LOS Group Research Articles

Combination of Losartan and Platinum Nanoparticles with Photothermal Therapy Induces Immunogenic Cell Death Effective Against Neuroblastoma.

Photothermal therapy (PTT) is a promising therapeutic procedure with minimal side effects, which can not only kill tumor directly but also cause immunogenic cell death (ICD). However, most solid tumors, including neuroblastoma, are abundant in fibroblasts, which limit the penetration and delivery of nanoparticles. Losartan is an antihypertensive drug approved by the FDA, and it has been proved to have the effect of breaking down excessive ECM network. In this study, we investigated the application and potential mechanism of the combination of mesoporous platinum nanoparticles (MPNs) and losartan in the PTT of neuroblastoma by establishing neuroblastoma models in vitro and in vivo. Compared to the MPNs group without 808 nm laser irradiation, Neuro-2a cells pretreated with PTT and losartan showed lower survival rates, increased surface calreticulin, and higher release of HMGB1 and ATP. The group also exhibited the highest anti-tumor efficacy in vivo, with a tumor suppression ratio of approximately 80%. Meanwhile, we found that CD3+ T cells, CD4+ T cells and CD8+ T cells from the peripheral blood of experimental group mice were significantly higher than control groups, and CD8+PD-1+ cells were significantly lower than those in MPNs + Los group and Los + laser group. And the expression of PD-1 and α-SMA in Neuro-2a tumors tissue was reduced. Furthermore, losartan could reduce damage of liver function caused by MPNs and laser treatment. This study demonstrated that losartan-induced fibroblasts ablation increased the penetration of MPNs into tumors. Enhanced penetration allowed PTT to kill more tumor cells and synergistically activate immune cells, leading to ICD, indicating the great promise of the strategy for treating neuroblastoma in vivo.

Gut microbiota in preterm infants with late-onset sepsis and pneumonia: a pilot case-control study

BackgroundLate-onset sepsis (LOS) and pneumonia are common infectious diseases, with high morbidity and mortality in neonates. This study aimed to investigate the differences in the gut microbiota among preterm infants with LOS, or pneumonia, and full-term infants. Furthermore, this study aimed to determine whether there is a correlation between intestinal pathogenic colonization and LOS.MethodsIn a single-center case‒control study, 16 S rRNA gene sequencing technology was used to compare gut microbiota characteristics and differences among the LOS group, pneumonia group, and control group.ResultsOur study revealed that the gut microbiota in the control group was more diverse than that in the LOS group and pneumonia group (P < 0.05). No significant differences in diversity were detected between the LOS and pneumonia groups (P > 0.05). Compared with the control group, the abundances of Akkermansia, Escherichia/Shigella, and Enterococcus increased, while the abundances of Bacteroides and Stenotrophomonas decreased in the LOS and pneumonia groups. The pathogenic bacteria in infants with LOS were consistent with the distribution of the main bacteria in the intestinal microbiota. An increase in Escherichia/Shigella abundance may predict a high risk of LOS occurrence, with an area under the curve (AUC) of 0.773.ConclusionChanges in the gut microbiota composition were associated with an increased risk of LOS and pneumonia. The dominant bacteria in the gut microbiota of the LOS group were found to be associated with the causative pathogen of LOS. Moreover, preterm infants exhibiting an elevated abundance of Escherichia/Shigella may be considered potential candidates for predicting the onset of LOS.

Synergistic Effects of Cinnamomum verum and Stingless Bee Honey on Isoproterenol-induced Cardiac Hypertrophic Murine Model

Abstract Objectives: This study aimed to validate the synergistic effects of Cinnamomum verum (C. verum) barks and stingless bee honey (SBH) against cardiac hypertrophy (CH). Materials and Methods: Isoproterenol (ISO-group II-30 mg/kg)-induced cardiac hypertrophic Wistar rats were used in this study. Hypertrophic rats were treated using the reference drug losartan (LOS Group III: 50 mg/kg) and aqueous extracts of C. verum barks and SBH (ACH Group IV: 250 mg/kg and 250 mg/kg). CH was characterized by electrocardiography, hypertrophic indices, and biochemical estimations such as total glucose, protein, albumin, lipid profiles, cardiac marker enzymes, and histopathological studies. Results: Rats received ISO had increased levels of glucose, protein, cholesterol, triglycerides, very low-density lipoprotein, and low-density lipoprotein, coupled with decreased levels of albumin and high-density lipoprotein. These levels were restored to near normal when treated with ACH extracts of the standard drugs. Contrary to the ISO-induced myocardial damaged hearts, ACH extracts had a profound effect compared to LOS, which was also reflected in histopathological studies. Conclusion: These data explicitly reveal that the ACH have a synergistic cardioprotective (antihypertrophic) effect.

