AAP Group Research Articles

COMPARATIVE CHARACTERISTICS OF THE INFORMATIVENESS OF THE LAL TEST AND PROCALCITONIN IN THE DIAGNOSIS OF INFECTIOUS COMPLICATIONS IN ACUTE ALCOHOLIC PANCREATITIS

Acute pancreatitis (AP) is an inflammatory condition of the pancreas, characterized by acute, intense abdominal pain. AP accounts for 20-30% of hospitalizations due to abdominal symptoms. The incidence of AP is increasing globally by 2-5% annually, ranging from 3.4 to 73.4 cases per 100,000 people. A critical concern in AAP is the potential development of infectious complications, which may require surgical intervention and increase mortality rates. Effective management and monitoring of these complications are essential. Research Justification. The diagnosis of AAP in clinical practice commonly relies on serum levels of α-amylase, lipase, C-reactive protein, and leukocyte counts. However, these markers have limitations and do not fully reflect the level of intoxication. The accuracy of C-reactive protein as a marker is not well established and is used mainly as a prognostic indicator. Serum α-amylase levels tend to decrease sharply after the fifth day of illness, regardless of the patient's condition. Lipase levels in diabetic patients can exceed reference values even without pathology, necessitating adjustments for AAP diagnosis. These criteria are most effective during the enzymatic phase of AAP (days 1-5). To predict the course of AAP and assess the adequacy of therapy, as well as to determine the need for surgical intervention, serum procalcitonin levels are commonly used. However, some studies question the diagnostic accuracy of procalcitonin, particularly regarding its correlation with organ failure, infectious complications, and patient mortality. Materials and Methods: This study involved 55 AAP patients, 51 men (92.7%) and 4 women (7.3%), with an average age of 49.49±9.87 years. Patients were categorized based on the severity of their condition: moderate (39 patients, 70.9%) and severe (16 patients, 29.1%). The control group consisted of 10 healthy individuals (9 men, 90.0%; 1 woman, 10.0%; average age 45.22±7.55 years). AAP was classified according to the Atlanta classification of acute pancreatitis. The study included patients with moderate to severe AAP who were hospitalized within 48 hours of symptom onset. All patients received treatment according to clinical guidelines, including intensive fluid therapy with Ringer's lactate. The Limulus Amebocyte Lysate (LAL) test and procalcitonin levels were measured on days 5, 8, 11, and 14 of hospitalization. For suspected infected necrosis, patients underwent contrast-enhanced computed tomography (CT) on day 14, with fine-needle aspiration biopsy or surgical intervention if necessary. Results. On day 5, LAL test values in the moderate and severe AAP groups were within reference ranges, and procalcitonin levels did not exceed 0.5 ng/ml. By day 14, a significant increase in LAL test values was noted in both groups, with a corresponding rise in procalcitonin levels. The ROC analysis for LAL test values on day 14 in the moderate AAP group showed an area under the curve (AUC) of 0.966, with 92.86% sensitivity and 96% specificity. For procalcitonin, the AUC was 0.723, with 71.43% sensitivity and 92% specificity. Conclusion. The LAL test is a sensitive and specific marker for detecting endotoxemia and monitoring the progression of AAP, particularly in predicting the development of infectious complications. The study demonstrates that LAL test values significantly correlate with the severity of AAP and may provide better diagnostic accuracy than procalcitonin, especially in the later stages of the disease.

Diversity in Acute Autoimmune Pericarditis: Nationwide Analysis of In-Hospital Outcomes and Recurrence

BackgroundAcute autoimmune pericarditis (AAP) is an uncommon disease with diverse etiology. Data regarding AAP diagnosis and outcomes are scant. ObjectivesThis study sought to describe the diagnosis and the rates of in-hospital mortality, cardiac tamponade, and readmission of AAP. MethodsThis study used a nationwide Japanese claim-based database to identify patients with AAP from April 2016 to March 2020 compared with patients with acute idiopathic pericarditis (AIP). ResultsOf 20,469 hospitalized patients with acute pericarditis, 170 had AAP and 5,027 had AIP of new onset. The diagnosis for AAP was systemic lupus erythematosus in 23.5% (40 of 170), rheumatoid arthritis in 19.4% (33 of 170), systemic sclerosis in 8.2% (14 of 170), other in 17.7% (30 of 170), and undifferentiated in 31.2% (53 of 170). During hospitalization, 1.8% (3 of 170) of patients with AAP and 1.5% (73 of 5,027) of patients with AIP died, and cardiac tamponade occurred in 8.8% (15 of 170) of AAP patients and 4.7% (237 of 5,027) of AIP patients. The incidence of cardiac tamponade was highest in patients with systemic lupus erythematosus (15.0%; 6 of 40). AAP was more associated with cardiac tamponade than AIP (adjusted OR: 1.82; 95% CI: 1.02-3.23). There was no difference between the AAP and AIP groups with regard to rehospitalization, although this was more common in patients with undifferentiated forms of autoimmune disease (P = 0.001). ConclusionsThis Japanese national registry study of acute pericarditis revealed no differences in rehospitalization for recurrence between patients with AAP and AIP. It also underscored the diversity in AAP diagnosis, with more than 30% of patients lacking a differentiated diagnosis.

