Higher ALP Levels Research Articles

Biochemical Assessment As Markers For Diagnosis And Evaluation Hepatitis B Virus (HBV)

Abstract 
 This paper summarizes assessment biochemical markers of the development of hepatitis B viruses (HBV), in which any possible connection between certain biochemical parameters and chronic hepatitis was identified. Liver function tests are helpful in diagnosing liver disease and dysfunction, assessing severity, tracking treatment, and determining prognosis. According to the findings of biochemical studies, chronic patients have higher levels of ALP, GPT, GOT, and TSB than carriers. The rise in liver enzymes strongly indicates hepatocellular damage, despite the fact that ALP, GPT, GOT, and TSB levels in the carrier group were all within normal parameters as compared to the reference group. Testing liver function in terms of protein level, albumin, and globulin, the concentration of protein profiles in chronic patients is clearly decreasing as compared to the carrier group. In severe or long-lasting liver disease, the significant decreasing profile of serum proteins is evident in some conditions, the release of tumor necrosis factor hampers the synthesis of albumin, however, induce the synthesis of the acute phase response, hypoalbuminemia is multifactorial, while the hepatic synthesis of albumin is decreased in liver disease.

Hypophosphatemic osteomalacia in neck femur fracture: Case series

Background: In adult acquired hypophosphatemic osteomalacia is generally associated with Biochemical abnormalities. Aims and Objective: To study Hypophosphatemic Osteomalacia in Neck femur fracture : A case series of 10 patients. Methodology: This was a cross-sectional study carried out in the department of Orthopedics from Aug 2015 to August 2016 in the patients who complained of Bilateral Hip (Groin) Pain and inability to walk were; Clinical, Radiological and all laboratory investigations whenever required were done and patients which were having final diagnosis of hypophosphatemic Osteomalacia in Neck femur fracture were included into the study during the study period. All details of the patients like age, sex and clinical features were noted. The data analysis was done by Excel software for windows 10. Result: In our study we have seen that the majority of the patients were in the age group of 60-70(40%), followed by 50-60 (20%), >70 (20%), 40-50 (10%), 30-40 (10%). The majority of the patients were Female (60%) and Males were 40%. The most common clinical features were Bilateral Hip (Groin) Pain (100%), Inability to walk (90%), Bilateral femur fracture (X-ray) in 30%, Unilateral femur fracture (X-ray ) in that Left was predominant i.e. 50% and Right were 20%. In the laboratory findings the all parameters were apparently normal except high Serum ALP level, low Serum Phosphorus level. Treatment and Outcome: Patient were treated conservatively they advised bed rest and supplementation of Tab. Endocal Forte OD, Protocol Supplement 2tsp with milk BD Adophos Sachet in ½ glass of Water QID, Tab. Rocaltrol (2.5) QID, average Patient were walking without support in an average 2 weeks, Pain decreased and also there is improvement of haematological parameter, X-ray shows signs of healing fracture. Conclusion: Hypophosphatemic Osteomalacia is commonly missed due to nonspecific signs and symptoms, but thorough investigation of blood and radiograph required for non-traumatic hip pain. This is rare condition needs high index of suspicion. This is totally curable by conservative Methods.

Treatment with bone maturation and average lifespan of HPP model mice by AAV8-mediated neonatal gene therapy via single muscle injection

Hypophosphatasia (HPP) is an inherited skeletal disease characterized by defective bone and tooth mineralization due to a deficiency in tissue-nonspecific alkaline phosphatase (TNALP). Patients with the severe infantile form of HPP may appear normal at birth, but their prognosis is very poor. To develop a practical gene therapy for HPP, we endeavored to phenotypically correct TNALP knockout (Akp2−/−) mice through adeno-associated virus type 8 (AAV8) vector-mediated, muscle-directed, TNALP expression. Following treatment of neonatal Akp2−/− mice with a single intramuscular injection of ARU-2801 (AAV8-TNALP-D10-vector) at 1.0 × 1012 vector genomes/body, high plasma ALP levels (19.38 ± 5.02 U/mL) were detected for up to 18 months, and computed tomography analysis showed mature bone mineralization. Histochemical staining for ALP activity in the knee joint revealed ALP activity on the surface of the endosteal bone of mice. Throughout their lives, the surviving treated Akp2−/− mice exhibited normal physical activity and a healthy appearance, whereas untreated controls died within 3 weeks. No ectopic calcification or abnormal calcium metabolism was detected in the treated mice. These findings suggest that ARU-2801-mediated neonatal intramuscular gene therapy is both safe and effective, and that this strategy could be a practical option for treatment of the severe infantile form of HPP.