Effects of a Losartan-Antioxidant Hybrid (GGN1231) on Vascular and Cardiac Health in an Experimental Model of Chronic Renal Failure.

Drugs providing antihypertensive and protective cardiovascular actions are of clinical interest in controlling cardiovascular events and slowing the progression of kidney disease. We studied the effect of a hybrid compound, GGN1231 (derived from losartan in which a powerful antioxidant was attached), on the prevention of cardiovascular damage, cardiac hypertrophy, and fibrosis in a rat model of severe chronic renal failure (CRF). CRF by a 7/8 nephrectomy was carried out in male Wistar rats fed with a diet rich in phosphorous (0.9%) and normal calcium (0.6%) for a period of 12 weeks until sacrifice. In week 8, rats were randomized in five groups receiving different drugs including dihydrocaffeic acid as antioxidant (Aox), losartan (Los), dihydrocaffeic acid+losartan (Aox+Los) and GGN1231 as follows: Group 1 (CRF+vehicle group), Group 2 (CRF+Aox group), Group 3 (CRF+Los group), Group 4 (CRF+Aox+Los group), and Group 5 (CRF+GGN1231 group). Group 5, the CRF+GGN1231 group, displayed reduced proteinuria, aortic TNF-α, blood pressure, LV wall thickness, diameter of the cardiomyocytes, ATR1, cardiac TNF-α and fibrosis, cardiac collagen I, and TGF-β1 expression. A non-significant 20% reduction in the mortality was also observed. This study showed the possible advantages of GGN1231, which could help in the management of cardiovascular and inflammatory processes. Further research is needed to confirm and even expand the positive aspects of this compound.

Paper 09: Revision rate following primary hip arthroscopy in patients given prophylactic oral losartan for the prevention of post-surgical fibrosis versus no losartan

Objectives: To evaluate whether postoperative treatment with Losartan decreased the revision rate in patients undergoing primary hip arthroscopy. Methods: Patients underwent primary hip arthroscopy with labral repair and CAM osteoplasty and rim trimming between 2012 and 2017. Patients who underwent microfracture, labral debridement or reconstruction, core decompression, ligamentous teres repair or reconstruction, or capsular reconstruction were excluded. Losartan was added to all patients’ post-operative protocol in December 2015. Patients who underwent hip arthroscopy prior to November 2015 were included in the no-Losartan group (NOLOS) and patients who had arthroscopy between December 2015 and Dec 2017 were included in the losartan group (LOS). Results: Of the 964 cases, follow-up was obtained on 673 patients (70%). There were 405 patients in the NOLOS group and 268 in the LOS group. There was no difference in gender distribution (P=0.128) between groups. The LOS group was significantly older (36.6 ±13 years) compared to the NOLOS group (34.1±11)(p=0.012). Average follow-up in the NOLOS group was 5.8±2 years and was 4.1±1 years in the LOS group. Revision hip arthroscopy was required in 35 (8.6%) patients in the NOLOS group and 6 (2.2%) patients in the LOS group(p=0.001). There was no difference in age between those patients who required revision (32±11 years) and those who did not(35±12 years)(p=0.137). Conclusions: The prevalence of revision hip arthroscopy was significantly lower (2.2%) in patients who took Losartan as part of their post-operative protocol compared to those who did not (8.6%). Reduction in the need for revision hip arthroscopy can improve patient outcomes and reduce healthcare dollars spent.

The role of nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in diagnosis of late onset neonatal sepsis.

Neonatal sepsis is a major cause of morbidity and mortality among neonates. Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a core element for innate immune protection. The study aims to estimate the expression of NLRP3 inflammasome in full term newborn infants who suffer from late onset sepsis, in order to assess its diagnostic value. This case-control study was conducted in NICU. 40 newborns with late onset sepsis, and 40 control neonates were included. The analysis of NLRP3 inflammasome was done by ELISA. There was a significant elevation of NLRP3 inflammasome in the serum of neonates with late onset sepsis group than the control group, P values were < 0.001, and the best cut off value of NLRP3 to detect late onset septic was > 3 ng/ml with sensitivity of 92.5% and specificity of 97.5%. Receiver operating characteristic curve showed that the best cut off point of NLRP3 to predict mortality in cases group was > 7.29 with sensitivity of 75.0%, specificity of 91.67%, PPV of 50.0%, NPV of 97.1% and total accuracy of 0.84%. n-SOFA scoring system increased significantly among LOS group and there was positive correlation with NLRP 3 inflammasome, P < 0.012. NLRP3 inflammasome can be used for the diagnosis of late onset neonatal sepsis. The increase of its values was not affected by gender, birth weight, gestational age and postnatal age. It was the novel sepsis markers that were not fully studied in neonatal population. The prognostic values may need further studies.

