PreD Group Research Articles

Treatment with Leflunomide in Conjunction with Glucocorticoids for Dogs with Immune-Mediated Polyarthritis Is Not Associated with Improved Outcomes: A Retrospective Cohort Study of 93 Dogs from Australia (2017–2024)

Immune-mediated polyarthritis (IMPA) has a relatively high relapse rate compared to other immune-mediated diseases. Leflunomide is frequently used to treat dogs with IMPA in conjunction with prednisolone. This retrospective cohort study aimed to evaluate the therapeutic efficacy of leflunomide as an adjunctive therapy to prednisolone in reducing relapse and mortality rates in dogs diagnosed with IMPA in Australia. The medical records of client-owned dogs diagnosed with IMPA at a specialist referral hospital in Southeast Queensland from 2017 to 2024 were reviewed. A total of 93 dogs were included in this study, divided into two groups based on the treatment received: Group PRED, consisting of 53 dogs treated with prednisolone as the sole immunosuppressive agent, and Group L+PRED, consisting of 40 dogs that received leflunomide as adjunctive therapy alongside prednisolone. Data collected included breed, age, weight, sex, serum C-reactive protein concentration, results of synovial fluid analysis and microbial culture, treatment protocol, relapse rates and time to relapse, and mortality rates. There was no difference in relapse or mortality rates, time to relapse, nor time to discontinue prednisolone between the PRED and L+PRED groups. The L+PRED group had higher body weights and lower prednisolone dose rate at discharge compared to those in the PRED group. This study demonstrated that the use of leflunomide as an adjunctive therapy to prednisolone for the treatment of dogs with IMPA had no improved outcomes, reduced relapse rates, or shortening in the duration of prednisolone therapy when compared to dogs receiving prednisolone monotherapy.

Outcome of incidental versus preoperatively diagnosed colorectal cancer during total proctocolectomy with ileal pouch-anal anastomosis for inflammatory bowel disease.

Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the treatment of choice for colorectal cancer (CRC) in inflammatory bowel disease. CRC may also be discovered incidentally at IPAA for other indications. We sought to determine whether incidentally found CRC at IPAA was associated with worse outcomes. Our institutional pouch registry (1983-2021) was retrospectively reviewed. Patients with CRC at pathology after IPAA were divided into two groups: a preoperative diagnosis (PreD) group and an incidental diagnosis (InD) group. Their long-term outcomes (overall survival, disease-free survival and pouch survival) were compared. We included 164 patients: 53 (32%) InD and 111 (68%) PreD. There were no differences in cancer staging, differentiation and location. After a median follow-up of 11 (IQR 3-25) years for InD and 9 (IQR 3-20) years for the PreD group, deaths were 14 (26%) in the InD group and 18 (16%) in the PreD group. Pouch failures were five (9%) in the InD group and nine (8%) in the PreD group, of which two (5%) and four (4%) were cancer related. Ten-year overall survival was 94% for InD and 89% for PreD (P = 0.41), disease-free survival was 95% for InD and 90% for PreD (P = 0.685) and pouch survival was 89% for InD and 97% for PreD (P = 0.80). Pouch survival at 10 years was lower in rectal versus colon cancer (87% vs. 97%, P = 0.01). No difference was found in outcomes in handsewn versus stapled anastomoses. Inflammatory bowel disease patients with incidentally found CRC during IPAA appear to have similarly excellent oncological and pouch outcomes to patients with a preoperative cancer diagnosis.

Poor obstetric outcomes in women with takayasu arteritis: a retrospective cohort study.

The objective of this study was to assess the pregnancy outcomes in a cohort of patients who experienced pregnancies before and/or after being diagnosed with Takayasu's arteritis (TA). The present investigation encompassed a total of 88 pregnancies seen in a cohort of 35 patients who met the criteria outlined by the American College of Rheumatology in 1990 for the classification of Takayasu arteritis (TA). Pregnancies were classified into two categories. 1. Pregnancies that occurred before the diagnosis (pre-d or pre-TA) 2. Pregnancies that happened following a diagnosis (post-d or post-TA). Fifty-nine pregnancies (67.0%) occurred in 21 TA patients before the diagnosis with and a complication rate of 15.2%, and twenty-nine pregnancies (33.0%) occurred in 14 patients concomitant with or after TA diagnosis and complication rate 100%. Although the hypertension rate was higher in the pre-d group than in the post-d group, it was not significant (32.2% vs. 10.3%, p = 0.160). However, preeclampsia (20.6% vs. 0%, p = 0.001), low birth weight (27.5% vs. 1.6%, p = 0.001), and prematurity (24.1% vs. 1.6%, p = 0.035) were observed more frequently in the post-d group compared to the pre-d group. The frequency of abortions and in-utero deaths were similar in both groups (p > 0.05). Patients with hypertension had significantly higher rates of preeclampsia (p = 0.003), preterm birth (p = 0.036), low birth weight (p = 0.250), abortion (p = 0.018), in utero death (p = 0.128), and cesarean section (p = 0.005) than those without hypertension. Renal artery involvement was detected in 15 (42.8%) patients. All patients with renal artery involvement had hypertension, and they had significantly more pregnancy complications than the other group (p = 0.001). TA negatively affects pregnancy outcomes. A good control of arterial hypertension before conception and during pregnancy is critical to improve both maternal and fetal outcomes. In addition, detecting renal artery stenosis before pregnancy is important in reducing possible negative pregnancy outcomes.