DJ-1 Can Replace FGF-2 for Long-Term Culture of Human Pluripotent Stem Cells in Defined Media and Feeder-Free Condition.

Conventional human pluripotent stem cell (hPSC) cultures require high concentrations of expensive human fibroblast growth factor 2 (hFGF-2) for hPSC self-renewal and pluripotency in defined media for long-term culture. The thermal instability of the hFGF-2 mandates media change every day, which makes hPSC culture costly and cumbersome. Human DJ-1 (hDJ-1) can bind to and stimulate FGF receptor-1. In this study, for the first time, we have replaced hFGF-2 with hDJ-1 in the essential eight media and maintained the human embryonic stem cells (hESCs), H9, in the defined media at feeder-free condition. After more than ten passages, H9 in both groups still successfully maintained the typical hESC morphology and high protein levels of pluripotency markers, SSEA4, Tra1-60, Oct4, Nanog, and ALP. DNA microarray revealed that more than 97% of the 21,448 tested genes, including the pluripotency markers, Sox2, Nanog, Klf4, Lin28A, Lin28B, and Myc, have similar mRNA levels between the two groups. Karyotyping revealed no chromosome abnormalities in both groups. They also differentiated sufficiently into three germ layers by forming in vitro EBs and in vivo teratomas. There were some variations in the RT-qPCR assay of several pluripotency markers. The proliferation rates and the mitochondria of both groups were also different. Taken together, we conclude that hDJ-1 can replace hFGF-2 in maintaining the self-renewal and the pluripotency of hESCs in feeder-free conditions.

A case of transient hyperphosphatasemia presenting with mild degree of bow legs

Introduction: Transient Hyperphosphatasia (TH) is a benign condition in which serum Alkaline Phosphatase is elevated without any underlying pathology. This is mainly seen in children compared to adults and it is usually an incidental finding. The hallmark of the condition is that normalization of ALP level will with time. However, not knowing the entity would lead to unnecessary investigations and referrals. Here we report a child with TH who presents with a mild degree of bow legs. Case report: A 1year and 8 months old boy was brought by his mother with a concern of bow legs. He was the first child born to non-consanguineous healthy parents following normal antenatal and perinatal periods. His birth weight was 3.5kg and he was growing in his birth centile. He had age-appropriate development and parents had been having a concern about bow legs after he started walking. He is getting an average Sri Lankan diet with animal food and he gets adequate sun exposure as well. There was no history to suggest the liver of renal diseases. On examination, he had a mild degree of bow legs without any features to suggest rickets. His cardiovascular, respiratory, abdominal, and neurology exams were normal. His bone profile showed a high value of ALP (3782 U/L) with normal calcium, phosphate, and vitamin D levels. Due to high ALP levels, he underwent liver and renal functions and that was within the normal range. The diagnosis was made as TH and he was followed up monthly with ALP values. He had a downward trend of ALP levels and in 3 months the ALP value dropped to (580 U/L). Parents were reassured about the condition and the diagnosis was confirmed as TH. Conclusion: It is important to rule out, bone, kidney, or a liver pathology if a child has markedly elevated ALP levels. However, it is important to recognize this entity to avoid unnecessary procedures and concerns.

MicroRNA treatment modulates osteogenic differentiation potential of mesenchymal stem cells derived from human chorion and placenta

Mesenchymal stem cells (MSCs) are important in regenerative medicine because of their potential for multi-differentiation. Bone marrow, chorion and placenta have all been suggested as potential sources for clinical application. However, the osteogenic differentiation potential of MSCs derived from chorion or placenta is not very efficient. Bone morphogenetic protein-2 (BMP-2) plays an important role in bone development. Its effect on osteogenic augmentation has been addressed in several studies. Recent studies have also shown a relationship between miRNAs and osteogenesis. We hypothesized that miRNAs targeted to Runt-related transcription factor 2 (Runx-2), a major transcription factor of osteogenesis, are responsible for regulating the differentiation of MSCs into osteoblasts. This study examines the effect of BMP-2 on the osteogenic differentiation of MSCs isolated from chorion and placenta in comparison to bone marrow-derived MSCs and investigates the role of miRNAs in the osteogenic differentiation of MSCs from these sources. MSCs were isolated from human bone marrow, chorion and placenta. The osteogenic differentiation potential after BMP-2 treatment was examined using ALP staining, ALP activity assay, and osteogenic gene expression. Candidate miRNAs were selected and their expression levels during osteoblastic differentiation were examined using real-time RT-PCR. The role of these miRNAs in osteogenesis was investigated by transfection with specific miRNA inhibitors. The level of osteogenic differentiation was monitored after anti-miRNA treatment. MSCs isolated from chorion and placenta exhibited self-renewal capacity and multi-lineage differentiation potential similar to MSCs isolated from bone marrow. BMP-2 treated MSCs showed higher ALP levels and osteogenic gene expression compared to untreated MSCs. All investigated miRNAs (miR-31, miR-106a and miR148) were consistently downregulated during the process of osteogenic differentiation. After treatment with miRNA inhibitors, ALP activity and osteogenic gene expression increased over the time of osteogenic differentiation. BMP-2 has a positive effect on osteogenic differentiation of chorion- and placenta-derived MSCs. The inhibition of specific miRNAs enhanced the osteogenic differentiation capacity of various MSCs in culture and this strategy might be used to promote bone regeneration. However, further in vivo experiments are required to assess the validity of this approach.

