (CIs) while adjusting for confounding factors. RESULTS: Within the total cohort, 220 (32.7%) women were diagnosed with UL. High intakes of fish and poultry showed an association with higher UL prevalence. Odds ratios (95% CIs) for the upper quartiles compared to the lower quartiles were 1.68 (1.01-2.81; p trend = 0.05) for fish intake and 1.87 (1.11-3.17; p trend = 0.06) for poultry intake. Conversely, an inverse relationship emerged between dairy product intake and UL prevalence, with an odds ratio of 0.58 (95% CI 0.35-0.96; p trend = 0.05). Stratifying the analysis by menopausal status revealed a parallel pattern, with heightened UL prevalence with fish intake and reduced prevalence with dairy product intake. However, the link between poultry intake and UL prevalence was primarily observed among postmenopausal women. Among premenopausal women, elevated vegetable intake was linked to a decreased UL prevalence (OR 0.45, 95% CI 0.21-0.97 for top vs. bottom quartiles; p trend = 0.01). CONCLUSION: We found that high consumption of fish and poultry, coupled with low intake of dairy products, correlated with an elevated prevalence of UL. Furthermore, vegetable intake exhibited an inverse relationship with UL prevalence, particularly among premenopausal women.

Development and application of a home-based exercise program for patients with cardiovascular disease: a feasibility study.

BACKGROUND: Cardiac rehabilitation (CR) is recommended for patients with cardiovascular disease. However, the participation and completion rates for hospital-based CR are low, and home-based CR has been suggested as an alternative. This study aimed to develop a home-based CR program and assess the feasibility of the program over a 6-week period in patients with left ventricular dysfunction or a history of myocardial infarction. METHODS: This feasibility study consisted of two phases. The initial phase (Study 1) focused on developing the home-based exercise protocol. Systematic approaches to developing evidence-based home-based exercise intervention were implemented including systematic review, patient surveys, and expert consensus. Study 2 aimed to evaluate the feasibility of a 6-week home-based CR program that was based on the results of Study 1. Study 2 included two exercise education sessions and four telephone counseling sessions. During this stage of the exercise program, the participants exercised on two separate days and their experiences while performing the aerobic and resistance exercises were surveyed. Eight participants participated in Study 1 and 16 participated in Study 2. RESULTS: Participants expressed overall satisfaction with the exercise program in Study 1. Heart rate increased in response to exercise, but this did not correspond with perceived exertion. The aim of the home-based CR exercise program was for participants to achieve exercise goals (≥150 min/week of aerobic type exercises as well as at least twice weekly resistance exercise using own body weights). We aimed to increase compliance and adherence to the home-based CR program. In Study 2, 13 out of 16 participants (81.3%) completed the 6-week home-based CR program, with a participation rate of 100% in both exercise education and phone counseling sessions. Adherence to the home-based exercise protocol was 83.1% and no serious adverse events were observed. At the beginning of the study, only three out of 13 participants (23.1%) met the requirements for both aerobic and resistance exercises, but at the end of the 6-week program, 10 out of 13 participants (76.9%) fulfilled the requirements. CONCLUSION: The exercise program developed in this study was safe and feasible, and the 6-week home-based CR program was feasible for patients with cardiovascular disease without any reported adverse effects.

Impact of sensitization and ABO blood types on the opportunity of deceased-donor kidney transplantation with prolonged waiting time.

The waiting time to deceased-donor kidney transplantation (DDKT) is long in Asian countries. We investigated the impact of sensitization and ABO blood type (ABO) on DDKT opportunity using two Korean cohorts: a hospital cohort from two centers and a national database. The impact of panel reactive antibody (PRA) based on the maximal PRA% and ABO on DDKT accessibility was analyzed using a competing risks regression model. In the hospital cohort (n = 4722), 88.2%, 8.7%, and 3.1% of patients belonged to < 80%, 80-99%, and ≥ 99% PRA groups, respectively, and 61.1%, 11.6%, and 27.3% belonged to A or B, AB, and O blood types, respectively. When PRA and ABO were combined, PRA < 80%/A or B and 80 ≤ PRA < 99%/AB had fewer DDKT opportunities (median, 12 years; subdistribution hazard ratio [sHR], 0.71) compared with PRA < 80%/AB (median, 11 years). Also, PRA < 80%/O, 80 ≤ PRA < 99%/A or B, and PRA ≥ 99%/AB had a much lower DDKT opportunity (median, 13 years; sHR, 0.49). Furthermore, 80 ≤ PRA < 99%/O and PRA ≥ 99%/non-AB had the lowest DDKT opportunity (sHR, 0.28). We found similar results in the national cohort (n = 18,974). In conclusion, an integrated priority system for PRA and ABO is needed to reduce the inequity in DDKT opportunities, particularly in areas with prolonged waiting times.