Risk Factors and Outcomes of Extended Length of Stay in Older Adults with Intertrochanteric Fracture Surgery: A Retrospective Cohort Study of 2132 Patients.

We aimed to identify the risk factors associated with an extended length of hospital stay (eLOS) in older hip-fracture patients and to explore the relationships between eLOS and mortality and functional outcomes. In this retrospective analysis of surgically treated intertrochanteric fracture (IF) patients, all variables were obtained and compared between the eLOS group and the normal LOS group. All participants were followed-up for a minimum of two years and the relation between the eLOS and all-cause mortality and functional outcomes were compared. After adjustment for potential confounders, we identified that patients with high modified Elixhauser's Comorbidity Measure (mECM) had the highest likelihood of eLOS, followed by obesity, admission in winter, living in urban, pulmonary complications, admission in autumn, and time from injury to surgery. In addition, our results showed no significant difference in the mortality and functional outcomes between the two groups during follow-up. By identifying these risk factors in the Chinese geriatric population, it may be possible to risk-stratify IF patients and subsequently streamline inpatient resource utilization. However, the differences between health care systems must be taken into consideration. Future studies are needed to preemptively target the modifiable risk factors to demonstrate benefits in diminishing eLOS.

Serum Levels of Selected IL-1 Family Cytokines in Patients with Morphea.

Morphea/localized scleroderma (LoS) represents an inflammatory-sclerotic skin disease, the pathogenesis of which is not fully understood. Given the important role of IL-1 family cytokines in the development and therapy of inflammatory diseases, including systemic sclerosis, we analyzed the clinical significance of serum levels of selected IL-1 family cytokines (IL-1α, IL-1β, IL-18, IL-33, IL-37 and IL-38) in LoS patients (n = 30) using the standardized disease assessment tools and comparison to healthy controls (n = 28). We also compared the pre- and post-treatment concentrations, i.e., before and after systemic (glucocorticosteroids and/or methotrexate) and/or topical (topical glucocorticosteroids and/or calcineurin inhibitors). Our findings did not reveal significant differences in baseline IL-1α, IL-1β, IL-18, IL-33, IL-37 and IL-38 levels between LoS group and HCs; however, after treatment, there were marked changes in concentrations of IL-1α and IL-33 within LoS group as well as in comparison to HCs. We also found significant negative correlations between PGA-A and IL-1α concentration as well as between mLoSSI and IL-1α after treatment. Furthermore, we showed an inverse correlation of baseline IL-1β levels with mLoSSI scores of borderline significance. We believe that IL-1α and IL-33, as well as Il-1β, may be potential mediators and targets of interest in LoS.

Renocardiac protective effects of SGLT2 inhibitor combined with angiotensin receptor blocker in salt sensitive Dahl rats

Abstract Background Kidney plays a central role in regulating salt-sensitivity of blood pressure (BP) to governs sodium excretion via several mechanisms including pressure natriuresis and the actions of renal sodium transporters. Purpose We clarified the effects of combination treatment of sodium-glucose cotransporter 2 (SGLT2) inhibitor and angiotensin receptor blocker (ARB) on BP and the pathogenesis of renocardiac injuries, and elucidated underlying molecular mechanisms involved in the regulation of renal sodium handling in the development of salt-sensitivity by comparing with each monotreatment in Dahl salt-sensitive (DSS) hypertensive rats. Methods DSS rats were treated orally for 8-weeks with normal salt diet (0.3% NaCl) (NS/Cont group), high salt diet (8% NaCl) (HS/Cont group), high salt diet with ipragliflozin (0.04%) (HS/Ipra group), high salt diet with losartan (0.05%) (HS/Los group), or high salt diet with combination of ipragliflozin and losartan (HS/Ipra+Los group). Results The combination group significantly reduced systolic BP compared with either high salt diet control group, losartan or ipragliflozin monotreatment groups (HS/Ipra+Los: 182.5±18.4mmHg vs HS/Cont: 227.7±26.1; HS/Ipra: 216.6±26.9; HS/Los: 208.6±21.6, at 8-weeks of treatment, P&amp;lt;0.05, respectively) (Figure 1A). The slope of pressure-natriuresis curve was significantly increased in the HS/Ipra+Los group compared to that in the HS/Cont group (interaction P=0.024), HS/Ipra group (P=0.009), and HS/Los group (P=0.084) using the linear regression model (Figure 1B), which indicated that only the combination treatment of ipragliflozin and losartan improved salt-sensitivity. The combined treatment significantly improved creatinine clearance (HS/Ipra+Los: 3.3±0.9mL/min vs HS/Cont: 1.1±0.5; HS/Ipra: 1.7±0.6; HS/Los: 1.9±0.8, P&amp;lt;0.05, respectively). The combination treatment also significantly ameliorated glomerulosclerosis, and improved cardiomyocyte hypertrophy and perivascular fibrosis (Figure 1C). Angiotensin II type 1 receptor (AT1R) protein expression level in the kidney was remarkably suppressed in the combination treatment group compared to the other high salt diet groups. The protein expression level of Na+/H+ exchanger isoform 3 (NHE3) and Na+-K+-Cl– cotransporter 2 (NKCC2), two of major sodium transports in the renal tubules, were significantly decreased with losartan monotreatment and combination treatment, but not with ipragliflozin monotreatment (Figure 2). Conclusions The dual inhibition of SGLT2 and AT1R effectively improved salt-sensitivity via reducing renal expression levels of the sodium transporters, which eventually lead to renocardiac protection. Thus, the combination treatment could be a novel and useful therapeutic strategy for treating salt-sensitive hypertension and renal injury in non-diabetic patients. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Grant-in-Aid for Scientific Research

