Major Risk Factor For Morbidity Research Articles

#2088 Renal outcome, cardio-vascular events and infections in patients with lupus nephritis: MassiLUP cohort 2001-2022

Abstract Background and Aims Most epidemiological studies in lupus nephritis (LN) report the risk of end-stage kidney disease (ESKD) (10-20% of patients at 10-15 years in developed countries), but less data is available on the long-term risk of chronic kidney disease (CKD), even though CKD is a major risk factor for morbidity and mortality. While immunosuppressive therapy for LN aims to reach and maintain remission in order to prevent CKD, it also exposes patients to cardiovascular, infectious and neoplastic adverse events. We conducted a retrospective cohort study to evaluate survival without CKD and adverse events in patients with LN. Method The MassiLUP cohort comprises all patients who underwent a kidney biopsy for a first flare of LN between 2001 and 2022 in the University Hospital of Marseille, France. We assessed patient survival, renal survival and survival without CKD (defined by an estimated glomerular filtration rate < 60 mL/min/1.73 m2), without cardiovascular event, without severe infection (requiring hospitalization, or zoster), and without cancer. Results A total of 168 patients (82.7% female; mean age 33 years; mean serum creatinine 102 µmol/L at the time of the first kidney biopsy) were included, with a mean follow-up of 9.6 ± 5.7 years. One (0.6%) patient had class I LN (ISN/RPS 2003 classification), 17 (10.1%) class II LN, 45 (26.8%) had class III (± V) LN, 73 (43.5%) had class IV (± V) LN, 29 (17.3%) patients had pure class V LN; 3 biopsies could not be classified. Four patients died during the follow-up (3 of severe infections and 1 of stroke); 41 (24.4%) patients developed CKD, among whom 19 (11.3%) patients reached ESKD; 34 (20.2%) patients presented a cardiovascular event, 59 (35.1%) a severe infection, and 12 (7.1%) a cancer. Survival rates without CKD were 82.9%, 74.6% and 67.3% at 5, 10 and 15 years, respectively. Survival rates without ESKD were 94.4%, 88.6% and 79.9% at 5, 10 and 15 years, respectively. Survival rates without cardiovascular event were 85.7%, 77.3% and 75.5% at 5, 10 and 15 years, respectively. Survival rates without severe infection were 76.3%, 63.8% and 51.8% at 5, 10 and 15 years, respectively. Survival rates without cancer were 96.3%, 92.9% and 85.6% at 5, 10 and 15 years, respectively. Conclusion Despite free access to treatment and care in France, the long-term prognosis of patients with lupus nephritis remains burdened by both a risk of CKD and ESKD, and a significant risk of cardiovascular and infectious events. This calls for continued efforts to improve therapeutic strategies, both in terms of efficacy and toxicity, and to strengthen the therapeutic alliance in the care of patients with LN.

Ursolic acid alleviates lupus nephritis by suppressing SUMO1-mediated stabilization of NLRP3

BackgroundSystemic lupus erythematosus (SLE) is a multi-system autoimmune disease that affects multiple organs and cause a wide range of severe clinical manifestations, including lupus nephritis (LN), which is a major risk factor for morbidity and mortality in individual with SLE. Ursolic acid (UA) is a natural compound with favorable anti-inflammatory properties and has been employed to treat multiple disease, including inflammatory diseases, diabetes, and Parkinson's disease. However, its therapeutic potential on LN and the underlying mechanisms remains unclear. PurposeThis aim of this study was to investigate the impact of UA on LN and its underlying mechanism. MethodsMRL/lpr lupus-prone mouse model was used and UA was administered orally for 8 weeks. Dexamethasone was used as a positive control. After 8 weeks of administration, the spleen-to-body-weight ratio, renal function, urine albumin excretion, cytokines levels, and the deposition of immune complex were measured. The primary mouse glomerular mesangial cells (GMCs) and SV40-MES-13 were stimulated by lipopolysaccharide (LPS), either alone or in combination with nigericin, to establish an in vitro model. The activation of NLRP3 inflammasome were investigated both in vivo and in vitro using qRT-PCR, immunoblotting, and immunofluorescence. ResultsOur results revealed that UA prominently alleviated LN in MRL/lpr lupus-prone mice, leading to a significant reduction in proteinuria production, infiltration of immune cells infiltration, and histopathological damage in the renal tissue. In addition, UA exerted inhibitory effects on the secretion of IL-1β, IL-18, and caspase-1, pyroptosis, and ASC speck formation in primary mouse GMCs and SV40-MES-13 cells. Furthermore, UA facilitated the degradation of NLRP3 by suppressing SUMO1-mediated SUMOylation of NLRP3. ConclusionUA possess a therapeutical effect on LN in MRL/lpr mice by enhancing the degradation of NLRP3 through inhibition of SUMO1-mediated SUMOylation of NLRP3. Our findings provide a basis for proposing UA as a potential candidate for the treatment of LN.