Effects Of Exercise Training And Chlorogenic Acid Supplementation On Hepatic Lipid Metabolism In Prediabetes Mice.

Since prediabetes is a risk factor for metabolic syndromes, it is important to promote a healthy lifestyle to prevent prediabetes. This study aimed to determine the effects of green coffee (GC), chlorogenic acid (CGA) intake, and exercise training (EX) on hepatic lipid metabolism in prediabetes male C57BL/6 mice. Forty-nine mice were randomly divided into two groups feeding with a normal diet (n=7) or a high-fat diet (HFD, n=42) for 12 weeks. Then, HFD mice were further divided into six groups (n=7/group): control (pre-D), GC, CGA, EX, GC+EX, and CGA+EX. After additional 10 weeks under the same diet, plasma, and liver samples were obtained. HFD-induced prediabetes conditions with increases in body weight, glucose, insulin, insulin resistance, and lipid profiles were alleviated in all treatment groups. Acsl3, a candidate gene identified through an in silico approach, was lowered in the pre-D group, while treatments partly restored it. HFD induced adverse alterations of de novo lipogenesis- and β oxidation-associated molecules in the liver. However, GC and CGA supplementation and EX reversed or ameliorated these changes. In most cases, GC or CGA supplementation combined with EX has no synergistic effect and the GC group had similar results to the CGA group. These findings suggest that regular exercise is an effective non-therapeutic approach for prediabetes, and CGA supplementation could be an alternative to partially mimic the beneficial effects of exercise on prediabetes.

Testosterone Replacement Therapy in Chronic Kidney Disease Patients

(Background) The aim of our study was to evaluate the efficacy and safety of testosterone replacement therapy (TRT) in men with chronic kidney disease and hypogonadism on conservative and hemodialysis treatment. (Methods) The studied population consisted of 38 men on hemodialysis (HD), 46 men with CKD stages II-IV (predialysis group, PreD) and 35 men without kidney disease who were similar in age to others (control group). Serum total testosterone level (TT) was measured, and free testosterone level (fT) was calculated. Hypogonadism criteria according to the EAU definition were fulfilled by 26 men on HD (68.4%) and by 24 men from the PreD group (52%). Testosterone replacement therapy (TRT) with testosterone enanthate in intramuscular injections every 3 weeks was applied in 15 men from HD and in 14 men from PreD. The safety of TRT was monitored by measuring PSA and overhydration. (Results) A significant rise of TT and fT was observed after 3 months of TRT, but no significant changes were observed after 6 and 12 months in the HD and PreD group. An intensity of clinical symptoms of hypogonadism measured by ADAM (androgen deficiency in the ageing male) questionnaire gradually decreased, and the intensity of erectile dysfunction measured by the IIEF-5 (international index of erectile functioning) questionnaire also decreased after 3, 6 and 12 months of TRT in the HD and PreD group. (Conclusions) The applied model of TRT is effective in the correction of clinical signs of hypogonadism without a significant risk of overhydration or PSA changes.

Evaluation of eryptosis in patients with chronic kidney disease.