25-hydroxy Vitamin D deficiency – A potential risk factor neonatal sepsis correlation with biochemical markers and neonatal sequential organ failure assessment score

Background: Sepsis could be a life-threatening organ dysfunction generated due to the dysregulation of the immunological response to infection. An operational definition of organ dysfunction applicable to neonates that predicts mortality within the infection setting is lacking. The neonatal sequential organ failure assessment (nSOFA) score was developed to predict mortality from late-onset neonatal sepsis in term babies (late-onset sepsis [LOS]). Objectives: This study aimed to focus on Vitamin D role in late-onset neonatal sepsis in term babies and to search out the correlation of Vitamin D levels with inflammatory markers, the severity of the disease, and association with nSOFA score and mortality risk. Patients and Methods: We screened all term newborns admitted to the neonatal intensive care unit (NICU) due to suspected or confirmed LOS during the study period. Our final cohort consisted of 148 patients with valid test results and data. Neonates with suspected LOS (Group 1 n = 52) confirmed LOS (Group 2 [n = 74]) or septic shock (group 3 [n = 24]). Baseline clinical data, nSOFA score within the first 24 h, cardiovascular support, the duration of mechanical ventilation, length of the NICU stay, 7th and 28th-day mortality recorded, plasma levels of 25-hydroxyvitamin D (25[OH] D), C-reactive protein, and pre- and procalcitonin were investigated. Newborns were followed until they discharge from the NICU or death. Results: Term newborns with late-onset neonatal sepsis had lower levels of 25(OH) D. We revealed a negative correlation between the levels of 25(OH) D and biochemical markers/nSOFA score in all patients with late-onset neonatal sepsis. Thirty-seven (25%) patients with LOS died within 28 days of NICU admission (with a median 25(OH) D level of 18.3 nmol (interquartile range: 8.7–23.8). There were 35 patients (23.64%) who received vasopressors (N-SOFA ≥3) during their NICU stay. These patients had significantly lower 25(OH) D levels.(P < 0.0001). Lower 25(OH) D levels among study groups were independently associated with a higher n-SOFA score. Conclusion: Our results showed that Vitamin D deficiency predisposed to the development of late-onset neonatal sepsis negatively correlated with biochemical markers and nSOFA score.

Peripheral chemoresponsiveness during exercise in male athletes with exercise‐induced arterial hypoxaemia