Effects of Acetaminophen on the Reproductive Parameters and the Ameliorative Effects of Rutin and Mesenchymal Stem Cells in Male Rats

The present study has been designed to evaluate the effects of acetaminophen on the reproductive parameters and the ameliorative effects of rutin and Mesenchymal stem cells in male rats. The rats were divided into two studies: firstly, twenty young male rats were used as a source of bone marrow-derived MSCs. Secondly, fifty adult male rats were divided into 5 groups: Control group (G1); rats were administrated of AAP (750 mg/kg b.w.) every 72h for 21 days, then left for 30 and 60 days without treatment (G2), rats were administrated of AAP for 21 days then treated with RT (25mg/kg b.w/d) for 30 and 60 days (G3), rats were administrated of AAP for 21 days then the rats were injected by BM-MSCs (1.5x 106 cells in 0.5 PBS) in the tail vein for 30 and 60 days (G4), and rats were administrated of AAP for 21 days then the rats were injected by BM-MSCs in the tail vein, then treated with RT for 30 and 60 days (G5). Administration of AAP produced a significant decrease in the mean value of the Te, LH, and FSH levels after 30 and 60 days as compared to the C groups. Whereas rats treated with RT and MSCs showed a significantly high increase in the mean values of these hormone levels after 30 and 60 days compared with the AAP group. In conclusion, this study demonstrated that RT and MSCs when treated in combination, are protected against the AAP-induced decrease in the hormone level of testicular.

Clinical Characteristics and Outcomes of Aortic Arch Emergencies: Takayasu Disease, Fibromuscular Dysplasia, and Aortic Arch Pathologies: A Retrospective Study and Review of the Literature.

In this study, 82 (1.07%) consecutive patients with NA-AAPs (including 38 TAKs, 26 FMDs, and 18 other AAPs) out of 7645 patients who underwent endovascular treatment (EVT) for the aortic arch and its side-branch diseases at a single institution between 2002 and 2022 were retrospectively reviewed. The recorded demographic, biochemical, diagnostic, operative, and postoperative factors were reviewed, and the functional outcomes were determined during follow-up. A systematic review of the literature was also performed. The study group comprised 65 (79.3%) female and 17 (21.7%) male subjects with a mean age of 46.1 ± 14.9 years. Overall, 62 (75.6%) patients were diagnosed with either cerebral ischemia symptoms or aortic arch dissection on admission. The EVT was feasible in 59 (72%) patients, whereas 23 (28%) patients were referred for medical treatment. In EVT patients, severe periprocedural complications occurred in two (3.39%) patients, including one periprocedural death and one cerebral hyperperfusion syndrome. During a median follow-up period of 64 months, cardiovascular events occurred in 24 (29.6%) patients (5 deaths, 13 ISs, and 6 myocardial infarctions). Repeated EVT for the index lesion was performed in 21/59 (35.6%) patients, including 19/33 (57.6%) in TAK and 2/13 (15.4%) in FMD. In the AAP group, one patient required additional stent-graft implantation for progressing dissection to the iliac arteries at 12 months. A baseline white blood count (odds ratio [HR]: 1.25, 95% confidence interval [CI]: 1.11-1.39; p < 0.001) was the only independent prognostic factor for recurrent stenosis, while a baseline hemoglobin level (HR: 0.73, 95%CI: 0.59-0.89; p = 0.002) and coronary involvement (HR: 4.11, 95%CI: 1.74-9.71; p = 0.001) were independently associated with a risk of major cardiac and cerebral events according to the multivariate Cox proportional hazards regression analysis. This study showed that AAPs should not be neglected in clinical settings, as it can be a life-threatening condition requiring a multidisciplinary approach. The knowledge of prognostic risk factors for adverse outcomes may improve surveillance in this group of patients.