Esophageal surgical Apgar score (eSAS): A predictor for postoperative morbidity in patients undergoing neoadjuvant therapy and esophagectomy.

The surgical Apgar score (SAS) quantifying three intraoperative indexes has been confirmed to be significantly associated with postoperative morbidity and prognosis in many surgical specialties. However, there are great limitations in its application for esophageal cancer (EC). This study aimed to assess the predictive capability of esophagectomy SAS (eSAS) in determining postoperative morbidity and overall survival (OS) in EC patients who had undergone neoadjuvant therapy. A retrospective evaluation was conducted on a cohort of 221 patients in which surgery- and tumor-related data were extracted and analyzed. Major morbidity was defined as complications meeting the criteria of Clavien-Dindo classification III or higher during hospitalization. Univariate and multivariate analyses were performed to identify potential risk factors for major morbidity. Kaplan-Meier analysis was utilized to calculate the OS and relapse-free survival (RFS). The results exhibited that eSAS demonstrated potential predictive value for postoperative morbidity with an optimal cutoff value of 6. The eSAS and diabetes mellitus were two independent risk factors for the major morbidity; however, no correlation between the eSAS and the OS or RFS was detected. The eSAS could be used as a predictor of major morbidity, while it was not correlated with OS and RFS.

Epigenetics in obesity: Mechanisms and advances in therapies based on natural products.

Obesity is a major risk factor for morbidity and mortality because it has a close relationship to metabolic illnesses, such as diabetes, cardiovascular diseases, and some types of cancer. With no drugs available, the mainstay of obesity management remains lifestyle changes with exercise and dietary modifications. In light of the tremendous disease burden and unmet therapeutics, fresh perspectives on pathophysiology and drug discovery are needed. The development of epigenetics provides a compelling justification for how environmental, lifestyle, and other risk factors contribute to the pathogenesis of obesity. Furthermore, epigenetic dysregulations can be restored, and it has been reported that certain natural products obtained from plants, such as tea polyphenols, ellagic acid, urolithins, curcumin, genistein, isothiocyanates, and citrus isoflavonoids, were shown to inhibit weight gain. These substances have great antioxidant potential and are of great interest because they can also modify epigenetic mechanisms. Therefore, understanding epigenetic modifications to target the primary cause of obesity and the epigenetic mechanisms of anti-obesity effects with certain phytochemicals can prove rational strategies to prevent the disease and develop novel therapeutic interventions. Thus, the current review aimed to summarize the epigenetic mechanisms and advances in therapies for obesity based on natural products to provide evidence for the development of several potential anti-obesity drug targets.

Combination of the biomarkers for aging and cancer? - Challenges and current status

The proportion of patients diagnosed with cancer has been shown to rise with the increasing aging global population. Advanced age is a major risk factor for morbidity and mortality in older adults. As individuals experience varying health statuses, particularly with age, it poses a challenge for medical professionals in the cancer field to obtain standardized treatment outcomes. Hence, relying solely on chronological age and disease-related parameters is inadequate for clinical decision-making for elderly patients. With functional, multimorbidity-related, and psychosocial changes that occur with aging, oncologic diseases may develop and be treated differently from younger patients, leading to unique challenges in treatment efficacy and tolerance. To overcome this challenge, personalized therapy using biomarkers has emerged as a promising solution. Various categories of biomarkers, including inflammatory, hematological, metabolic, endocrine, and DNA modification-related indicators, may display features related to both cancer and aging, aiding in the development of innovative therapeutic approaches for patients with cancer in old age. Furthermore, physical functional measurements as non-molecular phenotypic biomarkers are being investigated for their potential complementary role in structured multidomain strategies to combat age-related diseases such as cancer. This review provides insight into the current developments, recent discoveries, and significant challenges in cancer and aging biomarkers, with a specific focus on their application in advanced age.