Anemia in patients with chronic kidney disease (CKD) is the result of reduced erythropoietin, disturbed erythropoiesis and decreased lifespan of circulating erythrocytes. Excessive eryptosis or premature suicidal erythrocyte death is characterized by cell shrinkage and phosphatidylserine externalization. This study aimed to explore accelerated eryptosis and accompanying biochemical alterations in CKD patients. A total of 106 CKD patients (59 predialysis [PreD] patients, 26 haemodialysis [HD] patients and 21 peritoneal dialysis [PD] patients) and a control group composed of 29 healthy volunteers were included in this study. Data on superoxide dismutase (SOD) activity (U/mL), annexin-V binding (mean fluorescent intensity, MFI) and intracellular calcium ([Ca2+]i; MFI) as well as the hematologic and biochemical parameters were recorded. The [Ca2+]i levels were 3.05 ± 1.66 MFI, 2.24 ± 0.99 MFI, 2.38 ± 0.87 MFI and 1.71 ± 0.46 MFI in the PreD, HD, PD and control groups, respectively. Other than significantly higher [Ca2+]i levels in the PreD group than in the control group (p < 0.001), no significant difference was noted between study groups in terms of [Ca2+]i. Annexin-V binding was 1.05 ± 0.99 MFI in PreD group, 1.15 ± 0.56 MFI in HD group, 1.06 ± 0.87 MFI in PD group, and 0.88 ± 0.86 MFI in controls. Annexin-V binding was significantly higher in PreD, HD and PD groups compared with the control group (p < 0.001 for each). SOD activity was 0.07 ± 0.07 in the PreD group, 0.13 ± 0.08 in the HD group, 0.14 ± 0.07 in the PD group, and 0.03 ± 0.01 in the control group. SOD activity in both HD and PD groups were significantly higher than control and PreD groups (p < 0.001 for each). Lower albumin, higher ferritin, and higher parathormon levels were found to be correlated with eryptosis biomarkers. Patients treated vs. non-treated with calcium channel blockers had significantly lower annexin-V binding levels (p = 0.013). Patients treated vs. non-treated with erythropoietin (EPO) had elevated annexin-V binding level (p < 0.001) and lower [Ca2+]i (p = 0.014). In conclusion, our findings revealed the presence accelerated eryptosis, as a potential contributing factor to development of anemia, in patients with CKD stages 3-5D. Inflamation and parathormon can also accelerate eryptosis. Favorable effect of CCB and EPO on eryptosis needs to be confirmed in larger scale studies.

Salivary Exosome Proteomics and Bioinformatics Analysis in 7,12-Dimethylbenz[a]anthracene-Induced Oral Cancer with Radiation Therapy-A Syrian Golden Hamster Model.

Exosomes carry cellular proteins and contain molecules that can be potential biomarkers of diseases. This study used a Syrian golden hamster model of 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral squamous cell carcinoma with radiation therapy to exclude the confounding factors that may affect outcomes in clinical studies, and re-examine the role of exosomes during tumorigenesis. We used data-dependent acquisition-based quantitative proteomics and bioinformatics analyses and found unique proteins present (desmocollin-2) or absent (Glucagon-cAMP-PKA-CREB pathway-related proteins) in the salivary exosomes of the pre-radiation DMBA-treated group (PreD). Comparing our data to other studies, salivary exosomes in the PreD group were found carrying proteins that the tumor mass does not express and lacking the proteins needed during tumorigenesis. Immunohistochemistry staining showed p53 expression but a negative apoptotic signal in the PreD tumor tissue. We thus suggest that inhibition of desmocollin-2 expression in tumor tissue may impede the activation of cell apoptosis. However, both the origin of the salivary exosomes and main role of the salivary exosome proteins should be clarified in future studies.

Integrative Analysis of Gut Microbiota and Fecal Metabolites in Rats after Prednisone Treatment.

ABSTRACTPrednisone (PRED) is a synthetic glucocorticoid (GC) widely used in immune-mediated diseases for its immunosuppressive and anti-inflammatory properties. The effects of GC are achieved by genomic and nongenomic mechanisms. However, the nongenomic effects are largely unknown. Thus, we aimed to investigate how long-term prednisone therapy changes the composition of the gut microbiota and fecal metabolites in rats. Male Sprague-Dawley rats were randomly assigned to a control (CON) group and a PRED group, which received prednisone treatment daily for 6 weeks by gavage. The V3 to V4 regions of bacterial 16S rRNA genes were amplified and sequenced after the total bacterial DNA was extracted from fecal samples. The alpha and beta diversities were calculated. The compositional alteration of the gut microbiota at different taxonomic levels was analyzed using the Metastats method. Meanwhile, the fecal metabolites were quantitated in an ultra-performance liquid chromatography system. Similar microbial richness and diversity between the CON and PRED groups were indicated by the alpha diversity results. The gut microbial communities differed significantly between two groups. The relative abundances of the genera Eisenbergiella, Alistipes, and Clostridium XIVb decreased, whereas that of Anaerobacterium increased significantly in rats after the 6-week prednisone treatment. In total, 11 downregulated and 10 upregulated fecal metabolites were identified. Differential fecal metabolites were enriched in the pathways, including phenylalanine metabolism, butanoate metabolism, and propanoate metabolism. The lowered production of short-chain fatty acids was associated with the decreased relative abundance of the genera Alistipes and Clostridium XIVb and increased abundance of the genus Anaerobacterium. The composition of the gut microbiota and fecal metabolites was changed after long-term prednisone treatment. This may help us to understand the pharmacology of prednisone.IMPORTANCE Prednisone is widely used in chronic glomerular diseases, immunological disorders, and rheumatic diseases for its anti-inflammatory and immunosuppressive properties. It is a synthetic glucocorticoid (GC) that shows therapeutic effects after conversion to prednisolone by the liver. Prolonged GC therapy causes anti-inflammatory effects; it also results in a variety of adverse events, including obesity, hypertension, psychiatric symptoms, and dyslipidemia. The therapeutic effects and adverse events of GCs may be associated with changes in the gut microbiota, as the host might be affected by the metabolites generated by the altered gut microbes. Thus, we investigated how long-term prednisone therapy changed the composition of the gut microbiota and fecal metabolites in rats. This study may shed new light on the pharmacology of prednisone.