Protective Impact of Flaxseed Oil against Acetaminophen-Induced Nephrotoxicity in Rats: Antioxidant and Anti-inflammatory Pathway

Acetaminophen (AAP) is a commonly analgesic found in numerous non-prescription pharmaceuticals. High dose and chronic ingestion of AAP caused renal toxicity. This study is designed to assess the possible nephroprotective role of flaxseed oil (FSO) in male rats. Nephrotoxicity was induced in rats via ingested a single dose of AAP (3 g/kg). Five groups of rats were used; Control, AAP, FSO (1.5 ml/kg) + AAP, FSO (3 ml/kg) + AAP, and FSO (4.5 ml/kg) + AAP. Rats were received orally FSO for 30 days and at the 30th day received AAP 1 h before FSO. Serum renal function indices were determined. Also, antioxidants, oxidative stress, and pro-inflammatory cytokines indices were measured in serum. Ingestion of FSO (3 and 4.5 ml/kg) prior to AAP intoxication significantly decreased AAP-induced nephrotoxicity as evidenced by significant decrease in renal functions relative to the AAP group. Prevented the oxidative stress as evidenced by significant increases in SOD and GSH levels, concurrent with a significant decline in MDA level. Besides, there were significant decreases in IL-1α and TNF-α relative to the AAP group. FSO (3 and 4.5 ml/kg) preserved the renal parenchyma, glomerulus and tubules histological features induced by AAP. FSO (4.5 ml/kg) was markedly the most effective dose relative to the two other doses. In conclusion, FSO protects AAP-induced renal toxicity in a dose dependent manner via its potent antioxidant and anti-inflammatory activities.

Evaluation of the Efficacy of COVID-19 Booster Vaccinations in Healthcare Personnel

This study aimed to investigate the efficacy of different COVID-19 booster vaccines by measuring the serum antibody titer. SARS-CoV-2 anti-nucleocapsid protein antibody (N-Ab), anti-spike protein antibody (S-Ab), and neutralizing antibody (Neut.Ab) were measured before and 4-6 weeks after booster vaccinations in healthcare personnel with a previous vaccination within 3-6 months. Personnel who previously received two doses of ChAdOx1 vaccine or two doses of BNT162b2 vaccine received the BNT162b2 vaccine (AAP and PPP groups, respectively). Personnel who previously received two doses of mRNA-1273 received the same vaccine as a booster dose (MMM group). Of the 917 participants, the AAP, MMM, and PPP groups comprised 837 (91.3%), 27 (2.9%), and 53 (5.8%) participants, respectively. The pre-booster S-Ab and Neut.Ab titer were significantly lower in the AAP group. After the booster vaccination, all participants were positive for S-Ab and Neut.Ab; furthermore, the S-Ab and Neut.Ab titer significantly increased in all three groups, although the post-booster S-Ab was lower in the AAP group than in the other groups. The post-booster Neut.Ab titer showed no significant difference among the groups. Our study's results suggest that booster vaccination, after two prior vaccinations, shows a significant effect regardless of the type of vaccine administered.

Interaction between live vaccines for coccidiosis and phytogenic compounds in the diet of broilers.

This study aimed to determine whether live vaccines alone or associated with phytogenic compounds supplied via feed could improve performance, intestinal health, serum biochemistry, and coccidiostatic action in broilers up to 42days of age, challenged with Eimeria spp., compared with a traditional anticoccidial program. We used 800 birds divided into five treatments of eight repetitions each (n=20): NC - Negative control (absence of additives in the feed and without coccidian challenge); PC - Positive control (absence of additives and with coccidian challenge at 21days); AAP - Anticoccidial additives program, including salinomycin and nicarbazine, with coccidian challenge at 21days of life; VAC - Vaccination on day 1 of life (Hipracox HIPRA®) against coccidiosis and subsequent coccidian challenge at 21days; VAC+BPC - Vaccination (day 1 of life), the addition of 200ppm of blend phytogenic compound (BPC) based on carvacrol and cinnamaldehyde to the diet, with coccidian challenge at 21days of life. The birds in the AAP group more significant weight gain and greater body weight at 21days than the NC and 42days of age than the NC and VAC+BPC groups. The excretion of Eimeria oocysts in the excreta of birds was higher in PC than in NC, and in the litter, PC had higher counts than NC, AAP, and VAC+BPC. A higher mean score of intestinal lesions for Eimeria acervulina was observed in VAC and VAC+BPC birds, while for Eimeria maxima, the highest score was found in PC. Higher serum levels of total protein due to the increase in globulins were observed in birds of AAP and VAC than NC. Our findings suggest that vaccination for coccidiosis shortly after the birth of chicks allows performance similar to the conventional coccidiosis control program via diet.