ALKBH5 inhibitors as a potential treatment strategy in heart failure-inferences from gene expression profiling.

Heart Failure (HF) is a complex clinical syndrome in which the heart is unable to provide enough blood flow to meet metabolic needs and lacks efficient venous return. HF is a major risk factor for morbidity and mortality with cardiovascular diseases globally. Despite enormous research, the molecular markers relevant to disease prognosis and management remain not well understood. Here, we analyzed the whole transcriptomes of 18 failing hearts and 15 non-failing hearts (predominantly of Caucasian origin), by applying the standard in silico tools. The analyses revealed novel gene-markers including ALKBH5 of mRNA demethylation and KMT2E of histone modification processes, significantly over-expressed in the HF compared with the non-failing hearts (FDR < 0.05). To validate the over-expression of ALKBH5, we determined the global m6A level in hypoxic H9c2 cells using a dot blot assay. The global m6A level was found markedly lower in the hypoxic H9c2 cells than in the control cells. Additionally, the expression of ALKBH5 in the H9c2 cells was quantified by the qPCR and found to be 1.18 times higher at 12 h (p < 0.05), and 1.67 times higher at 24 h of hypoxia (p < 0.01) compared with the control cells, indicating a likely role of ALKBH5 in the failing cardiac cells. Furthermore, we identified several compounds through the virtual screening of 11,272 drug-like molecules of the ZINC15 database to inhibit the ALKBH5 in a molecular docking process. Collectively, the study revealed novel markers potentially involved in the pathophysiology of HF and suggested plausible therapeutic molecules for the management of the disease.

Prevalence of tobacco smoking between 2009 and 2015 among students and the general population in the Kingdom of Saudi Arabia.

Tobacco smoking is a major risk factor for morbidity and mortality. Studies on smoking in the Kingdom of Saudi Arabia (KSA) have shown inconsistent results. The purpose of this study was to provide a literature review on the prevalence of tobacco smoking among school students, university students, and the general population of KSA during 2009-2015, before the implementation of new tobacco control measures. We searched PubMed and Google for articles published in English from 2009 to 2015, focused on overall tobacco smoking and/or any form of tobacco smoking (e.g. tobacco, cigarette, and waterpipe) and conducted with a sample of ≥300 participants. Only the prevalence of current smoking was assessed. A narrative synthesis of the prevalence results was conducted. Of the 360 studies found in the primary search, 91 were selected for further examination for eligibility, and 20 studies were included in the review. Among school students, the prevalence of smoking any form of tobacco (cigarettes, waterpipes, or both) ranged 10.0-21.7%. The prevalence of cigarette smoking ranged 8.9-19.5% and for waterpipe smoking it was 9.5%. Among university students, the prevalence of smoking any form of tobacco ranged 11.1-25.3%, cigarette smoking 7.8-17.5%, and waterpipe 4.3-18.0%. In the general population, the prevalence of cigarette smoking ranged 19.6-23.5% and for waterpipe smoking it was 4.3%. Our study shows smoking levels were high in the KSA between 2009 and 2015. Studies utilizing standardized methodology with nationally representative samples are needed to better characterize the prevalence of different types of tobacco smoking. More research on national representative samples is needed, including studies on the same populations/groups/areas over time using standardized tools and definitions.

Evaluation of the effect of bun/albumin ratio on in-hospital mortality in hypertensive COVID-19 patients.