Pre-dilatation prior to carotid artery stenting in very severe carotid artery stenosis: beneficial or detrimental?

Abstract Background There are many technical variations in carotid artery stenting and there is not a clear recommendation in pre-dilatation (Pre-D) prior to stenting. In this study we investigated the role of Pre-D before carotid artery stenting in patients with very severe carotid artery stenosis (≥90%). Methods A total of 298 patients with a carotid stenosis equal to or more than 90% were included to our study. Patients were divided into two groups as Pre-D and No-Pre-D. In-hospital and 3-year long-term clinical outcomes were compared between the groups. Results During the hospitalization, major stroke was more common in Pre-D group [n=6 (5.5%) vs. n=3 (1.5%), respectively], whereas overall ipsilateral stroke rates were similar between the groups. The rates of myocardial infarction were similar between the groups. In- hospital mortality was significantly higher in the Pre-D group than non-pre-D group [n=4 (3.6%) vs. n=0 (0%), respectively]. During the 3-year follow up period, the rates of ipsilateral stroke, major stroke, transient ischemic attack, myocardial infarction, and mortality were similar between the groups. Conclusion According to the literature, this is the first study evaluates the role of Pre-D in very severe (&amp;gt;90%) carotid artery stenosis. The current study demonstrated that Pre-D might have a detrimental effect on in-hospital outcomes. Funding Acknowledgement Type of funding sources: None.

Influence of Prednisone Treatment Before and During Pregnancy in Rats on Immunometabolic Biomarkers and Fetal Development

Prednisone is a glucocorticoid drug with free access and can negatively affect both the maternal immunometabolic profile and fetal development. The objective of this study was to evaluate the effects of prednisone treatment on the immunometabolic and reproductive profile, and maternal- fetal repercussions of rats. Adult female Wistar rats were distributed in groups: during no- pregnancy period (NPP), there were CONT group (n= 15, treated with vehicle) and PRED group (n=30, treated with 5mg/Kg prednisone). The treatment was oral and daily for 15 days. Following, the rats were mated, and with a positive pregnancy diagnosis, the pregnancy period (PP) was initiated (21 days), with CONT group (n=13, treated with vehicle), and the PRED group was subdivided: PRED1 group (n=14, treated with vehicle) and PRED 2 group (n=13, treated with 5mg/Kg prednisone). The body weight, food and water intake, oral glucose tolerance test (OGTT), serum immunometabolic parameters were measured, followed by maternal reproductive performance and fetal analyzes. The PRED2 group showed a glycemic drop at 60' of TOTG, IgG and leukocyte cells, in addition to an increase in triglycerides and aspartate aminotransferase. For reproductive indices, these rats showed a decrease in maternal weight gain and litter weight but increased placental efficiency and occurrences of skeletal and visceral anomalies. It is concluded that the administration of prednisone in both experimental periods induced changes in hepatic and metabolic functioning and maternal leukopenia, causing such changes to negatively influence to fetal development.

Gastrointestinal Side Effects of Triple Immunosuppressive Therapy Evaluated by AC Biosusceptometry and Electrogastrography in Rats.

Triple immunosuppressive therapy is associated with several gastrointestinal disorders. The aim of this study was to investigate the effects induced by the triple immunosuppressive therapy on the gastrointestinal tract of rats. Male Wistar rats were randomly assigned into three experimental groups: Control: filtered water; TAC + MPS + PRED: treated with Tacrolimus plus Mycophenolate Sodium plus Prednisone; and CSA + AZA + PRED: treated with Cyclosporine plus Azathioprine plus Prednisone. The treatment was done for 14 days by gavage. Gastric emptying and contractility were evaluated by the Alternating Current Biosusceptometry (ACB) and Electrogastrography (EGG). Histological, biochemical and hematological analyses were also performed. Gastric emptying time was slower in the CSA + AZA + PRED group in comparison with control (p<0.01) and TAC + MPS + PRED groups (p<0.001). Animals treated with TAC + MPS + PRED showed accelerated gastric emptying (p<0.05) compared to control. The amplitude of gastric contractions in both immunosuppressed groups was higher than observed in the control. The frequency of gastric contractions for the CSA + AZA + PRED group was also increased (p<0.01). Results obtained by EGG were similar to those recorded with the ACB. The thickness of the circular layer from stomach muscle decreased in both immunosuppressed groups, while the longitudinal layer was reduced only in the CSA + AZA + PRED group. Triple immunosuppressive therapy alters gastric motility, compromises the muscular layers and the association between CSA, AZA, and PRED provokes the major alterations in the structure and gastric function. Specific gastrointestinal side effects resulting from different immunosuppressive therapies still need to be elucidated in order to provide more effective and personalized therapy for patients.