Evaluation of Oxidative Stress potential of some Nsaıds against Hydrogen Peroxide in experimental animal

Background: Oxidative stress is imbalance between aggressive and defensive system. Overproduction of oxidative stress contribute in pathogenesis of many diseasesincluding Parkinsonism, Alzheimer diseases, apoptosis, hepatic fibrosis ,chronic kidney failure and liver steatosis etc . There are several OTC drugs including NSAIDs that generate oxidative stress when administered. So there is a need to explore about these drugs. Therefore this study was designed to evaluate the oxidative stress potential of Acetaminophen, acetyl salicylic acid and Celecoxib NSAIDs. Objective: The present study is design to investigate the oxidative stress of NSAIDs of acetaminophen, aspirin and Celecoxib drug with reference to the hydrogen peroxide. Material and method: The Experimental protocol was designed for estimate the level of oxidative stress in NSAIDs treated animals against hydrogen peroxides. Animal of control group received only vehicle throughout experimental protocol. Rats of AAP group, ASA group ,CX group were exposed to acetaminophen (150mg/kg; orally) acetyl salicylic acid (300mg/kg ;orally) and Celecoxib (50mg/kg; orally) for forty two days . Rodent of HP group were challenged with Hydrogen peroxides (0.5%) with same schedule as above. At end of experimental protocols, all the animals were sacrificed and their organ were identified and collected for oxidative stress estimation and histological examination. Result: NSAIDs administration caused increase in oxidative stress measured in terms of SOD, CAT, MDA, GSH and GPx. HP administration produced maximum oxidative stress compare to all other groups. Oxidative parameter i.e. SOD, CAT, GSH and GPx were found to be decreased as compare to control rats. However MDA were found to be increased as compare to control rats. Additionally, CX produced less oxidative stress compare to other NDAIDs. Further, histological examinations support the biochemical results. Conclusion: From the above observations it can be concluded that NSAIDs have oxidative stress potential and generate oxidative stress and damage the organs when administrated chronically. Thus, these drugs should be used judiciously.

S0104 Diagnostic Trends and Clinical Course of Non-Gallstone Non-Alcohol-Associated Acute Pancreatitis Within a Large Health System

INTRODUCTION: Acute pancreatitis (AP) is a leading gastrointestinal cause of hospitalization in the United States. Up to two-thirds of cases are related to alcohol use (AAP) or gallstones (GAP). There is limited data on the prevalence, patient characteristics and severity of non-biliary-non-alcohol-associated AP (NNAP). We analyzed and contrasted real-world diagnostic trends and clinical outcomes of NNAP with AAP and GAP within a large multi-state health system. METHODS: ICD-10 codes for AP were used to identify adult patients presenting to emergency departments (ED) within the MedStar Health system between March 2015 and June 2019. These included ED visits and inpatient admissions. Manual review yielded 2542 charts with complete clinical information, 1212 of which have AP as defined by Revised Atlanta Classification (RAC) and documented etiologies as either GAP, AAP or NNAP. Charts with unknown etiology or idiopathic were excluded. GAP, AAP and NNAP groups were then compared for the following characteristics and outcomes: patient age, lipase, presenting symptoms, imaging received, workup of etiology, treatment variables, complication rate, readmission rate and length of stay. Statistical analysis was performed using GraphPad PRISM. RESULTS: A total of 1903 patients met RAC for AP and 690 patients were excluded due to having unknown or idiopathic etiology in documentation. The prevalence of NNAP was 10.7% and these patients were more likely to have elevated lipase (OR 1.65, P < 0.02) and AP defined by RAC (OR 2.01, P < 0.0001) compared to patients with GAP and AAP. Incidence of workup was higher in the NNAP group (OR 4.81, P < 0.0001). Drug-induced (DI, 37.6%), hypertriglyceridemia (TG, 21.7%) and anatomic abnormality (14.3%) were the 3 most common etiologies in patients with NNAP (Figure 1). Compared to GAP and AAP, the NNAP group was more likely to require ICU level of care (OR 1.88, P = 0.02), experience complications (OR 1.57, P = 0.02) and be readmitted within 30 days (OR 2.02, P = 0.0025). Length of stay was significantly longer for patients with NNAP compared to GAP and AAP (6.1 vs. 4.6 vs. 3.8 days, P = 0.0001; Figure 2). CONCLUSION: Patients with NNAP experienced higher morbidity, readmission rate and longer hospital stay. DI, TG and anatomic abnormality were the most common causes. This is an unique subset of patients who require closer monitoring and appropriate targeted therapies.Figure 1.: Etiologies of patients with acute pancreatitis other than gallstone or alcohol.Figure 2.: The average length of stay of patients with NNAP was significantly longer than that of patients with GAP and AAP (P < NNAP = non-gallstone-non-alcohol-associated acute pancreatitis GAP = gallstone-associated acute pancreatitis AAP = alcohol-associate acute pancreatitis.