The impact of COVID-19 infection still continues all over the world and is an important cause of mortality. The mortality rate due to infection varies between 1-5%. The mortality rate is higher in those with cardiovascular risk factors, especially in cases with hypertension. Some studies have shown that blood urea nitrogen (BUN) and albumin levels are associated with worse prognosis in patients with COVID-19. In our study, we aimed to investigate whether the BUN/albumin (BAR) ratio has an effect on in-hospital mortality in hypertensive COVID-19 patients. A total of 800 hypertensive COVID-19 patients, (618 of whom were alive and 182 died) were included in our study. Patients with a history of heart failure, malignancy, acute coronary syndrome, and myocarditis were excluded. The median age of the study population was 69 (60-77 IQR) years, and 305 (38%) of these patients were men. There was no statistically significant difference between the patients who died during follow-up and cases that remained alive in terms of comorbidities except chronic obstructive pulmonary disease (COPD) which was significantly lower in surviving group (p=0.014). Multivariable logistic regression analysis revealed that age [OR: 1.04, CI (1.01-1.06); p=0.002], male gender [OR: 1.85, CI (1.13-3.02); p=0.010], lymphocyte count [OR: 0.63, CI (0.40-0.98); p=0.038], SaO2 [OR: 0.82, CI (0.79-0.85); p<0.001] and BAR level [OR: 1.09, CI (1.04-1.16); p=0.001] were independent predictors of in-hospital mortality. ROC analysis yielded that BAR is a better predictor of in-hospital mortality compared to albumin and BUN alone. BUN, albumin, and BAR levels were found to be reliable predictors of in-hospital mortality in COVID-19 patients, and BAR was also found to be a more reliable predictor than BUN and albumin levels. Hypertension is one of the major risk factors for morbidity and mortality in COVID-19 and, BAR presents additional prognostic data in hypertensive COVID-19 patients that may direct physicians for treatment intensification.

Risk factors for postoperative morbidity, prolonged length of stay and hospital readmission after appendectomy for acute appendicitis

PurposeThe aim of the present study was to identify risk factors associated with postoperative morbidity and major morbidity, with a prolonged length of hospital stay and with the need of readmission in patients undergoing appendectomy due to acute appendicitis.MethodsWe performed a retrospective analysis of 1638 adult patients who underwent emergency appendectomy for preoperatively suspected acute appendicitis from 2010 to 2020 at the University Hospital Erlangen. Data including patient demographics, pre-, intra-, and postoperative findings were collected and compared between different outcome groups (morbidity, major morbidity, prolonged length of postoperative hospital stay (LOS) and readmission) from those patients with verified acute appendicitis (n = 1570).ResultsRate of negative appendectomies was 4%. In patients with verified acute appendicitis, morbidity, major morbidity and readmission occurred in 6%, 3% and 2%, respectively. Mean LOS was 3.9 days. Independent risk factors for morbidity were higher age, higher preoperative WBC-count and CRP, lower preoperative hemoglobin, longer time to surgery and longer duration of surgery. As independent risk factors for major morbidity could be identified higher age, higher preoperative CRP, lower preoperative hemoglobin and longer time to surgery. Eight parameters were independent risk factors for a prolonged LOS: higher age, higher preoperative WBC-count and CRP, lower preoperative hemoglobin, need for conversion, longer surgery duration, presence of intraoperative complicated appendicitis and of postoperative morbidity. Presence of malignancy and higher preoperative WBC-count were independent risk factors for readmission.ConclusionAmong patients undergoing appendectomy for acute appendicitis, there are relevant risk factors predicting postoperative complications, prolonged hospital stays and readmission. Patients with the presence of the identified risk factors should receive special attention in the postoperative course and may benefit from a more individualized therapy.

Obesity Is Associated with Increased F2-Isoprostanes and IL-6 in Black Women

Obesity affects over 40% of the adult population and is a major risk factor for morbidity and mortality due to cardiovascular disease. Black women have one of the highest prevalences of obesity, insulin resistance, hypertension, and cardiovascular events in the US. We previously found that free radical-mediated lipid peroxidation contributes to IL-6 production in dendritic cells leading to inflammation and hypertension. Thus, we hypothesized that F2-isoprostanes (F2-IsoPs), products and biomarkers of endogenous lipid peroxidation, contribute to increased inflammation and IL-6 production among obese Black women. We studied a total of 88 obese Black women of age 42.0 ± 9.8 years, weight 102 ± 16 kg, and body mass index (BMI) 37.68 ± 5.08. Systolic and diastolic blood pressure were 124 ± 14/76.2 ± 9.9 mmHg, heart rate was 68.31 ± 10.26 beats/min, and fasting insulin was 15.0 ± 8.7 uU/mL. Plasma F2-IsoPs were measured using gas chromatography/negative ion chemical ionization mass spectrometry (GC/NICI-MS). Plasma cytokines, including IL-6, IL-8, IL-10, IL-1β, TNF-a, and C-reactive proteins were measured using multiplex Luminex technology. Anthropometric measurements were performed using dual-energy X-ray absorptiometry. Using Pearson’s correlation analysis, we found that BMI was positively correlated with plasma F2-IsoPs, while inversely correlated with insulin sensitivity in obese Black women. Further, F2-IsoPs were positively correlated with inflammatory marker IL-6 levels while negatively correlated with anti-inflammatory marker IL-10. In addition, we found that plasma F2-IsoPs levels were significantly associated with reduced insulin sensitivity. These results suggest that F2-IsoPs may be associated with obesity-induced cardiovascular risk in Black women by increasing the production of inflammatory cytokine IL-6 and decreasing the production of anti-inflammatory IL-10.