Protein energy-wasting associated with nephrotic syndrome \u2013 the comparison of metabolic pattern in severe nephrosis to different stages of chronic kidney disease

BackgroundNephrotic syndrome (NS) is associated with a hypercatabolic state expressed as an exacerbated degradation of muscle mass. However, the clinical significance of this phenomenon has not yet been investigated.The aim of the study was to evaluate the nutritional status of patients with severe NS (defined as nephrotic range proteinuria with hypoalbuminemia ≤2.5 g/dL) and estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m2 in comparison to patients in different stages of chronic kidney disease (CKD).MethodsTwenty men with severe NS (NS group) and 40 men without proteinuria similar in term of serum creatinine (control group) were included into the study. A retrospective cohort of 40 men with CKD stage G4 (PreD group) and 20 haemodialysis men (HD group) were added to the analysis after matching for age, height and weight using propensity score matching. The bioimpedance spectroscopy and biochemical nutritional markers were evaluated.ResultsNephrotic patients had a significantly lower lean tissue mass (LTM; p = 0.035) and index (a quotient of LTM over height squared, LTI; p = 0.068), with an expected deficiency of LTM by 3.2 kg, and LTI by 0.9 kg/m2 when compared to the control group. A significant lean tissue deficit (defined as LTI below the lower limit of the reference range by 1.0 kg/m2) was observed in 12.5% of patients in the control group in comparison to 31.7% with advanced CKD (PreD+HD; p = 0.032) and 50% with NS (p = 0.003). NS group presented with higher phosphorus (p = 0.029), uric acid (p = 0.002) and blood urea (p = 0.049) than the control group. Blood urea was strongly negatively correlated with LTM in NS (r = − 0.64, p = 0.002). Nine nephrotic patients (45%) were identified as hypercatabolic based on severe hyperphosphatemia (> 5.0 mg/dL) and/or hyperuricemia (> 8.0 mg/dL), and were characterized by higher blood urea and lower prealbumin, as well as LTM lower by 5.6 kg than in less catabolic individuals.ConclusionsIn term of lean tissue amount, NS group was more similar to advanced CKD than to the control group. We concluded that specific metabolic pattern with elevated phosphorus, uric acid and blood urea, and lean tissue deficiency may be defined as protein-energy wasting associated with nephrotic syndrome (neph-PEW).

Alterations in the Urinary Microbiota Are Associated With Cesarean Delivery.

Similar to the gut, the bladder contains urinary microbiota, and its bacterial composition and structure are determined by the individual’s health status. Cesarean section is a traumatic event for women and it is correlated with postpartum complications. To better understand the urinary microbiota alterations caused by cesarean section, 16S rDNA sequencing was used to assess urine specimens collected by transurethral catheterization from 30 healthy women undergoing cesarean section pre-delivery (PreD) and post-delivery (PostD). A significant increase in bacterial diversity and more detectable bacteria at the phylum, family, and genus levels was observed in the PostD group compared to the PreD group, indicating that cesarean delivery (a process that includes surgery and delivery) altered the bacterial community. Specifically, the phylum Firmicutes and its affiliated family Lactobacillaceae and genus Lactobacillus dramatically decreased in the PostD group, suggesting that beneficial bacteria decreased after cesarean section, and clinicians should be aware that this might increase the risk of complications. Concurrently, the phylum Proteobacteria and its affiliated bacteria Pseudomonadaceae and Pseudomonas increased in the PostD group compared to the PreD group. This indicates that pathogen growth increases after cesarean section, making it important for clinicians to combat these changes to protect women from infectious diseases. Interestingly, several metabolic pathways, such as metabolism of energy, cofactors and vitamins were strengthened in the PostD group, whereas membrane transport was lessened in this group. This suggests that women’s metabolic disorders might be cured by balancing urinary microbiota. In conclusion, the altered urinary microbiota between the PreD and PostD periods appears to provide insight into how to prevent postpartum metabolic disorders.