Atypical presentation of acute pancreatitis: a single center case-match analysis of clinical outcomes.

Acute pancreatitis (AP) may present an aspecific clinical picture without abdominal symptoms (atypical AP). We compared clinical outcomes between typical and atypical AP. Thirty out of 1163 patients (2.6%) presented an atypical AP. Demographic, clinical data, laboratory and radiological findings, management type, length of hospital stay (LOS) and mortality rate were retrospectively reviewed. A case match analysis 2:1 was performed. The final groups comprised 50 typical APs (TAP group) and 25 atypical APs (AAP group). The AAP patients presented fever (36%), syncope (32%) and dyspnea (16%) as the most frequent symptoms. Laboratory values showed similarity between the two groups. We noted a comparable edematous AP rate in both groups (p=0.36). Ten (20%) TAP and 3 (12%) AAP patients needed ERCP, respectively (p=0.38). Cholecystectomy was similarly performed in both cohorts (p=0.81). One TAP patient underwent a percutaneous drainage and subsequent surgical necrosectomy compared to none in the AAP cohort (p=0.47). LOS and mortality rate were comparable (p=0.76 and 0.3, respectively). Similar outcomes have been reached in the two groups. Routine evaluation of the serum amylase values fundamentally contributed to early diagnosis and appropriate treatment.

Skeletal muscle DNA methylation modifications and psychopharmacologic treatment in bipolar disorder

Both severe mental illness and atypical antipsychotics have been independently associated with insulin resistance and weight gain. Altered regulation of skeletal muscle DNA methylation may play a role. We aimed to evaluate DNA methylation modifications in human skeletal muscle samples to further understand its potential role in the metabolic burden observed in psychiatric patients and psychopharmacologic treatment. Subjects were included in our study if they had a bipolar diagnosis and were currently treated with a mood stabilizer or atypical antipsychotic. A healthy control group free of psychiatric or physical disease was also included for comparisons. Anthropometric, BMI and hemoglobin A1C (HbA1C%) were measured. Fasting skeletal muscle biopsies were obtained and methylation levels of 5-methycytosine (5-mC), 5-hydroxymethylcytosine (5-hmC) and 5-formylcytosine (5-fC) were measured. Skeletal muscle global methylation of 5-mC and 5-fC were significantly higher in bipolar subjects compared to healthy controls. 5-mC was significantly higher in the AAP group compared to the mood stabilizer group. Significant correlations were observed between 5-fC methylation and HbA1C%. Our findings suggest that psychiatric disease and treatment may influence some methylation measures in the skeletal muscle of patients with bipolar disorder, which may be further influenced by medication treatment.

Impact of hormone-therapy used in CRPC patients: Evaluation of abiraterone acetate/prednisone or enzalutamide on activity and cognitive functions in aged castrated mice.

e16526 Background: Prostate cancer (PC) is a major public health problem and represents the most frequent cancer in elderly male patients. Although most patients initially respond to androgen deprivation therapy (ADT) through inhibition of gonadal testosterone biosynthesis, the majority of these patients will progress to metastatic castration-resistant PC (mCRPC). Novel oral agents targeting androgen signaling axis, abiraterone acetate (AA)+prednisone (P) and enzalutamide (ENZ) are available and used in mCRPC patients in addition to ADT, but their impact on cognition is not well understood. Recently, the AQUARiUS study (Thiery-Vuillemin et al., ESMO Open, 2018) showed that after treatment, median Quality of life score improved with AAP. Additionally, results from a phase 2 trial showed that a worsening of depression symptoms were more often detected in ENZ- than in AAP-treated patients (Khalaf et al., Eur Urol, 2018). Methods: Here we developed a preclinical animal model to clarify the potential impact of AAP or ENZ on emotional reactivity and cognitive functions including spontaneous activity, anxiety-like and depression-like behaviors or spatial memory and learning. Results: In aged castrated mice receiving per os vehicle or AAP or ENZ, we showed that, in contrast to AAP, exposure to ENZ reduced spontaneous activity and increased depressive-like behaviors. AAP-treated mice displayed diminished self-grooming suggesting lower arousal in a novel environment. None of the treatments provoked anxiety-like behavior, learning and memory deficits. However, the swimming strategies (Morris-water maze) in AAP and ENZ groups were slightly altered. Analysis of plasma from treated mice revealed a detectable level of corticosterone only in AAP group. Conclusions: These data establish the impact of ENZ on emotional reactivity and of both ENZ and AAP on subtle cognitive functions in castrated aged male subjects. It paves the road for future effective research that could lead to better management of quality of life in mCRPC.