Model to predict major complications following liver resection for HCC in patients with metabolic syndrome.

Metabolic syndrome (MS) is rapidly growing as risk factor for HCC. Liver resection for HCC in patients with MS is associated with increased postoperative risks. There are no data on factors associated with postoperative complications. The aim was to identify risk factors and develop and validate a model for postoperative major morbidity after liver resection for HCC in patients with MS, using a large multicentric Western cohort. The univariable logistic regression analysis was applied to select predictive factors for 90 days major morbidity. The model was built on the multivariable regression and presented as a nomogram. Performance was evaluated by internal validation through the bootstrap method. The predictive discrimination was assessed through the concordance index. A total of 1087 patients were gathered from 24 centers between 2001 and 2021. Four hundred and eighty-four patients (45.2%) were obese. Most liver resections were performed using an open approach (59.1%), and 743 (68.3%) underwent minor hepatectomies. Three hundred and seventy-six patients (34.6%) developed postoperative complications, with 13.8% major morbidity and 2.9% mortality rates. Seven hundred and thirteen patients had complete data and were included in the prediction model. The model identified obesity, diabetes, ischemic heart disease, portal hypertension, open approach, major hepatectomy, and changes in the nontumoral parenchyma as risk factors for major morbidity. The model demonstrated an AUC of 72.8% (95% CI: 67.2%-78.2%) ( https://childb.shinyapps.io/NomogramMajorMorbidity90days/ ). Patients undergoing liver resection for HCC and MS are at high risk of postoperative major complications and death. Careful patient selection, considering baseline characteristics, liver function, and type of surgery, is key to achieving optimal outcomes.

Exposure to loneliness cues reduces prosocial behavior: Evidence from N400 and P300.

Loneliness is a major risk factor for morbidity and mortality. However, the effect of loneliness on subsequent prosocial behavior is not well known. Understanding the neurobiological mechanisms underlying loneliness is necessary to address this research gap. We investigate the mechanism using a modified public goods game (PGG) wherein participants can choose to act for a collective or selfish interest after being exposed to loneliness cues. Both behavioral (Study 1) and event-related potential (ERP) (Study 2) measures were used to explore this relationship. In Study 1 (N = 131), we found that participants exhibited decreased prosocial actions under the loneliness priming condition as opposed to the control condition. In Study 2 (N = 17), frontal N400 and posterior P300 components were identified under the loneliness priming condition as opposed to the control condition. Increased (decreased) frontal N400 and posterior P300 lead to selfish (prosocial) choices. These results indicate that humans instinctively perceive loneliness as inconsistency with their desired social-relational life, which in turn stimulates coping strategies for self-preservation. This study contributes to our understanding of the neurobiological basis of loneliness associated with prosocial behavior.

Short- and long-term surgical outcomes of pancreatic resection for retroperitoneal sarcoma: A long-term single-center experience of 90 cases.

Resection of retroperitoneal sarcoma (RPS) en bloc with pancreas is challenging and controversial. This single-center retrospective study aimed to analyze the impact of pancreatic resection (PR) and its different types on short- and long-term outcomes in patients with RPS. Data from 242 consecutive patients with RPS who underwent surgical treatment at the Peking University Cancer Hospital Sarcoma Center between January 2010 and February 2021 were analyzed. Out of these, 90 patients underwent PR, including pancreaticoduodenectomy (PD) in 31 and distal pancreatectomy (DP) in 59. Patients in the PR group had a higher major morbidity (37.8% vs. 14.5%) and mortality (8.9% vs. 1.3%) than those in the non-PR group, with a similar 5-year overall survival (OS) rate (46.9% vs. 53.6%). Patients in the PD and DP groups had a slight difference in major morbidity (48.4% vs. 32.2%), mortality (6.4% vs. 10.2%), and 5-year OS rates (43.3% vs. 49.3%). The PR type was not an independent risk factor for major morbidity or OS. PR in RPS resection was associated with increased morbidity and mortality with minimal influence on survival. Patients with RPS undergoing PD and DP showed slight differences in terms of safety and OS.