Prevalence and severity of pruritus amongst patients with chronic kidney disease

Introduction: Skin problems are common and diverse in patients with chronic kidney disease (CKD). Pruritus is a highly prevalent condition in patients with chronic kidney disease. It is associated with poor sleep quality, anxiety and depression which may contribute to reduction in quality of life. Objective: To study the prevalence and severity of pruritus among patients with chronic kidney disease. Materials and Methods: An observational study was conducted in 77 consecutive chronic kidney disease patients receiving maintenance hemodialysis for more than 3 months at Manik hospital, Aurangabad, Maharashtra, India were studied during January 2015 to December 2015. Results: Out of 77 patients, 51 (66.23%) of males and 26 (23.67%) of females were examined. The mean age was 51.17 years. Xerosis was the commonest manifestation (87.01%), followed by pruritus (57.14%). Mild pruritus was reported in 59.09% patients whereas severe pruritus was noted in 22.27% patients. High urea, phosphate and ALP levels were noted in severe pruritus group, but difference not statistically significant. 32 patients with pruritus on maintenance HD were followed over next 6 months. Out of 32 patients followed, 37.5% had no change in pruritus. Pruritus improved in 28.12%, while it actually worsened in 34.37% patients. Conclusion: In this study, 57.14% of patients with chronic kidney disease experience pruritus. Gender, age, presence of DM, duration of dialysis was not statistically significant between pruritus and non-pruritus group. Also hematocrit was similar in pruritus and non-pruritus groups. There was no significant difference in calcium, phosphorus and alkaline phosphatase levels in pruritus and non-pruritus groups. Keywords: Pruritus, Skin Disorders, Hemodialysis.

Effect of allicin on antioxidant defense system, and immune response after carbofuran exposure in Nile tilapia, Oreochromis niloticus

In this work, allicin was evaluated as an immunostimulant and antioxidant agent preventing Nile tilapia; Oreochromis niloticus against carbofuran toxicity. Fish (60 ± 8 g) were allocated to five groups; the first group (control), the second group was fed 1 g/kg allicin–supplemented diets without carbofuran intoxication, the third group exposed to 1/10 LC50 carbofuran (0.246 mg/L). While the fourth, and fifth groups were fed allicin supplemented diet at concentration of 0.5 and 1 g/kg diet, respectively, and exposed to carbofuran at the same concentration similar to the one of the third group. After 30 days, fish exposed to carbofuran showed high ALT, AST, ALP, cholesterol, glucose, cortisol, uric acid, and creatinine levels. However, serum AChE, total proteins, immunoglobulins, and lysozyme activity were markedly (P ≤ 0.05) reduced in carbofuran exposed tilapia fish. Moreover, malondialdehyde (MDA) level was significantly increased in liver, and kidneys tissues of carbofuran exposed fish. Whereas, catalase (CAT) activity, superoxide dismutase (SOD), and total antioxidant capacity (TAC) were decreased (P ≤ 0.05) significantly in both liver, and kidneys tissues after exposure to carbofuran. Interestingly, tilapia fish treated with carbofuran (0.246 mg/L) and fed (0.5 and 1 g/kg diet) allicin in both the 4th & 5th groups, respectively, decreased serum biochemical parameters; and hepatorenal (MDA) levels, as well as increased AChE, immunological profile, and oxidative stress biomarkers. The results suggested that co- administration of allicin at the high dose is more capable of improving the biochemical, and immunological parameters, and tissue antioxidant responses of carbofuran treated fish.

Effects of fucoidan on the hematic indicators and antioxidative responses of Nile tilapia (Oreochromis niloticus) fed diets contaminated with aflatoxin B1.