Nutraceutical and Pharmaceutical Interventions Improve Fatigue Resistance in Dystrophic Skeletal Muscle

Progressive muscle injury and weakness are hallmarks of Duchenne muscular dystrophy (DMD), which is caused by the absence of functional dystrophin protein. Likewise, chronic muscle injuries are common in military personnel. We have previously shown PGC‐1α‐mediated protection of dystrophic muscle via gene transfer approaches, however, investigations using quercetin (Q) to activate the PGC‐1α pathway have been equivocal. Quercetin activates PGC‐1α through Sirtuin‐1, an NAD+‐dependent deacetylase, however, NAD+ may be depleted in dystrophic skeletal muscle. Therefore, the purpose of this investigation was to determine the extent to which supplementation with Q and nicotinamide riboside (NR), an NAD+ precursor, alone and in combination, improved function of dystrophic skeletal muscle. We hypothesized that the addition of Q or NR would improve diaphragm, soleus and extensor digitorum longus (EDL) muscle function, and when given in combination would cause synergistic effects. To address this hypothesis, muscle function from DBA (healthy), D2‐mdx (dystrophin deficient), and D2‐mdx mice fed Q (0.2% of diet), NR (400 mg/kg/d), and Q/NR was assessed. In addition, to mimic typical pharmacology of DMD patients an additional group was fed Q/NR and treated with prednisone (10 mg/L; Pred) and lisinopril (66 mg/L: Lis). Treatment was started at 4 mo of age under blinded conditions and ended upon tissue collection at 11 mo of age. Dystrophin deficiency impaired diaphragm specific tension and was not corrected by treatments, nor was fatigue resistance improved. In the EDL, dystrophin deficiency decreased resistance to contraction‐induced injury that was partially restored in the Q/NR/Lis/Pred group compared to untreated D2‐mdx. Specific tension in the EDL and soleus was decreased in dystrophic muscle and was not altered by treatments. Interestingly, Q, NR, and Q/NR increased soleus fatigue resistance through 1 min of a fatigue protocol compared to untreated dystrophic controls, but was similar thereafter (10 min). Fatigue resistance was increased throughout the fatigue protocol in the Q/NR/Lis/Pred group compared to D2‐mdx. This finding suggests that Q, NR or Q/NR may improve soleus glycolytic capacity resulting in sustained force production for the first minute of exercise and that the addition of Lis and Pred augments these effects. In total these data suggest that treatment with Q, NR, and Q/NR provide limited protection to dystrophic muscle that is enhanced by the addition of Lis/Pred. As many activities of daily living are completed within 1 min, increased fatigue resistance demonstrated herein, while modest, may decrease disease burden in DMD patients and in other chronic muscle injury conditions.Support or Funding InformationSupported by Parent Project Muscular Dystrophy, Ryan's Quest and Michael's Cause.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

P99. Use of high dose cortisosteroids in HELLP syndrome

Introduction Several reports have shown high levels of pro-inflammatory agents in maternal plasma in HELLP syndrome. Corticosteroids, as potent anti-inflammatory agents are maybe able to ameliorate inflammatory response and thereby positively influence the deterioration of disease. Even if several studies have showed a beneficial effect of corticosteroids in patients with HELLP syndrome, the possible effect of corticosteroids in HELLP syndrome is still under discussion. Objectives Corticosteroids in the management of HELLP syndrome has been introduced to our department in 2006. The therapeutic concept includes high-dose prednisolone administered one to three times. Background of this therapy is maximum impact; high dose; connected to the minimum of negative effects; no adrenal suppression and minimum of placental transfer. To evaluate the corticosteroid use at our department we analyzed the HELLP syndrome cases of the last 10 years. Methods Maternal and neonatal outcome in HELLP syndrome cases was analyzed in a retrospective study between 1st January 2005 and 31st December 2014. Data were presented in absolute numbers and percentages; statistic was performed using Chi square, Fisher’s exact test, independent T test and ANOVA calculation. A two-sided p-value of less than 0.05 was considered as significant. Results Pregnancies complicated by HELLP syndrome (n = 91) were divided in 3 groups: (1) PRED treated by high prednisolone administered one to three times (n = 61, 67.1%), (2) NO, receiving no corticosteroids (n = 18, 19.7%) and (3) MIX, received more than three doses and different types of corticosteroids (n = 12, 13.2%). The characteristics of the MIX group were different compared to the other groups: earlier gestational age at diagnosis, additional diseases and reasons with need of corticosteroid administration. The NO and PRED groups were similar regarding group distribution. Comparing NO with PRED group, there was a tendency (n.s.) to shorter intensive care and hospitalization times, decreased incidence of cesarean section and increased ratio of complete fetal lung maturation cycle in the PRED group. There were no differences between maternal morbidity or neonatal asphyxia. Conclusion The management of HELLP syndrome with a high dose prednisolone should be evaluated in a further prospective study. However, it seems that the use of high dose corticosteroids could improve the outcome of pregnancies complicated by HELLP syndrome. Adjustment of the therapy regime may be necessary in cases with very early HELLP syndrome before 25th week of gestation or additional morbidity. Due to the low placental transpass of prednisolone it can be advantageous over other corticosteroids in the use as HELLP syndrome therapy.