What is the central question of this study? Do highly trained male endurance athletes who develop exercise-induced arterial hypoxaemia (EIAH) demonstrate reduced peripheral chemoresponsiveness during exercise? What is the main finding and its importance? Those with the lowest arterial saturation during exercise have a smaller ventilatory response to hypercapnia during exercise. There was no significant relationship between the hyperoxic ventilatory response and EIAH. The findings suggest that peripheral chemoresponsiveness to hypercapnia during exercise could play a role in the development of EIAH. The findings improve our understanding of the mechanisms that contribute to EIAH. Exercise-induced arterial hypoxaemia (EIAH) is characterized by a decrease in arterial oxygen tension and/or saturation during whole-body exercise, which may in part result from inadequate alveolar ventilation. However, the role of peripheral chemoresponsiveness in the development of EIAH is not well established. We hypothesized that those with the most severe EIAH would have an attenuated ventilatory response to hyperoxia and hypercapnia during exercise. To evaluate this, on separate days, we measured ventilatory sensitivity to hyperoxia and separately hypercapnia at rest and during three different exercise intensities (25, 50% of and ventilatory threshold (∼67% of )) in 12 males cyclists ( =66.6±4.7mlkg-1 min-1 ). Subjects were divided into two groups based on their end-exercise arterial oxygen saturation (ear oximetry, ): a normal oxyhaemoglobin saturation group (NOS, =93.4±0.4%,n=5) and a low oxyhaemoglobin saturation group (LOS, =89.9±0.9%, n=7). There was no difference in (66.4±2.9vs.66.8±6.0mlkg-1 min-1 , respectively, P=0.9), peak ventilation during maximal exercise (182±15vs.197±32lmin-1 , respectively, P=0.36) or ventilatory response to hyperoxia (P=0.98) at any exercise intensity between NOS and LOS groups. However, those in the LOS group had a significantly lower ventilatory response to hypercapnia (P=0.004, (η2 =0.18). There was also a significant relationship between the mean hypercapnic response and end-exercise (r=0.75, P=0.009) but not between the mean hyperoxic response and end-exercise (r=0.21, P=0.51). A blunted hypercapnic ventilatory response may contribute to EIAH in highly trained men due to a failure to increase ventilation sufficiently to offset exercise-induced gas exchange impairments.

Telmisartan Exacerbates Cisplatin-Induced Nephrotoxicity in a Mouse Model.

Cisplatin (CDDP; cis-diamine dichloroplatinum)-induced nephrotoxicity is the main reason for dose limitations, which can reduce the efficacy of cancer treatment. Lower blood pressure and administration of renin angiotensin system (RAS) inhibitors have been reported as factors that exacerbate CDDP-induced nephrotoxicity; however, the detailed mechanisms remain unknown and the results of previous studies are conflicting. In this study, we examined the influence of various hypotensive drugs, including RAS inhibitors and calcium channel blockers, on CDDP-induced nephrotoxicity in BALB/c mice. The mice were divided into nine groups: (1) CDDP group (15 mg/kg CDDP), (2) AML group (5 mg/kg amlodipine), (3) ENA group (2.5 mg/kg enalapril), (4) telmisartan (TEL) group (10 mg/kg telmisartan), (5) LOS group (10 mg/kg losartan), (6) CDDP + AML group, (7) CDDP + ENA group, (8) CDDP + TEL group, and (9) CDDP + LOS group. Nephrotoxicity was evaluated by measuring serum creatinine (CRE) and blood urea nitrogen (BUN) levels. In addition, the kidney sections were stained with Masson's trichrome and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) to assess the renal fibrosis area and apoptotic area. Serum CRE and BUN levels were increased in the CDDP + ENA, CDDP + LOS, and CDDP + TEL groups compared to those in the CDDP alone group, and the CDDP + AML group showed an increasing trend. However, there was no correlation between ∆CRE or ∆BUN levels and ∆ systolic blood pressure. The CDDP + TEL group showed a significant increase in the renal fibrosis area. These results suggest that exacerbation of CDDP-induced nephrotoxicity is not correlated with systolic blood pressure but is associated with administration of RAS inhibitors, particularly TEL.

Dexamethasone and losartan combination treatment protected cigarette smoke-induced COPD in rats.

Chronic Obstructive Pulmonary Disease (COPD) is a dangerous prevalent smoking-related disease characterized by abnormal inflammation and oxidative stress and expected to be the third cause of death in the world next decade. Corticosteroids have low effects in decreasing numbers of inflammatory mediators specifically in long-term use. Our study designed to investigate the possible protective effects of combined dexamethasone (Dex) (2mg/kg) and losartan (Los) (30mg/kg angiotensin receptor blocker, it possesses antioxidant and anti-inflammatory properties in lung injury in mice) against cigarette -smoke (CS) induced COPD in rats compared with dexamethasone and losartan. Male Sprague Dawley rats (N = 40) divided into five groups (n = 8): control group, CS group, Dex group, Los group, and Dex +Los group. COPD induced in rats by CS exposure twice daily for 10 weeks. After the specified treatment period, bronchoalveolar lavage fluid (BALF) and lung tissue were collected for measurement of SOD, NO, MDA, ICAM-, MMP-9, CRP, NF-κB and histopathology scoring. Our results indicated that Los+Dex significantly prevent CS-induced COPD emphysema, congested alveoli, and elevation of lung injury parameters in BALF. They also showed a significant decrease in MDA, ICAM-1, MMP-9, CRP, and NF-κB and a significant increase in SOD and NO. In conclusion, adding Los to Dex potentiating their activity in inhibition the progression of COPD based on its activity on oxidative stress, inflammation, and NF-κB protein expression.