Fucoidan is a rich source of medicinally active immunostimulants that possess various pharmacological properties. This study examined the potential impact of fucoidan on the hematic indicators and antioxidative responses of Nile tilapia fed diets contaminated with aflatoxin B1 (AFB1). Fish (60 ± 6.1g) were allocated to five groups; the first (control) and second groups were fed 0% or 1% fucoidan-supplemented diets without AFB1 contamination, while the third, fourth, and fifth groups were fed diets contaminated with AFB1 and supplemented with 0%, 0.5%, and 1% fucoidan, respectively. After 30days, fish fed AFB1 showed high ALT, AST, ALP, cholesterol, urea, and creatinine levels; furthermore, total blood protein and tissue (liver, kidney, and gill) glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activity significantly (P ≤ 0.05) decreased in fish fed AFB1, while tissue malondialdehyde significantly increased (P ≤ 0.05). Interestingly, fish fed fucoidan showed decreased ALT, AST, ALP, cholesterol, urea, and creatinine, as well as increased blood protein, GSH, GPx, SOD, and CAT activity. The results suggested that fucoidan is capable of inducing protective activity against AFB1 toxicity in Nile tilapia by enhancing the serum biochemical and tissue antioxidant responses of fish.

Evaluation of Anti-Hyperlipidemic Activity of Extracted Alpha-linlenic Acid from Natural Linum Usitatissimum Compared with Atorvastatin in High Fat Diet Induced Rats

Linum Usitatissimum (LU) has a lipid-lowering action in both normal and diabetic animals. Because OS leaves are rich in oil, the present study was conducted to explain the anti-hyperlipidemic and organ-protective effect of LU fixed oil in rats fed with a high fat (HF) diet. LU fixed oil was extracted by hexane and the fatty acids composition identified by GC-MS. Four groups of male Wister rats included a normal control group, a high fat fed-diet (HF) group, a HF group treated with LU fixed oil, and a HF group treated with a reference drug Atorvastatin. The results show that LU fixed oil contains five kinds of fatty acids, of which alpha-linolenic acid was the major fatty acid. LU fixed oil depressed high serum levels of total cholesterol, triglyceride, LDL-C, and AI, whereas no significant effect on HDL-C was observed. LU fixed oil also suppressed high levels of liver cholesterol and triglyceride with no significant effect on both lipids in feces. In addition, LU fixed oil normalized the high serum levels of LDH and CK-MB but no significant effect on high serum levels of ALT, AST, and ALP was obtained. We conclude that treatment with LU fixed oil during the last three weeks of HF diet feeding decreased the high serum lipid profile and expressed anti artherogenic and cardio protective actions against hyperlipidemia. The anti-hyperlipidemic action of OS fixed oil was mainly resulted from the suppression of liver lipid synthesis. Linolenic acid and linoleic acid contained in LU fixed oil were possibly responsible for both lipid-lowering and cardiac protective action against hyperlipidemia.

Alkaline Phosphatase Levels Before and After Nonsurgical Periodontal Therapy

Introduction: Chronic periodontitis is a multifactorial disease resulting in the inflammation and destruction of the supporting structures. Early detection of periodontal changes, prognosis and efficacy of treatment have been monitored by Alkaline Phosphatase Levels (ALP) levels.
 Objective: This study was carried out to determine level of ALP in saliva and serum before and after periodontal therapy.
 Methods: This pretest posttest study included 22 patients with generalised chronic periodontitis (GCP). The patients received nonsurgical periodontal therapy (NSPT). Saliva and serum levels of ALP were measured at baseline and after two months of periodontal therapy.
 Results: Twenty-two patients of mean age 44 years were analysed. Participants had significantly better periodontal parameters after two months. Salivary ALP levels, which were high at baseline, decreased after periodontal treatment. A significant positive correlation (0.0001) was found between the salivary levels of ALP and periodontal inflammatory conditions. Gingival index was found directly proportional with salivary ALP level but not with serum ALP.
 Conclusion: Periodontal therapy lowered the levels of ALP saliva in GCP patients with high ALP levels. Biochemical analysis of enzymes found in saliva may help in patients’ evaluation to determine the control and progression of periodontal destruction and aid in a correct diagnosis, prognosis and, consequently, better treatment.