FP744COMPARISON OF DIFFERENT SEXUAL DYSFUNCTION SCALES IN FEMALES PATIENTS ON RENAL REPLACEMENT THERAPY

Introduction and Aims: Sexual dysfunction (SD) is commonly seen in the female dialysis population and is associated with depression and a lower quality of life. Although there have been many reports regarding the improvement of SD after kidney transplantation, those outcomes are not consistent. SD frequency in female patients has been evaluated with different scales in previous studies, and the ratios varies according to the used scales. In addition, there is no a study comparing several scales for SD in this population. This study aimed to investigate SD frequency with different scales, and risk factors in the females under renal replacement therapy and in the healthy ones. Methods: A total of 70 kidney transplant patients (Tx), 46 hemodialysis (HD) and 45 predialysis (PreD) patients and 54 healthy females were included into the study. Sociodemographic and risk factor survey forms, the hospital anxiety depression scale, the 36-Item Short Form Health Survey, Arizona Sexual Experiences Scale (ASEX), the Golombok Rust Inventory of Sexual Satisfaction (GRISS) and the Female Sexual Function Index (FSFI) were used. Results: Ages of the patients in the control and Tx groups were significantly lower than those of the HD and PreD groups. There were differences in the ratios of asthenia and fatigue, pelvic surgery, urinary incontinence, cystitis history, dyspareunia, smoking, use of antidepressant and beta blockers between the groups. The depression and anxiety ratios of the groups were similar. The physiological health scores of the control group were significantly higher than those of the PreD and Tx groups, and also scores of the Tx group than those of the HD and PreD groups. Mental health scores of the control group were significantly higher than those of the PreD and HD groups. The prevalence ratio for SD with ASEX in HD group (54.3%) was significantly higher than those of Tx (24.3%) and the control (25.9%) groups, and also the rate of PreD group (44.4%) than that of Tx. SD ratios of the groups with GRISS were similar. The SD ratio of Tx group with FSFI (16.1%) was significantly lower than that of HD group (41.9%). Logistic regression analysis showed systolic blood pressure, finding sexual information adequate and presence of anxiety with ASEX; age, presence of anxiety and education time of mother with GRISS; finding sexual information adequate, presence of anxiety and depression with FSFI as independent risk factors for SD. There were significant differences in all study population and Tx group between SD ratios with FSFI and GRISS. In all study population 15 persons had SD according to FSFI, but not to GRISS, and 31 persons had SD according to GRISS, but not to FSFI (p=0.026). According to FSFI, sensitivity of GRISS was 0.70, and specificity was 0.71. In Tx group 4 persons had SD according to FSFI, but not to GRISS, and 16 persons had SD according to GRISS, but not to FSFI (p=0.012). According to FSFI, sensitivity of GRISS was 0.60, and specificity was 0.69. Conclusions: As a result, different results were obtained when SD frequency and risk factors in the patients on renal replacement therapy were assessed with different scales in our study. Therefore, new scales in these patients should be developed and their reliability should be evaluated in larger patient groups. FP744 Table 1: The frequency of sexual dysfunction with different scales in the groups

Study of oxidative stress in patients with advanced renal disease and undergoing either hemodialysis or peritoneal dialysis

Oxidative stress (OS) is directly involved in the formation of atheroma plaque and has been shown to be present since the early stages of Chronic Kidney Disease (CKD); however, the net role that dialytica techniques may play in OS process is yet to be determined. We studied three groups: hemodialysis (HD, n = 30), peritoneal dialysis (PD, n = 31), predialysis (pre-D, n = 32), and one control group (C, n = 67). Using highresolution liquid chromatography columns (HPLC), the superoxide dismutase (SOD), glutathione oxidized/reduced ratio (GSSG/GSH), and nuclear, as well as mitochondrial 8-oxo-dG (8-oxo-dG mit) were measured in lymphocytes. Protein carbonyls and F2-isoprostanes were measured in plasma. The antioxidant enzyme activity was evaluated by a spectrophotometric assay of catalase, glutathione peroxidase (GPX), glutathione reductase (GSR), and superoxide dismutase (SOD). Compared to the control group, all groups had significantly higher levels of products derived from molecular oxidation with a significant decrease in antioxidant enzymes. Patients in the pre-D group showed higher values for most of the oxidized molecules. The PD group showed a better oxidative balance, with no significant differences in levels of mitochondrial 8-oxo-dG when compared to the control group. We speculated that the better control of OS observed in patients receiving PD might be explained by the fact that this technique is more biocompatible, and this might help reduce the risk of cardiovascular events.