The Preventive Effects of Standardized Extract of Zataria multiflora and Carvacrol on Acetaminophen-Induced Hepatotoxicity in Rat: - Zataria multiflora and Carvacrol and Hepatotoxicity.

ObjectivesThe hepatotoxicity induced by Acetaminophen (AAP) mostly mediated by effect on oxidative stress parameters. The Zataria multiflora (Z.M) is an herbal medicine with well-known antioxidant effect. The aim of this study is investigation of preventive effects of Z.M and Carvacrol (CAR) on AAP-induced hepatotoxicity in rats.MethodsRats were randomly divided into four groups including: 1) Control, 2) Acetaminophen (AAP), 3) and 4) CAR. The saline, Z.M (200 mg/kg) and CAR (20 mg/kg) were administrated orally for 6 days, after that AAP (600 mg/kg) was administrated in the 7th day. Blood sampling was performed on the first and last days. Also, the liver tissue was removed for evaluation of Malondyaldehide (MDA), Thiol content, Superoxide dismutase (SOD) and Catalase (CAT). Total Protein (tPro), Glutamic Oxaloacetic Transaminase (GOT), Glutamic Pyruvic Transaminase (GPT) and Alkaline Phosphatase (ALP) in liver tissue were evaluated. The changes (Δ) of enzymes activities were presented.ResultsThe Δ GOT, Δ GPT and Δ ALP in CAR group significantly decreased compared to AAP group (P < 0.01 to P < 0.001) and Δ GPT in Z.M group was significantly reduced in comparison with AAP group (P < 0.05). Also, MDA, Thiol, SOD and CAT levels in treated groups were attenuated compared to AAP group (P < 0.05 to P < 0.001).ConclusionZ.M and CAR have a powerful hepatoprotective effect. CAR is more effective than Z.M. Based on the results. Z.M and CAR could be potent supplementary agents against hepatotoxicity of AAP in patients.

Immunomodulatory effect of Artemisiaargyi polysaccharide on peripheral blood leucocyte of broiler chickens.

This study was conducted to investigate the immunomodulatory effect of a water-soluble polysaccharide extracted from Artemisiaargyi (AAP) in vitro. The effect was assessed in peripheral blood leucocytes (PBLs) of broilers, which were incubated with different AAP concentrations (0, 25, 50, 100, and 200μg/ml) for 24hr at 37°C in a 5% CO2 incubator. The results showed that, compared with the control group, immunoglobulin M (IgM) concentration was increased in the supernatant of the 100μg/ml AAP-treated group (p<.05), and immunoglobulin G (IgG) concentration was increased in the supernatant of the 200μg/ml of AAP group (p<.05). In terms of cytokine production, production of interleukin-1beta (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in the supernatant was enhanced in the AAP group in a dose-dependent function, as well as enhanced mRNA expressions were showed in the cells (p<.05). The highest concentration of these three cytokines was observed in different AAP groups (IL-1β for 25μg/ml of AAP, IL-6 for 100, and 200μg/ml of AAP, and TNF-α for 100μg/ml of AAP respectively). The concentration of nitric oxide(NO) was increased when using AAP at the concentration of 100μg/ml (p<.05) as compared to the control group. No significant effects on inducible nitric oxide synthase, Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 and nuclear factor Kappa B (NF-κB) mRNA level were observed at each concentration of AAP. In conclusion, we found that AAP can specifically promote the production of immunoglobulins (IgM and IgG), cytokines (IL-1β, IL-6 and TNF-α), as well as the NO concentration in vitro, but not through the activation of the TLR4/NF-κB signalling pathway.

Efficacy and safety of abiraterone acetate (AA) and low-dose prednisone (P) in Japanese patients with newly diagnosed, metastatic, hormone-naïve prostate cancer (mHNPC): Subgroup analysis of LATITUDE trial.