Coping With Diabetes During the COVID-19 Lockdown in Saudi Arabia: Lessons Learned in the Post-pandemic Era.

Uncontrolled diabetes has appeared as one of the major risk factors for morbidity and mortality in diabetic patients with coronavirus disease 2019 (COVID-19). Alterations in dietary habits, physical inactivity, and inability to take advice from the physician are some of the contributing factors. This study aimed to assess the impact of the COVID-19 lockdown in Saudi Arabia on medication accessibility, medication adherence, lifestyle, and quality of life of diabetes patients. A cross-sectional observational study was conducted among diabetic patients using a self-reported questionnaire developed on an online platform (SurveyMonkey®). The survey was distributed through social media platforms (WhatsApp, Telegram). For those who were digitally illiterate, responses were collected by family members. The targeted population was type 1, type 2 and gestational diabetes patients. The analysis of the data was done using IBM SPSS Statistics, version 26. Four hundred forty-nine participants completed the survey. Most of the participants had type 2 diabetes (n=359; 79.8%) and were well educated (83.2%) with a high school degree and above. Complications from COVID-19 infection were reported in 12% (n=54) patients. During quarantine, 78.8% (n=354) of participants measured their blood glucose regularly. Results showed that during quarantine, 68.3% (n=311) participants skipped their scheduled follow-up whereas only 5.1% (n=23) of them took their medication inappropriately. This study reported good levels of self-monitoring of blood glucose levels, whereas patients' accessibility to seek healthcare services seemed to be interrupted. Further efforts are needed in the post-pandemic era to empower patients' self-care behaviors and utilize telehealth models to facilitate timely access to medical care.

Income-Related Peripheral Artery Disease Treatment: A Nation-Wide Analysis from 2009-2018.

Economic status has a measurable and significant effect on cardiovascular health. Socioeconomic- and income-related disparities worsen cardiovascular risk factors. Peripheral artery disease (PAD) remains a major risk factor for morbidity and mortality. Not all patients benefit equally from recent advances in outpatient healthcare. The implementation of guideline recommendations regarding treatment is inadequate. Income-related disparities for PAD treatment are unknown. We aimed to analyse income-stratified PAD prevalence, outpatient treatment and pharmacotherapy. Associations of statutory health insurance physicians at the regional level, income-stratified PAD prevalence and differences in outpatient care and pharmacotherapy were analysed in 70.1 million statutorily insured patients/year between 2009 and 2018. Analysis was based on claims data (§295 of the social code (SGB V)) and drug-prescription data (§300 SGB V). The diagnosis of PAD was defined by ICD I70.2-9. Regional income data were derived from the German Census Bureau. PAD prevalence was higher in low-income than in high-income areas. Low-income patients more often presented to angiology outpatient care and more frequently received guideline recommended pharmacotherapy. High-income patients more often presented to outpatient vascular surgery. This was true for statins, antiplatelets, intermittent claudication and critical limb ischemia alike. These data indicate that PAD and income are associated. Regional income is related to insufficiencies in guideline-recommended treatment and contact to vascular specialists. Our results aim to encourage medical professionals to implement PAD guideline recommendations, especially in high-income areas. Further studies on associations between spatial-level income and healthcare in PAD are needed.

Is it worthy to perform total pancreatectomy considering morbidity and mortality?: Experience from a high-volume single center.