One-year mortality in displaced intracapsular hip fractures and associated risk: a report of Chinese-based fragility fracture registry

BackgroundThe purpose of this registry-based retrospective study was to investigate the risk factors related to one-year mortality in displaced intracapsular fragility hip fracture patients.MethodsPatients were screened from the Fragility Fracture Registry. Inclusion criterion was displaced intracapsular hip fracture patients with atypical or pathological fractures excluded. One-year mortality was investigated against risk factors including age, gender, past medical history, pre-fracture mobility (PFM), pre-operation ASA grade, delayed surgery over 48 h, post-surgical complications, and length of stay at acute orthopedic ward (LOS).ResultsA total of 1050 patients were included for further analysis. Gross one-year mortality was 14.9%. One-year mortality was significantly higher in patients who received non-operative treatment and those who received surgery but delayed over 48 h after admission (both p < 0.001). Male gender (OR = 2.708), advanced age (OR = 1.359), higher risk ASA grades (III to V) (OR = 1.990), past history of gastrointestinal disease (OR = 1.671), and renal impairment (OR = 1.984) were related to higher one-year mortality. The mortality of patients in PFM grade 3 and LOS group 3 was significantly higher (OR = 2.240 and 1.722, respectively).ConclusionsHigher age, male gender, past gastrointestinal disease and renal impairment, ASA grade over 3, indoor confined pre-fracture ambulatory, and stay at hospital over 15 days were risk factors related to higher one-year mortality in surgically treated displaced intracapsular hip fracture patients. A multi-disciplinary approach is advised to patients identified with these risks factors and co-managed by orthopedic surgeons, geriatricians, and fracture liaison nurses.

F122. CLINICAL CHARACTERISTICS OF LATE-ONSET SCHIZOPHRENIA IN COMPARISON WITH EARLY-ONSET SCHIZOPHRENIA: ONE YEAR FOLLOW-UP STUDY

BackgroundLate-onset schizophrenia (LOS) differs from early-onset schizophrenia (EOS) in several ways including predominance of women, better premorbid social adjustment and lower severity of positive/negative symptoms. However, no studies evaluated the longitudinal course of LOS. This study aimed to investigate the clinical characteristics of LOS in comparison with EOS and the longitudinal course of clinical symptoms and functioning in LOS.MethodsBy reviewing medical records, we assessed demographic data, clinical characteristics, and general functioning of 20 LOS (5 males) and 44 EOS (16 males) who admitted to National Health Insurance Service Ilsan Hospital. LOS and EOS were defined according to age at first onset: ≥40 years (LOS) and <40 years (EOS). The level of clinical symptoms were rated using the Positive and Negative Syndrome Scale (PANSS), and general functioning was evaluated using the General Assessment of Functioning (GAF).ResultsThere was no significant difference in gender between LOS and EOS. The mean ages of onset were 45.4 ± 3.97 (LOS) and 28.4 ± 6.69 (EOS) years. Significantly more LOS patients (90.0%) had a marital history including divorce than EOS (56.8%). There were no differences between LOS and EOS in the positive, negative, and general scores of PANSS measured at admission and 1 year after. LOS patients had significantly higher score of PANSS N2 item (Emotional withdrawal) both at admission (LOS: 4.00 ± 1.34; EOS: 3.43 ± 1.52) and 1 year after (LOS: 3.50 ± 1.00; EOS: 2.91 ± 1.05) than EOS. There were negative correlations between GAF (1 year after) and N2 item score (at admission: r= –0.45, p=0.04; 1 year after: r= –0.85, p<0.001) in the LOS group, but no significant correlation exists in the EOS group.DiscussionConsistent with previous studies, our study suggested that LOS patients had better premorbid social functioning because marital history can be regarded as index of premorbid social adjustment. However, on the contrary to previous findings, LOS patients had more severe emotional withdrawal and it was related to worse functioning. This finding may be due to cultural specificity in Korea; thus, further studies with larger samples are needed for confirmation.

The predictors of long-term hospitalization in Turkish heart failure population: A subgroup analysis of journey heart failure-TR study: On behalf of journey heart failure-TR investigators