286 Background: Patients with high-risk mHNPC have a poor prognosis. In Japan, mHNPC accounts for approximately 10% of newly diagnosed prostate cancers. AAP was approved for the treatment of castration-resistant prostate cancer in Japan in July 2014. We now report the clinical benefit of AAP with ADT in Japanese patients with newly diagnosed, high-risk mHNPC. Methods: Interim analysis of the multinational, randomized, double-blind, placebo-controlled, phase 3 study, LATITUDE, was previously reported at ASCO2017. We evaluated the superiority of AA 1g + P 5 mg + ADT (AAP group) to ADT+PBOs of AA and P (P group) in mHNPC with ≥ 2 of 3 risk factors (Gleason ≥ 8, ≥ 3 bone lesions, measurable visceral metastases) for the subgroup of Japanese patients. Results: Of 1199 total patients in LATITUDE trial, 70 patients were Japanese (AAP group, n = 35; P group, n = 35). The hazard ratio (HR) for overall survival in the AAP group versus the P group was 0.635 (95% confidence interval [CI], 0.152 to 2.659) and HR for radiographic progression-free survival was 0.219 (95%CI, 0.086 to 0.560). The incidence of adverse events (AE) was 97% (34/35) in both groups. AEs that occurred in the AAP group at a frequency ≥10% compared with the P group included hypertension, hypokalemia, rib fracture, hematuria and hyperbilirubinemia. The incidence of Grade 3 and 4 AEs was 66% in the AAP group and 20% in the P group. As a whole, efficacy and safety of Japanese patients in LATITUDE were shown to be consistent with those of overall population. Conclusions: AAP has shown a favorable risk/benefit balance and may serve as a new treatment option to improve the prognosis of Japanese mHNPC patients with high-risk prognostic factors. Clinical trial information: NCT01715285.

Real-world outcomes in second-line treatment of metastatic castration-resistant prostate cancer (mCRPC): The Prostate Cancer Registry.

5028 Background: The Prostate Cancer Registry is a prospective, international observational study that began in June 2013 and will assess the characteristics and management of &gt; 3000 mCRPC patients (pts) in routine clinical practice for ≤ 3 years. Methods: Data were collected from men with mCRPC irrespective of treatment (tx). This interim analysis reports baseline characteristics, txs and outcomes in pts with ≥ 12-month follow-up receiving second-line mCRPC tx following docetaxel as the only prior mCRPC tx. Results: The most commonly initiated second-line mCPRC txs (n ≥ 50) were abiraterone acetate + prednisone (AAP, n = 177), enzalutamide (ENZ, n = 94), or cabazitaxel (CAB, n = 70). Characteristics and outcomes are shown in the table below. TTP was not significantly different for AAP vs ENZ, AAP vs CAB or ENZ vs CAB (propensity score adjusted p = 0.5954, p = 0.5888 and p= 0.4808, respectively). Conclusions: In this real-world study, clinical outcomes reveal that, in pts receiving second-line mCRPC tx after docetaxel, TTP was similar across tx groups; QoL improved most in AAP and ENZ groups and no deterioration was observed most in AAP and CAB groups. Clinical trial information: NCT02236637. [Table: see text]

Chemically induced hepatotoxicity in human stem cell-induced hepatocytes compared with primary hepatocytes and HepG2.

Stem cell-induced hepatocytes (SC-iHeps) have been suggested as a valuable model for evaluating drug toxicology. Here, human-induced pluripotent stem cells (QIA7) and embryonic stem cells (WA01) were differentiated into hepatocytes, and the hepatotoxic effects of acetaminophen (AAP) and aflatoxin B1 (AFB1) were compared with primary hepatocytes (p-Heps) and HepG2. In a cytotoxicity assay, the IC50 of SC-iHeps was similar to that in p-Heps and HepG2 in the AAP groups but different from that in p-Heps of the AFB1 groups. In a multi-parameter assay, phenotypic changes in mitochondrial membrane potential, calcium influx and oxidative stress were similar between QIA7-iHeps and p-Heps following AAP and AFB1 treatment but relatively low in WA01-iHeps and HepG2. Most hepatic functional markers (hepatocyte-specific genes, albumin/urea secretion, and the CYP450 enzyme activity) were decreased in a dose-dependent manner following AAP and AFB1 treatment in SC-iHeps and p-Heps but not in HepG2. Regarding CYP450 inhibition, the cell viability of SC-iHeps and p-Heps was increased by ketoconazole, a CYP3A4 inhibitor. Collectively, SC-iHeps and p-Heps showed similar cytotoxicity and hepatocyte functional effects for AAP and AFB1 compared with HepG2. Therefore, SC-iHeps have phenotypic characteristics and sensitivity to cytotoxic chemicals that are more similar to p-Heps than to HepG2 cells.