Correlation between immune-related adverse events and prognosis in patients with gastric cancer treated with nivolumab

BackgroundRecent studies have shown that immune-related adverse events (irAEs) caused by immune checkpoint inhibitors were associated with clinical benefit in patients with melanoma or lung cancer. In advanced gastric cancer (AGC) patients, there have been few reports about the correlation between irAEs and efficacy of immune checkpoint inhibitors. In this study, we retrospectively investigated the correlation between irAEs and efficacy in AGC patients treated with nivolumab.MethodsThe subjects of this study were AGC patients received nivolumab monotherapy between January 2015 and August 2018. IrAEs were defined as those AEs having a potential immunological basis that required close follow-up, or immunosuppressive therapy and/or endocrine therapy. We divided the patients who received nivolumab into two groups based on occurrence of irAEs; those with irAEs (irAE group) or those without (non-irAE group). We assessed the efficacy in both groups.ResultsOf the 65 AGC patients that received nivolumab monotherapy, 14 developed irAEs. The median time to onset of irAEs was 30.5 days (range 3–407 days). Median follow-up period for survivors was 32 months (95% CI, 10.8 to 34.5). The median progression-free survival was 7.5 months (95% CI, 3.6 to 11.5) in the irAE group and 1.4 months (95% CI, 1.2 to 1.6) in the non-irAE group (HR = 0.11, p < 0.001). The median overall survival was 16.8 months (95% CI, 4.4 to not reached) in the irAE group and 3.2 months (95% CI, 2.2 to 4.1) in the non-irAE group (HR = 0.17, p < 0.001). Multivariate analysis demonstrated that number of metastatic sites ≥2 (HR = 2.15; 95% CI, 1.02 to 4.54), high ALP level (HR = 2.50; 95% CI, 1.27 to 4.54), and absence of irAEs (HR = 9.54, 95% CI, 3.34 to 27.30 for yes vs. no) were associated with a poor prognosis. The most frequent irAEs was diarrhea/colitis (n = 5). Grade 3 adverse events were observed in 6 patients; hyperglycemia (n = 2), diarrhea/colitis (n = 1), adrenal insufficiency (n = 1), aspartate aminotransferase increased (n = 1), peripheral motor neuropathy (n = 1). There were no grade 4 or 5 adverse events related to nivolumab.ConclusionsDevelopment of irAEs was associated with clinical benefit for AGC patients receiving nivolumab monotherapy.

Effects of parathyroidectomy on tumoral calcinosis in uremic patients with secondary hyperparathyroidism

BackgroundTumoral calcinosis (TC) is a rare disease derived from uremic secondary hyperparathyroidism (SHPT). However, parathyroidectomy (PTX) seems to be ineffective at relieving TC in some patients. In this study, we investigated the relationship between PTX and TC shrinkage.MethodsWe retrospectively followed up nine TC patients who underwent PTX, dividing them into two groups: those with TC size reduced by > 80% were in the “effective group” (group A), and the rest in the “ineffective group” (group B).ResultsWe enrolled nine patients (7 men; mean age 38.6 ± 10.9 years) with SHPT-related TC. One patient with calciphylaxis was excluded due to sudden death. The efficiency of PTX in causing TC regression was 62.5% (5 patients in group A). Group A had a shorter overall duration of TC (6 [5.5, 6.0] vs. 9 [8.0, 10.0] months; P = 0.02) and higher serum levels of alkaline phosphatase (ALP; 408.0 [217.9, 1101.7] vs. 90.8 [71.0, 102.1] pg/ml; P = 0.03) and high-sensitivity C-reactive protein (hs-CRP; 82.7 [55.0, 112.4] vs. 3.1 [3.1, 4.5] mg/l; P = 0.02). Average calcium supplementation within 1 week of surgery was significantly greater in group A than in group B (96.8 [64.1, 105.3] vs. 20.1 [13.1, 32.7] g; P = 0.04). Patients in both the groups demonstrated similar serum phosphate levels before PTX, but these levels were higher in group B than in group A at follow-up times (3 months, P = 0.03; 6 months, P = 0.03).ConclusionsThe shorter duration of pre-existing TC and higher ALP levels before PTX, as well as lower serum phosphate levels after PTX, were correlated with effective SHPT-TC shrinkage.

Bone metabolism markers and hungry bone syndrome after parathyroidectomy in dialysis patients with secondary hyperparathyroidism.