Effects of poly (ADP-ribose) polymerase inhibitor treatment on the repair process of ischemic acute kidney injury.

Excessive activation of poly (ADP-ribose) polymerase (PARP) contributes to ischemic acute kidney injury (AKI). PARP inhibition has been shown to be beneficial in renal ischemia-reperfusion injury (IRI) in the early phase, but its role in the repair process remains unclear. The effects of JPI-289, a novel PARP inhibitor, during the healing phase after renal IRI were investigated. IRI was performed on 9-week-old male C57BL/6 mice. Saline or JPI-289 100 mg/kg was intraperitoneally administered once at 24 h or additionally at 48 h after IRI. Hypoxic HK-2 cells were treated with JPI-289. Renal function and fibrosis extent were comparable between groups. JPI-289 treatment caused more prominent tubular atrophy and proinflammatory intrarenal leukocyte phenotypes and cytokines/chemokines changes at 12 weeks after unilateral IRI. JPI-289 treatment enhanced gene expressions associated with collagen formation, toll-like receptors, and the immune system in proximal tubules and endothelial cells after IRI. JPI-289 treatment at 3 or 6 h after hypoxia facilitated proliferation of hypoxic HK-2 cells, whereas further treatment after 24 h suppressed proliferation. Delayed inhibition of PARP after renal IRI did not facilitate the repair process during the early healing phase but rather may aggravate renal tubular atrophy during the late healing phase in ischemic AKI.

Group I pharmaceuticals of IARC and associated cancer risks: systematic review and meta-analysis.

We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for Research on Cancer working groups. Following the PRISMA guidelines, a comprehensive literature search was conducted using the PubMed database. Pharmaceuticals with few studies on cancer risk were identified in systematic reviews; those with two or more studies were subjected to meta-analysis. For the meta-analysis, a random-effects model was used to calculate the summary relative risks (SRRs) and 95% confidence intervals (95% CIs). Heterogeneity across studies was presented using the Higgins I square value from Cochran's Q test. Among the 12 group I pharmaceuticals selected, three involved a single study [etoposide, thiotepa, and mustargen + oncovin + procarbazine + prednisone (MOPP)], seven had two or more studies [busulfan, cyclosporine, azathioprine, cyclophosphamide, methoxsalen + ultraviolet (UV) radiation therapy, melphalan, and chlorambucil], and two did not have any studies [etoposide + bleomycin + cisplatin and treosulfan]. Cyclosporine and azathioprine reported increased skin cancer risk (SRR = 1.32, 95% CI 1.07-1.62; SRR = 1.56, 95% CI 1.25-1.93) compared to non-use. Cyclophosphamide increased bladder and hematologic cancer risk (SRR = 2.87, 95% CI 1.32-6.23; SRR = 2.43, 95% CI 1.65-3.58). Busulfan increased hematologic cancer risk (SRR = 6.71, 95% CI 2.49-18.08); melphalan was associated with hematologic cancer (SRR = 4.43, 95% CI 1.30-15.15). In the systematic review, methoxsalen + UV and MOPP were associated with an increased risk of skin and lung cancer, respectively. Our results can enhance persistent surveillance of group I pharmaceutical use, establish novel clinical strategies for patients with indications, and provide evidence for re-categorizing current group I pharmaceuticals into other groups.

Dietary Isoflavone Intake and Breast Cancer Prognosis: A Prospective Analysis and Meta-Analysis.