Total pancreatectomy (TP) is performed for diseases of the entire pancreas. However, reluctance remains regarding TP because of the fear of high morbidity and mortality. Our retrospective study aimed to evaluate the postoperative outcomes of TP performed at a high-volume single center and to identify the risk factors associated with major morbidities and mortality after TP. A total of 142 patients who underwent elective TP at Samsung Medical Center between 1995 and 2015 were included. TP was usually planned before surgery or decided during surgery [one-stage TP], and there were some completion TP cases that were performed to manage tumors that had formed in the remnant pancreas after a previous partial pancreatectomy [2-stage TP]. The differences between the 1-stage and 2-stage TP groups were analyzed. Chronological comparison was also conducted by dividing cases into 2 periods [the early and late period] based on the year TP was performed, which divided the total number of patients to almost half for each period. Among all TP patients, major morbidity occurred in 25 patients (17.6%), the rate of re-admission within 90-days was 20.4%, and there was no in-hospital and 30-days mortality. Between the 1-stage and 2-stage TP groups, most clinical, operative, and pathological characteristics, and postoperative outcomes did not differ significantly. Chronological comparison showed that, although the incidence of complications was higher, hospitalization was shorter due to advanced managements in the late period. The overall survival was improved in the late period compared to the early period, but it was not significant. A low preoperative protein level and N2 were identified as independent risk factors for major morbidity in multivariable analysis. The independent risk factors for poor overall survival were R1 resection, adenocarcinoma, and high estimated blood loss (EBL). TP is a safe and feasible procedure with satisfactory postoperative outcomes when performed at a high-volume center. More research and efforts are needed to significantly improve overall survival rate in the future.

Abstract P076: Obesity Is Associated With Increased F2-isoprostanes And Il-6 In Black Women.

Obesity affects over 40% of the adult population and is a major risk factor for morbidity and mortality due to cardiovascular disease. Black women have one of the highest prevalence of obesity in the United States and approximately 80% are overweight or obese with increased insulin resistance, hypertension, and cardiovascular events. We previously found that isolevuglandins formed in the F2-isoprostane pathway of free radical–mediated lipid peroxidation contributes to IL-6 production in dendritic cells leading to inflammation and hypertension. Thus, we hypothesized that F2-isoprostanes contribute to increased inflammation and IL-6 production among obese Black women. We recruited 88 Black women of age 42.0±9.8 years, weight 102±16 kg, body mass index (BMI) 37.68±5.08, systolic blood pressure 124±14 mmHg, diastolic blood pressure 76.2±9.9 mmHg, and insulin 15.0±8.7 uU/ml. We measured plasma F2-isoprostane levels using gas chromatography/negative ion chemical ionization mass spectrometry (GC/NICI-MS) at the Eicosanoid Core at Vanderbilt University Medical Center. We also measured plasma cytokines including TNF-α 68±174, IL-1β 135±372, IL-6 1615±2769, IL-8 3536±1901, and IL-10 324±633 pg/mL. Using Pearson’s correlation analysis, we found that increased BMI correlated with increased plasma F2-isoprostane levels (Fig. 1A, R=0.23, p=0.037). Interestingly among all the inflammatory cytokines, elevated IL-6 correlated with increased F2-isoprostanes (Fig. 1B, R= 0.44, p=.0025). These results suggest that F2-isoprostanes may contribute to the obesity-induced cardiovascular risk in Black women by increasing production of inflammatory cytokine IL-6.

Neonatal hypothermia and associated factors in preterm neonates admitted to neonatal intensive care units in southwest Ethiopia

BackgroundNeonatal hypothermia is a major risk factor for morbidity and mortality of neonates in the first 28 days since birth. However, few studies have investigated the occurrence of neonatal hypothermia in preterm newborns in southwest Ethiopia. This study aimed to determine the prevalence of and factors associated with neonatal hypothermia in preterm neonates admitted to a neonatal intensive care unit (NICU) in Southwest Ethiopia. MethodsAn institutional based prospective cross-sectional study was conducted in preterm infants admitted to the NICU at Bench Sheko, Kafa, and Sheka hospitals between March and September 2020, using systematic sampling technique. Binary logistic regression analysis was used to assess the association between neonatal hypothermia and explanatory variables. The strength of association was evaluated using an odds ratio at a 95% confidence interval, where statistical significance was considered at a threshold of p < 0.05. ResultsThe prevalence of neonatal hypothermia was 62.9% (95%CI: 58.4%–67.6%). Neonatal hypothermia was associated with their having been an antenatal care visit (AOR: 0.52; 95%CI: 0.29-0.94), obstetric complication during delivery (AOR: 4.7; 95%CI: 1.78–12.34), caesarian section delivery (AOR: 1.91; 95%CI: 0.740–4.96), non-vertex presentation (AOR: 2.59; 95%CI: 1.06–6.32), 5-min APGAR score <7 (AOR: 2.19; 95%CI: 1.148–4.17), practicing kangaroo mother care (AOR: 55; 95%CI: 0.340-0.893), and the initiation of breastfeeding between 1 and 2 h (AOR: 2.39; 95%CI: 1.29–4.415). ConclusionThe prevalence of neonatal hypothermia was high. Nearly two-thirds of neonates admitted to NICU in southwest Ethiopia had neonatal hypothermia. Healthcare professionals working in the delivery room and/or NICU must be made aware of factors associated with neonatal hypothermia to ensure the early detection and appropriate management of the condition and thus to improve outcomes in infants presenting with neonatal hypothermia.