Clinical Course of Steroid Sensitive Nephrotic Syndrome in Children: Outcome and Outlook

Introduction: The aim of our study was to investigate the relative efficiency and adverse effects of various treatments of steroid sensitive nephrotic syndrome (SSNS) in children, and to determine factors associated with relapse risk in these patients. Materials and Method: We retrospectively studied the data from 690 SSNS children treated in referral center over 25 years. The analyzed treatment protocols were: Prednisolone (PRED, eight weeks in a dose 1.5-2.0 mg/kg, then it tapering and given for 9-12 months), Chlorambucil (CHL, cumulative dose 28.5-30 mg/kg), Cyclophosphamide intravenously (CYC I.V., cumulative dose of 30-36 mg/kg, then supporting dose of CHL, cumulative dose of 20-25 mg/kg) and intramuscular (CYC I.M., cumulative dose of 120-150 mg/kg). The alkylating agents were used after remission induction by PRED and under its protection. Results: Cumulative relapse-free survival was 81.9%, 69.0% and 64.5% after 12, 36 and 60 months, respectively. In multivariate analyses, relapse risk was associated with age of treatment (<6 years), and both PRED and CYC I.V. The only predictive factor for early relapse was PRED, unlike two and more relapses group where PRED and CYC I.V. as well as age from 3 to 6 years was highly prognostic. The high probability of sustained remission in combination with relatively mild adverse effects was observed for PRED used at first episode and CHL used at relapse. Conclusion: To summarize, our protocols characterized by the prolonged PRED and CHL demonstrated promising results and should be considered as an efficient alternative strategy in SSNS management.

When Does the Cardiovascular Disease Appear in Patients With Chronic Kidney Disease?

Cardiovascular disease is a leading cause of long-term morbidity and mortality among children with chronic kidney disease (CKD). At which stage of CKD these appear in children is unknown. This study aimed to determine the prevalence of cardiovascular disease in pediatric CKD patients and to explore the relationship of these changes and treatment methods. The study enrolled pediatric patients with stages 1-5 CKD including 20 patients receiving predialysis (PreD), 8 receiving peritoneal dialysis, and 14 receiving hemodialysis. Aortic stiffness, defined as decreased aortic strain (S) and increased pressure strain normalized by diastolic pressure (Ep*), was described. Sonography of the common carotid artery and left ventricle was performed. The mean age of the children was 13.3 + or - 5.3 years. The patients had lower S values (0.35 + or - 0.23) than the control subjects (0.44 + or - 0.2) (P < 0.05) but higher Ep* (2.46 + or - 1.31 vs. 1.32 + or - 0.09; P < 0.05). Aortic stiffness was found in 13 patients. The PreD group had lower As levels than the dialysis group but higher levels than the control group. The patients (n = 32) had greater carotid intima-media thickness than the control subjects (0.58 + or - 0.14 vs. 0.35 + or - 0.12; P < 0.05). The intima-media thickness was greatest in the PreD group (P < 0.05). The patients had a higher left ventricular mass index (LVMI; 42.4 + or - 15.6) than the control subjects (28.8 + or - 8.47) (P < 0.05) and a larger left ventricle end diastolic diameter (LVEDD; 3.44 + or - 0.76 vs. 2.59 + or - 0.34; P < 0.05). Left ventricular hypertrophy was found in 32 patients. Both LVMI and LVEDD were higher in the groups receiving hemodialysis and lower in the PreD group. Increased carotid-intima media thickness and left ventricle hypertrophy appeared without hypertension in the PreD group. The indications and timing of dialysis should be reevaluated for children with CKD. In the dialysis groups, fewer cardiovascular changes were found with peritoneal dialysis than with hemodialysis. Therefore, peritoneal dialysis should be preferable to hemodialysis for children with CKD.

Assessment of female sexual function and quality of life in predialysis, peritoneal dialysis, hemodialysis, and renal transplant patients

Chronic renal failure (CRF) and renal replacement treatments have a negative effect on sexual function and quality of life (QoL). The literature on female sexual dysfunction (FSD) in patients with CRF is limited. The aim of this study is to compare the sexual function and QoL in predialysis (PreD), dialysis, and transplant patients. A total of 106 women including 21 PreD, 45 dialysis, 20 renal transplantation (Tx), and 20 control patients were enrolled in the study. The Female Sexual Function Index (FSFI) and SF-36 scales were used to assess all patients, and demographic and clinical variables were documented. The FSFI and QoL scale scores were compared among the groups. The rates of FSD were 50, 81, 66.7, 75, and 50% in the control, PreD, peritoneal dialysis (PD), hemodialysis (HD) and Tx patients respectively. Total FSFI scores for desire, arousal and orgasm scores in the PreD group were significantly lower than those in Tx and control patients (P < 0.05). Physical components of QoL in CRF patients were significantly worse than in the control group (P < 0.0001). On logistic regression analysis, age, glucose and creatinine were significantly associated with FSD. This preliminary study documented that Tx is the most effective way to retain good sexual function in women, and a diagnosis of FSD should be made routinely in CRF patients.