Background: Heart failure (HF) is an important public health problem. We aimed to investigate the predictors of long-term hospitalization in Turkish HF population. Materials and Methods: Journey-HF-TR study is a multicenter, cross-sectional, noninvasive, and observational study that was conducted in intensive care unit (ICU), coronary care unit (CCU), and cardiology wards in seven geographical regions of Turkey. In this subgroup analysis, patients were classified as two groups according to inhospital stay called the patient with the shorter length of stay (S-LOS) (inhospital stay <5 days; S-LOS) and patients with longer LOS (L-LOS) (inhospital stay ≥5 days; L LOS). Results: The study group was consisted of 1606 patients (57.2% male, mean age: 67. 8 ± 13.0 years old). One thousand and thirty seven patients, whom in-hospital stay duration were recorded in case report form, were included in this analysis. There were 487 patients (32.1%) in S LOS group and 1030 patients (67.9%) in L LOS group. In multivariate analysis, correlation was present for NYHA functional capacity, CKD, ACS related HF, right HF, cardiogenic shock, invasive and noninvasive ventilation, and hemodynamic monetarization. The longer inhospital stay increases the probability of morbidity and mortality. Conclusion: We demonstrated that there was positive correlation between longer hospital stay and HF severity (NYHA III-IV), CKD, cardiogenic shock, right ventricular HF, and HF related to ACS. HFpEF patients have less in-hospital stay than HFrEF and HFmrEF patients.

Treating Peripheral Artery Disease in the Wake of Rising Costs and Protracted Length of Stay

There has been growing scrutiny in the treatment of patients with peripheral artery disease due to the utilization of resources to manage this complex patient population. The purpose of this study was to determine the factors associated with prolonged length of stay (LOS > 7days) following lower extremity bypass using data from the Vascular Quality Initiative as well as to define the additional costs incurred due to prolonged LOS in our health system. Summary statistics were performed of patients undergoing lower extremity bypass from 2010 to 2015. Student's t-tests and χ2 tests were performed to compare those with and without prolonged LOS. Multivariable logistic regression was then performed to determine the independent predictors for increased LOS. We then compared our institutional LOS with that of representative institutions from the University Health System Consortium and evaluated the impact of prolonged LOS on limb salvage and survival. This study included 334 patients with a mean age of 66.4±12.4years, 64.7% males, 58.5% of white race, 11.1% on dialysis, 80.5% smokers, and 53.6% with diabetes. The mean LOS was 15.7±12.2days. Prolonged LOS was associated with transfer (15.4% vs. 2.3%, P=0.001), diabetes (58.3% vs. 40.2%, P=0.004), critical limb ischemia (71.3% vs. 49.4%, P<0.001), preoperative need for ambulatory assistance (44.5% vs. 16.1%, P<0.001), prior ipsilateral bypass (6.9% vs. 1.1%, P=0.042), urgent surgery (39.7% vs. 9.8%, P<0.001), tibial or distal target vessel (52.7% vs. 28.0%, P<0.001), use of vein (65.4% vs. 46.3%, P=0.002), return to operating room (42.6% vs. 1.2%, P<0.001), ambulatory assistance (65.0% vs. 34.1%, P<0.001) as well as discharge anticoagulant (22.8% vs. 9.8%, P=0.010). Multivariable logistic regression identified urgency (odds ratio [OR]=5.09, 95% confidence interval [CI] 2.16-12.02, P<0.001), critical limbischemia (OR=3.12, 95% CI 1.65-5.90, P<0.001), return to OR (OR=40.30, 95% CI 5.36-303.20, P<0.001), use of vein (OR=2.19, 95% CI 1.18-4.07, P=0.013), and the need for anticoagulation at discharge (OR=2.56, 95% CI 1.03-6.33, P=0.043) as independent predictors of LOS > 7days. Prolonged hospital stays accounted for an additional $40,561.64 in total cost and $26,028 in direct costs incurred. Despite these increased costs, limb salvage and overall survival were not adversely impacted in the prolonged LOS group in follow-up. Lower extremity bypass is associated with a longer than expected LOS in our health system, much of which can be attributed to return to the OR for minor amputations and wound issues. This led to added total and direct costs, where the majority of this increase was attributable to prolonged LOS. Limb salvage and overall survival were preserved, however, in this subset of patients in follow-up. These findings suggest that lower extremity bypass patients are a resource-intensive population of patients, but that these costs are worthwhile in the setting of preserved limb salvage and overall survival.

Interaction between interleukin‑6 and angiotensin II receptor 1 in the hypothalamic paraventricular nucleus contributes to progression of heart failure.