Association between body mass index and pupillary light reflex indices

Elevated body mass index (BMI) is a major risk factor for morbidity and mortality, and associated with autonomic nervous system (ANS) dysregulation, principally due to sympathetic over-activity. ANS is commonly evaluated using heart rate variability assay, which remains impractical for most clinical settings. To examine whether pupillometry indices reflective of dysautonomia correlates with high BMI levels in otherwise healthy individuals. In this cross-sectional study, 101 healthy participants were tested using an automated infrared pupilometer. Pupillary light reflex (PLR) parameters were acquired and averaged. Statistical analysis included a hierarchical linear regression, controlling for possible covariates. BMI values ranging 18.2–47.1 (mean 25.3 ± 4.4 kg/m 2 ) were positively correlated with average pupil dilatation velocity (ADV; r = 0.20, p = 0.05). After controlling for possible covariates, the results remained significant (β = 0.21, t = 2.13, p = 0.04). Separate analysis of participants with normal and increased BMI showed that ADV was significantly abnormal in the overweight group (p = 0.04). In seemingly healthy adults, BMI had a significant positive correlation with sympathetic over-activity manifested by pupillometry ADV values. ANS dysregulation is present even in individuals with moderate overweight. Further research is needed to establish standardized guidelines for PLR use as a marker for ANS dysfunction in individuals with cardiovascular risk factors. • Pupillary light reflex is a simple and practical method test to assess the ANS. • BMI is positively correlated with sympathetic activity measured by PLR indices. • ANS dysregulation was shown even in individuals with moderate overweight.

Glomerular Expression of S100A8 in Lupus Nephritis: An Integrated Bioinformatics Analysis.

IntroductionLupus nephritis (LN) is a major risk factor of morbidity and mortality. Glomerular injury is associated with different pathogeneses and clinical presentations in LN patients. However, the molecular mechanisms involved are not well understood. This study aimed to explore the molecular characteristics and mechanisms of this disease using bioinformatics analysis.MethodsTo characterize glomeruli in LN, microarray datasets GSE113342 and GSE32591 were downloaded from the Gene Expression Omnibus database and analyzed to determine the differentially expressed genes (DEGs) between LN glomeruli and normal glomeruli. Functional enrichment analyses and protein–protein interaction network analyses were then performed. Module analysis was performed using the Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape software. Immunofluorescence staining was performed to identify the glomerular expression of S100A8 in various International Society of Nephrology/Renal Pathology Society (ISN/RPS) class LN patients. The image of each glomerulus was acquired using a digital imaging system, and the green fluorescence intensity was quantified using Image-Pro Plus software.ResultsA total of 13 DEGs, consisting of 12 downregulated genes and one upregulated gene (S100A8), were identified in the microarray datasets. The functions and pathways associated with the DEGs mainly include inflammatory response, innate immune response, neutrophil chemotaxis, leukocyte migration, cell adhesion, cell–cell signaling, and infection. We also found that monocytes and activated natural killer cells were upregulated in both GSE113342 and GSE32591. Glomerular S100A8 staining was significantly enhanced compared to that in the controls, especially in class IV.ConclusionsThe DEGs identified in the present study help us understand the underlying molecular mechanisms of LN. Our results show that glomerular S100A8 expression varies in different pathological types; however, further research is required to confirm the role of S100A8 in LN.