To explore the short-term variation in bone metabolic markers and the characteristics of hungry bone syndrome (HBS) after parathyroidectomy (PTX) with forearm autotransplantation in uremic patients with secondary hyperparathyroidism (SHPT) and to provide a basis for the pathogenesis, diagnosis and treatment of metabolic bone disease in SHPT. A total of 115 patients with SHPT receiving PTX from July 2015 to December 2017, hospitalized at the First Affiliated Hospital of Nanjing Medical University, were enrolled in our study. We retrospectively analyzed the baseline clinical data, the levels of bone metabolism markers before and on the third day after PTX, and the risk factors predicting HBS. Preoperative baseline data showed that the levels of bone metabolic markers such as bone metabolism-regulating hormones: iPTH, calcitonin (CT); bone formation markers: phosphatase (ALP), osteocalcin (OC); bone resorption markers: type I collagen cross-linked N-telopeptides (NTX), type I collagen cross-linked C-telopeptides (CTX), tartrate-resistant acid phosphatase 5b (TRAP-5b) were all increased compared to normal levels. The levels of postoperative serum iPTH, CT, CTX and TRAP-5b decreased significantly compared to preoperative levels, while the levels of OC and ALP increased significantly. Of the 115 patients, 101 (87.8%) developed HBS after PTX. High preoperative serum ALP and low preoperative serum calcium level independently predicted the occurrence of HBS. Younger preoperative age, high preoperative serum ALP and iPTH level independently predicted the severity of HBS. In severe SHPT, both bone formation and resorption were active, which suggested the presence of high-turnover bone diseases characterized by up-regulation of osteoclasts-osteoblasts functionally coupling activation in the patients. PTX could promote osteoblast activity and reduce osteoclast activity. HBS was common after PTX. Preoperative higher serum ALP and lower calcium were independent predictors of the occurrence of HBS. Younger patients with higher preoperative ALP and PTH may need to closely monitor serum calcium levels and intensive calcium supplementation after PTX.

Correlation between immune-related adverse events and prognosis in patients with gastric cancer treated with nivolumab.

4049 Background: Recent studies have shown that immune-related adverse events (irAEs) caused by immune checkpoint inhibitors were associated with clinical benefit in patients with melanoma or lung cancer. In advanced gastric cancer (AGC) patients, there have been few reports about the correlation between irAEs and efficacy of immune checkpoint inhibitors. Therefore, in this study, we retrospectively investigated the correlation between irAEs and efficacy in AGC patients treated with nivolumab. Methods: The subjects of this study were AGC patients that had received nivolumab monotherapy between January 2015 and August 2018. IrAEs were defined as those AEs having a potential immunological basis that required close follow-up, or immunosuppressive therapy and/or endocrine therapy. We divided the patients who received nivolumab into two groups based on occurrence of irAEs; those with irAEs (irAE group) or those without (non-irAE group). We assessed the efficacy in both groups. Results: Of the 65 AGC patients that received nivolumab monotherapy, 14 developed irAEs. The median time to onset of irAEs was 30.5 days (range 3–407 days). Median follow-up period for survivors was 32 months (95% CI, 10.8 to 34.5). The median progression-free survival was 7.5 months (95% CI, 3.6 to 11.5) in the irAE group and 1.4 months (95% CI, 1.2 to 1.6) in the non-irAE group (HR = 0.11, p &lt; 0.001). The median overall survival was 16.8 months (95% CI, 4.4 to not reached) in the irAE group and 3.2 months (95% CI, 2.2 to 4.1) in the non-irAE group (HR = 0.17, p &lt; 0.001). Multivariate analysis demonstrated that high ALP level (HR = 2.88; 95% CI, 1.51 to 5.51) and absence of irAEs (HR = 3.06, 95% CI, 3.06 to 23.46 for yes vs. no) were associated with a poor prognosis. The most frequent irAEs was diarrhea/colitis (n = 5). Grade 3 adverse events were observed in 6 patients; hyperglycemia (n = 2), diarrhea/colitis (n = 1), adrenal insufficiency (n = 1), increased aspartate aminotransferase increased (n = 1), peripheral motor neuropathy (n = 1). One of the 14 patients experienced the irAE after discontinuation of nivolumab due to progression of disease. There were no grade 4 or 5 adverse events related to nivolumab. Conclusions: Development of irAEs was associated with clinical benefit for AGC patients receiving nivolumab monotherapy.

In vitro evaluation of a novel multiwalled carbon nanotube/nanohydroxyapatite/polycaprolactone composite for bone tissue engineering

Abstract

Clinical disparity of elevated serum alanine aminotransferase (ALT) levels among the working population of Taipei, Taiwan