We aimed to examine the association between dietary isoflavone intake and the risk of breast cancer recurrence and summarize evidence on the role of dietary isoflavone intake in breast cancer prognosis. This prospective study included 592 breast cancer survivors who completed a dietary assessment. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Of the studies published until May 31, 2023, that were searched in PUBMED and EMBASE databases, 14 studies were selected. Adjusted HRs were combined using fixed- or random-effects models. During the median follow-up of 4.3 years, 47 recurrences were identified. The HR (95% CI) for recurrence comparing the highest versus the lowest tertile of isoflavones intake was 1.29 (0.60-2.78). In a meta-analysis of previously published data and ours, dietary isoflavone intake was associated with a better breast cancer prognosis. The combined HRs (95% CIs) comparing the extreme categories were 0.81 (0.67-0.98) for recurrence and 0.85 (0.76-0.96) for all-cause mortality. A nonlinear inverse association was observed between isoflavone intake and the risk of recurrence and all-cause mortality. Our study suggests that dietary isoflavone intake is associated with a favorable prognosis in breast cancer survivors and warrants further investigation.

Effect of nitro-conjugated linoleic acid on the inflammatory response of murine macrophages activated with lipopolysaccharide derived from Prevotella intermedia.

Nitro-conjugated linoleic acid (NO2-CLA) has been observed to manifest salutary signaling responses, including anti-inflammatory and antioxidant properties. Here, the authors have explored the influence and underlying mechanisms of NO2-CLA on the proinflammatory reaction of murine macrophages that were challenged with lipopolysaccharide (LPS) derived from Prevotella intermedia, a putative periodontopathic bacterium. Treatment of LPS-activated RAW264.7 cells with NO2-CLA notably dampened the secretion of iNOS-derived NO, IL-1ß and IL-6 as well as their gene expressions and significantly enhanced the markers for M2 macrophage polarization. NO2-CLA promoted the HO-1 expression in cells challenged with LPS, and tin protoporphyrin IX, an HO-1 inhibitor, significantly reversed the NO2-CLA-mediated attenuation of NO secretion, but not IL-1ß or IL-6. We found that cells treated with NO2-CLA significantly increased mRNA expression of PPAR-γ compared to control cells, and NO2-CLA significantly reverted the decrease in PPAR-γ mRNA caused by LPS. Nonetheless, antagonists to PPAR-γ were unable to reverse the NO2-CLA-mediated suppression of inflammatory mediators. In addition, NO2-CLA did not alter the p38 and JNK activation elicited by LPS. Both NF-κB reporter activity and IκB-α degradation caused by LPS were notably diminished by NO2-CLA. NO2-CLA was observed to interrupt the nuclear translocation and DNA binding of p50 subunits caused by LPS with no obvious alterations in p65 subunits. Further, NO2-CLA attenuated the phosphorylation of STAT1/3 elicited in response to LPS. We propose that NO2-CLA could be considered as a possible strategy for the therapy of periodontal disease, although additional researches are certainly required to confirm this.

Inflammatory Markers and Fatigue in Individuals With Moderate to Severe Chronic Obstructive Pulmonary Disease.

BACKGROUND: Fatigue, a prevalent complex symptom among patients with chronic obstructive pulmonary disease (COPD), is considered an important clinical indicator of disease severity. However, the underlying mechanisms of COPD-related fatigue are not fully understood. OBJECTIVES: This analysis explored the relationships between peripheral inflammatory markers and COPD-related fatigue in people with moderate to severe COPD. METHODS: This is a secondary analysis of a longitudinal observational study of individuals with COPD examining the biological causes and functional consequences of depression. The data used in this study were collected at baseline. Systemic inflammation markers included C-reactive protein (CRP) and three pro-inflammatory cytokines consisting of interleukin-6 (IL-6), IL-8, and tumor necrosis factor-α. COPD-related fatigue was self-reported using the Chronic Respiratory Questionnaire. Covariates included age; gender; smoking status; disease severity; symptoms of depression, anxiety, and pain; and social support. Multivariable linear regression analyses were conducted. RESULTS: The sample included 300 adults living with COPD; 80% were male, and the average age was 67.6 years. Modest correlations were found between two systemic inflammatory markers (CRP and IL-8) and COPD-related fatigue. CRP was the only inflammatory marker significantly associated with fatigue symptoms after adjusting for covariates in multivariable analyses. Depression, pain, and education level were also significant predictors of COPD-related fatigue. DISCUSSION: The findings suggest that altered immune response based on CRP may contribute to COPD-related fatigue. Management of depression and pain may work as an effective treatment strategy for COPD-related fatigue. Further longitudinal studies with a broader range of inflammatory markers and multidimensional measures of fatigue symptoms are warranted.