The association between interleukin‑6 (IL‑6) and angiotensin II receptor 1 (AT1‑R) in modulating the progression of heart failure (HF) remains to be fully elucidated. The aim of the present study was to investigate the mechanism of IL‑6 and AT1‑R in a model of HF induced by surgery. Male Sprague‑Dawley rats were randomly divided into five groups, including sham surgery and vehicle groups. The animals were treated for 4weeks via paraventricular nucleus infusion with either vehicle, losartan (LOS; 200µg/day), IL‑6 (1µg/day) or LOS and IL‑6 together (LOS+IL‑6). The rats with HF had higher levels of IL‑6, corticotropin‑releasing hormone (CRH) and norepinephrine (NE), and a lower level of neuronal nitric oxide synthase (nNOS), compared with the rats in the sham surgery group. Treatment with LOS attenuated the decrease in nNOS and the increases in IL‑6, CRH and NE; whereas treatment with IL‑6 facilitated the lower expression of nNOS and higher expression levels of IL‑6, CRH and NE. No differences in the expression levels of nNOS, CRH or NE were found between the LOS group and LOS+IL‑6 group. The results of the study demonstrated that IL‑6 contributed to the progression of HF via the AT1‑R pathway.

Comparison of visual effects after LASIK in myopia between centered on the coaxially sighted corneal light reflex and line of sight

To compare visual acuity, refractive outcome, high order aberrations, contrast sensitivity and subjective symptom of myopia with laser in situ keratomileusis (LASIK) centered on the coaxially sighted corneal light reflex (CSCLR group) and the conventional ablation of line of sight (LOS group). With prospective, double-blind, randomized, controlled trial, the right eyes of patients were included and divided into two groups according to random stratified grouping. Two hundred and ten myopic eyes were treated with centration on the coaxially sighted corneal light reflex and 210 myopic eyes treated with centration on pupil center(line of sight). The parameters of visual acuity, refractive outcome, ablation center distance from visual axis, corneal high order aberrations, subjective discomfort glare and shadowing incidence rate, contrast sensitivity between the two groups were measured and compared up to 6months post operation. Consistent with the measurement data, normal distribution using the group t-test, non-normal distribution of measurement data using the group wilcoxon rank-sum test and count data using chi-square test. The data of postoperative UCVA, BCVA, MRSE efficacy index and safety index showed no statistical difference between the CSCLR and the LOS group up to 6months post operation(P> 0.05). 3% lost one line or more of BCVA in the CSCLR group,and 9% in the LOS group postoperatively, χ(2)= 6.38, P=0.01. The ablation center deviation was (0.19±0.15) mm from visual axis(pentacam system default setting) in CSCLR group and (0.43±0.22) mm in the LOS group. Ablation center deviation was statistically significantly shorter in the CSCLR group (t=-2.59, P<0.01). The postoperative increased total cornea higher order aberrations was 0.150 μm in CSCLR group and 0.193 μm in LOS group, the difference was statistically significant, Z=3.21, P=0.03. The increased corneal vertical coma of CSCLR group was 0.321 μm,smaller than in the LOS group(0.464 μm), Z=4.33, P<0.01. The increased horizontal coma was 0.242 μm in CSCLR group and also smaller than the LOS group(0.353 μm), Z=4.54,P<0.01. Subjective discomfort glare and shadowing incidence rates were 8.5% and 17.5% respectively in the CSCLR and LOS group, χ(2)=7.16,P< 0.01. The one month postoperative contrast sensitivity visual acuity in the CSCLR was 1.157 ± 0.253, significantly higher than the LOS group (0.797±0.218) on 18 c/d spatial frequency, t=- 2.55, P=0.01, but with no significant difference between the two groups at 3 and 6 months. Myopic LASIK centered on the CSCLR achieved significant lower induction of lost of BCVA, lower induction of high order aberrations, lower risk of subjective discomfort glare and shadowing and lower decline of early contrast sensitivity by comparison to centration on the LOS, improving the quality of vision after operation. (Chin J Ophthalmol, 2016, 52: 499-506).

83 - Effects of losartan on experimental varicocele-induced testicular germ cell apoptosis

Summary To investigate the potential protective effects of losartan on varicocele-induced germ cell apoptosis, 24 adult male Sprague Dawley rats were divided into three groups: a sham operation was performed in SHAM group, and experimental left varicocele was created in VAR and VAR + LOS groups. Additionally, in VAR + LOS group, losartan was administered for 30 days starting on the day of surgery. At the end of 30 days, all animals were sacrificed and left orchiectomy was performed. Testicular injury and spermatogenesis were evaluated according to Johnsen scoring system. To assess the nitrosative stress, immunohistochemical staining for endothelial nitric oxide synthase was used and evaluated by H-score and apoptotic index (AI) of germ cells was analysed by TUNEL method. A significant decrease in the mean Johnsen score (JS) was observed in VAR group compared with SHAM (p < .001). The mean H-score and AI were significantly higher in VAR group compared with SHAM (p < .001). After losartan administration, mean JS was significantly increased (p < .001) and mean H-score and AI were significantly decreased compared with VAR group (p < .001 and .01, respectively). Findings of this suggest that losartan acts as a potent protective agent against varicocele-induced germ cell apoptosis.