Purpose: To explore sex variations in the prevalence and factors of high serum alanine aminotransferase (ALT) level among the working population in Taipei, Taiwan.Methods: This study included 8,351 healthy adults (5,247 men and 3,104 women) who admitted to a teaching hospital voluntarily for a physical examination in 2009. The definitions of occupations include computer and mathematical occupations, architecture and engineering occupations, community and social service occupations, sales and related occupations, office and administrative support occupations, and production occupations. The age distribution of $\leq$ 29 yrs, 30-39 yrs, 40-49 yrs, and $\geq$ 50 yrs were 22.5\%, 36.8\%, 23.5\%, and 17.2\%, respectively. Fasting blood samples were drawn using venipuncture and participants were interviewed with a structured questionnaire.Results: The overall prevalence of high serum ALT level ($\geq $ 40 U/L) was 17.1\%. After stratified the data according to age into four age groups ($\leq$ 29yrs, 30-39 yrs, 40-49 yrs, and $\geq$ 50 yrs) , the men participants revealed a higher prevalence of high serum ALT levels for all age groups than the women participants. Bases on multiple logistic regression models, for the men, the significant factors were associated with high serum ALT level and included age (OR = 0.96, 95\% CI: 0.95-097), BMI [no matter whether overweight (OR = 2.45, 95\% CI: 1.99-3.02) or obese (OR = 4.02, 95\% CI: 3.22-5.03)], hypercholesterolemia (yes vs. no, OR = 1.25, 95\% CI: 1.05-1.48), hypertriglyceridemia (OR = 1.25, 95\% CI: 1.04-1.50), high FPG levels (OR = 1.48, 95\% CI: 1.05-2.09), high AST levels (OR = 26.71, 95\% CI: 19.00-37.54), hyperuricemia (OR = 1.48, 95\% CI: 1.25-1.76), high ALP levels (OR = 1.20, 95\% CI: 1.00-1.45), and high glutamic acid transaminase levels (OR = 4.31, 95\% CI: 3.61-5.14). For the women subjects, the statistically significant factors that were associated with high serum ALT level included BMI [no matter whether overweight (OR = 3.53, 95\% CI: 1.87-6.67) or obese (OR = 4.32, 95\% CI: 2.26-8.23)], high AST levels (yes vs. no, OR = 38.49, 95\% CI: 21.45-49.28), high BUN levels (yes vs. no, OR = 1.66, 95\% CI: 1.03-2.29), and high glutamic acid transaminase levels (yes vs. no, OR = 9.87, 95\% CI: 5.79-16.83).Conclusion: In conclusion, the clinical problem of elevated serum ALT level is important in the working population. Many subjects are asymptomatic and the diagnosis of high serum ALT level should be considered with sex, age, hyperuricemia, high AST levels, high ALP levels, high glutamic acid transaminase levels, and metabolic risk factors in mind.

P-264 - HGCSG1401: A retrospective cohort study evaluating the safety and efficacy of regorafenib in patients with metastatic colorectal cancer: Analysis of risk factors for liver dysfunction

Introduction: Regorafenib (REG) prolongs overall survival (OS) and progression-free survival (PFS) for patients (pts) with metastatic colorectal cancer (mCRC) in RCTs. However, there is a problem with REG-induced severe liver dysfunction (≥Grade 3) which occurs in 5-11% of treated Japanese pts. Therefore, we analyzed the incidence, therapeutic efficacy, and potential risk factors for REG-induced severe liver dysfunction in a community-based retrospective study (HGCSG1401) of pts treated with REG. Methods: 173 pts treated with REG were retrospectively registered from 22 centers in Japan. Survival analyses were performed with Kaplan-Meier method. Log-rank test and Cox-proportional hazard model were used to compare Grade 0-2 and 3-5. To identify risk factors for REG-induced severe liver dysfunction, a multivariate analysis was performed using the logistic regression analysis with backward elimination for variables with p < 0.10 in univariate analysis. Results: In 173 eligible pts, 24 (13.9%) experienced REG-induced severe liver dysfunction. The median PFS of Grade 0-2 and 3-5 were 2.2 and 1.6 months, respectively. The median OS of Grade 0-2 and 3-5 were 6.9 and 3.4 months, respectively. In the analysis of PFS and OS, there were significant difference between Grade 0-2 and 3-5 (PFS: HR 1.578, p = 0.045, OS: HR 1.799, p = 0.010). Univariate analyses showed that high AST, LDH, ALP, and GGT level at baseline were associated with REG-induced severe liver dysfunction. In multivariate analyses, high baseline AST level (≥ 50 U/L) was significantly associated with increased risk of REG-induced severe liver dysfunction (odds ratio=3.458, p = 0.032). Conclusion: Compared with previous reports, this analysis showed the slightly higher incidence of REG-induced severe liver dysfunction (13.9%). In multivariate analysis, it was inferred that high AST level (≥ 50 U/L) at baseline might be an independent risk factor. REG-induced severe liver dysfunction population significantly showed shorter OS than mild liver dysfunction. It is presumed that this patient population could not receive TAS-102 as post regorafenib therapy. Since this is an exploratory analysis, we consider it necessary to verify in large data set.