PH-Dependent synthesis of two new lead(II) coordination polymers with 4-aminoantipyrine and 5-nitroisophthalate ligands

Two novel lead(II) coordination polymers with the same mixed ligands, [Pb(AAP)(NIP)]n (I) and {[Pb(AAP)(NIP)] · 2H2O}n (II) (AAP = 4-aminoantipyrine and NIP2− = 5-nitroisophthalate), were prepared by controlling the pH value of the reaction mixture. Complexes I and II were characterized by X-ray single-crystal diffraction analyses (CIF files CCDC nos. 936101 (I) and 936102 (II)). Complex I with terminal AAP molecule displays a linear chain with hemidirected Pb2+ ions connected by bis-bidentate chelating-NIP2− anions. By contrast, complex II exhibits a dimeric {Pb2(AAP)2}-based coplanar layer extended by bidentate chelating-bidentate chelating and bridging-NIP2− anions. Obviously, the pH-directed structural difference is dominated by the competitive binding modes of the AAP and carboxylate groups of NIP2− ligands. Both complexes display different thermal stability due to structural difference and similar emissions originated from the intra- and/or inter-ligand electron transfer, suggesting their potential application as luminescent materials.

The combination effects of acetaminophen and N-acetylcysteine on cytokines production and NF-κB activation of lipopolysaccharide-challenged piglet mononuclear phagocytes in vitro and in vivo

Lipopolysaccharide (LPS) is a known activator of mononuclear phagocytes. LPS activates the pro-inflammatory gene expression and induces the release of mediators/cytokines by TLR4-NF-κB signaling pathway. The purpose of this study was to investigate the effects of acetaminophen (AAP) and N-acetylcysteine (NAC), individually as well as in combination on LPS-induced cytokines production and NF-κB activation in piglets. AAP (0.125–1.0mM) and NAC (0.0625–1.0mM) down-regulate the expression of cytokines and inhibit NF-κB p65 protein transfer from the cytoplasm to the nucleus in vitro. NAC enhances the inhibition action of AAP on cytokines expression in vitro. IL-6 in piglet plasma of the AAP group (mixed feed concentration of 600mg/kg) was significantly reduced (P<0.05) at 3h after LPS-challenge as compared with the LPS control group. IL-10 also significantly reduced (P<0.05) at 24h after LPS injection. The levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-10) in piglet plasma of the NAC group (mixed feeding concentration of 1200mg/kg) were significantly lower at 3h after LPS stimulation (P<0.05). IL-10 was significantly decreased in the NAC group at 24h after LPS stimulation (P<0.05). AAP or NAC treated alone could reduce the NF-κB p65 concentration ratio. The levels of cytokines (TNF-α, IL-1β, IL-6, and IL-10) in the group with piglet plasma of AAP (mixed feed concentration of 600mg/kg) plus NAC (mixed feeding concentration of 1200mg/kg) group were significantly lower (P<0.05) at 3h after LPS activation. The level of IL-10 in the group with AAP plus NAC was significantly lower (P<0.05) at 24h after LPS stimulation, while the rest of the inflammatory cytokines were returned to the original levels. The NF-κB p65 concentration ratio had significantly reduced (P<0.05) when AAP and NAC were used in combination. In summary, NAC could enhance the anti-inflammatory effects of AAP both in vitro and in vivo.

Reduction in Nausea and Vomiting in Children Undergoing Cancer Chemotherapy by Either Appropriate or Sham Auricular Acupuncture Points with Standard Care

Over 40% of children with cancer have reported that chemotherapy-induced nausea and vomiting (CINV) are the two most distressing side-effects of treatment even when antiemetic drugs have been used. The purpose of this article is to report the findings from a feasibility and pilot study using auricular point acupressure point for CINV in a small group of children in Taiwan. This was a crossover randomized design study. CINV symptoms were assessed on 10 patients just prior to and for 7 days following each of three rounds of chemotherapy drugs (CTX). They received standard care (SC) and were not entered into a test treatment group until they completed the baseline assessment, which was conducted during their first round of chemotherapy after entering the study. Just prior to receiving the second round of CTX, patients were randomized into one of two treatment conditions: auricular acupressure intervention, in addition to standard care (AAP) or auricular acupressure using sham auricular points (SAP) in addition to standard care. For the third round of CTX, they were switched to the other treatment group. The enrollment rate for this study was 77% of the children invited to participate and of those, 88% provided completed data sets for all three treatment conditions. Patients in the AAP group reported significantly lower occurrence and severity of nausea and vomiting than patients in the SC group (p<0.05). There were no significant differences of nausea and vomiting for patients between the AAP and SAP groups. All of the patients took antiemetic medication on the day they received CTX, and 80% of patients reported that the antiemetics did not help to treat CINV. These preliminary findings did show evidence that AAP is acceptable to the children and their parents to prevent/treat CINV. However, there were no statistically significant differences between the AAP and SAP groups in the prevention/treatment of CINV. There were clinical trend differences between the groups, which may due to the small sample size. In a larger study, it would be important to determine whether the effects of the AAP and SAP treatment are independent of any psychologic effects, such as the researcher's increased presence in both treatment groups.