Mo1268 ENDOSCOPIC BILIARY STENTING IS SIGNIFICANTLY ASSOCIATED WITH CHOLANGITIS AFTER ENDOSCOPIC ULTRASOUND IN PATIENTS WITH BILIARY STRICTURES

Endoscopic ultrasound (EUS) and EUS-guided fine needle aspiration (FNA) are considered as a safe modality for the diagnosis of pancreatobiliary lesions because of low risk of complications such as bleeding, perforation and pancreatitis. However, the risk of cholangitis after EUS/EUS-FNA in patients with biliary strictures has not been fully investigated. In this study, we examined the rate of cholangitis after EUS/EUS-FNA in these patients and investigated associated risk factors. We retrospectively reviewed the data of the inpatients with biliary strictures who underwent EUS/EUS-FNA at our institution between April 2013 and September 2017. We excluded 8 cases with percutaneous biliary drainage and 4 cases with difficulty in reaching duodenum. Cholangitis and its severity were diagnosed based on Tokyo Guidelines 2013. 114 patients (133 cases in total) were included; 59.4% were male; median age was 71; 85 patients (72.2%) were malignant (pancreatic cancer 46, distal cholangiocarcinoma 12, hilar cholangiocarcinoma 17, intrahepatic cholangiocarcinoma 2, gallbladder cancer 3 and the others 5) and 29 were benign (IgG4-related disease 11, primary sclerosing cholangitis 1, tumor-forming pancreatitis 1 and the others 16). The location of biliary strictures was 93 cases in distal (69.9%), 29 in hilar (21.8%), 4 in intrahepatic (3.0%) and 7 in spreading (5.3%). Endoscopic biliary stenting (EBS) had been already performed before EUS/EUS-FNA in 79 cases (59.4%). Median time from EBS to EUS/EUS-FNA was 20 days (range; 1-125 days). EUS-FNA was performed in 53 cases (39.8%). Cholangitis was observed in 4.6% (6/133). The severity was mild in 2, moderate in 3 and severe in 1 case. The patient who suffered from severe cholangitis underwent urgent endoscopic nasal biliary drainage at the day of EUS. The incidence of cholangitis in the cases with EBS was significantly higher than those without EBS (7.6% (6/79) vs. 0% (0/54), p=0.041). Other statistically significant risk factors of cholangitis were gamma-GTP levels (higher (7.7%, 6/78) vs. lower (0%, 0/55), p=0.037) and ALP levels (higher (11.3%, 6/53) vs. lower (0%, 0/80), p=0.003). Age, gender, malignant/benign disease, the location of biliary strictures, endoscopic sphincterotomy, examination time, examination with/without EUS-FNA, WBC, CRP, AST and ALT were not significant risk factors. Cholangitis occurred in 17.6% of the cases with EBS and higher ALP levels (6/34), while no cholangitis occurred in the cases only with higher ALP levels (0/19). Cholangitis after EUS/EUS-FNA occurred in 4.6% of the cases with biliary strictures. The use of prophylactic antibiotics might be beneficial in these cases, especially with EBS and biliary enzyme elevation. Further prospective study in a larger scale is required.

Clinical Characteristics and Prognostic Factors in Bone Metastases from Lung Cancer.

BackgroundThis study investigated the prognostic factors of bone metastases from lung cancer.Material/MethodsFrom March 2014 to March 2015, 168 patients with bone metastases from lung cancer treated at our hospital were included and the clinical data were reviewed. The Kaplan-Meier survival curves were calculated and analyzed using the log-rank univariate test. Multivariate regression analysis was conducted using Cox’s regression model.ResultsThe overall median survival of the 168 patients was 13 months. The 1-year survival was 54.3% and the 2-year survival was 12.9%. Univariate regression analysis indicated that the pathologic types, number of bone metastases, clinical stage, ECOG scores, and serum ALP levels were significantly correlated with survival (P<0.05). Multivariate regression analysis indicated that the number of bone metastases, clinical stage, and serum ALP levels were significantly correlated with prognosis (P<0.05). The risk associated with multiple bone metastases was 1.72 times of that of single bone metastasis (P=0.029); the risk associated with advanced clinical stage was 1.49 times of that of early clinical stage (P=0.001); and the risk associated with a high serum ALP level was 1.75 times of that of the low serum ALP level (P=0.006).ConclusionsPathologic types, number of bone metastases, clinical stage, ECOG scores, and serum ALP levels were the prognostic factors for bone metastases from lung cancer.